Parames Chandra Sil
Parames Chandra Sil
Senior Professor, Division of Molecular Medicine
PhD: Bose Institute (University of Calcutta), 1990
Through the last decades, our research was focused on unravelling the mechanism(s) of cell injury in multiple organs and exploration of the prophylactic activity of several bioactive molecules in the amelioration of the organ dysfunction. In recent years our laboratory is also focusing on selective induction of apoptosis in cancer cells mediating oxidative stress and nanoparticle-mediated targeted drug and gene delivery into cancer cells to achieve synergistic anticancer effects.
Division of Molecular Medicine
P-1/12 C.I.T. Scheme VII-M
Kolkata - 700054, India
Research in our laboratory encompasses several major areas of organ pathophysiology (hepatotoxicity, gastropathy, cardiotoxicity, neurotoxicity, and nephrotoxicity), diabetes, colitis, cancer and its protection via bio-active molecules. However, special emphasis is placed upon:
To understand the mechanisms of antioxidant potentials of phytochemicals.
Chemical and drug induced mechanisms of cell injury/death (both in vitro and in vivo).
Studies on the signal transduction mechanism of cell death and survival. To understand the anti-cancer potential of different phytochemicals and synthesized derivatives.
Targeted drug delivery through different nanoparticles to enhance the efficiency.
Ongoing research work:
Diabetic nephropathy remains the prevalent cause of chronic renal disease in the world. Despite improvements in the current therapeutic standard for diabetic nephropathy which involved blood pressure and glycemic control in Type1 Diabetic patients, the pathophysiology is relentlessly progressing. Hyperglycemia, cellular stress, inflammation etc. contribute to the development of diabetic nephropathy. Keeping this background in mind, much emphasis has been laid in the discovery of new therapeutic targets and naturally occurring molecules having therapeutic potential to combat against the pathophysiology. A rodent model has been chosen for the present study in which streptozotocin is the diabetogenic agent which induces hyperglycemia through excessive free radical production, whereas; ferulic acid has been chosen from a stringent screening of several molecules due to its wide range of biological activities such as anti-diabetic, antioxidant, anti-inflammatory etc. The study is concerned with the signaling mechanism through which ferulic acid provides protection against stress mediated diabetic nephropathy.
Targeting inflammation with various bioactive molecules
Inflammation and oxidative stress play a pivotal role in origin and progress of inflammatory bowel disease (IBD). Gaseous mediators produced in the body possess anti-inflammatory properties. Sulfur dioxide is one such gaseous compound having diverse physiological functions. Till date little is known about its effect on IBD (colitis). It is a crucial need of the era to elucidate the detail molecular mechanism exerted by sulfur dioxide on colon in IBD.
Inflammation is a physiological phenomenon which paves way for chemotherapeutic drug-induced pathophysiology. Detailed study of the toxic effect of the chemotherapeutic drug, cisplatin in various organs (Spleen, kidney, heart) and the effect of bioactive molecules (taurine, carnosine) on cisplatin-induced organ pathophysiology needs to be investigated.
Deleterious effects of oxidative stress in brain
Brain is one of the main organs of the body having a governing role in all other major body organs like liver, kidney, lungs, hearts, reproductive organs etc. Again damage to organs like kidney cause indirect deleterious effects in brain. Various endogenous and environmental factors affect the brain directly. So, our lab tries to elucidate the mechanism involved in such brain damages and the ameliorative effect of various natural antioxidant polyphenols against such abnormal alterations (mangiferin, genistein).
Nanocarrier-mediated targeted co-delivery of doxorubicin and siRNA for synergistic cancer therapy
Co-delivery of small interfering RNA (siRNA) and chemotherapeutic drugs to tumor cells is a vital means to silence malignant oncogenes and/or drug resistant genes during the course of cancer chemotherapy for an improved chemotherapeutic effect. However, it was found that simultaneously delivering therapeutic siRNA and chemotherapeutic drugs co-loaded in a single nanocarrier was more effective in treating cancers compared to sequential administration of two separate nanocarriers with one drug in each. In the proposed research scheme, therefore we would like to synthesize tumor-targeted nanoparticles for effective co-delivery of therapeutic siRNA and anticancer drugs into cancer cells and tumor in vivo. The biggest challenge in co-delivery drugs and gene agents is to find appropriate carriers since the physicochemical properties of negatively charged oligonucleotides are drastically different from those of small hydrophobic drug molecules; therefore, separate mechanisms are usually required to encapsulate these two distinct payloads. Besides, development of nanoparticle-drug conjugates with tumor-site specific (low pH microenvironment) drug delivering ability is crucial in order to minimize its toxic side effects to normal tissues.
Targeted delivery of nanoparticles
Mesoporous silica nanoparticles (MSN) are an emerging drug delivery system for its unique features including relatively very low toxicity among other inorganic nano delivery systems. We have used MSNs to improve the bioavailability of some polyphenolic natural antioxidants like curcumin. We have also pegylated MSNs to further improve its blood circulation lifetime by escaping phagocytosis. In vivo results showed enhanced bioavailability and hence anti-cancer activity of curcumin effectively.
Published papers: 135
Published Book Chapter: 9
List of Publications
1. Bhattacharyya S, Banerjee S, Guha C, Ghosh S, Sil PC (2017). A 35 kDa Phyllanthus niruri protein suppresses indomethacin mediated hepatic impairments: Its role in Hsp70, HO-1, JNKs and Ca 2+ dependent inflammatory pathways. Food and Chemical Toxicology, 102, 76-92.
2. Ghosh S, Sarkar A, Bhattacharyya S, Sil PC (2016) Silymarin protects mouse liver and kidney from thioacetamide induced toxicity by scavenging reactive oxygen species and activating PI3K-Akt pathway. Frontiers in Pharmacology, 2016;7.
3. Chowdhury S, Ghosh S, Rashid K, Sil PC (2016) Deciphering the role of ferulic acid against streptozotocin-induced cellular stress in the cardiac tissue of diabetic rats. Food and Chemical Toxicology, 97, 187-198.
4. Sarkar A, Ghosh S, Chowdhury S, Pandey B, Sil, PC (2016) Targeted delivery of quercetin loaded mesoporous silica nanoparticles to the breast cancer cells. Biochimica et Biophysica Acta (BBA)-General Subjects, 1860(10), 2065-2075.
5. Sadhukhan P, Saha S, Sinha K, Brahmachari G, Sil PC (2016) Selective Pro-Apoptotic Activity of Novel 3, 3′-(Aryl/Alkyl-Methylene) Bis (2-Hydroxynaphthalene-1, 4-Dione) Derivatives on Human Cancer Cells via the Induction Reactive Oxygen Species. PLoS ONE, 11(7), e0158694.
6. Chowdhury S, Sinha K, Banerjee S, Sil PC (2016) Taurine protects cisplatin induced cardiotoxicity by modulating inflammatory and endoplasmic reticulum stress responses. BioFactors 42 (6), 647-664.
7. Saha S, Sadhukhan P, Sil PC (2016) Mangiferin: A xanthonoid with multipotent anti‐inflammatory potential. BioFactors 42 (5), 459-474.
8. Saha S, Rashid K, Sadhukhan P, Agarwal N, Sil PC (2016) Attenuative role of mangiferin in oxidative stress mediated liver dysfunction in arsenic intoxicated murines. BioFactors 42 (5), 515-532.
9. Saha S, Sadhukhan P, Sinha K, Agarwal N, Sil PC (2016) Mangiferin attenuates oxidative stress induced renal cell damage through activation of PI3K induced Akt and Nrf-2 mediated signaling pathways. Biochem Biophys Rep 5:313–327.
10. Rashid K, Sil PC (2015) Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats. Toxicol Appl Pharmacol 282:297–310.
11. Pal S, Ghosh M, Ghosh S, Bhattacharyya S, Sil PC (2015) Atorvastatin induced hepatic oxidative stress and apoptotic damage via MAPKs, mitochondria and ER dependent pathways. Food Chem Toxicol 83:36-47.
12. Sinha K, Sadhukhan P, Saha S, Pal PB, Sil PC (2015) Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway. Biochim. Biophys. Acta [General Subjects] 1850:769-783.
13. Sadhukhan P, Saha S, Sil PC (2015) Targeting Oxidative Stress: A Novel Approach in Mitigating Cancer. Biochem Anal Biochem 4 (236):2161-1009.1000236.
14. Rashid K, Sil PC (2015) Curcumin ameliorates testicular damage in diabetic rats by suppressing cellular stress mediated mitochondria and endoplasmic reticulum dependent apoptotic death. Biochim. Biophys. Acta [Molecular Basis of Disease] 1852:70-82.
15. Ghosh S, Banjerjee S, Sil PC (2015) The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update. Food Chem Toxicol 83:111-124.
16. Das J, Sarkar A, Sil PC (2015) Hexavalent chromium induces apoptosis in Human Liver (HepG2) cells via redox imbalance. Toxicol Rep 2:600-608.
17. Pal S, Sarkar A, Pal PB, Sil PC (2015) Protective effect of arjunolic acid against atorvastatin induced hepatic and renal pathophysiology via MAPK, mitochondria and ER dependent pathways. Biochimie 112:20-34.
18. Ghosh S, Bhattacharyya S, Rashid K, Sil PC (2015) Curcumin protects rat liver from streptozotocin-induced diabetic pathophysiology by counteracting reactive oxygen species and inhibiting the activation of p53 and MAPKs mediated stress response pathways. Toxicol Rep 2:365–376.
19. Bhattacharyya S, Sinha K, Sil PC (2014) Cytochrome P450s: mechanisms and biological implications in drug metabolism and its interaction with oxidative stress. Curr Drug Metab 15:719-742.
20. Pal PB, Sinha K, Sil PC (2014) Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFα related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats. PLoS ONE 9(9):e107220.
21. Saha S, Sadhukhan P, Sil PC (2014) Genistein: A phytoestrogen with multifaceted therapeutic properties. Mini-Rev Medicinal Chem 14:920-940.
22. Ghosh M, Pal S, Sil PC (2014) Taurine attenuates nano copper induced oxidative hepatic damage via mitochondria dependent and NF-B/TNF- mediated pathway. Toxicol Res 3:474–486.
23. Bhattacharyya S, Ghosh S, Sil PC (2014) Amelioration of Aspirin Induced Oxidative Impairment and Apoptotic Cell Death by a Novel Antioxidant Protein Molecule Isolated from the Herb Phyllanthus niruri. PLoS ONE 9(2):e89026.
24. Sarkar A, Sil PC (2014) Iron oxide nanoparticles mediated cytotoxicity via PI3K/AKT pathway:Role of quercetin. Food Chem Toxicol 71:106-115.
25. Sinha K, Pal PB, Sil PC (2014) Cadmium (Cd2+) exposure differentially elicits both cell proliferation and cell death related responses in SK-RC-45. Toxicol In Vitro 28:307-318.
26. Sarkar A, Ghosh M, Sil PC (2014) Nanotoxicity: Oxidative stress mediated toxicity of metal and metal oxide nanoparticles. J Nanosci Nanotech 14:730-743.
27. Rashid K, Sinha K, Sil PC (2013) An update on oxidative stress-mediated organ pathophysiology. Food Chem Toxicol 62:584-600.
28. Sinha K, Das J, Pal PB, Sil PC (2013) Oxidative stress: the mitochondrial dependent and independent pathways of apoptosis. Arch Toxicol 87(7):1157-1180.
29. Bhattacharya S, Gachhui R, Sil PC (2013) Effect of Kombucha, a fermented black tea in attenuating oxidative stress mediated tissue damage in alloxan induced diabetic rats. Food Chem Toxicol 60:328-340.
30. Manna P, Das J, Sil PC (2013) Role of sulfur containing amino acids as an adjuvant therapy in the prevention of diabetes and its associated complications. Curr Diabetes Rev 9(3):237-248.
31. Bhattacharyya S, Pal PB, Sil PC (2013) A 35 kD Phyllanthus niruri protein modulates iron mediated oxidative impairment to hepatocytes via the inhibition of ERKs, p38 MAPKs and activation of PI3k/Akt pathway. Food Chem Toxicol 56:119-130.
32. Ghosh J, Sil PC (2013) Arjunolic acid: A new multifunctional therapeutic promise of alternative medicine. Biochimie 95(6):1098-1109.
33. Bhattacharya S, Gachhui R, Sil PC (2013) The prophylactic role of D-saccharic acid-1,4-lactone against hyperglycemia-induced hepatic apoptosis via inhibition of both extrinsic and intrinsic pathways in diabetic rats. Food Func 4(2):283-296.
34. Pal PB, Sinha K, Sil PC (2013) Mangiferin, a natural xanthone, protects murine liver in Pb(II) induced hepatic damage and cell death via MAP kinase, NF-
35. Bhattachary S, Manna P, Gachhui R, Sil PC (2013) D-saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via NF-
36. Rashid K, Das J, Sil PC (2013) Taurine ameliorate alloxan induced oxidative stress and intrinsic apoptotic pathway in the hepatic tissue of diabetic rats. Food Chem Toxicol 51(1):317-329.
37. Manna P, Ghosh M, Ghosh J, Das J, Sil PC (2012) Contribution of nano-copper particles to in vivo liver dysfunction and cellular damage: Role of IκBα/NF-κB, MAPKs and mitochondrial signal. Nanotoxicology 6(1):1-21.
38. Bhattacharyya S, Ghosh J, Sil PC (2012) Iron induces hepatocytes death via MAPK activation and mitochondria-dependent apoptotic pathway: beneficial role of glycine. Free Radic Res 46(10):1296-1307.
39. Das J, Sil PC (2012) Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats. Amino Acids 43(4):1509-1523.
40. Pal S, Ahir M, Sil PC (2012) Doxorubicin-induced neurotoxicity is attenuated by a 43-kD protein from the leaves of Cajanus indicus L. via NF-κB and mitochondria dependent pathways. Free Radic Res 46(6):785-798.
41. Roy A, Sil PC (2012) Tertiary butyl hydroperoxide induced oxidative damage in mice erythrocytes: Protection by taurine. Pathophysiology 19(2):137-148.
42. Pal S, Sil PC (2012) A 43 kD protein from the leaves of the herb Cajanus indicus L. modulates doxorubicin induced nephrotoxicity via MAPKs and both mitochondria dependent and independent pathways. Biochimie 94:1356-1367.
43. Ghosh M, Das J, Sil PC (2012) D(+) galactosamine induced oxidative and nitrosative stress-mediated renal damage in rats via NF-B and inducible nitric oxide synthase (iNOS) pathways is ameliorated by a ployphenol xanthone, mangiferin. Free Radic Res 46(2):116-132.
44. Das J, Vasan V, Sil PC (2012) Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis. Toxicol Appl Pharmacol 258:296–308.
45. Pal PB, Pal S, Manna P, Sil PC (2012) Traditional extract of Pithecellobium dulce fruits protects mice against CCl 4 induced renal oxidative impairments and necrotic cell death. Pathophysiology 19(2):101-114.
46. Pal PB, Pal S, Das J, Sil PC (2012) Modulation of mercury-induced mitochondria-dependent apoptosis by glycine in hepatocytes. Amino Acids 42:1669–1683.
47. Roy A, Sil PC (2012) Taurine protects murine hepatocytes against oxidative stress-induced apoptosis by tert-butyl hydroperoxide via PI3K/Akt and mitochondrial-dependent pathways. Food Chem 131:1086-1096.
48. Manna P, Sil PC (2012) Arjunolic acid: benefi cial role in type 1 diabetes and its associated organ pathophysiology. Free Radic Res 46(7):815-830.
49. Das J, Ghosh J, Roy A, Sil PC (2012) Mangiferin exerts hepatoprotective activity against D-galactosamine induced acute toxicity and oxidative/nitrosative stress via Nrf2- Toxicol Appl Pharmacol 260:35–47.
50. Manna P, Sil PC (2012) Impaired redox signaling and mitochondrial uncoupling contributes vascular inflammation and cardiac dysfunction in type 1 diabetes: Protective role of arjunolic acid. Biochimie 94:786-797.
51. Das J, Ghosh J, Manna P, Sil PC (2012) Taurine protects rat testes against doxorubicin-induced oxidative stress as well as p53, Fas and caspase 12-mediated apoptosis Amino Acids 42:1839–1855.
52. Rashid K, Bhattacharya S, Sil PC (2012) Protective role of D-saccharic acid-1,4-lactone in alloxan induced oxidative stress in the spleen tissue of diabetic rats is mediated by suppressing mitochondria dependent apoptotic pathway. Free Radic Res 46(3):240–252.
53. Das J, Roy A, Sil PC (2012) Mechanism of the protective action of taurine in toxin and drug induced organ pathophysiology and diabetic complications: a review. Food Func 3(12):1251–1264.
54. Ghosh J, Das J, Manna P, Sil PC (2011) The protective role of arjunolic acid against doxorubicin induced intracellular ROS dependent JNK-p38 and p53 mediated cardiac apoptosis. Biomaterials 32(21):4857-4866.
55. Bhattacharya S, Manna P, Gachhui R, Sil PC (2011) D-saccharic acid-1,4-lactone ameliorates alloxan-induced Diabetes mellitus and oxidative stress in rats through inhibiting pancreatic beta-cells from apoptosis via mitochondrial dependent pathway. Toxicol Appl Pharmacol 257:272-283.
56. Sarkar A, Manna P, Das J, Sil PC (2011) Nano-copper induces oxidative stress and apoptosis in kidney via both extrinsic and intrinsic pathways. Toxicology 290:208-217.
57. Sarkar K, Sil PC (2011) Cajanus indicus leaf protein: Beneficial role in experimental organ pathophysiology. A review. Pathophysiology 18(4):295-303.
58. Datta P, Mukhopadhyay AP, Manna P, Tiekink ER, Sil PC, Sinha C (2011) Structure, photophysics, electrochemistry, DFT calculation, and in-vitro antioxidant activity of coumarin Schiff base complexes of Group 6 metal carbonyls. J Inorg Biochem 105(4):577-588.
59. Das J, Ghosh J, Manna P, Sil PC (2011) Taurine suppresses doxorubicin-triggered oxidative stress and cardiac apoptosis in rat via up-regulation of PI3-K/Akt and inhibition of p53, p38-JNK. Biochem Pharmacol 81(7):891-909.
60. Pal S, Pal PB, Das J, Sil PC (2011) Involvement of both intrinsic and extrinsic pathways in hepatoprotection of arjunolic acid against cadmium induced acute damage in vitro. Toxicology 283(2-3):129-139.
61. Ghosh M, Manna P, Sil PC (2011) Protective role of a coumarin derived schiff base scaffold against TBHP induced oxidative impairment and cell death via MAPKs, NFκB and mitochondria dependent pathways. Free Radic Res 45(5): 620-637.
62. Bhattacharya S, Gachhui R, Sil PC (2011) Hepatoprotective properties of Kombucha tea against TBHP-induced oxidative stress via suppression of mitochondria dependent apoptosis. Pathophysiology 18(3):221-234.
63. Manna P, Bhattacharyya S, Das J, Ghosh J, Sil PC (2011) Phytomedicinal Role of Pithecellobium dulce against CCl4-mediated Hepatic Oxidative Impairments and Necrotic Cell Death. Evid-Based Compl Altern Med Article ID 832805, 17 pages, doi: 10.1155/2010/neq065.
64. Bhattacharya S, Chatterjee S, Manna P, Das J, Ghosh J, Gachhui R, Sil PC (2011) Prophylactic role of D-saccharic acid-1,4-lactone in tertiary butyl hydroperoxide induced cytotoxicity and cell death of murine hepatocytes via mitochondria dependent pathways. J Biochem Mol Toxicol 25:341-354.
65. Bhattacharya S, Manna P, Gachhui R, Sil PC (2011) Protective effect of Kombucha tea against tertiary butyl hydroperoxide induced cytotoxicity and cell death in murine hepatocytes. Indian J Exp Biol 49(7):511-524.
66. Ghosh J, Das J, Manna P, Sil PC (2010) Hepatotoxicity of di-(2-ethylhexyl)phthalate is attributed to calcium aggravation, ROS-mediated mitochondrial depolarization, and ERK/NF-κB pathway activation. Free Radic Biol Med 49:1779-1791.
67. Ghosh J, Das J, Manna P, Sil PC (2010) Protective effect of the fruits of Terminalia arjuna against cadmium-induced oxidant stress and hepatic cell injury via MAPK activation and mitochondria dependent pathway. Food Chem 123:1062-1073.
68. Das J, Ghosh J, Manna P, Sil PC (2010) Protective Role of Taurine against Arsenic-Induced Mitochondria--JNK Pathway. PLoS ONE 5:e12602.
69. Sarkar MK, Sil PC (2010) Prevention of tertiary butyl hydroperoxide induced oxidative impairment and cell death by a novel antioxidant protein molecule isolated from the herb, Phyllanthus niruri. Toxicol In Vitro 24:1711–1719.
70. Manna P, Das J, Ghosh J, Sil PC (2010) Contribution of type 1 diabetes to rat liver dysfunction and cellular damage via activation of NOS, PARP, IκBα/NF-κB, MAPKs, and mitochondria-dependent Prophylactic role of arjunolic acid. Free Radic Biol Med 48:1465–1484.
71. Manna P, Ghosh J, Das J, Sil PC (2010) Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: Protective role of arjunolic acid. Toxicol Appl Pharmacol 244:114-129.
72. Ghosh J, Das J, Manna P, Sil PC (2010) Arjunolic acid, a triterpenoid saponin, prevents acetaminophen (APAP)-induced liver and hepatocyte injury via the
inhibition of APAP bioactivation and JNK-mediated mitochondrial protection. Free Radic Biol Med 48:535-553.
73. Das J, Ghosh J, Manna P, Sil PC. (2010) Taurine protects acetaminophen-induced oxidative damage in mice kidney through APAP urinary excretion and CYP2E1 inactivation. Toxicology 269(1):24-34.
74. Ghosh J, Das J, Manna P, Sil PC (2010) Acetaminophen induced renal injury via oxidative stress and TNF-alpha production: Therapeutic potential of arjunolic acid. Toxicology 268:8-18.
75. Das J, Ghosh J, Manna P, Sil PC (2010) Acetaminophen induced acute liver failure via oxidative stress and JNK activation: Protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res 44(3):340-355.
76. Manna P, Sinha M, Sil PC (2009) Prophylactic role of arjunolic acid in response to streptozotocin mediated diabetic renal injury: Activation of polyol pathway and oxidative stress responsive signaling cascades. Chem Biol Interact 181:297-308.
77. Sinha M, Manna P, Sil PC (2009) Induction of necrosis in cadmium-induced hepatic oxidative stress and its prevention by the prophylactic properties of taurine. J Trace Elem Med Biol 23(4):300-313.
78. Roy A, Manna P, Sil PC (2009) Prophylactic role of taurine on arsenic mediated oxidative renal dysfunction via MAPKs/NF-kappaB and mitochondria dependent pathways. Free Radic Res 43:995-1007.
79. Ghosh J, Das J, Manna P, Sil PC (2009) Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-kappaB, p38 and JNK MAPK pathway. Toxicol Appl Pharmacol 240:73-87 [Cover page].
80. Das J, Ghosh J, Manna P, Sinha M, Sil PC (2009) Arsenic-induced oxidative cerebral disorders: protection by taurine. Drug Chem Toxicol 32(2):93-102.
81. Das J, Ghosh J, Manna P, Sinha M, Sil PC (2009) Taurine protects rat testes against NaAsO2-induced oxidative stress and apoptosis via mitochondrial dependent and independent pathways. Toxicol Lett 187:201-210.
82. Sarkar MK, Kinter M, Mazumder B, Sil PC (2009) Purification and characterization of a novel antioxidant protein molecule from Phyllanthus niruri. Food Chem 111:1405-1412.
83. Manna P, Sinha M, Sil PC (2009) Protective role of arjunolic acid in response to streptozotocin-induced type-I diabetes via the mitochondrial dependent and independent pathways. Toxicology 257 (1-2):53-63.
84. Manna P, Sinha M and Sil PC (2009) Taurine plays a beneficial role against cadmium-induced oxidative renal dysfunction. Amino Acids 36(3):417-428.
85. Ghosh A, Sil PC (2009) Protection of acetaminophen induced mitochondrial dysfunctions and hepatic necrosis via Akt-NF-protein. Chem Biol Interact 177 (2):96-106.
86. Ghosh J, Das J, Manna P, Sil PC (2008) Cytoprotective effect of arjunolic acid in response to sodium fluoride mediated oxidative stress and cell death via necrotic pathway. Toxicol In Vitro 22:1918-1926.
87. Manna P, Sinha M, Sil PC (2008) Taurine triggers a chemoprevention against cadmium induced testicular oxidative injury. Reprod Toxicol. 26:282-291.
88. Sinha M, Manna P and Sil PC (2008) Terminalia arjuna protects mice hearts against sodium fluoride-induced oxidative stress. J Med Food 11:733-740.
89. Sinha M, Manna P, Sil PC (2008) Taurine protects antioxidant defense system in the erythrocytes of cadmium treated mice. BMB Reports 41:657-663.
90. Sinha M, Manna P, Sil PC (2008) Cadmium induced neurological disorders: Prophylactic role of taurine. J Appl Toxicol. 28:974-986.
91. Das J, Ghosh J, Manna P, Sil PC (2008) Taurine provides antioxidant defense against NaF-induced cytotoxicity in murine hepatocytes. Pathophysiology15:181-190.
92. Manna P, Sinha M, Sil PC (2008) Amelioration of cadmium-induced cardiac impairment by taurine. Chem Biol Interact 174:88-97.
93. Sinha M, Manna P, Sil PC (2008) Arjunolic acid attenuates arsenic-induced nephrotoxicity. Pathophysiology 15:147-156.
94. Ghosh A, Sil PC (2008) A protein from Cajanus indicus Spreng protects liver and kidney against mercuric chloride-induced oxidative stress. Biol Pharm Bull 31:1651-1658.
95. Manna P, Sinha M, Sil PC (2008) Arsenic induced oxidative myocardial injury: Protective role of arjunolic acid. Arch Toxicol. 82:137-149.
96. Manna P, Sinha M, Sil PC (2008) Protection of arsenic-induced testicular oxidative stress by arjunolic acid. Redox Rep. 13:67-77.
97. Sinha M, Manna P, Sil PC (2008) Protective Effect of Arjunolic Acid Against Arsenic-Induced Oxidative Stress in Mouse Brain. J Biochem Mol Toxicol 22:15-26.
98. Manna P, Sinha M, Pal P, Sil PC (2007) Arjunolic acid, a triterpenoid saponin, ameliorates arsenic-induced cyto-toxicity in hepatocytes. Chem Biol Interact 170:187-200.
99. Sinha M, Manna P, Sil PC (2007) Taurine, a conditionally essential amino acid, ameliorates arsenic-induced cytotoxicity in murine hepatocytes. Toxicol In Vitro 21:1419-1428.
100. Sinha M, Manna P, Sil PC (2007) Attenuation of cadmium chloride induced cytotoxicity in murine hepatocytes by a protein isolated from the leaves of the herb Cajanus indicus L. Arch Toxicol. 81:397-406.
101. Ghosh A, Sil PC (2007) Anti-oxidative effect of a protein from Cajanus indicus L against acetaminophen-induced hepato-nephro toxicity. J Biochem Mol Biol 40:1039-1049.
102. Sarkar MK, Sil PC (2007) Hepatocytes are protected by herb Phyllanthus niruri protein isolate against thioacetamide toxicity. Pathophysiology 14:113-120.
103. Sarkar K, Sil PC (2007) Attenuation of acetaminophen-induced hepatotoxicity in vivo and in vitro by a 43-kD protein isolated from the herb Cajanus indicus L. Toxicol Mech Methods 17:305-315.
104. Bhattacharjee R, Sil PC (2007) Protein isolate from the herb, Phyllanthus niruri L. (Euphorbiaceae), plays hepatoprotective role against carbon tetrachloride induced liver damage via its antioxidant properties. Food Chem Toxicol 45:817-826.
105. Manna P, Sinha M, Sil PC (2007) A 43 kD protein isolated from the herb Cajanus indicus L attenuates sodium fluoride-induced hepatic and renal disorders in vivo. J Biochem Mol Biol 40:382-395.
106. Manna P, Sinha M, Sil PC (2007) Protection of arsenic-induced hepatic disorder by arjunolic Acid. Basic Clin Pharmacol Toxicol 101:333-338.
107. Manna P, Sinha M, Sil PC (2007) Galactosamine-induced hepatotoxic effect and hepatoprotective role of a protein isolated from the herb Cajanus indicus L in vivo. J Biochem Mol Toxicol 21:13-23.
108. Manna P, Sinha M, Sil PC (2007) Phytomedicinal activity of Terminalia arjuna against carbon tetrachloride induced cardiac oxidative stress. Pathophysiology 14:71-78.
109. Sinha M, Manna P, Sil PC (2007) Amelioration of galactosamine-induced nephrotoxicity by a protein isolated from the leaves of the herb, Cajanus indicus L. BMC Complement and Altern Med 7:11.
110. Sinha M, Manna P, Sil PC (2007) A 43 kD protein from the herb, Cajanus indicus L, plays protective role against sodium fluoride induced oxidative stress in mice erythrocytes. Pathophysiology 14:47-54.
111. Chatterjee M, Sil PC (2007) Protective role of Phyllanthus niruri against nimesulide induced hepatic damage. Ind J Clin Biochem 22:109-116.
112. Sinha M, Manna P, Sil PC (2007) Aqueous extract of the bark of Terminalia arjuna plays protective role against sodium fluoride induced hepatic and renal oxidative stress. J Nat Med 61:251-260.
113. Sarkar K, Ghosh A, Kinter M, Mazumder B, Sil PC (2006) Purification and characterization of a 43kD hepatoprotective protein from the herb Cajanus indicus L. Protein J 25:411-421.
114. Sarkar K, Sil PC (2006) A 43kD protein from the herb Cajanus indicus L. protects thioacetamide induced cytotoxicity in hepatocytes. Toxicol In Vitro 20:634-640.
115. Ghosh A, Sarkar K, Sil PC (2006) Protective effect of a 43kD protein from the leaves of the herb, Cajanus indicus L on chloroform induced hepatic-disorder. J Biochem Mol Biol 39:197-207.
116. Chatterjee M, Sarkar K, Sil PC (2006) Herbal (Phyllanthus niruri) protein isolate protects liver from nimesulide induced oxidative stress. Pathophysiology 13:95-102.
117. Bhattacharjee R, Sil PC (2006) Protein isolate from the herb, Phyllanthus niruri, protects liver from acetaminophen induced toxicity. Biomed Res 17:75-79.
118. Manna P, Sinha M, Sil PC (2006) Aqueous extract of Terminalia arjuna prevents carbon tetrachloride induced hepatic and renal disorders. BMC Complement and Altern Med 6:33.
119. Chatterjee M, Sil PC (2006) Hepatoprotective effect of aqueous extract of Phyllanthus niruri on nimesulide-induced oxidative stress in vivo. Indian J Biochem Biophys 43:299-305.
120. Ghosh A, Sil PC (2006) A 43kD protein from the leaves of the herb, Cajanus indicus L, modulates chloroform induced hepatotoxicity in vitro. Drug Chem Toxicol 29:397-413.
121. Bhattacharjee R, Sil PC (2006) The protein fraction of Phyllanthus niruri plays a protective role against acetaminophen induced hepatic disorder via its antioxidant properties. Phytother Res. 20:595-601.
122. Bhattacharjee R, Sil PC (2006) Protein isolate from the herb, Phyllanthus niruri, modulates carbon tetrachloride-induced cytotoxicity in hepatocytes. Toxicol Mech Methods. 17:41-47.
123. Sarkar K, Ghosh A and Sil PC. (2005) Preventive and curative role of a 43kD protein from the leaves of the herb Cajanus indicus L on thioacetamide-induced hepatotoxicity in vivo. Hepatol Res 33:39-49.
124. Sarkar M, Sarkar K, Bhattacharjee R, Chatterjee M and Sil PC. (2005) Curative role of the aqueous extract of the herb, Phyllanthus niruri, against nimesulide induced oxidative stress in murine liver. Biomed Res 16:171-176.
125. Adhikary G, Gupta S, Sil P, Saad Y and Sen S. (2005) Characterization and functional significance of myotrophin: a gene with multiple transcripts. Gene 353:31-40.
126. Sil P, Gupta S, Young D, and Sen S. (2004) Effect of high pressure and pulsatile stretch on myotrophin gene expression. Mol Cell Biochem 262:79-89.
127. Sarkar S, Leaman DW, Gupta S, Sil P, Young D, Morehead A, Mukherjee D,Ratliff N, Sun Y, Rayborn M, Hollyfield J, Sen S. (2004) Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart failure in transgenic mice. J Biol Chem 279:20422-20434.
128. Mandal AK, Roy K, Yadav SP, Sil PC Sen PC (2001) Purification and characterization of a 70 kDa inhibitor protein of Na+, K+-ATPase from goat testis cytosol. Mol Cell Biochem 223:7-14.
129. Sil P, Kandoswamy V, Sen S (1999) Increased protein kinase C activity in myotrophin induced myocyte growth. Circ Res 82:1173-1188.
130. Pathak M, Sil P, Young D, Sen S (1998) Ang II stimulated collagen production influenced by fibroblast myocyte cross talk. Circulation 98:3284.
131. Sil P, Sen S (1997) Angiotensin II and myocyte growth: Role of fibroblasts. Hypertension 30:209-216.
132. Sivasubramanian N, Adhikary G, Sil PC, Sen S (1996) Cardiac Myotrophin Exhibits rel/NF-B Interacting Activity in vitro. J Biol Chem 271: 2812-2816.
133. Sil P, Mukherjee D, Sen S (1995) Quantification of myotrophin from spontaneously hypertensive and normal rat hearts. Circ Res 76:1020-1027.
134. Sil PC, Chaudhuri TK and Sinha NK. Basic Trypsin-Subtilisin Inhibitor from Marine Turtle Egg-white: Hydrodynamic and Inhibitory Properties. (1993) J Protein Chem 12:71-78.
135. Sil P, Misono K, Sen S (1993) Myotrophin in Human cardiomyopathic Heart. Circ Res 73:98-108.
List of book chapters
i) Sukanya Saha, Pritam Sadhukhan, Parames C. Sil (2017) “Beneficial Upshots of Naturally Occurring Antioxidant Compounds against Neurological Disorders” chapter in the book entitled, “Neuroprotective Natural Products” Edited by Prof. Goutam Brahmachari, Professor of Organic Chemistry, Laboratory of Natural Products & Organic Synthesis, Department of Chemistry, Visva-Bharati University, India. Publisher: John Wiley & Sons, Inc.
ii) Kahkashan Rashid, Parames C. Sil (2016) “Identification and extraction of anti-diabetic antioxidants from natural sources” chapter in the book entitled, “Drug Discovery and Development of Antidiabetic Agents from Natural Products” (Multi-Volume SET)-Volume I. “Natural Product Drug Discovery” Edited by Prof. Goutam Brahmachari, Professor of Organic Chemistry, Laboratory of Natural Products & Organic Synthesis, Department of Chemistry, Visva-Bharati University, India. Publisher: Academic Press (Elsevier; in press).
iii) Krishnendu Sinha, Jyotirmoy Ghosh, Parames C. Sil (2016) “New pesticides: a cutting-edge view of contributions from nanotechnology for the development of sustainable agricultural pest control” Chapter in the book entitled, “Nanotechnology in Food Industry” (Multi-Volume SET, I-X)–Volume IV. Agriculture & New pesticides” Edited by Alexandru Mihai Grumezescu, Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, Romania. Publisher: Academic Press (Elsevier; in press)
iv) Sudip Bhattacharyya, Sayantani Chowdhury, Parames C. Sil (2016) “Bioactive Natural Compounds: Biological significance and Clinical implementation in Organ Pathophysiology" Chapter in the book entitled, "Advances in natural products discovery". Edited by Ana Rita Gomes, University of Coimbra, Portugal. Publisher: Nova Science Publishers, Inc. (in press)
v) Jyotirmoy Ghosh, Parames C Sil (2015) “Natural Bioactive Molecules: Mechanism of Actions and Perspectives in Organ Pathophysiology” Chapter in the book entitled, “Studies in Natural Product Chemistry” Volume 45; Pages: 458-483. Edited by Atta-ur-Rahman, International Center for Chemical and Biological Sciences, H.E.J. Research Institute of Chemistry, University of Karachi, Karachi, Pakistan. Publisher: Academic Press (Elsevier)
vi) Pabitra B Pal, Shatadal Ghosh, Parames C Sil (2015) “Beneficial effect of naturally occurring antioxidants against oxidative stress mediated organ dysfunctions” Chapter in the book entitled, “Bioactive Natural Products: Chemistry and Biology”. Pages: 199-240. Edited by Gautam Brahmachary, Department of Chemistry, Visva-Bharati University, India. Publisher: John Wiley & Sons.
vii) Jyotirmoy Ghosh, Parames C Sil (2014) “Mechanism for Arsenic-induced Toxic Effects” Chapter in the book entitled,”Handbook of Arsenic Toxicology”. Pages 203-231. Edited by Swaran Jeet Singh Flora, Defence Research & Development Establishment, Jhansi Road Gwalior-474 002, India. Publisher: Academic Press (Elsevier)
viii) Joydeep Das, Parames C Sil (2013) “The Protective Role of Taurine in Cardiac Oxidative Stress under Diabetic Conditions” Chapter in the book entitled, “Diabetes: Oxidative Stress and Dietary Antioxidants”. Page: 173-182. Edited by Victor R. Preedy, Department of Nutrition and Dietetics, School of Medicine, King’s College, London, UK. Publisher: Academic Press (Elsevier)
ix) Jyotirmoy Ghosh, Parames C Sil (2013) “Therapeutic Efficacy of Macro and Small Bioactive Molecules in Organ Pathophysiology” Chapter in the book entitled, “Natural Bioactive Molecules: Impacts and Prospects”. Page: 10.1-10.30. Edited by Gautam Brahmachary, Department of Chemistry, Visva-Bharati University, India. Publisher: NarosaView More
|Mousumi Kundu||JRF||Division of Molecular Medicine||Centenary||25693243||mousumi|
|Noyel Ghosh||JRF||Division of Molecular Medicine||Centenary||25693243||noyel|
|Poulami Sarkar||JRF||Division of Molecular Medicine||Centenary||25693243||poulamisarkar|
|Pritam Sadhukhan||SRF||Division of Molecular Medicine||Centenary||25693243||pritam|
|Priyanka Basak||JRF||Division of Molecular Medicine||Centenary||25693243||priyanka|
|Sayanta Dutta||SRF||Division of Molecular Medicine||Centenary||25693243||sayanta|
|Sayantani Chowdhury||SRF||Division of Molecular Medicine||Centenary||25693243||sayantani|
|Sharmistha Banerjee||SRF||Division of Molecular Medicine||Centenary||25693243||sharmistha|
|Sharmistha Chatterjee||JRF||Division of Molecular Medicine||Centenary||25693243||sharmisthac1994|
|Shatadal Ghosh||SRF(I)||Division of Molecular Medicine||Centenary||25693243||dalshata|
|Sukanya Saha||SRF||Division of Molecular Medicine||Centenary||25693243||sukanya|
|Sumit Ghosh||SRF||Division of Molecular Medicine||Centenary||25693243||sumit|
|Sushweta Mahalanobish||JRF||Division of Molecular Medicine||Centenary||25693243||sushwetaboseinstitute|
|Uday Hossain||JRF||Division of Molecular Medicine||Centenary||25693243||uday|
Current Group Members
1. Mr Shatadal Ghosh, SRF, email@example.com
2. Ms Sukanya Saha, SRF, firstname.lastname@example.org
3. Ms Sayantani Chowdhury, SRF, email@example.com
4. Mr Pritam Sadhukhan, SRF, firstname.lastname@example.org
5. Ms Sharmistha Banerjee, SRF, email@example.com
6. Mr Sumit Ghosh, JRF, firstname.lastname@example.org
7. Mr Sayanta Dutta, JRF, email@example.com
8. Ms Priyanka Basak, JRF, firstname.lastname@example.org
9. Ms Shusweta Mahalanobish, JRF, email@example.com
10. Ms Mousumi Kundu, JRF, firstname.lastname@example.org
11. Ms Poulami Sarkar, JRF, email@example.com
Curcumin provides protection to spleen from inflammation and ER-dependent apoptosis in diabetic pathophysiology
Spleen is a secondary lymphoid organ and plays an active role in the immune system by producing various antibodies. Chronic hyperglycemic state in diabetes leads to damage of various organs including spleen due to oxidative stress. The present study has been conducted to explore the role of polyphenolic curcumin on spleen tissue in diabetes. For this purpose adult male Wistar rats were made diabetic by injecting them with a single intraperitoneal dose of streptozotocin (STZ, at a dose of 65 mg/kg body weight). Animals with blood glucose level above 300 mg/dL were considered as diabetic. Consistent with our previous studies we observed reduction in the body weight as well as serum insulin level and increment in the oxidative stress-related parameters in the type-1 diabetic model. In addition, damage spleen anatomy with depleted white pulp has also been found in the same group. Investigation of the cellular mechanism for the oxidative stress-dependent and inflammation mediated splenic damage in diabetes showed upregulation in the level of different proinflammatory cytokines (TNF-a, IL-1b and IL-6), chemokine (MCP-1), adhesion molecules (ICAM-1 and VCAM-1) and translocation of transcription factor NF-kB in the nucleus. Activation of the downstream signaling molecules of NF-kB like COX-2 and iNOS were also observed in diabetes. Moreover, upregulation in the expression of phospho-eIF2a, GRP-78, CHOP, calpain-1, caspases (12 and 3) and phospho-JNK has been found in case of endoplasmic reticulum (ER) dependent apoptotic death of the spleen cells under the hyperglycemic state. However, curcumin at oral dose of 100 mg/kg body weight ameliorate all the changes to a significant extent near to control. This study suggests curcumin provide protection to spleen in diabetes by attenuating the upregulation of various proteins related to inflammation and cell death. Therefore, it could be a probable candidate for the treatment of oxidative stress mediated splenic damage in diabetes. Data of this study is about to publish.
Improving the bioavailability of curcumin by pegylation and the administration of Mesoporous silica nanoparticles
Curcumin (obtained from Curcuma longa) has been found to be effective against many diseases like diabetes, cancer, etc. In spite of its wide range of pharmacological and therapeutic effects, its poor solubility, as well as low bioavailability, remains a major drawback.
Mesoporous Silica Nanoparticles (MSN) is one of the major emerging drug delivery systems. We have loaded curcumin into the MSNs and studied its effect in breast cancer cell lines. Results showed that MSN mediated delivery of curcumin not only enhance the bioavailability of curcumin thereby showing its therapeutic activity at a relatively lower dose. The study showed that at the same concentration there was a threefold increase in the percentage of apoptotic cells in case of MSN-Cur compared to free curcumin. In vivo studies also showed improved bioavailability of MSN-Cur. Then we have modified MSN by pegylation and loaded with curcumin. The distribution of this conjugate has been shown by in vivo imaging.
Study of the ameliorative effects of ferulic acid on STZ induced cardiomyopathy in diabetic rats
The cardiomyocytes are one of the major sources of hyperglycemia-induced ROS generation. Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is a natural potent phytochemical which exhibits a wide range of biological activities such as anti-inflammatory, antimicrobial, hepatoprotective, anticarcinogenic, antiviral, vasodilator actions, etc. Our study focuses on the ameliorative role of ferulic acid in combating cardiac complications in diabetic rats. Diabetes was induced by STZ in male Wistar rats and the body weight, plasma insulin level, blood glucose level have been assessed. The diabetic rats have been post-treated with varying doses of ferulic acid. Following the assessment of effective dose of ferulic acid in respect to the amelioration of diabetes, changes in the intracellular antioxidant machinery and histological variations are also being assessed. Expression levels of molecules associated with the insulin signaling pathway, ER stress and apoptosis are being studied through immunoblot analyses. For further validation of apoptosis, DNA Fragmentation Assay will be carried out. Pharmacokinetic and pharmacodynamic studies will be carried out to determine the period of retention of ferulic acid in the general circulation.
Prophylactic role of mangiferin in oxidative stress-mediated liver dysfunction in arsenic intoxicated murines
Mangiferin, a natural xanthone derived mainly from mangoes, possesses great potentials, antioxidative being a primary one. The present study has been carried out to investigate the hepatoprotective role of mangiferin, against arsenic-induced oxidative damages in the murine liver. Arsenic, a well-known toxic metalloid, is ubiquitously found in nature and has been reported to negatively affect nearly all the organs of the human body via oxidative injury. Administration of As in the form of sodium arsenite (NaAsO2) at a dose of 10 mg/kg body weight (3 months) abruptly increased reactive oxygen species (ROS) level, led to oxidative stress and significantly depleted the first line of antioxidant defense system in the body. Moreover, arsenic caused apoptotic cell death in hepatocytes. Treatment with mangiferin at a dose of 40 mg/kg for body weight for 30 days simultaneously and separately after NaAsO2 administration decreased the ROS production and attenuated the alterations in the activities of all antioxidant indices. Mangiferin also protected liver against the NaAsO2-induced apoptosis and disintegrated hepatocytes, thus counteracting with arsenic-induced toxicity. It could significantly inhibit the expression of different proapoptotic caspases and upregulate the expression of survival molecules such as Akt and Nrf2. On inhibiting Akt (by PI3K inhibitor) and ERK1/2 (by ERK1/2 inhibitor) specifically, caspase 3 got activated abolishing mangiferin’s protective role on arsenic-induced hepatotoxicity. So here, we have briefly elucidated the signaling cascades involved in arsenic-induced apoptotic cell death in the liver and also the detailed cellular mechanism by which mangiferin provides protection to this organ.
Selective anticancer activity of different novel synthetic derivatives mediating oxidative stress
Cancer is one of the leading cause of death in most of the countries. Cancer develops when somatic cells mutate and escape the restraints that normally restrict them in their problematic expansion. Many signaling pathways that are linked to tumorigenesis can also regulate the metabolism of ROS through direct or indirect mechanisms. High ROS levels are generally detrimental to normal cells, but the redox status of cancer cells usually differs from that of normal cells. Because of metabolic and signaling aberrations, cancer cells exhibit elevated ROS levels. On the contrary, it is also accepted that cancer cells are more vulnerable to exogenous insult of ROS, therefore manipulation of the ROS level may be a way in specifically killing the cancer cells without harming the normal cell.
Selective induction of apoptosis in cancer cells barring the normal cells is considered as an effective strategy to combat cancer. In a present study, a series of bis-lawsone derivatives and bis-coumarin were assayed for their pro-apoptotic activity in different cancerous and normal cell lines using different cytotoxicity assay. These test compounds, were found to be effective in inducing apoptosis in many cells (such as CCF-4 cells and HeLa cells) among the different cancerous cell lines used in the study. The activity of these compounds, were again compared to a popular anticancer drug cisplatin, having limitation usage because of its nephrotoxic nature. In a study, with a bis-lawsone derivatives, 1j derivative showed very less toxicity to the normal kidney cells compared to cisplatin, thus, indicating the superiority of 1j as a possible anticancer agent. This compound was observed to induce apoptosis in the glioma cells by inducing the caspase-dependent apoptotic pathways via ROS and downregulating the PI3K/AKT/mTOR pathway. Estimation of different oxidative stress markers also confirms the induction of oxidative stress in 1j exposed cancer cells. The toxicity of 1j compound toward cancer cells was confirmed further by different flow-cytometrical analyzes to estimate the mitochondrial membrane potential and cell cycle. The sensitivity of malignant cells to apoptosis, provoked by this synthetic derivative in vitro, deserves further studies in suitable in vivo models. These studies not only identified a novel anticancer drug candidate but also help to understand the metabolism of ROS and its application in cancer treatment.
Moreover, we intend to study the detailed mode of action of different effective compounds found in other cancer cells. Moreover, we would like to identify more active compounds, designed and synthesized with desired bioactive compounds. We would also like to extend this study on in vivo cancer models, and establish the molecular pathway by which these compounds induces cytotoxicity on tumor cells without affecting normal physiological conditions.
Prophylactic activity of carnosine in chemotherapeutic drug-induced toxicity of spleen
cis-Diamminedichloroplatinum (cisplatin) is a widely used chemotherapeutic agent used to treat various types of solid tumors. Biodistribution of cisplatin to other organs due to poor targeting towards only cancer cells constitutes the backbone of cisplatin-induced toxicity. Although cisplatin-induced nephrotoxicity is well studied the adverse effect of this drug on spleen is not well characterized so far. Therefore, we have set our goal to explore the mechanism of the cisplatin-induced pathophysiology of the spleen and whether carnosine, can ameliorate the pathophysiological response of spleen. We found a dose and time-dependent increase of the pro-inflammatory cytokine, TNF-α in the spleen tissue of the experimental mice exposed to 10 and 20 mg/kg of cisplatin. The increase in inflammatory cytokine leads to the activation of the transcription factor, NF-kB which aids in the transcription of other pro-inflammatory cytokines and cellular adhesion molecules. ROS production and oxidative stress also lead to the activation of NF-kB further augmenting inflammatory response. Cisplatin administration also leads to increased expression of iNOS that causes nitrosative stress. The additive effect of inflammation, oxidative stress and nitrosative stress results in activation of cellular stress-related MAP Kinase, JNK. Eventually, the persistence of inflammatory response and oxidative stress leads to apoptosis through extrinsic pathway via the activation of caspase 8. Carnosine has been found to restore the expression of inflammatory molecules and antioxidant to normal level through inhibition of pro-inflammatory cytokines, oxidative stress, NF-kB and JNK. It also protected the spleen from apoptosis induced by cisplatin. For the first time, our study elucidated the detailed mechanism of cisplatin-induced spleen toxicity and use of carnosine as a protective agent against this cytotoxic response. Future work will involve investigation of the role of mitochondria and endoplasmic reticulum in cisplatin induced immunotoxicity.
Studies on the protective effects of some natural antioxidants against rotenone induced parkinson’s disease in rat model
Parkinson’s disease (PD) is a neurodegenerative disorder associated with motor dysfunctions. It is induced by the selective loss of dopaminergic neurons in the substantia nigra of the brain. Deposition of mutated α-synuclein protein in various parts of the brain along with the accumulation of neuromelanin and iron leads to the generation of Lewy bodies.
Pesticide exposure is a major environmental factor for the induction of neuronal disorders. Rotenone is one such pesticide which is reported to be a major causative agent for the induction of Parkinsonism. It is a complex I inhibitor which causes selective dopaminergic degeneration and α -synuclein accumulation. The use of rotenone as a pesticide and an organ pesticide is quite common in India. It is used for fishing in the villages. It also finds its applications in treatment of scabies, head lice, mites etc. As an organ pesticide, rotenone in its powdered form is applied in the vegetable gardens for killing the beetles, cabbage worms and other arthropods. However, bioaccumulation of this compound in fishes and vegetables and their subsequent entry into the human body when such contaminated food is being consumed induces toxicity.
The natural antioxidants help in reducing oxidative stress associated with different disease manifestations. Owing to their easy commercial availability, cheap price and practically no side-effects, natural antioxidants can be considered as potent therapeutic agents for the treatment of different diseases. Therefore, we want to preliminarily screen for the most potent neuro-protective effects of different natural antioxidants in maintaining viability of rotenone treated SH-SY5Y cells (Human neuroblastoma cells).
Following this study, we want to investigate the pathophysiological manifestations and signaling pathways associated with rotenone induced Parkinson’s disease in rat model and their amelioration by the most potent protective molecule.
Neuroinflammation plays an important role in the progressive loss of nigral dopaminergic neurons. Inflammatory responses manifested by the increased release of pro-inflammatory cytokines, glial reactions and infiltration of T cells are important features of PD. Therefore, we want to study the role of inflammatory markers in the manifestation of rotenone induced toxicity.
Apoptosis, necrosis and autophagy are important cell death pathways associated with the pathogenesis of the disease. Therefore, we want to perform elaborate experimentations to determine the therapeutic effects provided by the most potent protective molecule against such cell death pathways in rotenone induced Parkinson model.