EFFECT OF HEPTOPLUS ON ISONIAZID AND RIFAMPICIN INDUCED HEPATOTOXICITY IN LIVER CELL LINES

Authors

  • M. Sankar Assistant professor, Department of biotechnology, Rajalakshmi Enginerring College, Chennai, Tamilnadu, India.
  • Johanna Rajkumar Rajalakshmi Enginerring College, Chennai, Tamilnadu, India
  • Sridhar . Rajalakshmi Enginerring College, Chennai, Tamilnadu, India

Keywords:

Isoniazid, Rifampicin, Oxidative stress, Apoptosis and Heptoplus

Abstract

Objective: To evaluate the hepato protective role of Heptoplus (HP), a ployherbal formulation as a supplementary agent for the Isoniazid and Rifampicin induced oxidative stress and apoptosis in liver.

Methods: Liver cell lines were divided in to five groups. Group I is control, group II is treated with 30ng/ml of INH+RIF, group III, IV and V are supplemented with 50, 100 and 200 ng/ml of HP. At the end of the experimental period, biochemical tests for liver marker enzymes and antioxidant profile were studied. Gene expression for apoptosis and CYP2E1 was also studied.

Result: Cells in group II suffer from severe oxidative stress and hepatotoxicity, as seen by significant decreases of (p≤0.001) reduced glutathione, catalase (p≤0.01) and superoxide dismutase (p≤0.001) and significant increase (p≤0.01) of liver marker enzymes. However, liver cell lines nourished with 50, 100 and 200 ng/ml of HP were protected from oxidative stress and maintained normal antioxidant profile and liver marker enzymes in a dose dependent manner. Hepatocytes in group II, displayed significant (p≤0.001) up regulation of CYP2E1, BAX, P53 and caspases 3 and significant (p≤0.001) down regulation of Bcl2 gene expression. Concomitant applications of HP protected the hepatocytes from programmed cell death by conserving normal CYP2E1expression and enhancing the protective action of Bcl2 by up regulating the expression on dose dependent manner.

Conclusion: Heptoplus prevented oxidative stress and apoptosis, in hepatocytes.

 

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References

Sharma A, Chakraborti KK, Handa SS. Anti-hepatotoxic activity of some Indian herbal formulations as compared to silymarin. Fitoterapia 1991;62:229-35.

Rangnekar AS, Fontana RJ. An update on drug induced liver injury. Minerva Gastroenterol Dietol 2011;57(2):213–29.

Shi Q, Hong H, Senior J, Tong W. Biomarkers for drug-induced liver injury. Expert Rev Gastroenterol Hepatol 2010;4(2):225–34.

Thattakudian Sheik Uduman MS, Sundarapandian R, Muthumanikkam A, Kalimuthu G, Parameswari SA, Vasanthi Srinivas TR, et al. Protective effect of methanolic extract of Annona squamosa Linn in isoniazid-rifampicin induced hepatotoxicity in rats. Pak J Pharm Sci 2011;24(2):129-34.

Yue J, Peng R, Chen J, Liu Y, Dong G. Effects of rifampin on CYP2E1-dependent hepatotoxicity of isoniazid in rats. Pharmacol Res 2009;59(2):112-9.

Singh M, Sasi P, Gupta VH, Rai G, Amarapurkar DN, Wangikar PP. Protective effect of Curcumin, silmarin and N-acetyl cysteine on antitubercular drug induced hepatotoxicity assessed in invitro mode. Hum Exp Toxicol 2012;8:788-97.

Nelson SD, Mitchell JR, Timbrell JA, Snodgrass WR, Corcoran GB. Isoniazid and iproniazid: activation of metabolites to toxic intermediates in man and rat. Sci 1976;193(4256):901-3.

Tayal V, Kalra BS, Agarwal S, Khurana N, Gupta U. Hepatoprotective effect of tocopherol against isoniazid and rifampicin induced hepatotoxicity in albino rabbits. Indian J Exp Biol 2007;45(12):1031-6.

Asduq SA, Kaiser P, Sharma SC, Johri RK. Potentiation of isoniazid-induced liver toxicity by rifampicin in a combinational therapy of antitubercular drugs (rifampicin, isoniazid and pyrazinamide) in Wistar rats: a toxicity profile study. Hepatol 2007;37(10):845-53.

Pal R, Rana S, Vaiphei K, Singh K. Effect of different doses of carotenoids in isoniazid-rifampicin induced hepatotoxicity in rats. Trop Gastroenterol 2008;29(3):153-9.

Chowdhury A, Santra A, Bhattacharjee K, Ghatak S, Saha DR, Dhali GK. Mitochondrial oxidative stress and permeability transition in isoniaizd and Rifampicin induced liver injury in mice. J Heapatol 2006;45(1):117-26.

Claiborne A, Fridovich I. Purification of the o-dianisidine peroxidase from Escherichia coli B. Physicochemical characterization and analysis of its dual catalatic and peroxidatic activities. J Biol Chem 1979;254:4245-52.

Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clinic Chem 1988;34:497-500.

Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 1978;186:189–95.

Ellman George L. Tissue sulfhydryl groups. Arch Biochem Biophy 1959;82(1):70-7.

Nicoletti NF, Rodrigues Junior V, Santos AA Jr, Leite CE, Dias AC, Batista EL Jr, et al. Protective effects of resveratrol on hepatotoxicity induced by isoniazid and rifampicin via SIRT1 modulation. J Nat Prod 2014;77(10):2190-5.

Jeyakumar R, Rajesh R, Rajaprabhu D, Ganesan B, Buddhan S, Anandan R. Hepatoprotective effect of Picrorrhiza Kurroa on antioxidant defense system in antitubercular drugs induced hepatotoxicity in rats. AJB 2009;8:1314-5.

Gopi sudheer kumar J, Bala Krishan RB, Vijay Kumar G, Ranganayakulu D. Hepatoprotecive and antioxidant activity of the alcoholic extract of ipomoea turpetnm against anti TB drugs induced hepatotoxicity in rats. JADR 2010;1:10-8.

Jadhav VB, Thakare VN, Suralkar AA, Deshpande AD, Naik SR. Hepatoprotective activity of Luffa acutangula against CCl4 and rifampicin induced liver toxicity in rats: a biochemical and histopathological evaluation. Indian J Exp Biol 2010;48(8):822-9.

Kanchana N, Mohamed sadiq. Hepatoprotective effect of plumbago zeylanica on paracetamol induced liver toxicity in rats. Int J Pharm Pharm Sci 2011;3:151-4.

Smith C, Marks A, Lieberman M. Basic Medical Biochemistry. A Clinical Approach. 2nd ed. Maryland: Lippincott Williams and Wilkins; 2005:842-61.

Bhadauria S, Mishra R, Kanchan R, Tripathi C, Srivastava A, Tiwari A, et al. Isoniazid-induced apoptosis in HepG2 cells: generation of oxidative stress and Bcl-2 down-regulation. Toxicol Mech Methods 2010;20(5):242-51.

Sheela CG, Augusti KT. Antiperoxide effects of S-allyl cysteine sulphoxide isolated from Allium sativum Linn and gugulipid in cholesterol diet fed rats. Indian J Exp Biol 1995;33(5):337-41.

Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci 2000;7(6):444-58.

Shih TY, Young TH, Lee HS, Hsieh CB, Hu OY. Protective effects of kaempferol on isoniazid-and rifampicin-induced hepato toxicity. AAPSJ 2013;15(3):753-62.

Kaszuba Zwoinsk J, Chorobik P, Juszczak K, Zaraka W, Thor PJ. Pulsed electromagnetic field affects intrinsic and endoplasmatic reticulum apoptosis induction pathway in monoMac6 cell line culture. J Physiol Pharmacol 2012;63:537-45.

Haupt S, Berger M, Goldberg Z, Haupt Y. Apoptosis-the p53 network. J Cell Sci 2003;116(20):4077-85.

Published

01-05-2015

How to Cite

Sankar, M., J. Rajkumar, and S. . “EFFECT OF HEPTOPLUS ON ISONIAZID AND RIFAMPICIN INDUCED HEPATOTOXICITY IN LIVER CELL LINES”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 5, May 2015, pp. 215-9, https://journals.innovareacademics.in/index.php/ijpps/article/view/5263.

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