Hesperidin alleviates antitubercular drug induced oxidative stress, inflammation and apoptosis in rat liver
DOI:
https://doi.org/10.7439/ijbr.v7i7.3414Abstract
Background : Drug induced hepatotoxicity is a serious health problem that leads to treatment interruption and change in the treatment regimen during the course of therapy. Isoniazid (H), Rifampicin(R) and pyrazinamide (Z) are the commonly used drugs for the treatment of tuberculosis but leads to undesirable side effects, such as hepatotoxicity. Hence the present study undertaken to investigate the hepatoprotective activity of Hesperidin (HDN) against Isoniazid, Rifampicin and Pyrazinamide induced hepatotoxicity. Methods: Wistar albino rats were randomly divided into four groups of six animals each. Isoniazid, Rifampicin, Pyrazinamide were used to induce Hepatotoxicity, Hesperidin 200mg/kg was given one hour prior administration of antitubercular drugs (HRZ), Silymarin 100mg/kg was used as a standard drug daily for 50 days. Results: Antitubercular drug induces hepatotoxicity was evident by increased in the levels of liver marker enzyme (AST, ALT, ALP and LDH) and also a significant rise in the level of LPO along with decline in the level of both enzymatic and non enzymatic antioxidant enzymes (SOD,CAT,GSH,VIT C and VIT E) . Moreover, antitubercular drug causes hepatic damage by inducing apoptotic death and inflammation in hepatic cells, manifested by an increase in the expression of Bax, caspase-3, caspase-9, NF-?B, IL- 10, TNF- ? and decrease in Bcl-2 expression. These results were further supported by the histopathological examination of liver. All these features of antitubercular drugs induced toxicity were reversed by the co-administration of Hesperidin. Conclusion: Therefore, our study favors the view that Hesperidin may be a useful modulator in alleviating antitubercular drug induced oxidative stress, inflammation and apoptosis.Downloads
References
World Health Organization (WHO), Global tuberculosis report WHO; 2015.
Tasduq SA, Peerzada K, Koul S, Bhat R, Johri RK. Biochemical manifestations of anti-tuberculosis drugs induced Hepatotoxicity and the effect of Silymarin. Hepatol Res 2005; 31:132-5.
British Medical Research Council (Hong Kong Chest Service). Controlled trial of 2, 4 and 6 months of pyrazinamide in 6 month, three times weekly regimens for smear positive pulmonary tuberculosis, including an assessment of a combined preparation of isoniazid, rifampin and pyrazinamide. Ann Rev Respir Dis 1991; 143: 700-6.
Steele MA, Burk RF, DesPrez RM. Toxic hepatitis with isoniazid and rifampicin. Chest 1991; 99:465?71.
Crozier A, Jaganath IB, Clifford MN. Dietary phenolics: Chemistry, bioavailability and effects on health. Nat Prod Rep 2009; 26:1001-43.
Garg A, Garg S, Zaneveld LJ and Singla AK. Chemistry and pharmacology of the citrus bioflavonoid hesperidin. Phytother Res 2001; 15(8): 655
Loscalzo LM, Wasowski C, Paladini AC, Marder M. Opoid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines. Eur J Pharmacol 2008, 580: 306-13.
Chanet A, Milenkovic D, Manach C, Mazur A, Morand C. Citrus fla-vanones: what is their role in cardiovascular protection. J. Agric. Food Chem 2012; 60: 8809
Kamaraj S, Anandakumar P, Jagan S, Ramakrishnan G, Devaki T. Modulatory effect of hesperidin on benzo (a) pyrene induced experimental lung carcinogenesis with reference to COX-2, MMP-2 and MMP-9. European Journal of Pharmacology 2010; 649: 320
Cho J. Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin. Arch Pharm Res 2006; 29:699-706.
Ahmad ST, Arjumand W, Nafees S, Seth A, Ali N, Rashid S, Sultana S. Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation. Toxicol. Lett 2012; 208:149-161.
Basini Jyothi, S. Mohanalakshmi, Anitha k. Protective effect of Mirabilis jalapa leaves on Anti-tubercular drugs induced hepatotoxicity. Asian J Pharm Clin Res 2013; 6(suppl 3): 221-224.
Chandane RD, Jaju JB, Ghadlinge MS, Bhosale RR, Chandrakapure AR. Effect of honey on hepatotoxicity induced by antitubercular drugs in albino rats. Int J Basic Clin Pharmacol 2013; 2:177-81.
Ohkawa H, Ohishi N, Yagi K. Assay of lipid peroxide in animal tissue by TBA reaction. Anal Biochem 1979; 95:351-8.
Kakkar P, Das B and Viswanathan PN. A modified spectrophotometric assay of SOD. Indian J Biochem Biophys 1984; 21(2): 130-132.
Sinha AK. Colorimetric assay of catalase. Anal. Biochem 1972; 47: 389-394.
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: Biochemical role as a component of glutathione peroxidase. Science 1973; 179: 588-590.
Omaye ST, Turnbull JD, Sauberlich, HE. Selected methods for the determination of ascorbic acid in animal cells, tissues and fluids. Methods Enzymol 1979; 62: 1
Desai ID. Vitamin E analysis methods for animal tissues. Methods Enzymol 1984; 105: 138-144.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ .Protein measurement with Folin
Mary C, Kasturi S, Parames C S. Herbak (Phyllanthus niruri) protein isolate protects liver from nimesulide induced oxidative stress; Pathophysiol 2006; 13:95-102.
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.
Talib Hussain T, Ramesh K Gupta, Sweety K, Mohd SK, Md Safaraj Khan, Mdarif, et al. Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents. Asian Pac J Tropical Biomed 2012; 2:454
Attri S, Rana SV, Vaiphei K, Sodhi CP, Katyal R, Goel RC, Nain CK, Singh K. Isoniazid and rifampicin induced oxidative hepatic injury protection by N-acetylcysteine. Hum. Exp. Toxicol 2000; 19:517-522.
Young IS, Woodside JV. Antioxidants in health and disease. J Clin Pathol 2001; 54(3):176-86.
Mannan Hajimahmoodi, Ghazaleh Moghaddam, Seyed Mohsen Mousavi, Naficeh Sadeghi, Mohammad Reza Oveisi and Behrooz Jannat. Total Antioxidant Activity, and Hesperidin, Diosmin, Eriocitrin and Quercetin Contents of Various Lemon Juices. Tropical Journal of Pharmaceutical Research 2014; 13 (6): 951-956
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.
Wu C-C, Bratton SB. Regulation of the intrinsic apoptosis pathway by reactive oxygen species. Antioxidants & redox signalling 2013; 19: 546
Desagher S and Martinou JC.
Budihardjo I, Oliver H, Lutter M, Luo X, and Wang X.
Czaja MJ. Cell signalling in oxidative stress induced liver injury. Semin. Liver Dis 2007; 27: 378-389.
Martin MU and Wesche H, Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family. Biochim Biophys Acta 2002; 1592(3): 265-80.
Devin A, Cook A, Lin Y, Rodriguez Y, Kelliher M and Liu Z. The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation. Immunity 2000; 12(4): 419-29.
Tacke FT, Luedde and trautwein C. Inflammatory pathways in liver homeostasis and liver injury. Clin. Rev. Allergy. Immunol 2009; 36:4-12.
Leifeld L, Nattermann J, Fielenbach M, Schmitz V, Sauerbruch T, Spengler U. Intrahepatic activation of caspases in human fulminant hepatic failure. Liver Int 2006; 26: 872
Bourdi M, Masubuchi Y, Reilly TP, Amouzadeh HR, Martin JL, George JW, Shah AG, Pohl LR. Protection against acetaminophen-induced liver injury and lethality by interleukin 10: Role of inducible nitric oxide synthase. Hepatology 2002; 35: 289
Dhingra S, Sharma A.K, Arora RC, Slezak J, Singal PK. IL-10 attenuates TNF-alpha-induced NF kappa B pathway activation and cardiomyocyte apoptosis. Cardiovasc. Res 2009; 82: 59
Shiekh Tanveer Ahmada, Wani Arjumanda, Sana Nafeesa, Amlesh Sethb, Nemat Ali a, Summya Rashida, Sarwat Sultanaa. Hesperidin alleviates acetaminophen induced toxicity in wistar rats by abrogation of oxidative stress, apoptosis and inflammation. Toxicology Letters 2012; 208:149
Lucken-Ardjomande S and Martinou JC. Regulation of Bcl-2 proteins and of the permeability of the outer mitochondrial membrane. CR Biol 2005; 328: 616-631.
Downloads
Published
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
- An author must submit Copyright form After acceptance of the article.