Protective Effects of Quercetin against Isoniazid and Rifampicin Induced Hepatotoxicity in Rats

Gulala Ibrahim Qader¹, RoshnaShawkat Aziz¹, ZheenAorahman Ahmed¹, ZanaFaeq Abdullah² and Saad Abdulrahman Hussain^3,

¹Department of Pharmacology, School of Medicine, Faculty of medical Sciences, University of Sulaimani, Kurdistan, Iraq

²School of Pharmacy, Faculty of Medical Sciences, University of Sulaimani, Kurdistan, Iraq

³Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq

Cite this paper:
Gulala Ibrahim Qader, RoshnaShawkat Aziz, ZheenAorahman Ahmed, ZanaFaeq Abdullah and Saad Abdulrahman Hussain. Protective Effects of Quercetin against Isoniazid and Rifampicin Induced Hepatotoxicity in Rats. American Journal of Pharmacological Sciences. 2014; 2(3):56-60. doi: 10.12691/ajps-2-3-3

Abstract

Drug-induced liver injury is a problem of increasing significance, but has been a long-standing concern in the treatment of tuberculosis (TB). The present study evaluates the possible hepatoprotective effects of Quercetin against the experimentally induced hepatotoxicity with isoniazid (INH) and rifampicin (RFP) in rats. Twenty-four rats wereallocated into 4 groups (6 rats in each group), and treated as follow: group I, received normal saline orally; group II, receivednormal saline + (INH 10mg/Kg/day and RFP 10 mg/Kg/day orally); group III, received Quercetin (300mg/kg/day) + (INH and RFP as in group II);group IV, received N-acetyl cysteine (NAC) (50 mg/Kg/day) + (INH and RFP as in group II).After 42 days, the rats were scarified; blood samples obtained for evaluation of total antioxidant status (TAS), CRP, and the activities of ALT, AST, and ALP. Liver tissue sections were prepared for histopathologicalevaluation. The results clearly demonstrate that Quercetin provides significant protection against INH and RFP-induced toxicity in liver of rats, revealed as reduction in AST and ALT activities, increase in total antioxidant capacity, and improvements histopathologicalpicture of the liver. In conclusion, orally administered Quercetin protects the liver against INH and RFP-induced hepatotoxicity in rats.

Keywords:
Quercetin INH rifampicin hepatotoxicity rats

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References:

[1]	Klaassen CD; (Ed.); Casarett and Doull's toxicology; the basic science of poisons;7th Edition;Mc-Graw Hill, New York; 2008; p. 557-576.
[2]	Nanashima K, Mawatari T, Tahara N, Higuchi N, Nakaura A, et al. Genetic variants in antioxidant pathway: risk factors for hepatotoxicity in tuberculosis patients. Tuberculosis, 92: 253-259. 2012.
[3]	Santhosh S, Sini TK, Anandan R, Mathee PT. Hepatoprotective activity of chitosan against isoniazid and rifampicin-induced toxicity in experimental rats. Eur. J. Pharmacol., 572:69-73. 2007.
[4]	Flanagan RJ, Meredith TJ. Use of N-acetylcysteine in clinical toxicology.Am. J. Med., 91(Suppl. C): 131S-139S. 1001.
[5]	Brack C, Bechter-Thuring E, Labuhn M. N-acetylcysteine slows down aging and increase the life span of Drosophila melanogaster. Cellular Mol. Life Sci., 53(11-12): 960-966. 1997.
[6]	Harwood M, Danielewska-Nikiel B, Borzelleca JF, et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem. Toxicol., 45: 2179-2205. 2007.
[7]	Powers SK, DeRuisseau KC, Quindry J, Hamilton KL.Dietary antioxidants and exercise.J. Sports Sci., 22: 81-94. 2004.
[8]	Reid MB. Free radicals and muscle fatigue: of ROS, canaries, and the IOC. Free Radic. Biol. Med., 44: 169-179. 2008.
[9]	Jaeschke H. Preservation injury: mechanisms, prevention and consequences.J.Hepatol., 25:774-780. 1996.
[10]	Georgieva N, Gadjeva V, Tolekova A. New isonicotinylhydrazones with SSA protect against oxidative-hepatic injury of isoniazid. TJS., 2: 37-43. 2004.
[11]	Arsad SS, EsaNM, Hamzah H. Histopathologic changes in liver and kidney tissues from male SpragueDawley rats treated with Rhaphidophoradecursiva (Roxb.) schott extract. J CytolHistol., 4: 1-6. 2014.
[12]	Robin MA, Le Roy M, Descatoire V, Pessayre D. Plasma membrane cytochromes-P450 as neoantigens and autoimmune targets in drug-induced hepatitis. J.Hepatol., 26(Suppl. 1):23-30. 1997.
[13]	Yun CH, Okerholm RA, Guengerich FP. Oxidation of the antihistaminic drug terfenadine in human liver microsomes: role of cytochrome P-450 3A(4) in N-dealkylation and C-hydroxylation. Drug Metab.Dispos., 21: 403-409. 1993.
[14]	Trauner M, Meier PJ, Boyer JL. Molecular pathogenesis of cholestasis.N. Engl. J. Med., 339: 1217-1227. 1998.
[15]	Reed JC. Apoptosis-regulating proteins as targets for drug discovery.Trends Mol. Med., 7: 314-319. 2001.
[16]	Pessayre D, Berson A, Fromenty B, Mansouri A. Mitochondria in steatohepatitis. Semin. Liver Dis., 21: 57-69. 2001.
[17]	Saad EI, El-Gowilly SM, Sherhaa MO, Bistawroos AE. Role of oxidative stress and nitric oxide in the protective effects of α-lipoic acid and aminoguanidine against isoniazid-rifampicin-induced hepatotoxicity in rats.Food Chem. Toxicol., 48: 1869-1875. 2010.
[18]	Chen X, Xu J, Zhang C, Yu T, Wang H, et al. The protective effects of ursodeoxycholic acid on isoniazid plus rifampicin induced liver injury in mice. Eur. J. Pharmacol., 659: 53-60. 2011.
[19]	Metushi IG, Nakagawa T, Uetrecht J. Direct oxidation and covalent binding of isoniazid to rodent liver and human hepatic microsomes: humans are more like mice than rats. Chem. Res. Toxicol., 25: 2567-2576. 2012.
[20]	Yamamoto T, Kikkawa R, Yamada H, Horii I. Identification of oxidative stress-related proteins for predictive screening of hepatotoxicity using a proteomic approach. J.Toxicol. Sci., 30(3): 213-227. 2005.
[21]	Jaeschke H, Ho YS, Fisher MA, Lawson JA, Farhood A. Glutathione peroxidase-deficient mice are more susceptible to neutrophil-mediated hepatic parenchymal cell injury during endotoxemia: importance of an intracellular oxidant stress. Hepatology, 29(2): 443-450. 1999.
[22]	Leiro-Fernandez V, Valverde D, Vazquez-Gallardo R, Botana-Rial M, Constenla L, et al. N-acetyltransferase-2 polymorphisms and risk of anti-tuberculosis drug-induced hepatotoxicity in Caucasians. Int. J.Tuberc. Lung Dis., 15:1403-1408. 2011.
[23]	Tostmann A, Boeree MJ, Aarnoutse RE, de Lange WC, van der Ven AJ, et al. Antituberculosis drug-induced hepatotoxicity: concise up-to-date review. J. Gastroenterol.Hepatol., 23: 192-202. 2008.
[24]	Zhang ZH, Tang JH, Zhan ZL, Zhang XL, Wu HH, et al. Cellular toxicity of isoniazid together with rifampicin and the metabolites of isoniazid on QSG-7701 hepatocytes. Asian Pac. J. Trop. Med., 5: 306-309. 2012.
[25]	Yew WW, Leung CC. Anti-tuberculosis drugs and hepatotoxicity. Respirology, 11: 699-707. 2006.
[26]	Yousef MI, Omar SA, EI-Guendi MI, Abdelmegid LA. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and hematotoxicity in rat.Food Chem. Toxicol., 48: 3246-3261. 2010.
[27]	Tolman KG. The liver and lovastatin.Am. J.Cardiol., 89: 1374-1380. 2002.
[28]	Rivera L, Moron R, Sanchez M, Zarzuelo A, Galisteo M. Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese zucker rats. Obesity, 16: 2081-2087. 2008.
[29]	Kobori M, Masumoto S, Akimoto Y, Takahashi Y. Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin induced disturbance of hepatic gene expression in mice. Mol. Nutr. Food Res., 53: 859-868. 2009.
[30]	Chen X. Protective effects of quercetin on liver injury induced by ethanol. Pharmacogn. Mag., 6: 135-141. 2010.