THE INFLUENCE OF ANTIRETROVIRAL AND ANTITUBERCULOSIS AGENTS ON THE BIOCHEMICAL AND HISTOPATHOLOGICAL INDICES OF LIVER FUNCTION IN RATS
DOI:
https://doi.org/10.11603/ijmmr.2413-6077.2015.1.2821Анотація
Background. Standard antituberculosis treatment and highly active antiretroviral therapy are frequently associated with hepatotoxicity leading to drugs discontinuation.Objective. This study aimed to assess the signs of hepatotoxicity in albino rats in case of simultaneous usage of tuberculostatics (TBS) and antiretroviral agents (ART).
Methods. Healthy rats were divided in 4 groups: 1st control group; 2nd group was given tuberculostatics (isoniazid – 50 mg/kg, rifampicin – 50 mg/kg and pyrazinamide – 1500 mg/kg); 3rd group was given ART (efavirenz – 150 mg/kg and stavudine – 5 mg/kg); 4th group was given TBS and ART. The animals were sacrificed painlessly on the 29th day; blood and liver samples were obtained. The main biochemical and histopathological indices were determined.
Conclusions. Comparing with control group, repeated usage of TBS caused the prominent liver injury with cytolysis and cholestasis signs, decreasing of CYP3A and CYP2E1 isozymes activity and dysfunction of protein synthesis by the liver. ART (efavirenz and stavudine) caused the elevation of transaminases activity with the increase of serum bilirubin level at the background of increase in cytochrome 450 isoforms 3A and 2E1 activities and total serum protein. The antiretroviral agents in case of simultaneous administration with the antituberculosis drugs diminished the hepatotoxic effects of first-line drugs for tuberculosis treatment which was confirmed by the study of liver histopathology. Such results of our experimental study give encouragement for further detailed clinical research of drug-drug interaction of both pharmacological groups due to the rising cases of HIV-associated tuberculosis in the whole world.
KEY WORDS: Isoniazid, rifampicin, pyrazinamide, efavirenz, stavudine, liver, cytochrome P450.
Посилання
World Health Organization. Global tuberculosis report 2014. Available at http://www.who.int/tb/publications/ global_report/en/. Accessed October 3, 2014
Kwara A, Flanigan TP, Carter EJ Highly active antiretroviral therapy (HAART) in adults with tuberculosis: current status. Int J Tuberc Lung Dis 2005; 9(3): 248-257.
Lawn SD, Kranzer K, Wood R. Antiretroviral therapy for control of the HIV-associated tuberculosis epidemic in resource-limited settings. Clin Chest Med 2009; 30(4): 685-699.
Cattamanchi A, Smith R, Steingart KR et al. Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals: a systematic review and meta-analysis. J Acquir Immune Defic Syndr 2011; 56: 230-238.
Samandari T, Agizew TB, Nyirenda S, et al. 6- month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial. Lancet 2011; 377: 1588-1598.
Kwara A. Pharmacokinetics of efavirenz when coadministered with rifampin in TB/HIV co-infected patients: pharmacogenetic effect of CYP2B6 variation. J Clin Pharmacol 2008; 48(9): 1032-1040.
Saukkonen JJ, Powell K, Jereb JA. Monitoring for tuberculosis drug hepatotoxicity: moving from opinion to evidence. Am J Respir Crit Care Med 2012; 185(6): 598-599.
Neuman MG, Schneider M, Nanau RM, et al. HIV- antiretroviral therapy induced liver, gastrointestinal, and pancreatic injury. Int J Hepatol 2012, Article ID:760706, 1-23.
Andreeva L, Kogemiakin L, Kishkun A. Modification of lipid peroxidation evaluation method according to the reaction with thiobarbituric acid. Lab delo 1988; 11: 41-3 (in Russian).
Koroliuk MA, Ivanova LI, Majorova IG, et al. Method of catalase activity assessment. Lab delo 1988; 1: 16-19 (in Russian).
Kamyshnikov VS. Handbook of clinical and biochemical studies and laboratory diagnosis. Moscow: MEDpress-inform; 2004: 920 (In Russian).
Gavrilov VB, Mishkorudnaya MI. Spectrophotometric assessment of lipid hydroperoxides quantity in blood plasma. Lab delo 1983; 3: 33-35 (in Russian).
Chevary S, Chaba I, Sekuy I. Role of superoxide dismutase in cellular oxidative processes and method of assessment of its biological activity. Lab delo 1985; 11: 678-681 (in Russian).
Ellman GL. Tissue sulfhydryl groups. Arch. Biochem. Biophys, 1959; 82: 70-77.
Karuzina II, Archakov AI. The selection of microsome fraction of liver and characteristic of its oxidizing systems. The modern methods in biochemistry. (in) Orechovich VN (ed). Moscow: Medicina; 1977: 49-62 (in Russian).
Hrebennik LI. About the determination of isonicotinic acid hydrazide derivatives and their transformation products in the body. Probl tuberc 1961; 4: 69-74 (in Russian).
Karim SA, Naidoo K, Grobler A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med 2010; 362: 697-706.
Kaplan JE, Benson C, Holmes KH, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV MedicineAssociation of the Infectious Diseases Society ofAmerica. MMWR Recomm Rep 2009; 58(RR-4): 1-207.
Berruet N, Sentenac S, Auchere D, et al. Effect of efavirenz on intestinal p-glycoprotein and hepatic p450 function in rats. J. Pharm. Pharmaceut. Sci 2005; 8 (2): 226-234.
Mouly S, Rizzo-Padoin N, Simoneau G. Effect of widely used combinations of antiretroviral therapy on liver CYP3A4 activity in HIV-infected patients. Br. J. Clin. Pharmacol. 2006; 62: 200-209.
Di Perri G, Marucco AD, Mondo A, et al. Drug- drug interactions and tolerance in combining antituberculosis and antiretroviral therapy Expert Opin Drug Saf 2005; 4(5): 821-836.
Kovalenko VM, Shayakhmetova AM, Bondarenko LB, et al. The influence of cytochrome P-450 2E1 on biochemical and histomorphological indices of rats liver. Suchasni problemy toksikologii. 2006;3. Available at http://www.medved.kiev.ua/arhiv_mg/st_2006/ 06_3_5.htm (in Ukrainian). Accessed October 4, 2014
Yue J, Peng Ren-xiu, YANG J, et al. CYP2E1 mediated isoniazid-induced hepatotoxicity in rats. Acta Pharmacol Sin 2004 May; 25 (5): 699-704.
McRae MP, Lowe CM, Tian X. Ritonavir, Saquinavir, and Efavirenz, but not Nevirapine, inhibit bile acid transport in human and rat hepatocytes. J Pharmacol Exp Ther 2006; 318(3):1068-1075.
Tedla Z, Nyirenda S, Peeler C, et al. Isoniazid- associated hepatitis and antiretroviral drugs during tuberculosis prophylaxis in HIV-infected adults in Botswana. Am. J. Respir. Crit. Care Med. 2010. Available at http://ajrccm.atsjournals.org/cgi/reprint/200911- 1783OCv1. Accessed October 4, 2014
Vengerovsky AI. Pharmacological approaches to regulation of liver function. Bull Sib Med 2002; 1: 25-29 (in Russian).
De Rosa HJ, Baldan HM, Brunetti IL, Ximenes VF, Machado RG. The effect of pyrazinamide and rifampicin on isoniazid metabolism in rats. Biopharm Drug Dispos 2007; 28(6): 291-296.
Possuelo LG, Castelan JA, deBrito TC, et al. Association of slow N-acetyltransferase 2 profile and anti- TB drug-induced hepatotoxicity in patients from Southern Brazil. Eur J Clin Pharmacol 2008; 64: 673-681.
Nepomnyashchikh GI, Dyubanova GA, Nepomnyashchikh DL, et al. Universal markers of hepatotoxic influence of medical agents. Bulletin SO RAMN 2008; 6(134): 86-92 (In Russian).
Chen J, Raymond K. Roles of rifampicin in drug-drug interactions: underlying molecular mechanisms involving the nuclear pregnane X receptor. Ann Clin Microbiol Antimicrob 2006; 5:3. Available at http:// www.ann-clinmicrob.com/content/5/1/3. Accessed October 4, 2014
Huang Y-S, Chern H-D, Su W-J, et al. Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Hepatology 2003; 37(4): 924-930.
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