_______________________________________________________________________________________________________________________________ OA Maced J Med Sci. 2015 Dec 15; 3(4):545-550. 545 ID Design 2012/DOOEL Skopje Open Access Macedonian Journal of Medical Sciences. 2015 Dec 15; 3(4):545-550. http://dx.doi.org/10.3889/oamjms.2015.110 eISSN: 1857-9655 Basic Science Lamivudine-Induced Liver Injury Lamidi W. B. Olaniyan 1* , Emmanuel N. Maduagwu 2 , Olalekan Wasiu Akintunde 3 , Oladimeji O. Oluwayelu 4 , Bartholomew I. C. Brai 5 1 Biochemistry Department, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria; 2 Biochemistry Department, College of Medicine, University of Ibadan, Ibadan, Nigeria; 3 Anatomy Department, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology Ogbomoso, Ogbomoso, Nigeria; 4 Veterinary Microbiology and Parasitology Department, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria; 5 Molecular Biology and Biotechnology Division, Nigerian Institute of Medical Research Lagos, Lagos, Nigeria Citation: Olaniyan LWB, Maduagwu EN, Akintunde OW, Oluwayelu OO, Brai BIC. Lamivudine-Induced Liver Injury. OA Maced J Med Sci. 2015 Dec 15; 3(4):545-550. http://dx.doi.org/10.3889/oamjms.2015.110 Key words: Embryonated egg; Histopathology; Lamivudine cytotoxicity; Oxidative; stress. * Correspondence: Dr. Olaniyan Lamidi W.B. Ladoke Akintola University of Technology, Ogbomoso Nigeria, Biochemistry Department, Ogbomoso, Oyo, Nigeria. E- Mail: waheedolaniyan@yahoo.com Received: 17-Apr-2015; Revised: 07-May-2015; Accepted: 09-Jun-2015; Online first: 16-Oct-2015 Copyright: © 2015 Lamidi W. B. Olaniyan, Emmanuel N. Maduagwu, Olalekan Wasiu Akintunde, Oladimeji O. Oluwayelu, Bartholomew I. C. Brai. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Competing Interests: The authors have declared that no competing interests exist. Abstract BACKGROUND: Lamivudine is a nucleoside analogue antiretroviral drug, known for its low toxicity at clinically prescribed dose. However, the toxicity or mechanism of toxicity and target tissue effects during prolonged administration of higher doses were hardly given sufficient laboratory attention. AIM: The present work was designed to investigate the biochemical and histopathological changes in the liver of rat administered with prolonged doses of lamivudine. MATERIAL AND METHODS: Lamivudine in multiple doses of five ranging from 4 mg/kg to 2500 mg/kg were administered, in vitro, by injection into the air-sac of 10–day old fertile embryonated eggs of Gallus domesticus. Also, female rats of the Wistar strain received oral doses, up to 500 mg/kg singly or repeatedly for 15 or 45 days, respectively. Spectrophotometric techniques were employed to monitor activities of the aminotransferases (ALT and AST), γ–glutamyltransferase (GGT) and total protein concentration in serum while activities of glutathione S–transferase (GST), GGT and superoxide dismutase (SOD) as well as concentrations of malondialdehyde (MDA) and protein were determined in liver. Histopathological studies were carried out on liver. Data were analysed using ANOVA and were considered significant when p < 0.05. RESULTS: The LD50 for the drug calculated from the incubation experiment was 427 mg/kg. Total serum protein concentration significantly reduced while enzymes activities significantly increased at 500 mg/kg only among the repeat-dosed rats. Hepatic GGT, GST and SOD activities as well as MDA concentration were significantly elevated at 20 mg/kg. Histopathological studies showed multifocal lymphoid cell population in the liver sinusoid of the chicken and hydropic degeneration of hepatocytes were recorded among rats repeatedly exposed to the drug respectively at doses ≥ 100 mg/kg. CONCLUSION: Lamivudine toxicity in rat liver appeared to be mediated by oxidative stress. Introduction Lamivudine is a cytidine - analogue antiretroviral pro-drug. It is metabolically activated into 51-triphosphorylated derivative by cytosolic kinases in a step-wise manner in the liver. The actively metabolised drug inhibits polymerase gamma, the enzyme that catalyses the synthesis of mitochondrial DNA which may lead to mitochondrial dysfunction in the susceptible tissue [1] with the accompanied clinical effects. Oxidative stress, an imbalance between prooxidant and antioxidant levels favouring the former may arise profoundly as a result of mitochondrial dysfunction, underlies mechanism of a number of drug toxicities [2, 3]. Lamivudine is largely excreted in the urine unchanged or to a minor extent as a trans-sulphoxide [4]. Although the drug has been reported to have limited toxicity relative to its pharmacologic counterparts [5], pancreatitis [6], polyneuropathy [7]