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Lamivudine (L(-)21,31–dideoxy–3-thiacytidine) is an antiretroviral drug which exhibits tissue toxicity leading to peripheral neuropathy and parkinsonism. The exact mechanism of cytotoxicity and effects on target tissues are not well understood. This study was designed to elucidate the effects of lamivudine on biochemical indices in the liver, kidney and brain of rats. Female Wistar rats (180-200g) were randomly assigned into 5 groups of 6 rats each treated orally for 45 days with normal saline (Control), 4 mg/kg, 20 mg/kg, 100 mg/kg and 500 mg/kg lamivudine respectively. Rats were sacrificed after 12 hours fast and blood (6 mL) collected. Serum obtained was used for biochemical analysis. Serum Alanine and Aspartate Aminotransferases (ALT and AST), Quinine Oxidase (QO), γ–GlutamylTransferase(GGT), urinary trehalase activities as well as urinary creatinine and protein were determined by spectrophotometric techniques while urinary magnesium (Mg2+) level was determined by atomic absorption spectrophotometry. In the liver, kidney and brain, the activities of Superoxide Dismutase (SOD), Glutathione-S-Transferase (GST) and levels of malondialdehyde (MDA, index of lipid peroxidation) were determined. Histology of the liver and kidney was assessed using hematoxylin and eosin stain. Data were analysed using ANOVA at p=0.05. Lamivudine (500 mg/kg) produced significant increases in the activities of serum ALT, AST, GGT and QO (33.2±3.9, 56.4±7.2, 16.3±1.8 IU/L and 10.1±1.7 Baier’s Unit (BU)) relative to controls (21.3±1.5, 42.6±1.9, 11.1±0.7 IU/L and 4.9±1.0 BU) respectively. The drug at 20, 100 and 500 mg/kg increased hepatic …