Acute and Chronic Toxicity Studies of Antiretroviral Regimens in Albino Rats

Uade Richard OVIOSUN, M. G. Abubakar, S. W. Hassan, B. M. Agaie, S. M. Sahabi

Abstract


The acute and chronic oral toxicity studies of antiretroviral regimens were evaluated in albino rats. For chronic toxicity study, the antiretroviral drugs were administered singly and in combination (CMB). Lamivudine (3TC), Zidovudine (AZT) and Nevirapine (NVP) at single doses of 5000 mg/kg each produced treatment related signs of toxicity in tested animals during the first few hours but returned to normal after 48 hours therefore the 48 hours LD50 of each drug was estimated to be more than 5000 mg/kg. Chronic toxicity showed an initial percentage increase in weight between 0-6 weeks and a corresponding decrease in weight from 6-13 weeks was observed. There was no significant (P>0.05) change in serum electrolyte levels in the treated groups when compared to the control group. Aspartate transaminase (AST) was significantly (P<0.05) increased in groups administered with 3000 mg/kg of CMB, 4000 mg/kg of CMB and at all administered doses of NVP.

Similarly all administered doses of NVP caused a significant (P<0.05) increase in the level of 5 nucleotidase (5NT). At administered doses of 2000 mg/kg and 4000 mg/kg body weight, NVP caused a significant (p<0.05) increase in total cholesterol (TC) upon comparison with the control. Administered doses of CMB and NVP, except at 1000 mg/kg body weight respectively, showed a significant (p<0.05) increase in the level of malondialdehyde (MDA) when compared with the control group. Catalase activity recorded a significant (P<0.05) decrease at doses of 3000 mg/kg and 4000 mg/kg body weight of CMB and NVP. Histopathological examination of the liver showed changes in the treated group when compared with the control group. These changes were corroborated by the non-invasive results. The above results indicate that NVP was the potent hepatotoxic agent, followed by CMB, AZT and 3TC. The hepatotoxicity was also dose dependent.


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