Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used in the treatment of HIV infections. It has been reported that NVP has a toxic effect on the liver, kidney and male reproductive system. This study was designed to assess the NVP toxic effects on these tissues (liver, kidney and testis) and its possible genotoxic and mutagenic effects. Forty adult male albino rats were divided into 4 groups (10 rats each): (A) negative control group, (B) positive control group received 1ml/ day of corn oil, (C) NVP1 treated group received 3.6mg (loading dose) of the drug for 2 weeks and (D) NVP2 treated group received the loading dose of the drug for 2 weeks then 7.2 mg (maintenance dose) for 2 weeks more. The results of present study revealed the followings: NVP did not alter the body weight gain or kidney weight, but it increased liver weight in (group C) and decreased testis weight in (group D). NVP caused a high significant increase of liver function tests (serum aspartate transferase, alanine transaminase, alkaline phosphatase and total bilirubin), a high significant decrease in hormonal levels of testes (testosterone, FSH and LH) and no significant difference on kidney function tests (urea and creatinine). Histopathological changes in liver and testis in NVP-treated groups were observed as compared to control groups. Comet assay showed that NVP caused a highly significant damage in blood cells in a dose dependent fashion. This result suggests for the first time that this drug might induce genotoxicity in the whole blood. In conclusion, oral exposure of adult albino rats to NVP at a human therapeutic dose daily for 4 weeks leads to toxic effects on liver and damaging effect on male reproductive system in addition to the genotoxicity. |
