Antioxidant modulation of nevirapine induced hepatotoxicity in rats

Abstract

HIV/AIDS related mortality has been dramatically reduced by the advent of antiretroviral therapy (ART). However, ART presents with associated adverse effects. One of such adverse effects is hepatotoxicity observed with nevirapine (NVP) containing ART. Since previous studies showed that NVP hepatotoxicity may be due to oxidative stress via generation of oxidative radicals, this study sought to evaluate the protective effects of antioxidants in alleviating NVP induced hepatotoxicity. Rats were divided into 6 groups with 8 animals per group and received doses of the antioxidants jobelyn (10.7 mg/kg/day), vitamin C (8 mg/kg/day), vitamin E (5 mg/kg/day) and/or NVP (6 mg/kg/day) for 60 days. The animals were sacrificed on day 61 by cervical dislocation, blood samples were collected for biochemical and hematological examination. The liver of the sacrificed animals was weighed and subjected to histopathological examination. There was a statistically significant (p<0.05) elevation in MDA level observed in the NVP group as compared with control. The results further showed non-significant decreases in the levels of MDA in the NVP plus antioxidant groups, except vitamin C, when compared with the NVP alone group. Vitamin E and Vitamin E plus C treated groups showed significantly (p<0.05) higher levels of SOD, CAT and GSH. The results also showed statistically significantly (p<0.05) lower levels of ALT and AST in the antioxidant treated groups There was an observed significantly (p<0.05) higher level of TP and urea in the antioxidant treated rats. A significantly (p<0.05) higher white blood cell count was observed in the antioxidant groups. Histopathological assessment of the liver extracted from the rats showed no visible pathology across the groups. Observations from this study suggest a potentially positive modulatory effect of antioxidants and may be indicative for the inclusion of antioxidants in nevirapine containing ART.

Highly Active Antiretroviral Therapy Depletes Some Antioxidant Parameters and Increases Free Radical Generation in Drosophila melanogaster

“…Highly active antiretroviral therapy (HAART) has hitherto reduced the burden of HIV-related illnesses and deaths among HIV patients compared to HIV positive but untreated [1]. Nevertheless, HAART induces oxidative stress [2,3,4] and life expectancy in HAART treated HIV patients is shorter than the uninfected population [3].…”

“…Both in vivo and in vitro studies have reported antiretroviral drugs-induced ROS generation [1][2][3]. The polymerase gamma toxicity theory of the nucleoside reverse transcriptase inhibitors (NRTIs (e.g.…”

“…The polymerase gamma toxicity theory of the nucleoside reverse transcriptase inhibitors (NRTIs (e.g. Lamivudine and Tenofovir), is a common conceptual framework upon which some of these studies on antiretroviral toxicities revolves [1][2][3]. Briefly, NRTIs competes with natural nucleosides for binding site on polymerase gamma (pol ), the sole polymerase in the mitochondrial responsible for mitochondria DNA synthesis and repair, thus resulting to DNA chain termination.…”

Nevirapine mitigates monosodium glutamate induced neurotoxicity and oxidative stress changes in prepubertal mice

“…However, in mice with MSG-induced neurotoxicity, an increase in Plasma and brain SOD and NO was observed; with nevirapine mitigating MSG-induced oxidative stress and antioxidant derangement when administered at 7, 15 and 30 mg/kg. A number of other studies have also reported increased lipid peroxidation and decreased antioxidant activity (superoxide dismutase and catalase) in the plasma or tissues of rats administered nevirapine alone with increasing doses (36,37).…”

Antioxidants as recipes for efavirenz-induced liver damage: A study in albino rats

“…Similarly Awodele and co-researchers reported the ameliorative effects of vitamins C and E on nevirapine-induced hepatotoxicity in rats. 59 Also, Naglaa et al, 2015 60 reported the beneficial effect of NAC on acetaminophen-induced hepatotoxicity in rats.…”