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.
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Adikwu E Brambaifa N (2013). Concentration effect incidence and mechanism of nevirapine hepatotoxicity. Am J Pharmacol Toxicol8(1): 20–30.
Adikwu E Brambaifa N Deo O Oru-Bo PG (2013). Antiretroviral Toxicity and Oxidative Stress. Am J Pharmacol Toxicol8(4): 187–196.
Awodele O Agbaje EO Adesina EA. and Akintonwa A (2011). Hepatoprotective Role of NeutrosecR on Hepatic Damage Induced by Combination of Zidovudine and Combined Anti-tuberculous Agents in Rats. Tokai J Exp Clin Med36(2): 31–36.
Bain PJ (2003). Clinical Pathology. In Latimer KS Mahaffey EA and Prasse KW (eds.) Duncan and Prasse’s Veterinary Laboratory Medicine. 4th ed. pp.193–214. Iowa State Press Ames.
Batterham M Gold J Naidoo D Lux O Sadler S Bridle S Ewing M Oliver C (2001). A preliminary open label dose comparison using an antioxidant regimen to determine the effect on viral load and oxidative stress in men with HIV/AIDS. Eur J Clin Nutr55: 107–114.
Carol SJ Claudia GM Srilakshmi JC (1993). Vitamin C elevates red blood cell glutathione in healthy adults. Am J Clin Nutr58: 103–105.
Clancy J McVicar AJ Baird N (2002). Fundamentals of Homeostasis in Perioperative Practice (Clancy J McVicar AJ eds). Routledge London.
Costagliola C Menzione M (1990). Effect of Vitamin E on the Oxidative state of glutathione in the plasma. Clin Physio/Biochem8: 140–143.
Douglas KT (1987). Mechanism of action of glutathione-dependent enzymes. Adv Enzymol Relat Areas Mol Biol59: 103–167.
Drain PK Kupka R Mugusi F Fawzi WW (2007). Micronutrients in HIV-positive persons receiving highly active antiretroviral therapy Am J Clin Nutr85: 333–345.
EMEA (2005). Efficacy and safety concerns regarding the coadministration of tenofovir disoproxil fumarate (TDF Viread) and didanosine (ddI Videx). EMEA Public Statement (EMEA/6231/2005). No. II/0049.
Emejulu AA Ujowundu CO Igwe CU Ouwuliri VA (2010). Hepatotoxicity of antiretroviral drugs in HIV seropositive Nigerian patients. Aust. J. Basic Applied Sci4: 4275–4278.
Gavrila A Sotirios T Doweiko J Nagy GS Brodovicz K Hsu W Karchmer AW Mantzoros CS (2003). Exercise and vitamin E intake are independently associated with metabolic abnormalities in human immunodeficiency virus–positive subjects: a cross-sectional study. Clin Infect Dis36: 1593–1601.
Gurer H Ozgunes H Saygin E Ercal N (2001). Antioxidant effect of Taurine against Lead –induced Hepatotoxicity in rats. Pakistan J Biol Sci14(3): 219–225.
Hess JL (1993). Antioxidants in Higher Plants (Alscher RG and Hess JL eds.) pp. 111–134. CRC press Boca Raton.
Hughes PJ Cretton-Scott E Teague A Wensel TM (2011). Protease inhibitors for patients with HIV-1 infection: A comparative overview. P T36(6): 332–345.
Kashou AH Agarwal A (2011). Oxidants and antioxidants in the pathogenesis of HIV/AIDS. Open Reproductive Sci J3: 154–161.
Onyema O Ebenezer O Godwin E Agwu U Godffery O (2006). Effect of Vitamin E on Monosodium Glutamate hepatotoxicity and Oxidative stress in rats. In J biochem biophys43: 20–24.
Sappey C Legrand-Poels S Best-Belpomme M Favier A Rentier B Piette J (1994). Stimulation of glutathione peroxidase activity decreases HIV type 1 activation after oxidative stress. AIDS Res Hum Retroviruses10: 1451–1461.
Scholz RW. Graham KS. Gumpricht E. Reddy CC (1989). Mechanism of interaction of vitamin E and glutathione in the protection against membrane lipid peroxidation. Ann NY Acad Sci570: 514–517.
Simsek S Yuce A Utuk AE (2006). Determination of serum malondialdehyde levels in sheep naturally infected with Dicrocoelium dendriticum. Fırat Üniver-sitesi Sağlık Bilimleri Dergisi (Veteriner) 20: 217−220.
Singh A Bhat TK Sharma OP (2011). Clinical Biochemistry of Hepatotoxicity. J Clinic ToxicolS4: 001.
Soriano V Puoti M Garcia-Gasco P Rockstroh KJ Benhamou Y Barreiro P Mc-Govern B (2008). Antiretroviral drugs and liver injury. AIDS22: 1–13.
Taylor EW Nadimpalli RG Ramanathan CS (1997). Genomic structures of viral agents in relation to the biosynthesis of selenoproteins. Biol Trace Elem Res56: 63–91.
Thapa BR Walia A (2007). Liver function tests and their interpretation. Indian J Pediatr74: 663–671.
Umar RA Ladan MJ Hassan SW Sa’id Y Abbas AY and Oduolisaeme IB (2007). Administration of Antiretroviral Drugs has no untoward effect on Haematological profile in Albino rats. Asian J Biochem2(2): 147–151.
US Food and Drug Administration Center for Drug Evaluation and Research [www.fda.gov]. FDA public health advisory for nevirapine (Viramunet) (19 January 2005). Available at: www.fda.gov/cder/drug/advisory/nevirapine.htm.
Valle LGD Hernandez RG Avila JP (2013). Oxidative stress associated to disease progression and toxicity during antiretroviral therapy in human immunodeficiency virus infection. J Virol Microbiol2013: 1–15 DOI: 10.5171/2013.279685.
Van Haaften RIM Evelo CTA Haenen GRM Bast A (2001). Alpha Tocopherol inhibits glutathione S-transferase P1-1(GST P1-1). Biochem Biophys Res Commun280(3): 631–633.
Wei YH Lu CY Lee HC Pang CY Ma YS (1998). Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann N Y Acad Sci854: 155–170.
World Health Organization (2006). The World Health Report: Working Together for Health. 1st Edn pp209. Geneva ISBN-10: 241563176.
Yamamoto T Kikkawa R Yamada H Horii I (2005). Identification of oxidative stress-related proteins for predictive screening of hepatotoxicity using a proteomic approach. J Toxicol Sci30: 213–227.
Zelen I Mitrovic M Jurisic-Skevin A Arsenijevic S (2010). Activity of superoxide dismutase and catalase and content of malondialdehyde in seminal plasma of infertile patients. Med Pregl63(9–10): 624–629.
Zhao L Cox AG Ruzicka JA Bhat AA Zhang W Taylor EW (2000). Molecular modeling and in vitro activity of an HIV-1-encoded glutathione peroxidase. Proc Natl Acad Sci97: 6356–6361.