Adejoke Yetunde ONAOLAPO, Olakunle James ONAOLAPO

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

Aim: We investigated the effects of nevirapine on changes in body weight, lipid peroxidation/antioxidant status, apoptotic markers and neuromorphology following monosodium glutamate-induced neurotoxicity in prepubertal mice.Material and Methods: Eighty male mice which were randomly divided into eight groups of ten mice each (n=10) were used. Mice in each group were administered oral vehicle, monosodium glutamate (MSG) at 2g/kg, or one of three doses of nevirapine (at 7.5, 15 and 30 mg/kg) alone or co-administered with MSG. Vehicle or nevirapine were administered daily for 28 days, while MSG was administered on days 1-7. On day 28, animals were euthanized and blood was collected for estimation of plasma malondialdehyde (MDA) and antioxidant levels; while sections of the cerebrum and hippocampus were either fixed and processed for general histology, or homogenized for the estimation of brain biochemical parameters.Results: Results showed that administration of nevirapine alone (or when co-administered with MSG) was associated with a reduction in weight gain, increase in plasma/brain MDA levels, morphologic/morphometric evidence of dose-related hypercellularity; and varying degrees of neuroprotection, with co-administration. Nitric oxide levels and caspase-3 activity increased only with MSG, while superoxide dismutase activity decreased.Conclusions: In conclusion, subchronic administration of nevirapine was associated with dose-related alterations of the measured parameters; indicating possible neuroprotection and mitigation of MSG neurotoxicity at some of the doses studied.

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Nikanjam M, Kabamba D, Cressey TR, et al. Nevirapine exposure with WHO pediatric weight band dosing: enhanced therapeutic concentrations predicted based on extensive international pharmacokinetic experience. Antimicrob. Agents Chemother 2012;56:5374-80.
de Bethune MP. Non-nucleoside reverse transcriptase inhibitors (NNRTIs), their discovery, development, and use in the treatment of HIV-1 infection: a review of the last 20 years (1989–2009). Antiviral Res 2010;85:75-90.
Milinkovic A, Martinez E. Nevirapine in the treatment of HIV. Expert Rev. Anti Infect Ther 2004;2:367-73.
FDA (U. S. Food and Drug Administration) Viramune (nevirapine) prescribing information. 2010; http://www.accessdata.fda.gov/drugsatfda_
Cooper ER, Charurat M, Mofenson L, et al. Combination antiretroviral strategies for the treatment of pregnant HIV-1- infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr 2002;29:484-94.
Mas CM, Miller TL, Cordero C, et al. The effects of foetal and childhood exposure to antiretroviral agents. J AIDS Clinic Res 2011;2:001.
Chou M, Bertrand J, Segeral O, et al. Population pharmacokinetic-pharmacogenetic study of nevirapine in HIV-infected Cambodian patients. Antimicrob Agents Chemother 2010;54:4432-9.
King JR, Nachman S, Yogev R, et al. Efficacy tolerability and pharmacokinetics of two nelfinavir-based regimens in human immunodeficiency virus-infected children and adolescents: pediatric AIDS clinical trials group protocol 403. Paediatr. Infect. Dis. J. 2005;24:880-5.
Chokephaibulkit K, Cressey TR, Capparelli E, et al. Pharmacokinetics and safety of a new paediatric fixed-dose combination of zidovudine/lamivudine/nevirapine in HIV-infected children. Antivir. Ther 2011;16:1287-95.
Shenton JM, Teranishi M, Abu-Asab MS, et al. Characterization of a potential animal model of an idiosyncratic drug reaction: nevirapine-induced skin rash in the rat. Chem. Res Toxicol 2003;16:1078-89.
Shenton JM, Popovic M, Chen J, et al. Evidence of an immune-mediated mechanism for an idiosyncratic nevirapine-induced reaction in the female Brown Norway rat. Chem Res Toxicol 2005;18:1799-813.
Pollard RB, Robinson P, Dransfield K. Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection. Clin Ther 1998;20:1071-92.
Hall DB, MacGregor TR, Case-control exploration of relationships between early rash or liver toxicity and plasma concentrations of nevirapine and primary metabolites. HIV Clin Trials 2007;8:391-9.
Patel SM, Johnson S, Belknap SM, et al. Serious Adverse cutaneous and hepatic toxicities associated with nevirapine use by non-HIV-infected individuals. J Acquir Immune Defic Syndr 2004;35:120-5.
de Maat MM, Huitema AD, Mulder JW, etal. Population pharmacokinetics of nevirapine in an unselected cohort of HIV-1-infected individuals. Br J Clin Pharmacol 2002;54:378-85.
Kappelhoff BS, Huitema AD, van Leth F, et al. Pharmacokinetics of nevirapine: once-daily versus twice-daily dosing in the 2NN study. HIV Clin Trials 2005;6:254-61.
Capparelli EV, Sullivan JL, Mofenson L, et al. Pharmacokinetics of nelfinavir in human immunodeficiency virus-infected infants. Pediatr Infect Dis J 2001;20:746-51.
Dailly E, Raffi F, Perré P, et al. Influence of darunavir coadministration on nevirapine pharmacokinetics in HIV-infected patients: a population approach. HIV Med 2009;10:586-9.
King JR, Kimberlin DW, Aldrovandi GM, et al. Antiretroviral pharmacokinetics in the paediatric population: a review. Clin. Pharmacokinet 2002;41:1115-33
Luzuriaga K, Bryson Y, Krogstad P, et al. Combination treatment with zidovudine, didanosine, and nevirapine in infants with human immunodeficiency virus type 1 infection. N Engl J Med 1997;336:1343-9.
Kovacs A, Montepiedra G, Carey V, et al. Immune reconstitution after receipt of highly active antiretroviral therapy in children with advanced or progressive HIV disease and complete or partial viral load response. J. Infect. Dis. 2005;192:296-302.
L’homme RF, Kabamba D, Ewings FM, et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22:557-65.
Sharma AM, Li Y, Novalen M, Bioactivation of nevirapine to a reactive quinone methide: implications for liver injury. Chem Res Toxicol 2012;25:1708-19.
Akay, C. Cooper M, Odeleye A, et al. Antiretroviral drugs induce oxidative stress and neuronal damage in the central nervous system. J. Neurovirol 2014;20:39-53.
Swamy AH, Patel NL, Gadad PC, et al. Neuroprotective activity of pongamia pinnata in monosodium glutamate-induced neurotoxicity in rats. Indian J Pharm Sci 2013;75:657-63.
Anafi S, Kwanashie H, Anuka J, Muktar H, Agbaji A. Co-administration of artemether and nevirapine has no undesirable effect on blood glucose level in Wistar rats co-administration of artemether and nevirapine has no undesirable effect on blood glucose level in Wistar rats. African J. Pharm. Pharmacol. 2014;8:1012-7
Onaolapo AY, Onaolapo OJ, Nwoha PU. Aspartame and the hippocampus: Revealing a bi-directional, dose/time-dependent behavioural and morphological shift in mice. Neurobiol Learn Mem 2017;139:76-88.
Onaolapo AY, Onaolapo OJ, Nwoha PU. Methyl aspartylphenylalanine, the pons and cerebellum in mice: An evaluation of motor, morphological, biochemical, immunohistochemical and apoptotic effects. J Chem Neuro 2017;86:67-77.
Onaolapo AY, Adebayo AA, Onaolapo OJ. Oral phenytoin protects against experimental cyclophosphamide-chemotherapy induced hair loss Pathophysiol 2018;25:31-9.
Onaolapo OJ, Onaolapo AY, Akanmu MA, et al. Evidence of alterations in brain structure and antioxidant status following ‘low-dose’ monosodium glutamate ingestion. Pathophysiol 2016;23:147-56.
Oleksandra AS, Oleksandr VV, Falalyeyeva TM, et al. The efficacy of probiotics for monosodium glutamate-induced obesity: Dietology concerns and opportunities for prevention EPMA J 2014;5:2.
Marmo MR, Dolnikoff MS, Kettelhut IC, et al. Neonatal monosodium glutamate treatment increases epididymal adipose tissue sensitivity to insulin in three-month old rats Braz J Med Biol Res 1994;27:1249-53.
Umoren EB, Obembe AO, Osim EE. Chronic administration of the antiretroviral nevirapine increases body weight, food, and water intake in albino Wistar rats. J Basic Clin Physiol Pharmacol 2012;23:89-92.
Umoren EB, Obembe AO, Osim EE. Influence of nevirapine on gastrointestinal function. J Gastrointest Dig Syst 2015;5:326.
Saghayam S, Kumarasamy N, Cecelia AJ, et al. Weight and body shape changes in a treatment-naive population after 6 months of nevirapine-based generic highly active antiretroviral therapy in South India. Clin Infect Dis 2007;44:295-300.
Adaramoye OA, Adesanoye OA, Adewumi OM, et al. Studies on the toxicological effect of nevirapine, an antiretroviral drug, on the liver, kidney and testis of male Wistar rats. Hum Exp Toxicol 2012;31:676-85.
Awodele O, Popoola T, Rotimi K, et al. Antioxidant modulation of nevirapine induced hepatotoxicity in rats. Interdiscip Toxicol 2015;8:8-14.
Le DA, Wu Y, Huang Z, et al. Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation. Proc Natl Acad Sci U S A 2002;99:15188-93.
Fujikawa DG. The Role of excitotoxic programmed necrosis in acute brain injury. Comput Struct Biotechnol J 2015;13:212-21.
Streck EL, Scaini G, Rezin GT, et al. Effects of the HIV treatment drugs nevirapine and efavirenz on brain creatine kinase activity. Metab Brain Dis 2008;23:485-92.
Streck EL, Ferreira GK, Scaini G, et al. Non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine inhibit cytochrome C oxidase in mouse brain regions. Neurochem Res 2011;36:962-6.
Gongvatana, A Harezlak J, Buchthal S, et al Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy. J Neurovirol 2013;19:209-18.