IBRO Neuroscience Reports (Jun 2022)
Brain antioxidants and hippocampal microanatomical alterations following the administration of Efavirenz/Lamivudine/Tenofovir disoproxil fumarate and Lamivudine/Nevirapine/Zidovudine in adult male Wistar rats
Abstract
Highly active antiretroviral therapies (HAARTs) are used for the management of human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS). The present study was designed to characterize the neurotoxicity profile of two popular HAARTs on the brains’ antioxidants and hippocampal microanatomical alterations in an in vivo model. Fifteen adults male Wistar rats, were assigned to three groups (n = 5); group I the normal control (NC) received distilled water (5 mL/kg b.wt), groups II administered with oral therapeutic doses of Efavirenz/ Lamivudine/ Tenofovir disproxil fumerate (TLE 17.14 mg/kg b.wt), and group III with Lamivudine/ Nevirapine/ Zidovudine (LNZ 9.28 mg/kg b.wt), respectively which were available for use in University of Uyo Teaching Hospital Nigeria at the time of this experiment. After a 30-day administration, biochemical parameters (catalase, superoxide dismutase, reduced glutathione, glutathione S-transferase, malondialdehyde, glutathione peroxidase, vitamins A, C and E) were determined via serum from blood of ketamine (100 mg/kg, i.p) anesthetized rats. Brains were carefully removed and post-fixed for tissue processing employing hematoxylin and eosin (H&E), cresyl fast violet (CFV) stains, and glial fibrillary acidic protein (GFAP) antibody expression. Results revealed significantly (p < 0.05) decreased antioxidant concentrations and increase in oxidative markers in HAART-administered groups. Normal histoarchitecture was shown in NC, but TLE-administered group demonstrated some neuronal atrophy, and degeneration of pyramidal neurons, with milder distortions in LNZ. TLE-administered group demonstrated intense Nissl substances with chromatolysis compared to LNZ and NC, while GFAP was strongly expressed in TLE-administered group compared to LNZ. In conclusion, TLE is more neurotoxic compared with LNZ.
