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.
ABSTRACT
Many artemisinin-based combination therapies (ACTs) have been approved for malaria treatment, yet reports indicate that some ACTs pose reversible testicular toxicity; however there is no comparative study of these ACTs on the testes in a curative malarial model. We investigated the ameliorative activity of six ACTs on Plasmodium berghei (PB) induced perturbations in testicular antioxidants, serum testosterone levels, sperm motility and the testes microanatomy. Forty male Swiss mice were divided into 8 groups of 5 each: Group 1 normal control (NC), uninfected and untreated, received placebo; group 2 was parasitized non-treated (PNT), while groups 3 - 8 received PB inoculum intraperitoneally. Initial parasitemia was established after 72 hours. Groups 3 - 8 thereafter received oral therapeutic doses of artesunate/amodiaquine (PBAA), artesunate/mefloquine (PBAM), artesunate/sulfadoxine-pyrimethamine (PBASP), artemisinin-piperaquine (PBAP), dihydroartemisinin/piperaquine (PBDP) and artemether/lumefantrine (PBAL) per kg body weight respectively. final parasitemia was performed 24 hours after last treatment, and animals euthanized. Result for parasitemia level was significantly (p < 0.05) declined in ACT-treated groups, except PBASP compared with PNT. Enzymatic antioxidants were significantly (p < 0.0001) altered in ACT-treated groups compared to PNT. Non-enzymatic antioxidants were significantly (p < 0.0001) increased in PBDP compared to NC and PNT. Progressive sperm motility significantly (p < 0.0001) declined in PNT, PBASP, PBAP and PBDP groups compared to NC. Testosterone showed decreasing trend in PBAP compared to PNT, and severe testicular distortions were demonstrated in PNT, PBASP, PBAP and PBDP. This study concludes that therapeutic doses of AA, AM and AL moderately protects against the deleterious effects of Plasmodium berghei-induced testicular toxicity in Swiss mice
No disponible