Hippocampal Neurohistology Following Prolonged Tenofovir Disoproxil Fumarate, Lamivudine, Dolutegravir (TLD) Use and Quercetin Supplementation in Adult Male Wistar Rats
Solomon Ochanya Abang *
Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Calabar, Nigeria.
Aniekan Imo Peter
Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Uyo, Nigeria.
Kelly Kingsley Onawu
Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Calabar, Nigeria.
Christabel Ojibima Francis
Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Calabar, Nigeria.
David Onah Egbanabo
Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Calabar, Nigeria.
Andrew Osam Akikpo
Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Calabar, Nigeria.
Solomon Utum Ubana
Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Calabar, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Background: Prolonged exposure to some anti-retroviral agents may induce neuronal alterations, changes in synaptic plasticity, mitochondrial dysfunction, and oxidative stress, although findings remain inconsistent and the underlying mechanisms are not fully understood. This study aimed to determine the potential effects of quercetin on dolutegravir/lamivudine/tenofovir disoproxil fumarate (TLD)-induced histological, immunohistochemical, and biochemical changes in the hippocampus of adult male Wistar rats.
Methodology: Thirty adult male Wistar rats were randomly divided into six groups of five rats each (n = 5). Group A (control) was given distilled water, Group B was given 25 mg/kg of quercetin, Group C was given 24 mg/kg of TLD, Group D received quercetin and TLD for seven days after which TLD alone continued until the end of the experiment, Group E received quercetin and TLD throughout the experiment, and Group F received quercetin and TLD for seven days after which quercetin alone was continued till the end of the experiment. Treatments were administered orally once daily for 30 days. At the end of treatment, the animals were euthanised with ketamine (100 mg/kg, i.p.), the hippocampi were processed for oxidative stress markers, and histological (H&E) and immunohistochemical (GFAP) analyses were conducted. Data were analysed using GraphPad Prism, version 10. One-way analysis of variance (ANOVA) and Tukey's test were performed and p < 0.05 was considered statistically significant.
Results: Treatment with dolutegravir-containing combination therapy (TLD) was associated with extensive architectural deformation with pyknotic neuronal cells and obliterated neurons in the hippocampus. MDA levels increased significantly, alongside significant reductions in GSH levels and antioxidant enzyme (SOD and CAT) activities compared with the other treatment groups (p < 0.05).
Conclusion: Treatment with quercetin was associated with restoration of neuronal histopathological features, increased levels of the antioxidants SOD, GSH and CAT, and reduced MDA levels in the hippocampus.
Keywords: Quercetin, hippocampus, tenofovir disoproxil fumarate, lamivudine, dolutegravir, antiretroviral