Effect of Lamivudine Administration on Serum Corticosterone Levels in Adult Male Wistar Rats

Abstract

Background: Lamivudine is a nucleoside reverse transcriptase inhibitor widely used in the management of Human Immunodeficiency Virus (HIV) infection and chronic Hepatitis B virus disease. Although considered relatively safe, accumulating evidence suggests that prolonged exposure to nucleoside analogues may induce mitochondrial dysfunction and oxidative stress, which could potentially affect endocrine regulation, particularly the hypothalamic–pituitary–adrenal (HPA) axis. Given the central role of glucocorticoids in metabolic homeostasis and stress adaptation, evaluating the effects of Lamivudine on adrenal function is of considerable importance. Objective: This study investigated the effect of graded doses of Lamivudine on serum corticosterone levels and adrenal gland histology in adult male Wistar rats. Methods: Sixteen adult male Wistar rats aged 8–10 weeks were randomly assigned into four groups (n = 4). Group A served as control and received distilled water, while Groups B, C, and D received Lamivudine at doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg respectively for 30 consecutive days via oral gavage. Serum corticosterone levels were measured using enzyme-linked immunosorbent assay (ELISA). Adrenal glands were harvested for histological evaluation using hematoxylin and eosin staining. Data were analyzed using one-way analysis of variance (ANOVA) followed by least significant difference (LSD) post hoc test, with statistical significance set at p ≤ 0.05. Results: A mild dose-dependent increase in serum corticosterone levels was observed in Lamivudine-treated groups compared to control; however, these differences were not statistically significant (p ≥ 0.05). Histological examination revealed increased lipid accumulation within the zona fasciculata of treated groups, indicating enhanced steroidogenic activity. No evidence of cellular degeneration, necrosis, or architectural distortion was observed. Conclusion: Lamivudine administration may lead to mild activation of the HPA axis without causing significant endocrine disruption. The findings suggest that Lamivudine is relatively safe with respect to adrenal function, although subtle biochemical and histological changes indicate the possibility of subclinical effects that warrant further investigation, particularly in long-term exposure scenarios.