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All Journal International Journal of Health and Medicine Health System and Medical Journal
Ezeuko, V.C
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Health Professions Medicine & Pharmacology Public Health

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Toxicity Potentials of Dolutegravir-Base Antiretroviral Therapy on the Ovary and Uterus of Adult Wistar Rats Ogbe, O.C.; Ataman, J.E; Ezeuko, V.C
International Journal of Health and Medicine Vol. 2 No. 2 (2025): April : International Journal of Health and Medicine
Publisher : Asosiasi Riset Ilmu Kesehatan Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.62951/ijhm.v2i2.383

Abstract

Background: Human immunodeficiency virus (HIV) remains a critical global health issue, with 88.4 million infections and 42.3 million AIDS-related deaths to date. In 2024 alone, 39.9 million individuals are living with HIV, 630,000 deaths occurred, and 1.3 million new infections were recorded. Tenofovir Disoproxil Fumarate/Lamivudine/Dolutegravir (TLD) is a widely used antiretroviral therapy, but its reproductive and oxidative effects remain underexplored in female models, particularly in the South-South region of Nigeria.Objective: This study aimed to evaluate the reproductive toxicity and oxidative stress effects of TLD on the ovaries and uterus of adult female Wistar rats.Methods: Ten adult female Wistar rats (156–187g) were divided into control and treatment groups (n=5). The control group received standard diet and distilled water, while the treated group received daily doses of TLD (Tenofovir 5 mg, Lamivudine 5 mg, and Dolutegravir 0.8 mg/kg body weight) for 90 days. At the end of the treatment, animals in estrus phase were sacrificed for biochemical, histological, and hormonal analysis.Results: The treated group showed a significant reduction in body weight but no significant changes in ovarian or uterine weight. Oxidative stress analysis revealed decreased MDA and increased SOD, GPx, and CAT in the uterus. Hormonal levels were not significantly different. Histologically, the treated group displayed impaired follicular development, atretic follicles, cysts, enlarged endometrial cavities, and thicker endometria.Conclusion: TLD administration induced notable reproductive alterations in female Wistar rats, highlighting potential implications for its use in women of reproductive age.
Histological and Oxidative Stress Toxicity of Dolutegravir-Based Antiretroviral Therapy on the Placenta of Adult Wistar Rats Ogbe, O.C; Ataman, J.E; Ezeuko, V.C
Health System and Medical Journal Vol. 1 No. 1 (2025): May : Health System and Medical Journal
Publisher : CV.MEDINSIGHT PUBLISHING

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Abstract

Tenofovir Disoproxil Fumurate/Lamivudine/Dolutegravir (TLD) is a fixed dose combination antiretroviral therapy recommended by World Health Organization (WHO) as preferred first and second-line antiretroviral therapy for people living with HIV. However, a relationship between placenta histology and oxidative toxicity of TLD is unknown. This study was designed to investigate the histological and oxidative stress toxicity of TLD on the placenta of adult Wistar rats. Ten rats weighing between 154-194g were randomly assigned into two groups; a control and TLD-treated. After pregnancy was achieved, the treated group was still administered combination drugs of Tenofovir Disoproxil Fumurate in 5mg/kg, Lamivudine in 5mg/kg and Dolutegravir in 0.8mg/kg body weight daily for 90 days. Dams were weighed on gestational day (GD) 0, 7, 14 and 21. At GD21, the dams were sacrificed, and placenta were harvested, counted, weighed, measured, and submitted for biochemical oxidative stress assessments and a section taken for histological evaluation. The findings revealed significant decrease in the body weight, placenta weight, diameter, and thickness of the treated group. Also, there was a significant decreased in placenta tissue reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase was decreased with insignificant difference, the concentration of malondialdehyde increased with insignificant difference in the treated compared to the control group. There was no significant difference in the number of number of placenta between the control and treated groups. The placenta histology of the TLD treated revealed vacuolation, congestion, and dilatation of the fetal-maternal vascular bed. These findings suggest TLD administration during pregnancy have negative effects on the placenta and could lead to abortion or cause serious negative consequences for the developing foetus. Concerns over long-term usage; especially during pregnancy, cannot be overemphasized.
Co-Authors Ataman, J.E Ogbe, O.C Ogbe, O.C.