Owembabazi Elna, Nkomozepi Pilani, Calvey Tanya, Mbajiorgu Ejikeme Felix
School of Anatomical Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Department of Human Anatomy, Kampala International University, Western Campus, Uganda.
Anat Cell Biol. 2023 Jun 30;56(2):236-251. doi: 10.5115/acb.22.229. Epub 2023 Feb 10.
Alcohol consumption alongside combination antiretroviral therapy (cART) has attracted research interest, especially because of increasing male infertility. This study investigated the combined effects of alcohol and cART on testicular morphology, biomarkers of oxidative stress, inflammation, and apoptosis. Rats, weighing 330-370 g, were divided into four groups of six animals each; control, alcohol treated (A), cART, and alcohol plus cART treated (A+cART). Following 90 days treatment period, animals were euthanized, testis extracted, and routinely processed for histology and immunohistochemical analysis. Significantly decreased epithelial area fraction, increased luminal and connective tissue area fractions, and reduction of epithelial height and spermatocyte number, were recorded in the treated groups compared to control. Extensive seminiferous epithelial lesions including widened intercellular space, karyolysis, and sloughing of germinal epithelium were recorded in all the treated groups. Furthermore, upregulation of inducible nitric oxide synthase and 8-hydroxydeoxyguanosine, interleukin-6, and caspase 3 recorded in treated animals, was more significant in A+cART group. Also, the levels of interleukin-1β and tumor necrosis factor-α were more elevated in A and cART treated groups than in A+cART, while MDA was significantly elevated in cART and A+cART treated groups compared to control group. Altogether, the results indicate testicular toxicity of the treatments. It is concluded that consuming alcohol or cART induces oxidative stress, inflammation, and apoptosis in testis of rats, which lead to testicular structural and functional derangements, which are exacerbated when alcohol and cART are consumed concurrently. The result will invaluably assist clinicians in management of reproductive dysfunctions in male HIV/AIDS-alcoholic patients on cART.
抗逆转录病毒联合疗法（cART）与饮酒问题引发了研究兴趣，尤其是考虑到男性不育问题日益严重。本研究调查了酒精和cART对睾丸形态、氧化应激生物标志物、炎症及细胞凋亡的联合影响。体重330 - 370克的大鼠被分为四组，每组六只；分别为对照组、酒精处理组（A）、cART处理组以及酒精加cART处理组（A + cART）。经过90天的治疗期后，对动物实施安乐死，取出睾丸，并进行常规组织学和免疫组化分析。与对照组相比，处理组的上皮面积分数显著降低，管腔和结缔组织面积分数增加，上皮高度和精母细胞数量减少。所有处理组均出现广泛的生精上皮病变，包括细胞间隙增宽、核溶解以及生精上皮脱落。此外，处理组动物中诱导型一氧化氮合酶、8 - 羟基脱氧鸟苷、白细胞介素 - 6和半胱天冬酶3的上调在A + cART组更为显著。同时，白细胞介素 - 1β和肿瘤坏死因子 - α的水平在A组和cART处理组中比A + cART组更高，而丙二醛（MDA）在cART组和A + cART处理组中相比对照组显著升高。总体而言，结果表明这些处理具有睾丸毒性。研究得出结论，饮酒或使用cART会在大鼠睾丸中诱导氧化应激、炎症和细胞凋亡，并导致睾丸结构和功能紊乱，而同时饮酒和使用cART时这种紊乱会加剧。该结果将为临床医生管理接受cART治疗的男性HIV/AIDS - 酒精成瘾患者的生殖功能障碍提供宝贵帮助。
