A significant number of individuals on combination anti-retroviral therapy (cART) are also chronic alcohol consumers. Alcohol and cART independently induce perturbed intestinal function, but their combined effects on Paneth cells (PCs) and intestinal stem cells (ISCs) remain unclear. Thirty-two adult male Sprague-Dawley rats were divided into 4 groups and treated with normal saline, alcohol treated (AC), cART, and a combination of alcohol and cART (AC+cART) for 90 days.Sections of the small intestine were studied for histomorphology, PC granules, crypts, and ISCs in the jejunum and ileum using hematoxylin and eosin, Alcian Blue Periodic Acid-Schiff, Masson trichrome stains, and immunohistochemistry. This study reveals alcohol-induced collagen increase and cART-induced impairment in the crypts, PC granules, and diminished Musashi-1 expression of ISCs, in the jejunum and ileum. Additionally, depleted goblet cells, crypt depth, and number, but increased intestinal wall thickness and collagen in the ileum of the AC+cART group. Minimal PC granules in the stem cell and transit amplifying zone, with reduced Musashi-1 expression in the jejunum and ileum of the AC+cART group. Moreover, all the independent effects of alcohol and cART are exacerbated in the AC+cART group, resulting in perturbations of the small intestine epithelium, ISC, and PC granules, which may adversely affect the regulation of gut innate immunity, intestinal absorptive function, with adverse health outcomes when exposed to infections. These findings are clinically invaluable in managing patients who receive cART prophylaxis, considering the critical significance of PCs and ISCs in the absorption of medications and necessary nutrients for better treatment outcomes.

The study aims to compare the action of Pleurotus cornucopiae and glibenclamide on alloxan-induced diabetes and ascertain how an aqueous extract of the edible mushroom regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), oxidative stress biomarkers and renal toxicity in a diabetic male Wistar rat model. Twenty-five adult male Wistar rats were randomly grouped into five groups with five rats per. Group 1 and those in the treatment groups received normal feed and water ad libitum. Group 2 received intraperitoneal administration of alloxan monohydrate (150 mg/kg body weight).Group 3 received alloxan monohydrate and glibenclamide (5 mg/kg body weight bwt), group 4 received alloxan monohydrate plus the extract (250 mg/kg bwt) and group 5 received alloxan monohydrate plus the extract (500 mg/kg bwt). The administration of glibenclamide plus the extract was oral for 14 days. Glibenclamide and the extract lowered blood glucose level, catalase, and glutathione peroxidase activities, increased the superoxide dismutase (SOD) activity in rats with alloxan induced diabetes. The extract at 500 mg/kg bwt reduced the plasma urea and sodium concentration in the treated rats. The extract and glibenclamide could detoxify alloxan and restore its induced renal degeneration and glomeruli atrophy, intra renal hemorrhage and inflammation and oxidative biomarkers through activation of Nrf2 expression. The drug glibenclamide and P. cornucopiae have appreciable hypoglycemic activity and potential to restore the normal renal architecture in the rats, hence they offer similar curative effects. Additionally, the extract at 500 mg/kg bwt activated SOD and Nrf2 expression more than glibenclamide in rats with alloxan-induced diabetes.

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.