Potential role of inducible nitric oxide synthase (iNOS) activity in testicular dysfunction following co-administration of alcohol and combination antiretroviral therapy (cART) in diabetic rats: an immunohistochemistry study.

Diabetes, alcohol abuse, and combination antiretroviral therapy (cART) use have been reported to cause multi-organ complications via induction of oxidative stress and inflammation. Moreover, these are the most common factors implicated in male reproductive dysfunctions. This study evaluated testicular oxidative stress, inflammation, apoptosis, and germ cell proliferation in diabetic rats receiving alcohol or cART and their combination. Thirty adult male Sprague Dawley rats were divided into five groups, each consisting of six rats; control, diabetic only (DM), diabetic treated with alcohol (DM + A), diabetic treated with cART (DM + cART), and diabetic treated with both alcohol and cART (DM + A + cART). After 90 days of treatment, the rats were terminated, and the testes were extracted and processed for immunohistochemistry analysis for oxidative stress, inflammatory cytokines, apoptosis, and cell proliferation marker. In comparison to the control, oxidative stress markers, inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHDG) increased significantly in all treated groups. Expression of testicular proinflammatory cytokines, interleukin-1ß, and tumor necrosis factor-α was upregulated in all treated groups, but interleukin-6 was upregulated in DM, DM + cART, and DM + A + cART treated groups and was downregulated in the DM + A treated group. All treated animal groups showed an upregulation of apoptotic marker (caspase 3) and a downregulation of proliferation marker (Ki-67). However, Ki-67 staining intensity significantly increased in treated animals compared to the control. These findings suggest that diabetes, alcohol abuse, cART use, and their combination via iNOS activity upregulation can induce inflammation and oxidative stress in testicular tissue, stimulating germ cell apoptosis and proliferation inhibition leading to failure of spermatogenesis.

Co-administration of alcohol and combination antiretroviral therapy (cART) in male Sprague Dawley rats: A study on testicular morphology, oxidative and cytokines perturbations.

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-1ß 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.

Calcium and s100a1 protein balance in the brain-heart axis in diabetic male Wistar rats.

Objectives Calcium deregulation in diabetes mellitus (DM) is central to the brain-heart axis pathology. This has led to the use of medical plants in complementary medicine such as Amaranthus hypochondriacus (GA). The objective of the study was to establish the effects of grain amaranth feed supplementation on calcium, s100al protein and antioxidant levels on the brain-heart axis in diabetic male Wistar rats. Methods The study involved six groups (n=5) with DM being induced in 20 rats. To the diabetic rats, Group I received mixtard®, Group II was positive control, Groups III and IV received GA feed supplementation at 25 and 50%. In the nondiabetic rats (n=10), Group V received 50% grain amaranth while Group VI was the negative control. The brain and heart tissues were harvested after five weeks and processed using standard methods. Results Grain amaranth feed supplementation led to improved calcium levels in DM as compared to the positive control. This also led to increased s100a1, antioxidant levels in the brain-heart axis during DM. This then protected the tissues against oxidative damage, thus preserving tissue function and structure. Conclusions Grain amaranth's actions on calcium signaling subsequently affected s100a1 protein levels, leading to improved tissue function in diabetes.