Histo-morphological and seminal evaluation of testicular parameters in diabetic rats under antiretroviral therapy: interactions with Hypoxis hemerocallidea.

OBJECTIVES: Broad range of metabolic changes associated with highly active antiretroviral therapy (HAART) has been reported over decades including reproductive perturbations. The current study aimed at investigating the role of Hypoxis hemerocallidea (Hyp) in the seminal and morphometric alterations in the testes of streptozotocin-nicotinamide-induced diabetic rats under HAART. MATERIALS AND METHODS: Sixty-two adult male Sprague-Dawley rats were divided into A-H groups, containing 6 rats in the control group A and 8 rats in the treatment groups B-H. Diabetes was induced by intraperitoneal injection of nicotinamide (110 mg/kg BW) followed by streptozotocin (45 mg/kg BW). The animals were then subjected to various treatments with HAART, Hyp, and melatonin. RESULTS: weights (body and testicular), histological, histochemical, seminal fluid, and morphometric analyses were carried out. Sperm count and motility were reduced in HAART (P<0.05/0.003) and Hyp200 (P<.003) groups compared with normal and diabetic controls, respectively. Sperm count was higher (P<.003) in HAART+ Mel and HAART+Hyp100 groups. Morphometry showed the reduction in germinal epithelium height and basement membrane thickness (P<.003) in the Hyp100 group compared with diabetic controls. Adjuvant use of Hyp and melatonin with HAART did not significantly raise these indices (P>.05). Histological slides showed gross distortions in HAART, diabetic and HAART +Hyp groups with marked atrophy in tubules, germ cell loss and areas of focal depletion of the cell. PAS staining revealed detached basement membrane in diabetic groups with strong PAS-stain. CONCLUSION: The use of Hyp or melatonin does not ameliorate the testicular damages in diabetic animals under antiretroviral therapy.

Impaired expression of testicular androgen receptor and collagen fibers in the testis of diabetic rats under HAART: the role of Hypoxis hemerocallidea.

INTRODUCTION: Wide spectrum of alterations associated with highly active antiretroviral therapy (HAART) has been reported. The current study aimed at evaluating the role of Hypoxis hemerocallidea (HH) aqueous extract on the testosterone levels, expression of androgen receptors and collagen fibers in the testes of streptozoto-cin-nicotinamide-induced diabetic rats under HAART regimen. MATERIAL AND METHODS: Sixty two adult male Sprague-Dawley rats (189.0 ± 4.5 g) were divided into eight groups (8 animals in each treatment groups and 6 rats in the control group). Diabetes was induced by a single intraperi-toneal injection of nicotinamide (110 mg/kg bw) followed by streptozotocin (45 mg/kg bw) and the animals were then subjected to various treatments with HAART, HH extract or melatonin. At the end of the experiment, blood samples were collected to measure serum testosterone levels. Testes were fixed in buffered formaldehyde and paraffin processed. The expression of androgen receptor (AR) was assessed by immunohistochemistry and collagen fibers were visualized by Masson trichrome staining. RESULTS: Serum testosterone level was drastically (p < 0.0001) reduced in all rats with induced diabetes. In the testis of diabetic rats increased collagen fibers deposition with varying derangements in germinal epithelium of spermatogenic layers were observed. Intertubular hemorrhages and absence of spermatozoa were also noted in the testes of diabetic rats subjected to HAART. Reduced immunoexpression of ARs was found in the nuclei of Sertoli cells and the cytoplasm of spermatogonia and spermatocytes in III-IV stages of the seminiferous epithelium cycle of diabetic animals treated with different dosages of HH alone and those treated with HAART concomitantly with melatonin and HH. The expression of ARs was almost negative in the testes of rats treated with HAART alone. CONCLUSIONS: Concomitant treatment of rats with aqueous HH extract during the HAART did not change se-rum testosterone level nor mitigate the altered expression of collagen fibers and androgen receptor resulting from STZ-nicotinamide-induced diabetes. Therefore, anti-diabetic properties of Hypoxis extract require further investigation.

Hepatic histomorphological and biochemical changes following highly active antiretroviral therapy in an experimental animal model: Does Hypoxis hemerocallidea exacerbate hepatic injury?

As the roll-out of antiretroviral therapy continues to drive downwards morbidity and mortality in people living with HIV/AIDS (PLWHAs), organ toxicities (especially the liver) are frequently becoming a major concern for researchers, scientists and healthcare planners. This study was conducted to investigate the possible protective effect of Hypoxis hemerocallidea (AP) against highly active antiretroviral therapy (HAART)-induced hepatotoxicity. A total of 63 pathogen-free adult male Sprague-Dawley rats were divided into 9 groups and treated according to protocols. While no mortality was reported, animals treated with adjuvant HAART and AP recorded least% body weight gain. Significant derangements in serum lipid profiles were exacerbated by treatment of with AP as LDL (increased p < 0.03), triglycerides (increased p < 0.03) with no change in total cholesterol levels. Adjuvant AP with HAART caused reduction in LDL (p < 0.05 and 0.03), increased HDL (p < 0.05) and TG (p < 0.05 and 0.001 for AP100 and AP200 doses respectively). Markers of liver injury assayed showed significant increase (p < 0.003, 0.001) in AST in AP alone as well as HAART+ vitamins C and E groups respectively. Adjuvant HAART and AP and vitamins C and E also caused significant declines in ALT and ALP levels. Serum GGT was not markedly altered. Disturbances in histopathology ranged from severe hepatocellular distortions, necrosis and massive fibrosis following co-treatment of HAART with vitamins C and E as well as HAART alone. These results warrant caution on the adjuvant use of AP with HAART by PLWHAs as implications for hepatocellular injuries are suspect with untoward cardiometabolic changes.