No abstract

SUMMARYThe increased accessibility of antiretroviral therapy continues to positively drive the reduction in viral load and survival of patients despite the attendant reproductive toxicities. We propose that testicular damage caused by highly active antiretroviral therapy (HA-ART) can be attenuated by antioxidant treatment by investigating the testicular histomorphologic and stereological effects of antiretroviral drugs and its interaction with antioxidants using an experimental animal model. Sprague-Dawley rats were divided into seven groups of six rats per group (A, B. . . G) using simple random sampling and treated orally with 0.9% normal saline as placebo, a HAART cocktail of stavudine, lamivudine and nevirapine using the adjusted human therapeutic doses of 200, 600 and 350-400 mg/ day, respectively, and antioxidants ascorbic acid (vitamin C) and I.M a-tocopherol (vitamin E). Animals were killed after 4 weeks and testicular tissue harvested and processed for light microscopy and stereological evaluations. The results were interpreted by a Veterinary pathologist blinded to the study. No animal died during the experimental period. The histopathological assessment of the testis of animals treated with placebo, ascorbic acid alone and a-tocopherol alone as well as vitamin E + HAART displayed normal testicular microanatomy. Groups treated with HAART alone, HAART + vitamin C + vitamin E and vitamins C + HAART showed extensive seminiferous tubular atrophy, necrosis and hypocellularity in the histoarchitectural patterns. While testicular cross-sectional area of seminiferous tubules remained unaffected by HAART, epithelial heights significantly decreased (p < 0.05) when compared with controls. There was marked (p < 0.05) increased in testicular-body weight ratio in HAART group. The results show that vitamin E could be useful in protecting testicular tissue from toxicities of HAART regimes as these results mirrors stereological data for the groups. HAART presents with deleterious histopathological changes in the testes causing tubular atrophy with altered morphometric indices. Supplementation with vitamin E appears to be a better adjuvant antioxidant that ameliorates these deleterious effects.

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A–D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

As antiretroviral therapy becomes increasingly accessible, the associated improvements in the health, quality of life, and survival of patients are anticipated to influence the fertility determinants of patients, specifically young males, within the reproductive axis. Therefore, the understanding of testicular histology in patients with HIV/AIDS undergoing therapeutic management is essential, because the sexual route is one of the main means of transmission of HIV, which is localized primarily in the germ cells of the testes. It is also important to determine whether any changes have occurred in the testicular histologic patterns in the course of the HIV/AIDS therapy. This review highlights the views of experts that current therapy and prolongation of survival in HIV/AIDS patients are associated with a shift in the histologic findings of testes toward a more pronounced loss of germ cells. There have been attempts to use stereologic size and number estimators to quantify the volume or number of biologically significant reference spaces and objects from their appearance on two-dimensional sections without introducing bias from inappropriate assumptions, models, or correction formulas. Therefore, morphologic changes related to altered distribution of highly active retroviral therapy within the testis and the consequent endocrine perturbations characteristic of a potential complication of antiretroviral treatment regimens can be analyzed in stereologic dimensions.

SUMMARYHighly active antiretroviral therapy has evolved over the years, leading to a boost in the quality of life in people living with HIV and AIDS. However, growing evidence has shown that highly active antiretroviral therapy has deleterious effects on the testes and the overall reproductive capacity. Therefore, this study is to determine the adjuvant potential of Naringenin on highly active antiretroviral therapy-induced perturbations in fertility of male Sprague-Dawley rats. Thirty adult male Sprague-Dawley rats were divided into six groups viz -Control; H: 30 mg/kg of highly active antiretroviral therapy (EFV, 600 mg + FTC, 200 mg + TDF, 300 mg); N40: Naringenin, 40 mg/kg; N80: Naringenin, 80 mg/kg; HN40: highly active antiretroviral therapy + Naringenin, 40 mg/kg; HN80: highly active antiretroviral therapy + Naringenin, 80 mg/kg. The rats were euthanized after 4 weeks. Results showed that there was a significant decrease in sperm count (p < 0.001), spermatozoa with normal morphology (p < 0.001) and progressive sperm motility (p < 0.05) of H compared to the control and the HN groups. Likewise, fragmentations increased (p < 0.05) in tail lengths of sperm DNA in H compared to control. HN40 and HN80 decreased tail lengths compared to H (p < 0.001). There was also a decrease in %tail DNA and tail moment in HN40 (p < 0.001) compared to H. Luteinizing hormone significantly increased (p < 0.05) in HN40, HN80, and N40 (p < 0.001) but decreased in H (p < 0.05) compared to control. The diameter of the seminiferous tubules also decreased (p < 0.05) in H compared to control, N80, and HN40. Likewise, the area of the seminiferous tubules in group H decreased (p < 0.05) compared to N80 and HN80. The seminiferous tubules epithelium increased (p < 0.05) in N40 and HN40 compared to H. This study establishes that highly active antiretroviral therapy has deleterious effects on the testicular microanatomy, sperm parameters, and sperm DNA of Sprague-Dawley rats, which may impair fertility but Naringenin is a potential complimentary adjuvant.