E. C. S. Naidu

Testicular histomorphologic and stereological alterations following short-term treatment with highly active antiretroviral drugs (HAART) in an experimental animal model

The 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 (HAART) 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 α‐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 α‐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.

Effect of co-administration of Hypoxis hemerocallidea extract and antiretroviral therapy (HAART) on the histomorphology and seminal parameters in Sprague Dawley rats.

Although the successful introduction and rollout of antiretroviral therapy has impacted positively on morbidity and mortality of HIV‐positive patients, its interaction with plant‐based adjuvants remain sparsely investigated. We report the interaction and effects of adjuvant treatment with highly active antiretroviral therapy (HAART) and Hypoxis hemeocallidea (HH) extracts on testicular structure of rats. A total of 63 pathogen‐free adult male Sprague Dawley rats were divided into nine groups and treated according to protocols. HAART cocktail predisposed to significant negative testicular parameters of sperm count, motility and seminiferous tubular epithelial height (quantitatively) (p < .03) and also altered the histomorphology of tubules with diffuse hypoplasia in seminiferous tubules. The higher dose of HH showed a better ability to mitigate the altered parameters and compares favourably with vitamin C in this protocol. While HH did not show any deleterious impact on morphometric data, its role as adjuvant did not significantly reduce the negative impact of HAART on morphometric indices especially with the lower dosage. Further investigations are warranted on the interactions between HAART and Hypoxis.

Naringenin attenuates highly active antiretroviral therapy-induced sperm DNA fragmentations and testicular toxicity in Sprague-Dawley rats

Highly 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.

Adjuvant potential of virgin coconut oil extract on antiretroviral therapy-induced testicular toxicity: An ultrastructural study

The effects of Virgin coconut oil as an adjuvant to highly active antiretroviral therapy (HAART) were investigated on the testicular ultrastructure and biochemical markers in rats. Twenty male Sprague‐Dawley rats, weighing 153‐169 g were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (HAART+Virgin coconut oil 10 ml/kg) and D (Virgin coconut oil [VCO] 10 ml/kg). Testicular segments were evaluated using transmission electron microscopy. Serum was assayed for testosterone, luteinising hormone, follicle stimulating hormone and testicular tissue for malondialdehyde and glutathione. Ultrastructure of basement membrane (Bm), mitochondria and spermatocytes was normal in the control group. HAART‐treated group showed significant increase (p < .01) in Bm thickness with significant decrease in Leydig cell nuclear diameter (p < .05) and volume (p < .01) when compared with control group. Mitochondrial cristae appear collapsed, and Sertoli cells showed cytoplasmic vacuolations. HAART+VCO group showed improved ultrastructural details in Bm, and Sertoli cell and Leydig cells show abundant lipid droplets. Virgin coconut oil‐treated group showed thinning of Bm with otherwise normal ultrastructural features of organelles. HAART‐treated group showed significant increase (p < .01) in testosterone levels. There was no significant effect on malondialdehyde and glutathione levels. Virgin coconut oil improved testicular morphology and reversed HAART‐induced ultrastructural alterations. Further studies on putative mechanism are required.

Sex determination using humeral dimensions in a sample from KwaZulu-Natal: an osteometric study

The morphological characteristics of the humeral bone has been investigated in recent times with studies showing varying degrees of sexual dimorphism. Osteologists and forensic scientists have shown that sex determination methods based on skeletal measurements are population specific, and these population-specific variations are present in many body dimensions. The present study aims to establish sex identification using osteometric standards for the humerus in a contemporary KwaZulu-Natal population. A total of 11 parameters were measured in a sample of n=211 humeri (males, 113; females, 98) from the osteological collection in the Discipline of Clinical Anatomy, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. The difference in means for nearly all variables were found to be significantly higher in males compared to females (P<0.01) with the most effective single parameter for predicting sex being the vertical head diameter having an accuracy of 82.5%. Stepwise discriminant analysis increased the overall accuracy rate to 87.7% when all measurements were jointly applied. We conclude that the humerus is an important bone which can be reliably used for sex determination based on standard metric methods despite minor tribal or ancestral differences amongst an otherwise homogenous population.

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.

Nephrotoxicity and highly active antiretroviral therapy: Mitigating action of Momordica charantia

Graphical abstract

Vitamin E and Testicular Damage Protection in Highly Active Antiretroviral Therapy

Abstract Despite the devastating toll of the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) on morbidity and mortality, the changing epidemiologic landscape has been largely due to the successful introduction and rollout of highly active antiretroviral therapy (HAART). Together with lifestyle changes, HAART has led to improved quality of life and optimism that HIV/AIDS can be managed similarly to other chronic diseases. Despite these positive outcomes, HAART has been associated with an increasing number of metabolic and anthropometric abnormalities including endocrine perturbations potentially contributing to deranged reproductive lifestyle. Evidence from various studies implicates oxidative stress as mediating many HAART-related reproductive derangements, with discordances regarding the use of supplemental antioxidants such as vitamin E in mitigating these effects. This review describes the evolving dynamics regarding HAART impact on testicular morphology and the unresolved issues relating to the roles of vitamin E as a free radical scavenger. Reproductive function is an unmet need in patients who may desire to have a normal reproductive life and therefore warrants attention.

Virgin coconut oil extract mitigates testicular-induced toxicity of alcohol use in antiretroviral therapy

The consumption of alcohol by people living with HIV/AIDS is associated with a graver prognosis. Long‐term use of antiretrovirals may have certain health challenges that may be aggravated by concomitant alcohol use. This study investigated virgin coconut oil (VCO) as an adjuvant to the deleterious effects of highly active antiretroviral therapy (HAART) and alcohol on the cyto‐architecture and functioning of the testis. Forty adult male Sprague‐Dawley rats, weighing 165~176 g, were divided into eight groups and treated according to protocol. Testicular histology, stereological parameters, seminal fluid, testosterone, luteinizing hormone, follicle‐stimulating hormone, the antioxidants marker malondialdehyde (MDA), and antioxidant glutathione (GSH) were examined. The use of ethanol alone and ethanol + HAART showed extensive degeneration in the seminiferous epithelium, decreased semen quality, disorganized basement membrane and widened, hypocellular interstitium. GSH was significantly decreased in the ethanol alone treated group with no significant effect on testosterone, LH, and MDA levels. Adjuvant treatment with VCO at low dose (2.5 mL/kg/bw) improved sperm motility with a partial restoration of the histopathological alterations. High doses of VCO (5.0 mL/kg/bw) showed greater improvement with respect to sperm counts, increased FSH hormonal and GSH antioxidant levels, and a well‐preserved testicular cyto‐architecture.

Hypoxis hemerocallidea alters metabolic parameters and hepatic histomorphology in streptozotocin-nicotinamide-induced diabetic male rats under antiretroviral therapy

Introduction Highly active antiretroviral therapy (HAART) and HIV/AIDS have been demonstrated to induce endocrine/metabolic dysfunction with a consequential increase in morbidity/mortality due to organ toxicities. This study aimed at investigating the possible protective effect of Hypoxis hemerocallidea (HH) against metabolic and hepatic histomorphology of diabetic rats under HAART. Material and methods Sixty-two adult male Sprague-Dawley rats were divided into a normoglycemic group A (n = 6) and 7 diabetic (110 mg/kg nicotinamide + 45 mg/kg streptozotocin) groups (B–H) (n = 8) and treated according to protocols. Concomitant treatment with adjuvant HH and HAART resulted in the least %body weight gain as the liver weight decreased in all treated animals. Results Significant changes in serum lipids were aggravated by treatment with HH and HAART, triglycerides and total cholesterol levels were elevated (p < 0.001/0.05), but changes in high-density lipoprotein (HDL) and total protein levels were insignificant. While artherosclerotic and cardiopulmonary indexes remained insignificant, concomitant use of HH with HAART in diabetes resulted in reduction of low-density lipoprotein (LDL) (p < 0.001), and increased triglyceride (p < 0.05) and total cholesterol (p < 0.001). The parameters of liver injury showed a significant (p < 0.05) increase in ALT of animals treated with HH alone, HAART + HH and melatonin; however, an insignificant decline in AST level was recorded. Treatment with adjuvant HAART, HH and melatonin resulted in significant (p < 0.005/0.0001) up-regulation of ALP and total bilirubin levels. Histopathology derangement ranged from severe hepatocellular distortions, necrosis with reduced glycogen expression following co-treatment of HAART+melatonin, HH and HAART alone in diabetes. Conclusions Presumptive hypoglycemic use of HH with HAART by people living with HIV/AIDS requires caution as implications for hepatocellular injuries are suspected with further uncontrolled metabolic disorder.