Testicular 3beta hydroxysteroid dehydrogenase in naringenin adjuvant under highly active antiretroviral therapy (HAART); preliminary data using Sprague-Dawley rats

HAART has brought relief to many living with HIV/AIDS, decreasing morbidity and mortality rates. In spite of these benefits, the treatment has been associated with reproductive disorders. This study is aimed at investigating the effects of Naringenin (Nar) on the expression of testicular 3ß-Hydroxysteroid dehydrogenase (3ß HSD) in HAART-treated Sprague-Dawley rats. 30 adult male Sprague-Dawley rats were randomly divided into six groups. The rats were fed with 30 mg/kg of HAART (Efavirenz+Embtricitabine+Tenofovir), 40mg/kg and 80 mg/kg of Nar and a combination of both HAART and Nar for a period of 70 days. Thereafter, the animals were euthanized and the testes processed. The results showed a significant decrease (p<0.05) in the expression of 3ß HSD in the HAART group compared to controls. However, the co-treatment of HAART with 40 mg/kg Nar increased significantly (p<0.05) the expression of 3ß HSD, compared to HAART and control. The relative volume fraction also showed significant increase (p<0.05) in germinal epithelium, lumen and Leydig cells of animals treated with 80 mg/kg Nar, and HAART+40 mg/kg Nar compared to control and HAART respectively. In conclusion, HAART is causes a deficiency in testicular 3ß HSD, thereby limiting spermatogenesis. However, co-treatment with 40 mg/kg Naringenin increases testicular 3ß HSD expression and enhances spermatogenesis

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Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study.

Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman's space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

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.

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs.

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.