title: Testicular histomorphologic and stereological alterations following short-term treatment with highly active antiretroviral drugs (HAART) in an experimental animal model.
abstract: 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.
authors.affiliation: Discipline of Clinical Anatomy, Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
authors.forename: O O
authors.initials: OO
authors.lastname: Azu
authors.forename: E C S
authors.initials: EC
authors.lastname: Naidu
authors.forename: J S
authors.initials: JS
authors.lastname: Naidu
authors.forename: T
authors.initials: T
authors.lastname: Masia
authors.forename: N F
authors.initials: NF
authors.lastname: Nzemande
authors.forename: A
authors.initials: A
authors.lastname: Chuturgoon
authors.forename: S
authors.initials: S
authors.lastname: Singh
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000494:pharmacology; D000975:Antioxidants / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001205:Ascorbic Acid / Q000627:therapeutic use; D001284:Atrophy / Q000473:pathology / Q000517:prevention & control; D019259:Lamivudine / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D009336:Necrosis / Q000473:pathology / Q000517:prevention & control; D019829:Nevirapine / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000473:pathology*; D018119:Stavudine / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000975:Antioxidants; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; D024502:alpha-Tocopherol; D001205:Ascorbic Acid
keywords: HAART; antioxidant; histology; stereology; testicular morphology