Effects of Atripla® and alcohol with low protein diet intake in the epididymis of adult male Sprague Dawley rats.

Nyirenda Trust
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The efficacy and high compliance of Atripla® (efavirenz, emtricitabine and tenofovir disoproxyl fumarate) has increased demand for therapeutic use among HIV/AIDS patients, thereby necessitating investigation into drug toxicity. Therefore, the present study was designed to investigate the in vivo effects of Atripla® and ethanol co-administration in the epididymis of protein malnourished rats. Sixty-four adult male Sprague Dawley rats were randomised into two diet groups: normal protein diet (NP, 23%) and low protein diet (LP, 6%) groups. Each diet group was further divided into four sub-groups (with eight rats each). Under both normal and low protein diet groups, the first group served as control (NPC, LPC) and received vehicle only. The second group received Atripla® (A Tp) only [NPA Tp, LPA Tp ], the third group received ethanol (E) only [NPE, LPE] and the fourth group received both A Tp and E (NPEA Tp, LPEA Tp ). Atripla® (27.5 mg/kg body weight per rat) was administered using gelatine rectangles (2cm3) once a day orally. 6% ethanol in distilled water was provided ad libitum to appropriate groups. After ninety days of treatment, the rats were euthanised, epididymides harvested, weighed and processed for analyses. Changes in epididymal histo-achitecture, histo-morphometric indices (epididymal tubular diameter [ETD], tubular area (Ac] and epithelial height [EH]) and principal cell nuclear androgen receptor immuno-reactivity (AR-ir] percentages were evaluated. Epididymal tissue alterations which include depletion of cauda sperm concentration, increased interstitial space and increased luminal debri were observed in all treatment groups compared to NPC (study control group). Severity in tissue alterations was greater in E only treated groups relative to ATp only treated groups within both NP and LP diet groups. Incidence and severity in tissue alterations was higher among the LP treated groups compared to NPC group and their NP treated cohorts. Severe tissue alterations and significant reductions in ETD values were recorded in the LPE and LPEATp groups compared to NPC (p=0.01). AR-ir percentage values were significantly low in all treatment groups compared to NPC group, but generally lower among LP treated groups. The study reveals that both Atripla® and ethanol can independently and concurrently cause epididymal functional derangements. Ethanol caused greater toxicity to the epididymis relative to Atripla®. Protein malnutrition exacerbated reproductive toxicity in the epididymis due to Atripla® and ethanol, especially when the two are used concurrently.
Dissertation submitted to the University of the Witwatersrand towards the fulfillment of the requirements for the Degree of Master of Science in Medicine Faculty of Health Sciences University of the Witwatersrand Johannesburg