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Combination antiretroviral therapy (cART), which is a lifelong therapy for people living with human immunodeficiency virus, has been associated with nephrotoxicity and hepatotoxicity leading to its discontinuation. This study aimed at investigating the ameliorative potential of naringenin and quercetin on cART-induced hepatotoxicity and nephrotoxicity. Seventy male Wistar rats (225–260 g) were divided into seven groups as control, cART, naringenin, quercetin, dimethyl sulfoxide (DMSO), naringenin/cART (CN) and quercetin/cART (CQ). cART (24 mg/kg), naringenin (50 mg/kg) and quercetin (50 mg/kg) were dissolved in 1% v/v DMSO and administered orally for 56 days. Combination of cART and bioflavonoids had significant increase in superoxide dismutase (P < 0.05), catalase (P < 0.01), reduced glutathione (P < 0.001) and decreased malondialdehyde (P < 0.001) compared to cART only. Tumor necrosis factor Alpha (TNFα) level increased significantly in cART and CQ (P < 0.01) groups, while others showed no significant changes compared to control. TNFα also significantly decreased in CQ level compared to cART (P < 0.001). In addition, significant increase in creatinine level in cART only indicated progressive renal toxicity. Also, progressive pathological changes including congested blood vessels and hepatocellular necrosis were found in the liver, while the kidney had glomerular atrophy, and tubular distortion in cART-only group. Control, naringenin- and quercetin-treated groups showed normal renal and hepatic cytoarchitecture. These findings elucidate that progressive renal and hepatic toxicity is associated with the continuous use of cART; however, a combination of quercetin and naringenin with cART showed possible potential of ameliorating the damages posed by cART.

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Background Female reproductive functions are susceptible to various disruptive agents including environmental factors and therapeutic agents. Such disruptions often include irregularity of menstrual/estrous cycle and anovulation. Many of the disruptive agents’ mechanism of action is the production of free radicals and it is thus proposed that agents with antioxidant capacity can potentially mitigate their disruptive effects. Objective This study investigated the ameliorative potential of Riboceine, vitamin D and Calcium. Methods 40 female Sprague‐Dawley (SD) rats were randomly divided into two main groups. Group A, estrous cycle study, and Group B, the ovulation study. Group A consisted of 20 rats divided into 4 sub‐groups. Sub‐group A1 (control) received distilled water, A2‐ Amodiaquine 12 mg/kg body weight, A3‐ Amodiaquine 12 mg/kg and vitamin D 30mcg/kg and Calcium 1800mg/kg, A4‐ Amodiaquine 12 mg/kg and Riboceine 30mg/kg, administered orally, daily for 6 cycles. Sub‐group B1 (control B) received distilled water, B2‐ Amodiaquine 12 mg/kg, B3‐Amodiaquine 12 mg/kg and vitamin D 30mcg/kg and Calcium 1800mg/kg, B4‐ Amodiaquine 12 mg/kg and Riboceine 30mg/kg, administered orally, at 9 a.m on proestrus (only once), to determine the effects of Vitamin D with Calcium and Riboceine on Amodiaquine‐induced anovulation. At the end of the administration, rats were sacrificed to collect blood and ovarian tissue for hormonal, oxidative stress and histological analyses. Results The cycling patterns showed that rats administered only amodiaquine, had prolonged diestrus phases while rats that had co‐administration of amodiaquine and riboceine had elongated estrus phases. Rats administered amodiaquine, vitamin D and Calcium, had almost normal cycling patterns. There was a significant decrease in malondialdehyde concentration of all other sub‐groups compared to control, A1 at p<0.05, with the lowest concentration in sub‐group A4. Glutathione reductase was higher in all subgroups (A2, A3, A4) in comparison to control, but A3 and A4 showed a significant increase when compared to control (A1) at p<0.05. Catalase was highest in A2 and statistically significant compared to the control at p<0.05. The concentration of follicle‐stimulating hormone (FSH) was significantly higher in “A4” when compared to the control at p<0.05. Although other subgroups were higher in comparison to the control, they were not statistically significant. Luteinizing hormone (LH) was highest and significant in A4 compared to the control. The cytoarchitecture of ovaries in A4, and B4 showed well‐preserved cells, especially in A4 in which there were more cystic ovarian follicles seen, compared to A2 and A1. In A3, there were reduced atretic follicles, compared to A2, in which abundant atretic follicles were seen. Conclusion The results from show that factors that increase fertility chances were observed in all subgroups that had supplements co‐administered with amodiaquine. The results showed that the fertility‐enhancing factors are more pronounced in Riboceine‐tr...