Microscopic and biochemical changes on liver and kidney of Wistar rats on combination antiretroviral therapy: the impact of naringenin and quercetin

Abstract

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.

Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl4-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses

“…It protected against sepsis-induced acute kidney injury in a previous study [ 69 ]. When combined with quercetin, naringenin ameliorated reno- and hepatotoxicity in rats [ 70 ]. Naringenin also attenuated the nephrotoxicity triggered by oxytetracycline via it antioxidant activities [ 71 ].…”

The synergistic ameliorative activity of peroxisome proliferator‐activated receptor‐alpha and gamma agonists, fenofibrate and pioglitazone, on hippocampal neurodegeneration in a rat model of insulin resistance

“…The amount of MDA formed in each of the samples was assessed by measuring the optical density of the supernatant at 532 nm as described by Olufunke et al 6,62 Glutathione (GSH) level was assayed by measuring the optical density of the supernatant at 412 after the addition of Ellman's reagent. 63,64 2.8 | Histological and immunohistochemical studies…”