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Microscopic and biochemical changes on liver and kidney of Wistar rats on combination antiretroviral therapy: the impact of naringenin and quercetin
Toxicology Research ( IF 2.1 ) Pub Date : 2020-08-29 , DOI: 10.1093/toxres/tfaa060
Edidiong Nnamso Akang 1 , Olufunke O Dosumu 1 , Ini-Ibehe Essien Okoko 1 , Oluwatomisin Faniyan 1 , Ademola A Oremosu 1 , Alani Sulaimon Akanmu 2
Affiliation  

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.


中文翻译:

联合抗逆转录病毒治疗 Wistar 大鼠肝肾的微观和生化变化:柚皮素和槲皮素的影响

摘要
联合抗逆转录病毒疗法 (cART) 是一种针对人类免疫缺陷病毒感染者的终生疗法,与肾毒性和肝毒性有关,导致其停药。本研究旨在调查柚皮素和槲皮素对 cART 诱导的肝毒性和肾毒性的改善潜力。70 只雄性 Wistar 大鼠 (225-260 g) 分为七组作为对照、cART、柚皮素、槲皮素、二甲基亚砜 (DMSO)、柚皮素/cART (CN) 和槲皮素 / cART (CQ)。cART (24 mg/kg)、柚皮素 (50 mg/kg) 和槲皮素 (50 mg/kg) 溶解在 1% v/v DMSO 中并口服给药 56 天。cART与生物类黄酮的组合显着增加了超氧化物歧化酶(P  < 0.05),过氧化氢酶(P < 0.01)、减少的谷胱甘肽 ( P  < 0.001) 和减少的丙二醛 ( P  < 0.001) 与仅 cART 相比。cART和CQ 组的肿瘤坏死因子α(TNFα)水平显着增加(P <0.01),而其他组与对照组相比没有显着变化。与 cART 相比,TNFα 的 CQ 水平也显着降低(P < 0.001)。此外,cART 中肌酐水平的显着增加仅表明进行性肾毒性。此外,在仅使用 cART 的组中,肝脏出现血管充血和肝细胞坏死等进行性病理变化,而肾脏出现肾小球萎缩和肾小管变形。对照组、柚皮素和槲皮素治疗组显示正常的肾和肝细胞结构。这些发现阐明了进行性肾和肝毒性与持续使用 cART 相关;然而,槲皮素和柚皮素与 cART 的组合显示出可能改善 cART 造成的损害的潜力。
更新日期:2020-11-04
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