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Venlafaxine mitigates cisplatin-induced nephrotoxicity via down-regulating apoptotic pathway in rats
Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2018-05-29 , DOI: 10.1016/j.cbi.2018.05.015
Dalia H. El-Kashef , Maha H. Sharawy

The antidepressant venlafaxine, a norepinephrine and serotonin reuptake inhibitor, is recently identified for its anti-inflammatory role against many experimental models. In this study, the effect of venlafaxine against cisplatin-induced nephrotoxicity and bladder rings hypersensitivity towards acetylcholine were explored. Single injection of cisplatin (7 mg/kg, ip) in Sprague-Dawley rats instigated nephrotoxicity evidenced by hindering renal function (changes in kidney/body weight ratio, serum creatinine, BUN, albumin and urinary total protein levels which were supported by histopathology). In addition, cisplatin caused a profound oxidative stress, inflammation and apoptosis. Treatment with venlafaxine (50 mg/kg, po) managed to alleviate the nephrotoxicity indices and rehabilitate the antioxidant parameters (MDA, GSH, SOD and CAT) in addition to retaining NOx levels to the normal levels. Moreover, venlafaxine caused a decline in LDH and NF-κB levels supporting its anti-inflammatory effect. Additionally, the antiapoptotic effect was demonstrated by increasing Bcl-2, suppressing p53 and Bax renal levels, decreasing caspase-3 expression and by flow cytometry (annexin V and PI) that showed an increase in viable cells and a decrease in early apoptotic and necrotic cells. Furthermore, venlafaxine ameliorated bladder rings hyperreactivity to acetylcholine and improved histopathologic findings. In brief, venlafaxine ameliorated nephrotoxicity and bladder rings hyperreactivity caused by cisplatin through acting as an antioxidant, anti-inflammatory and antiapoptotic agent.



中文翻译:

文拉法辛通过下调大鼠凋亡途径减轻顺铂诱导的肾毒性

抗抑郁药文拉法辛(一种去甲肾上腺素和5-羟色胺再摄取抑制剂)最近因其对许多实验模型的抗炎作用而得到鉴定。在这项研究中,研究了文拉法辛对顺铂诱导的肾毒性和膀胱环对乙酰胆碱超敏反应的作用。在Sprague-Dawley大鼠中单次注射顺铂(7 mg / kg,ip)会激发肾毒性,其表现为肾功能障碍(肾脏/体重比,血清肌酐,BUN,白蛋白和尿液总蛋白水平的变化,这受到组织病理学的支持) 。此外,顺铂引起了深刻的氧化应激,炎症和细胞凋亡。服用文拉法辛(50 mg / kg,口服)除了将NOx含量保持在正常水平外,还设法减轻了肾毒性指数并恢复了抗氧化剂参数(MDA,GSH,SOD和CAT)。此外,文拉法辛引起LDH和NF-κB水平下降,支持其抗炎作用。此外,通过增加Bcl-2,抑制p53和Bax肾水平,降低caspase-3表达并通过流式细胞术(膜联蛋白V和PI)证明抗凋亡作用表明活细胞增加,早期凋亡和坏死细胞减少。细胞。此外,文拉法辛改善了膀胱环对乙酰胆碱的过度反应性,并改善了组织病理学发现。简而言之,文拉法辛通过作为抗氧化剂,改善了顺铂引起的肾毒性和膀胱环反应性,

更新日期:2018-05-29
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