肾毒性是顺铂(CP)诱导的急性肾损伤(AKI)的原因,限制了其作为抗癌剂的有用性。Diminazene,血管紧张素转换酶2激活剂,在肾脏疾病大鼠模型上表现出肾脏保护特性。这项研究旨在研究与赖诺普利或缬沙坦相比,在CP诱导的AKI中,dimplazene的有益作用。第一组和第二组大鼠口服载体(蒸馏水)9天,分别在第6天和生理盐水注射或腹膜内CP(6mg/kg)。第三,第四,第五组在第6天接受腹膜内注射CP和Dimpinazene(15mg/kg/天,口头),赖诺普利(10mg/kg/天,口头),或缬沙坦(30毫克/千克/天,口头),9天,分别。治疗最后一天后24h,在麻醉下取出血液和肾脏进行生化和组织病理学检查。还收集了在处死大鼠之前的最后24小时期间的尿液。CP显著增加血浆尿素,肌酐,中性粒细胞明胶酶相关脂质运载蛋白,钙,磷,和尿酸。它还增加了尿白蛋白/肌酐比率,N-乙酰-β-D-氨基葡萄糖苷酶/肌酐比值,肌酐清除率降低,以及血浆炎症细胞因子的浓度[血浆肿瘤坏死因子-α,和白细胞介素-1β],和显著降低的抗氧化剂指数[过氧化氢酶,谷胱甘肽还原酶,和超氧化物歧化酶]。组织病理学,CP治疗引起肾小管坏死,管状铸模,缩小的肾小球,肾脏纤维化增加。Diminazine,赖诺普利,缬沙坦改善了CP诱导的生化和组织病理学变化。使用的三种药物的有益效果是,至少部分地,由于它们的抗炎和抗氧化作用。关键词:顺铂,Diminazene,ACE2激活剂,赖诺普利,缬沙坦,急性肾损伤。
Nephrotoxicity as a cause of acute kidney injury (AKI) induced by cisplatin (CP), limits its usefulness as an anticancer agent.
Diminazene, an angiotensin converting enzyme 2 activator, exhibited renoprotective properties on rat models of kidney diseases. This research aims to investigate the salutary effect of
diminazene in comparison with lisinopril or valsartan in CP-induced AKI. The first and second groups of rats received oral vehicle (distilled water) for 9 days, and saline injection or intraperitoneal CP (6 mg/kg) on day 6, respectively. Third, fourth, and fifth groups received intraperitoneal injections of CP on day 6 and
diminazene (15 mg/kg/day, orally), lisinopril (10 mg/kg/day, orally), or valsartan (30 mg/kg/day, orally), for 9 days, respectively. 24h after the last day of treatment, blood and kidneys were removed under anesthesia for biochemical and histopathological examination. Urine during the last 24 h before sacrificing the rats was also collected. CP significantly increased plasma urea, creatinine, neutrophil gelatinase-associated lipocalin, calcium, phosphorus, and uric acid. It also increased urinary albumin/creatinine ratio, N-Acetyl-beta-D-Glucosaminidase/creatinine ratio, and reduced creatinine clearance, as well the plasma concentrations of inflammatory cytokines [plasma tumor necrosis factor-alpha, and interleukin-1beta], and significantly reduced antioxidant indices [catalase, glutathione reductase , and superoxide dismutase]. Histopathologically, CP treatment caused necrosis of renal tubules, tubular casts, shrunken glomeruli, and increased renal fibrosis. Diminazine, lisinopril, and valsartan ameliorated CP-induced biochemical and histopathological changes to a similar extent. The salutary effect of the three drugs used is, at least partially, due to their anti-inflammatory and antioxidant effects. Keywords: Cisplatin,
Diminazene, ACE2 activator, Lisinopril, Valsartan, Acute kidney injury.