Abstract

Nephrotoxicity is a major limitation of adriamycin (ADR) chemotherapy. We hypothesized that administration of standardized aqueous bark extract of Gmelina arborea Roxb. (GA) (Family; Verbenaceae), a traditional therapeutic agent, may reduce the nephrotoxicity caused by ADR in Wistar rats. The dose-dependent nephroprotective activity of the standardized GA extract was investigated in ADR-induced (20 mg/kg, ip) nephrotoxicity in male Wistar rats (n = 6/group). The lyophilized powder of the aqueous refluxed (4 h) GA extract was administered at 100, 300 and 500 mg/kg doses orally for three consecutive days. Fosinopril sodium (0.09 mg/kg) was used as the positive control. Assessment of biochemical parameters on serum, urine and histopathology on H and E stained kidney sections were done at the end of the intervention. The treatment with GA and fosinopril decreased the elevation of serum creatinine, blood urea nitrogen, cystatin C, β₂-microglobulin and loss of total protein in urine in nephrotoxic rats in a dose-dependent manner (p < 0.05). In contrast, serum concentrations of albumin and total protein were increased significantly (p < 0.05). H and E stained kidney sections showed an attenuation of renal parenchymal injury following the treatment. The aqueous extract of GA demonstrated antioxidant potential in vitro. Present findings conclude that the standardized aqueous extract of GA stem bark exerted a dose-dependent protection against ADR-induced nephrotoxicity in vivo and may be a promising adjunct in ADR chemotherapy.

摘要

肾毒性是阿霉素 (ADR) 化疗的主要局限。我们假设给予Gmelina arborea Roxb的标准化水性树皮提取物。(GA) (Family; Verbenaceae) 是一种传统的治疗药物，可降低 Wistar 大鼠 ADR 引起的肾毒性。标准化 GA 提取物的剂量依赖性肾保护活性在雄性 Wistar 大鼠 ( n = 6/组）。以 100、300 和 500 mg/kg 剂量连续三天口服给予含水回流（4 小时）GA 提取物的冻干粉末。福辛普利钠 (0.09 mg/kg) 用作阳性对照。在干预结束时对血清、尿液和 H 和 E 染色的肾脏切片组织病理学的生化参数进行评估。GA和福辛普利治疗可降低肾毒性大鼠血清肌酐、血尿素氮、胱抑素C、β2-微球蛋白的升高_和尿中总蛋白的丢失，且呈剂量依赖性（p  < 0.05）。相比之下，血清白蛋白和总蛋白浓度显着增加（p < 0.05)。H 和 E 染色的肾切片显示治疗后肾实质损伤减弱。GA 的水提取物在体外显示出抗氧化潜力。目前的研究结果得出结论，GA 茎皮的标准化水提取物在体内对 ADR 诱导的肾毒性发挥剂量依赖性保护作用，并且可能是 ADR 化疗的有希望的辅助手段。