Ameliorative Potential of Clerodendrum volubile Ethanol Leaf Extract on Doxorubicin-Induced Hepatorenal Toxicities in Rats

A. Adeneye, O. Olorundare, A. Akinsola, D. Sanni, J. Ntambi, H. Mukhtar
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引用次数: 1

Abstract

Background and Purpose: Hepatorenal toxicity is a side effect of the anthracycline cytotoxic antibiotics, doxorubicin that is used in cancer treatment. The study investigated the ameliorative potential of Clerodendrum volubile ethanol leaf extract (CVE) on doxorubicin (DOX)-induced hepatorenal toxicities. Methods: Male Wistar rats were pretreated with Clerodendrum volubile ethanol leaf extract (50 - 400 mg/kg/day, p.o) followed by intraperitoneal injection of 2.5 mg/kg of DOX on alternate days for 14 days. Hepatorenal toxicity was assessed using renal function parameters (serum electrolytes, blood urea and creatinine), hepatic function endpoints [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), total protein (TP), albumin (ALB) and total bilirubin (TB)]. In addition, the antioxidant activity in the kidney and liver tissues were assayed and histological studies of these tissues were also conducted. Results: Oral pretreatment with 50 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day and 400 mg/kg/day of CVE remarkably ameliorated DOX-induced liver and kidney injury by lowering the serum ALT, AST, ALP, Cr and BUN levels. CVE pretreatment remarkably ameliorated DOX-induced increases in the CAT, SOD and GPx activities and MDA levels compared to the DOX-treated rats. The biochemical changes were corroborated by improvements in the DOX-induced histological lesions seen in the hepatic and renal tissues examined. Conclusions: Overall, these findings suggest that Clerodendrum volubile ethanol leaf extract elicits protective effect against DOX-induced hepatorenal toxicities mediated primarily via oxidative stress suppression and improvement in the free radicals scavenging activities of CVE.
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石竹叶乙醇提取物对阿霉素所致大鼠肝肾毒性的改善作用
背景和目的:肝肾毒性是用于癌症治疗的蒽环类细胞毒性抗生素阿霉素的副作用。本研究探讨了蔓越橘乙醇叶提取物(CVE)对多柔比星(DOX)诱导的肝肾毒性的改善潜力。方法:以雄性Wistar大鼠为研究对象,采用叶提取物(50 ~ 400 mg/kg/d, p.o)预处理,隔日腹腔注射DOX 2.5 mg/kg,连续14 d。采用肾功能指标(血清电解质、血尿素和肌酐)、肝功能终点[天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)和碱性磷酸酶(ALP)、总蛋白(TP)、白蛋白(ALB)和总胆红素(TB)]评估肝肾毒性。此外,还测定了肾和肝组织的抗氧化活性,并对这些组织进行了组织学研究。结果:口服CVE 50 mg/kg/d、100 mg/kg/d、200 mg/kg/d和400 mg/kg/d预处理小鼠血清ALT、AST、ALP、Cr和BUN水平均显著降低,改善dox诱导的肝肾损伤。与dox处理的大鼠相比,CVE预处理显著改善了dox诱导的CAT、SOD、GPx活性和MDA水平的升高。在肝脏和肾脏组织中观察到的dox诱导的组织学病变的改善证实了生化变化。结论:总的来说,这些研究结果表明,蔓越橘叶乙醇提取物对dox诱导的肝肾毒性具有保护作用,主要是通过抑制氧化应激和提高CVE的自由基清除活性来介导的。
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