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辣木乙醇提取物对三聚氰胺诱导的肝肾损伤的预防作用:KIM-1、TIMP-1、氧化应激、细胞凋亡和炎症相关基因的变化。

Prevention of melamine-induced hepatorenal impairment by an ethanolic extract of Moringa oleifera: Changes in KIM-1, TIMP-1, oxidative stress, apoptosis, and inflammation-related genes.

机构信息

Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.

Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.

出版信息

Gene. 2021 Jan 5;764:145083. doi: 10.1016/j.gene.2020.145083. Epub 2020 Aug 26.

DOI:10.1016/j.gene.2020.145083
PMID:32860902
Abstract

BACKGROUND/AIMS: Melamine (ML) is a common food adulterant and contaminant. Moringa oleifera is a well-known medicinal plant with many beneficial biological properties. This study investigated the possible prophylactic and therapeutic activity of an ethanolic extract of M. oleifera (MEE) against ML-induced hepatorenal damage.

METHOD

Fifty male Sprague Dawley rats were orally administered distilled water, MEE (800 mg/kg bw), ML (700 mg/kg bw), MEE/ML (prophylactically) or MEE+ML (therapeutically). Hepatic aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphate (ALP) in serum were measured. Serum total bilirubin, direct bilirubin, indirect bilirubin, protein, albumin, and globulin contents were also assayed, and urea and creatinine levels were determined. Moreover, antioxidant enzyme activity of glutathione peroxidase (GPx) and catalase (CAT) in serum levels were quantified. Complementary histological and histochemical evaluation of renal and hepatic tissues was conducted, and expression of oxidative stress (GPx and CAT) and apoptosis-related genes, p53 and Bcl-2, in hepatic tissue were assessed. In parallel, transcriptional expression of inflammation and renal injury-related genes, including kidney injury molecule 1 (KIM-1), metallopeptidase inhibitor 1 (TIMP1), and tumor necrosis factor alpha (TNF-α) in the kidney tissue were determined.

RESULTS

ML caused significant increases in serum levels of ALT, AST, ALP, total bilirubin, direct bilirubin, indirect bilirubin, urea, and creatinine. Further, ML treated rats showed significant reductions in serum levels of protein, albumin, globulin, GPx, and CAT. Distinct histopathological damage and disturbances in glycogen and DNA content in hepatic and renal tissues of ML treated rats were observed. KIM-1, TIMP-1, and TNF-α gene expression was significantly upregulated in kidney tissue. Also, GPx, CAT, and Bcl-2 genes were significantly downregulated, and p53 was significantly upregulated in liver tissue after ML treatment. MEE significantly counteracted the ML-induced hepatorenal damage primarily for co-exposed rats.

CONCLUSION

MEE could be an effective therapeutic supplement for treatment of ML-induced hepato-renal damage, probably via modulating oxidative stress, apoptosis, and inflammation.

摘要

背景/目的:三聚氰胺(ML)是一种常见的食品掺杂物和污染物。辣木(Moringa oleifera)是一种具有多种有益生物特性的著名药用植物。本研究旨在探讨辣木乙醇提取物(MEE)对 ML 诱导的肝肾功能损伤的可能预防和治疗作用。

方法

50 只雄性 Sprague Dawley 大鼠分别口服蒸馏水、MEE(800mg/kg bw)、ML(700mg/kg bw)、MEE/ML(预防性)或 MEE+ML(治疗性)。检测血清中天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)和碱性磷酸酶(ALP)。还测定血清总胆红素、直接胆红素、间接胆红素、蛋白质、白蛋白和球蛋白含量,并测定尿素和肌酐水平。此外,还定量测定血清中谷胱甘肽过氧化物酶(GPx)和过氧化氢酶(CAT)的抗氧化酶活性。对肾和肝组织进行补充的组织学和组织化学评估,并评估肝组织中氧化应激(GPx 和 CAT)和凋亡相关基因 p53 和 Bcl-2 的表达。同时,测定肾组织中炎症和肾损伤相关基因(包括肾损伤分子 1(KIM-1)、金属肽酶抑制剂 1(TIMP1)和肿瘤坏死因子 α(TNF-α))的转录表达。

结果

ML 导致血清 ALT、AST、ALP、总胆红素、直接胆红素、间接胆红素、尿素和肌酐水平显著升高。此外,ML 处理的大鼠血清蛋白、白蛋白、球蛋白、GPx 和 CAT 水平显著降低。ML 处理大鼠的肝和肾组织明显出现组织病理学损伤,肝组织中糖原和 DNA 含量紊乱,肾组织中也出现类似情况。肾组织中 KIM-1、TIMP-1 和 TNF-α 基因表达显著上调。此外,ML 处理后肝组织中 GPx、CAT 和 Bcl-2 基因显著下调,p53 基因显著上调。MEE 对 ML 诱导的肝肾功能损伤有明显的拮抗作用,可能主要是通过调节氧化应激、凋亡和炎症。

结论

MEE 可能是治疗 ML 诱导的肝肾功能损伤的有效治疗补充剂,可能通过调节氧化应激、凋亡和炎症。

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