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左旋肉碱减轻顺铂诱导的肝毒性和肾毒性。

Alleviation of cisplatin-induced hepatotoxicity and nephrotoxicity by L-carnitine.

作者信息

Hassan Snur Mohammad Amen, Saeed Azad K, Rahim Omed Omer, Mahmood Shler A F

机构信息

Department of Anatomy and Histopathology, College of Veterinary Medicine, Sulaimani University, Sulaimani, 4601, KRG, Iraq.

Department of Food Science and Quality Control, Bakrajo Technical Institute, Sulaimani Polytechnic University, Sulaimani, 4601, KRG, Iraq.

出版信息

Iran J Basic Med Sci. 2022 Jul;25(7):897-903. doi: 10.22038/IJBMS.2022.65427.14395.

Abstract

OBJECTIVES

To assess the protective effect of L-carnitine in reducing cisplatin toxicity via estimating biochemical tests, histomorphometric, and immunohistochemistry (IHC) of β-catenin and cyclin D.

MATERIALS AND METHODS

Fifteen adult male rabbits were used in this study and allocated into 3 groups; Group 1 (Control negative), rabbits of this group were not given any treatment. In group 2, the animals were injected with cisplatin single-dose/per week. Group 3 rabbits were treated with Cisplatin+L-carnitine orally by gavage tube for 29 days. At the end of the experiments, blood samples from all rabbits were taken from the earlobe, and then the biochemical test was done, the kidney and tissue sections were prepared for both H& E and IHC for both β-catenin and cyclin D genes.

RESULTS

Treatment with L-carnitine reduced the injury effect of cisplatin via a decline in serum creatinine, urea, bilirubin, GPT, GOP, and ALP significantly (0.05). Also, administration of LC attenuates the histopathologic abnormality in the kidney (15.71% vs 85.18%) and liver (score 3 vs 15 ) induced by cisplatin. L-carnitine elevates the expression of β-catenin and cyclin D in renal and hepatic parenchyma by diffuse, moderate-strong positivity vs cisplatin that showed local-weak staining.

CONCLUSION

These findings imply that L-carnitine, by its pleiotropic actions in activating signaling, alleviates cisplatin-induced renal and hepatic destruction. It might be a method of preventing cisplatin-related nephrotoxicity and hepatotoxicity.

摘要

目的

通过评估生化检测、组织形态计量学以及β-连环蛋白和细胞周期蛋白D的免疫组织化学(IHC),来评估左旋肉碱在降低顺铂毒性方面的保护作用。

材料与方法

本研究使用了15只成年雄性兔子,分为3组;第1组(阴性对照),该组兔子未接受任何治疗。第2组,动物每周注射单剂量顺铂。第3组兔子通过灌胃管口服顺铂+左旋肉碱,持续29天。实验结束时,从所有兔子的耳垂采集血样,然后进行生化检测,制备肾脏和组织切片用于苏木精-伊红(H&E)染色以及β-连环蛋白和细胞周期蛋白D基因的免疫组织化学检测。

结果

左旋肉碱治疗通过显著降低血清肌酐、尿素、胆红素、谷丙转氨酶(GPT)、谷草转氨酶(GOP)和碱性磷酸酶(ALP),减轻了顺铂的损伤作用(P<0.05)。此外,给予左旋肉碱还减轻了顺铂诱导的肾脏(15.71%对85.18%)和肝脏(评分3对15)的组织病理学异常。与顺铂表现出局部弱阳性染色相比,左旋肉碱通过弥漫性、中度-强阳性提高了肾实质和肝实质中β-连环蛋白和细胞周期蛋白D的表达。

结论

这些发现表明,左旋肉碱通过其在激活信号传导中的多效性作用,减轻了顺铂诱导的肾脏和肝脏损伤。它可能是一种预防顺铂相关肾毒性和肝毒性的方法。

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