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姜黄素通过抑制氧化应激缓解 N-二乙基亚硝胺和铁氮川三乙酸诱导的小鼠肾细胞肿瘤的治疗潜力:对癌症化学预防的意义。

The therapeutic potential of curcumin in alleviating N-diethylnitrosamine and iron nitrilotriacetate induced renal cell tumours in mice via inhibition of oxidative stress: Implications for cancer chemoprevention.

机构信息

Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia.

Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia; Borneo Marine Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia.

出版信息

Biomed Pharmacother. 2021 Jul;139:111636. doi: 10.1016/j.biopha.2021.111636. Epub 2021 May 3.

Abstract

This study was designed to reveal the protective effects of dietary supplementation of curcumin against renal cell tumours and oxidative stress induced by renal carcinogen iron nitrilotriacetate (Fe-NTA) in ddY male mice. The results showed that mice treated with a renal carcinogen, Fe-NTA, a 35% renal cell tumour incidence was noticed, whereas renal cell tumour occurrence was elevated to 80% in Fe-NTA promoted and N-diethylnitrosamine (DEN)-initiated mice as compared with saline- treated mice. No incidence of tumours has been observed in DEN-initiated non-promoted mice. Diet complemented with 0.5% and 1.0% curcumin fed prior to, during and after treatment with Fe-NTA in DEN-initiated animals, tumour incidence was reduced dose-dependently to about 45% and 30% respectively. Immunohistochemical studies also revealed the increased formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney tissue of mice treated with an intraperitoneal injection of Fe-NTA (6.0 mg Fe/kg body weight.). Furthermore, Fe-NTA treatment of mice also resulted in significant elevation of malondialdehyde (MDA), serum urea, and creatinine and decreases renal glutathione. However, the changes in most of these parameters were attenuated dose-dependently by prophylactic treatment of animals with 0.5% and 1% curcumin diet, this may be due to its antioxidative impact of curcumin. These results suggest that intake of curcumin is beneficial for the prevention of renal cell tumours and oxidative stress damage mediated by renal carcinogen, Fe-NTA.

摘要

本研究旨在揭示膳食补充姜黄素对肾细胞肿瘤和铁氮三乙酸(Fe-NTA)肾致癌剂诱导的氧化应激的保护作用。结果表明,用肾致癌剂 Fe-NTA 处理的小鼠,肾细胞肿瘤发生率为 35%,而在 Fe-NTA 促进和 N-二乙基亚硝胺(DEN)引发的小鼠中,肾细胞肿瘤发生率升高至 80%,与生理盐水处理的小鼠相比。在 DEN 引发的非促进小鼠中未观察到肿瘤发生。在 DEN 引发的动物中,在 Fe-NTA 治疗前、治疗中和治疗后补充 0.5%和 1.0%姜黄素饮食,肿瘤发生率分别剂量依赖性地降低至约 45%和 30%。免疫组织化学研究还表明,用腹腔注射 Fe-NTA(6.0 mg Fe/kg 体重)处理的小鼠肾组织中 4-羟基-2-壬烯醛(HNE)修饰蛋白加合物和 8-羟基-2'-脱氧鸟苷(8-OHdG)的形成增加。此外,Fe-NTA 处理还导致小鼠血清丙二醛(MDA)、尿素和肌酐升高,肾谷胱甘肽降低。然而,这些参数的大多数变化通过用 0.5%和 1%姜黄素饮食对动物进行预防性治疗而剂量依赖性地减弱,这可能是由于姜黄素的抗氧化作用。这些结果表明,摄入姜黄素有益于预防由肾致癌剂 Fe-NTA 介导的肾细胞肿瘤和氧化应激损伤。

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