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
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
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DOI：
10.1016/j.biopha.2021.111636
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发表时间：
2021-05-03
影响因子：
7.5
通讯作者：
Okada, Shigeru
中科院分区：
文献类型：
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作者：
Iqbal, Mohammad;Shah, Muhammad Dawood;Okada, Shigeru
本研究旨在揭示膳食补充剂姜黄素对 ddY 雄性小鼠肾细胞肿瘤和肾癌物质次氮基三乙酸铁 (Fe-NTA) 诱导的氧化应激的保护作用。结果显示，用肾致癌物Fe-NTA治疗的小鼠，肾细胞肿瘤发生率为35%，而与盐水治疗的小鼠相比，Fe-NTA促进和N-二乙基亚硝胺(DEN)启动的小鼠肾细胞肿瘤发生率升高至80%。在 DEN 启动的非促进小鼠中没有观察到肿瘤的发生。在用 Fe-NTA 治疗之前、期间和之后，在 DEN 启动的动物中补充 0.5% 和 1.0% 姜黄素的饮食，肿瘤发生率随剂量依赖性分别降低至约 45% 和 30%。免疫组织化学研究还表明，腹腔注射 Fe-NTA（6.0 mg Fe/kg 体重）治疗的小鼠肾组织中 4-羟基-2-壬烯醛 (HNE) 修饰的蛋白加合物和 8-羟基-2'-脱氧鸟苷 (8-OHdG) 的形成增加。此外，Fe-NTA 治疗小鼠还导致丙二醛 (MDA)、血清尿素和肌酐显着升高，并降低肾谷胱甘肽。然而，通过用 0.5% 和 1% 姜黄素饮食对动物进行预防性治疗，大多数这些参数的变化均呈剂量依赖性减弱，这可能是由于姜黄素的抗氧化作用。这些结果表明，摄入姜黄素有利于预防肾细胞肿瘤和肾致癌物 Fe-NTA 介导的氧化应激损伤。
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.