首页> 外文期刊>The Journal of Nutritional Biochemistry >Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage.
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Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage.

机译:高剂量吡啶甲酸铬对db / db小鼠的肾脏和血糖作用:DNA损伤评估。

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摘要

This study examined renal and glycemic effects of chromium picolinate [Cr(pic)3] supplementation in the context of its purported potential for DNA damage. In preventional protocol, male obese diabetic db/db mice were fed diets either lacking or containing 5, 10 or 100 mg/kg chromium as Cr(pic)3 from 6 to 24 weeks of age; male lean nondiabetic db/m mice served as controls. Untreated db/db mice displayed increased plasma glucose and insulin, hemoglobin A1c, renal tissue advanced glycation end products, albuminuria, glomerular mesangial expansion, urinary 8-hydroxydeoxyguanosine (an index of oxidative DNA damage) and renal tissue immunostaining for gamma H2AX (a marker of double-strand DNA breaks) compared to db/m controls. Creatinine clearance was lower in untreated db/db mice than their db/m controls, while blood pressure was similar. High Cr(pic)3 intake (i.e., 100-mg/kg diet) mildly improved glycemic status and albuminuria without affecting blood pressure or creatinine clearance. Treatment with Cr(pic)3 did not increase DNA damage despite marked renal accumulation of chromium. In interventional protocol, effects of diets containing 0, 100 and 250 mg/kg supplemental chromium, from 12 to 24 weeks of age, were examined in db/db mice. The results generally revealed similar effects to those of the 100-mg/kg diet of the preventional protocol. In conclusion, the severely hyperglycemic db/db mouse displays renal structural and functional abnormalities in association with DNA damage. High-dose Cr(pic)3 treatment mildly improves glycemic control, and it causes moderate reduction in albuminuria, without affecting the histopathological appearance of the kidney and increasing the risk for DNA damage.
机译:这项研究检查了吡啶甲酸铬[Cr(pic)3]补充剂在肾脏和血糖方面的作用,据称其可能引起DNA损伤。在预防方案中,从6至24周龄,给雄性肥胖的db / db糖尿病小鼠饲喂缺乏或含有5、10或100 mg / kg铬作为Cr(pic)3的饮食;雄性瘦非糖尿病db / m小鼠作为对照。未经治疗的db / db小鼠显示血浆葡萄糖和胰岛素增加,血红蛋白A1c升高,肾脏组织晚期糖基化终产物,蛋白尿,肾小球肾小球系膜扩张,尿中的8-羟基脱氧鸟苷(氧化性DNA损伤的指标)和对γH2AX的肾脏组织免疫染色(一种标记物)与db / m对照相比)。未经治疗的db / db小鼠的肌酐清除率低于其db / m对照,而血压相似。摄入大量Cr(pic)3(即100 mg / kg饮食)可以轻度改善血糖状况和蛋白尿,而不会影响血压或肌酐清除率。尽管肾脏有明显的铬累积,但用Cr(pic)3的治疗并没有增加DNA损伤。在干预方案中,在db / db小鼠中检查了12至24周龄饮食中含有0、100和250 mg / kg补充铬的饮食的影响。结果通常显示出与预防方案的100 mg / kg饮食相似的效果。总之,严重高血糖的db / db小鼠表现出与DNA损伤相关的肾脏结构和功能异常。大剂量Cr(pic)3处理可轻度改善血糖控制,并引起蛋白尿适度减少,而不会影响肾脏的组织病理学外观并增加DNA损伤的风险。

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