Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage.
Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage.
复制标题
DOI：
10.1016/j.jnutbio.2011.05.004
复制
发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Abebe W
中科院分区：
文献类型：
--
作者：
Mozaffari MS;Baban B;Abdelsayed R;Liu JY;Wimborne H;Rodriguez N;Abebe W
这项研究考察了补充吡啶甲酸铬(Cr(Pic)3)对肾脏和血糖的影响，并对其潜在的DNA损伤进行了研究。在预防性方案中，雄性肥胖糖尿病db/db小鼠从6~24周龄开始饲喂不含铬或含铬5、10或100 mg/kg的饲料，以非糖尿病雄性db/m小鼠为对照。与db/m对照组相比，未经治疗的db/db组小鼠的血糖和胰岛素、血红蛋白A1c、肾组织晚期糖基化终产物(AGE)、蛋白尿、肾小球系膜扩张、尿8-羟基脱氧鸟苷(8-OHdG，氧化脱氧鸟苷损伤指数)和肾组织γH_2AX(双链DNA断裂的标志)免疫染色均增加。未经治疗的db/db小鼠与其db/m对照组相比，肌酐清除量较低，而血压相似。高铬(Pic)3摄入量(即100 mg/kg饮食)可轻微改善血糖状况和蛋白尿，而不影响血压或肌酐清除。尽管铬在肾脏中显著积累，但铬(Pic)3处理并未增加DNA损伤。在干预方案中，研究了12-24周龄db/db小鼠饲喂含铬0、100和250 mg/kg的饲料的效果。结果总体上显示出与100毫克/公斤预防方案饮食相似的效果。总而言之，严重高血糖db/db小鼠表现出与DNA损伤相关的肾脏结构和功能异常。大剂量的铬(Pic)3治疗可轻微改善血糖控制，导致蛋白尿适度减少，而不影响肾脏的组织病理学外观和增加DNA损伤的风险。
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 (AGE) products, albuminuria, glomerular mesangial expansion, urinary 8-hydroxydeoxyguanosine (8-OHdG, an index of oxidative DNA damage) and renal tissue immunostaining for γH2AX (a marker of double-strand DNA breaks) compared to db/m controls. Creatinine clearance was lower while blood pressure was similar between untreated db/db mice and their db/m controls. 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 histopathological appearance of the kidney and increasing the risk for DNA damage.