title: Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage.
abstract: 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 γH2AX (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.
authors.affiliation: Department of Oral Biology, College of Dental Medicine, Georgia Health Sciences University, Augusta, GA 30912-1128, USA. mmozaffa@georgiahealth.edu
authors.forename: Mahmood S
authors.initials: MS
authors.lastname: Mozaffari
authors.forename: Babak
authors.initials: B
authors.lastname: Baban
authors.forename: Rafik
authors.initials: R
authors.lastname: Abdelsayed
authors.forename: Jun Yao
authors.initials: JY
authors.lastname: Liu
authors.forename: Hereward
authors.initials: H
authors.lastname: Wimborne
authors.forename: Nancy
authors.initials: N
authors.lastname: Rodriguez
authors.forename: Worku
authors.initials: W
authors.lastname: Abebe
mesh_terms: D000419:Albuminuria / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D010848:Picolinic Acids / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D006657:Histones; D007328:Insulin; D010848:Picolinic Acids; C030614:picolinic acid; C475961:gamma-H2AX protein, mouse