Chromium picolinate (Cr(pic)3) is proposed as adjuvant therapy for impaired glucose tolerance/ type 2 diabetes mellitus because it improves glucose metabolism. Improved glycemic control should preserve renal function because oxidative stress, a major sequel of chronic hyperglycemia, contributes importantly to pathogenesis of diabetic nephropathy. On the other hand, the kidney is not only the principal route of elimination for chromium but also an organ that preferentially accumulates it. Thus the impact of Cr(pic)3 on the kidney in conditions associated with altered renal function requires careful study. We show that chronic treatment of uninephrectomized, but normoglycemic rats with Cr(pic)3 improves their ability to dispose of a saline volume challenge. Since the uninephrectomized rats develop impaired renal function with age, it is plausible that the beneficial effects of Cr(pic)3 on the kidney in hyperglycemic states would be even more prominent because of attendant improvement in glycemic control.
Specific Aim 1, tests the hypothesis that chronic Cr(pic)3 therapy improves glycemic control in association with reduction in biomarkers of oxidative stress such as oxidized glutathione, malonyldialdehyde, advanced glycation end products and DNA damage.
Specific Aim 2 tests the hypothesis that the beneficial effect of Cr(pic)3 on glucose metabolism will improve renal function.
Specific Aim 3 testes the hypothesis that chronic Cr(pic)3 treatment, and associated improvement in glucose metabolism, ameliorates structural alterations of the diabetic kidney. The studies will utilize genetic (e.g, obese Zucker rat and db/db mouse) and non-genetic (hypertensive-glucose intolerant rat) animal models of the disease which display derangements in renal function and structure. In addition, we will determine whether the disease state affects renal tissue content of chromium. Collectively, the results should provide insight into renal effects of Cr(pic)3 in health and disease conditions for which its use is advocated, an aspect that has received too little attention. Further, the studies will address the prevailing concern and controversy regarding clastogenic potential of Cr(pic)3, an aspect that remains to be established using relevant animal models of type 2 diabetes. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AT003012-01A2
Application #
7314246
Study Section
Special Emphasis Panel (ZAT1-DB (26))
Program Officer
Moen, Laura K
Project Start
2007-09-01
Project End
2009-04-30
Budget Start
2007-09-01
Budget End
2008-04-30
Support Year
1
Fiscal Year
2007
Total Cost
$217,680
Indirect Cost
Name
Georgia Regents University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
966668691
City
Augusta
State
GA
Country
United States
Zip Code
30912
Mozaffari, Mahmood S; Baban, Babak; Abdelsayed, Rafik et al. (2012) Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage. J Nutr Biochem 23:977-85
Mozaffari, Mahmood S; Abdelsayed, Rafik; Liu, Jun Yao et al. (2012) Renal distal tubule proliferation and increased aquaporin 2 level but decreased urine osmolality in db/db mouse: treatment with chromium picolinate. Exp Mol Pathol 92:54-8
Yeghiazaryan, Kristina; Schild, Hans H; Golubnitschaja, Olga (2012) Chromium-picolinate therapy in diabetes care: individual outcomes require new guidelines and navigation by predictive diagnostics. Infect Disord Drug Targets 12:332-9
Mozaffari, Mahmood S; Abdelsayed, Rafik; Zakhary, Ibrahim et al. (2011) Submandibular gland and caries susceptibility in the obese Zucker rat. J Oral Pathol Med 40:194-200
Yeghiazaryan, Kristina; Peeva, Viktoriya; Shenoy, Aparna et al. (2011) Chromium-picolinate therapy in diabetes care: molecular and subcellular profiling revealed a necessity for individual outcome prediction, personalised treatment algorithms and new guidelines. Infect Disord Drug Targets 11:188-95
Abebe, Worku; Liu, Jun Yao; Wimborne, Hereward et al. (2010) Effects of chromium picolinate on vascular reactivity and cardiac ischemia-reperfusion injury in spontaneously hypertensive rats. Pharmacol Rep 62:674-82