Abstract
BackgroundChromium picolinate (Cr(pic)3) is advocated as adjuvant therapy for impaired glycemic control, despite concerns for DNA damage. Potential toxicity of Cr(pic)3 should be greater for the kidney that accumulates chromium. Therefore, we tested the hypothesis that Cr(pic)3 treatment of obese Zucker rats (OZR) exacerbates renal abnormalities associated with dysglycemia.MethodsMale OZR were treated with diets lacking or containing 5 and 10 mg/kg of chromium, as Cr(pic)3, for 20 weeks; lean Zucker rats (LZR) served as controls. Glycemic and renal effects of Cr(pic)3 were determined in the context of indices of oxidative stress and inflammation.ResultsThe OZR displayed increased fasting plasma glucose and insulin in association with enlarged pancreatic islets exhibiting collagen and periodic acid Schiff-positive deposits compared to LZR; Cr(pic)3 treatment did not affect these parameters. The OZR, irrespective of Cr(pic)3, excreted more albumin than LZR. Also, other indices of renal function or histopathology were not affected by Cr(pic)3 treatment. Urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), an index of oxidative DNA damage, was greater in the OZR than LZR; dietary Cr(pic)3 treatment attenuated 8-OHdG excretion. However, immunostaining of kidney for 8-OHdG revealed similar staining pattern and intensity, despite significant renal accumulation of chromium in Cr(pic)3-treated groups. Finally, increased renal nitrotyrosine and cyclooxygenase-2 levels and urinary excretion of monocyte chemoattractant protein-1 of OZR were partially reversed by Cr(pic)3 treatment.ConclusionDietary Cr(pic)3 treatment of OZR does not beneficially influence glycemic status or increase the risk for oxidative DNA damage; rather, the treatment attenuates indices of oxidative stress and inflammation.
Highlights
The worldwide epidemic of obesity is a major predisposing factor for the ever increasing prevalence and incidence of glucose intolerance and type 2 diabetes [1,2]
The obese Zucker rats (OZR) display marked obesity, dyslipidemia, severe insulin resistance, increased oxidative stress and a proinflammatory state compared to the lean Zucker rats (LZR) [7,8,9]
The OZR can serve as a useful animal model for determination of potential influences of therapies aimed at prevention or attenuation of obesity/ type 2 diabetes-related abnormalities
Summary
The worldwide epidemic of obesity is a major predisposing factor for the ever increasing prevalence and incidence of glucose intolerance and type 2 diabetes [1,2]. Obesity and impaired glucose tolerance/type 2 diabetes markedly increase the risk for development of renal and cardiovascular complications [3,4]. Of various animal models of obesity and type 2 diabetes mellitus, the obese Zucker rats (OZR) have been used extensively for studies focused on consequences of the disease and the contributing mechanisms. The OZR display marked obesity, dyslipidemia, severe insulin resistance, increased oxidative stress and a proinflammatory state compared to the lean Zucker rats (LZR) [7,8,9]. The OZR can serve as a useful animal model for determination of potential influences of therapies aimed at prevention or attenuation of obesity/ type 2 diabetes-related abnormalities. We tested the hypothesis that Cr(pic) treatment of obese Zucker rats (OZR) exacerbates renal abnormalities associated with dysglycemia
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