Effects of chromium picolinate on glycemic control and kidney of the obese Zucker rat

Abstract

Background: Chromium 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.

Methods: Male 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.

Results: The 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.

Conclusion: Dietary 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.

Figure 1

Body weight and blood pressure. Panel A shows time-course of changes in body weight while panel B shows blood pressure of lean Zucker rats (LZR), untreated obese Zucker rats (OZR) and OZR treated with diets containing 5 and 10 mg/kg of chromium as Cr(pic)3 (i.e., OZR; 5 Cr and OZR; 10 Cr, respectively). The treatments were initiated at 6 weeks of age (i.e., time 0). Data are means ± SEM of 9-10 animals/group. * p < 0.05 compared to the other groups at the same time point.

Figure 2

Pancreas histopathology. Panels show representative H&E-stained sections (A-D; 100×), PAS-stained sections (E-H; 200×) and trichrome-stained section (I-L; 200×) of pancreas from experimental groups as described in Figure 1. Also shown is the immunohistochemical localization of 8-OHdG in pancreas of experimental groups (Panels M-P, 200×)

Figure 3

Kidney histopathology. Panels A-D show representative H&E-stained while panels E-H show representative PAS-stained kidney sections from experimental groups as described in Figure 1 (100× and 200×, respectively). Also shown are representative panels for Oil-Red-O stained renal tissue from experimental groups (panels I-L, 200×; arrows point to lipid droplets).

Figure 4

Kidney nitrotyrosine content. Bar graphs show renal tissue nitrotyrosine level in experimental groups as described in Figure 1; data are expressed as percent of the LZR group. Also shown are representative blot for each group. Data are means ± SEM of 7-9 animals per group. * p < 0.05 compared to the LZR group.

Figure 5

Urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG) in experimental groups as described in Figure 1. Data are means ± SEM of 9-10 animals/group. * p < 0.05 compared to the LZR or OZR;10 Cr groups.

Figure 6

Kidney 8-OHdG and CD 68 immunostaining. Panels A-D show representative 8-OHdG-immunostained kidney sections from experimental groups while panels E-H show immunostaining for CD68 positive tissue histiocytes (200× except panel E which is shown at 100×).

Figure 7

Urinary excretion of MCP-1 in experimental groups as described in Figure 1. Data are means ± SEM of 9-10 animals/group. * p < 0.05 compared to LZR group.

Figure 8

Renal expression of cyclooxygensae-2 for experimental groups as described in Figure 1. Data are normalized to β-actin and expressed as percent of the LZR group. Data are means ± SEM of 7-9 animals per group. Also shown is representative blot for each group and its β-actin control. * p < 0.05 compared to the LZR or OZR; 10 Cr groups.

Figure 9

Renal tissue chromium content in experimental groups as described in Figure 1. PPB: Parts Per Billion. * p < 0.05 compared to either the LZR or untreated OZR groups. # p < 0.05 compared to other groups.