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Published in: BMC Complementary Medicine and Therapies 1/2015

Open Access 01-12-2015 | Research article

Anti-diabetic potential of chromium histidinate in diabetic retinopathy rats

Authors: Mustafa Ulas, Cemal Orhan, Mehmet Tuzcu, Ibrahim Hanifi Ozercan, Nurhan Sahin, Hasan Gencoglu, James R Komorowski, Kazim Sahin

Published in: BMC Complementary Medicine and Therapies | Issue 1/2015

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Abstract

Background

Chromium (Cr) is commonly used as a complementary medicine for diabetes mellitus. Several studies suggest that Cr intakes may improve glucose metabolism and decrease oxidative stress. Therefore, we aimed to assess the effects of chromium histidinate (CrHis) supplementation using a range of reliable biomarkers of oxidative damage and histopathological changes in rats with diabetic retinopathy.

Methods

Diabetes was induced with streptozotocin [(STZ), 55 mg/kg] by intraperitoneal injection in male Long-Evans rats. Three weeks after STZ injection, rats were divided into four groups, namely, untreated normal controls, normal rats receiving CrHis (110 μg/kg/day); untreated diabetics and diabetics treated with CrHis (110 μg/kg/day) orally for 12 weeks.

Results

In the untreated diabetic group, levels of serum glucose, glycosylated haemoglobin (HbA1c), total cholesterol (TC) and retina malondialdehyde (MDA) were significantly increased, while expressions of retina insulin, and glucose transporter 1 (GLUT 1) and glucose transporter 3 (GLUT3) and level of serum insulin were decreased. CrHis supplementation was found to reduce the levels of glucose, HbA1c, total cholesterol and MDA and to improve the GLUT1, GLUT3 and insulin expressions in STZ-induced diabetic rats. CrHis prevents the changes in the expressions of GLUT1, GLUT3 and insulin and the level of MDA in the retina tissue, confirming the protective effect of CrHis supplementation against the retinopathy caused by STZ. Histopathologic findings suggest that the CrHis-treated diabetic group had normal retinal tissue appearance compared with the untreated diabetic group.

Conclusions

These results verify that CrHis has critical beneficial effects against retinal complications. Although detailed studies are required for the evaluation of the exact mechanism of the ameliorative effects of CrHis against diabetic complications, these preliminary experimental findings demonstrate that CrHis exhibits antidiabetic effects in a rat model of diabetic retinopathy by regulating the glucose metabolism and suppressing retinal tissue damage.
Literature
1.
go back to reference Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. J Am Med Assoc. 2007;298:902–16.CrossRef Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. J Am Med Assoc. 2007;298:902–16.CrossRef
2.
go back to reference Marshall SM, Flyvbjerg A. Prevention and early detection of vascular complications of diabetes. British Med J. 2006;333:475–80.CrossRef Marshall SM, Flyvbjerg A. Prevention and early detection of vascular complications of diabetes. British Med J. 2006;333:475–80.CrossRef
3.
go back to reference Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care. 1996;19:257–67.CrossRefPubMed Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care. 1996;19:257–67.CrossRefPubMed
4.
go back to reference Mitsuhashi J, Morikawa S, Shimizu K, Ezaki T, Yasuda Y, Hori S. Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats. Exp Eye Res. 2013;106:64–73.CrossRefPubMed Mitsuhashi J, Morikawa S, Shimizu K, Ezaki T, Yasuda Y, Hori S. Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats. Exp Eye Res. 2013;106:64–73.CrossRefPubMed
5.
go back to reference Santos JM, Tewari S, Kowluru RA. A compensatory mechanism protects retinal mitochondria from initial insult in diabetic retinopathy. Free Radic Biol Med. 2012;53:1729–37.CrossRefPubMedPubMedCentral Santos JM, Tewari S, Kowluru RA. A compensatory mechanism protects retinal mitochondria from initial insult in diabetic retinopathy. Free Radic Biol Med. 2012;53:1729–37.CrossRefPubMedPubMedCentral
6.
go back to reference Kowluru RA, Chan P-S. Oxidative stress and diabetic retinopathy. Exp Diabetes Res. 2007;2007:Article ID 43603, 1-12. doi:10.1155/2007/43603. Kowluru RA, Chan P-S. Oxidative stress and diabetic retinopathy. Exp Diabetes Res. 2007;2007:Article ID 43603, 1-12. doi:10.1155/2007/43603.
7.
go back to reference Rajah TT, Olson AL, Grammas P. Differential glucose uptake in retinaand brain-derived endothelial cells. Microvasc Res. 2001;62:236–42.CrossRefPubMed Rajah TT, Olson AL, Grammas P. Differential glucose uptake in retinaand brain-derived endothelial cells. Microvasc Res. 2001;62:236–42.CrossRefPubMed
8.
go back to reference Angulo C, Maldonado R, Pulgar E, Mancilla H, Córdova A, Villarroel F. Vitamin C and oxidative stress in the seminiferous epithelium. Biol Res. 2011;44:169–80.CrossRefPubMed Angulo C, Maldonado R, Pulgar E, Mancilla H, Córdova A, Villarroel F. Vitamin C and oxidative stress in the seminiferous epithelium. Biol Res. 2011;44:169–80.CrossRefPubMed
9.
go back to reference Sahin K, Onderci M, Tuzcu M, Ustundag B, Cikim G, Ozercan IH, et al. Effect of chromium on carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus: the fat-fed, streptozotocin-treated rat. Metab Clin Exp. 2007;56:1233–40.CrossRefPubMed Sahin K, Onderci M, Tuzcu M, Ustundag B, Cikim G, Ozercan IH, et al. Effect of chromium on carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus: the fat-fed, streptozotocin-treated rat. Metab Clin Exp. 2007;56:1233–40.CrossRefPubMed
10.
go back to reference Vincent JB. Recent developments in the biochemistry of chromium(III). Biol Trace Elem Res. 2004;99:1–16.CrossRefPubMed Vincent JB. Recent developments in the biochemistry of chromium(III). Biol Trace Elem Res. 2004;99:1–16.CrossRefPubMed
11.
go back to reference Sahin K, Tuzcu M, Orhan C, Ali S, Sahin N, Gencoglu H, et al. Chromium modulates expressions of neuronal plasticity markers and glial fibrillary acidic proteins in hypoglycemia-induced brain injury. Life Sci. 2013;18(93):1039–48.CrossRef Sahin K, Tuzcu M, Orhan C, Ali S, Sahin N, Gencoglu H, et al. Chromium modulates expressions of neuronal plasticity markers and glial fibrillary acidic proteins in hypoglycemia-induced brain injury. Life Sci. 2013;18(93):1039–48.CrossRef
12.
go back to reference Kleefstra N, Houweling ST, Bakker SJ, Verhoeven S, Gans RO, Meyboom-de Jong JB, et al. Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled trial. Diabetes Care. 2007;30(5):1092–6.CrossRefPubMed Kleefstra N, Houweling ST, Bakker SJ, Verhoeven S, Gans RO, Meyboom-de Jong JB, et al. Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled trial. Diabetes Care. 2007;30(5):1092–6.CrossRefPubMed
13.
go back to reference Anderson RA, Polansky MM, Bryden NA. Stability and absorption of chromium and absorption of chromium histidinate complexes by humans. Biol Trace Elem Res. 2004;101:211–8.CrossRefPubMed Anderson RA, Polansky MM, Bryden NA. Stability and absorption of chromium and absorption of chromium histidinate complexes by humans. Biol Trace Elem Res. 2004;101:211–8.CrossRefPubMed
14.
go back to reference Cefalu WT, Wang ZQ, Zhang XH, Baldor LC, Russell JC. Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats. J Nutr. 2002;132(6):1107–14.PubMed Cefalu WT, Wang ZQ, Zhang XH, Baldor LC, Russell JC. Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats. J Nutr. 2002;132(6):1107–14.PubMed
15.
go back to reference Ulu R, Dogukan A, Tuzcu M, Gencoglu H, Ulas M, Ilhan N, et al. Regulation of renal organic anion and cation transporters by thymoquinone in cisplatin induced kidney injury. Food Chem Toxicol. 2012;50:1675–9.CrossRefPubMed Ulu R, Dogukan A, Tuzcu M, Gencoglu H, Ulas M, Ilhan N, et al. Regulation of renal organic anion and cation transporters by thymoquinone in cisplatin induced kidney injury. Food Chem Toxicol. 2012;50:1675–9.CrossRefPubMed
16.
go back to reference Sahin K, Tuzcu M, Orhan C, Gencoglu H, Ulas M, Atalay M, et al. The effects of chromium picolinate and chromium histidinate administration on NF-κB and Nrf2/HO-1 pathway in the brain of diabetic rats. Biol Trace Elem Res. 2012;150:291–6.CrossRefPubMed Sahin K, Tuzcu M, Orhan C, Gencoglu H, Ulas M, Atalay M, et al. The effects of chromium picolinate and chromium histidinate administration on NF-κB and Nrf2/HO-1 pathway in the brain of diabetic rats. Biol Trace Elem Res. 2012;150:291–6.CrossRefPubMed
17.
18.
go back to reference Harman-Boehm I, Sosna T, Lund-Andersen H, Porta M. The eyes in diabetes and diabetes through the eyes. Diabetes Res Clin Pract. 2007;78:51–8.CrossRef Harman-Boehm I, Sosna T, Lund-Andersen H, Porta M. The eyes in diabetes and diabetes through the eyes. Diabetes Res Clin Pract. 2007;78:51–8.CrossRef
19.
go back to reference Giansanti R, Rabini RA, Romagnoli F, Fumelli D, Sorichetti P, Boemi M, et al. Coronary heart disease, type 2 diabetes mellitus and cardiovascular disease risk factors: a study on a middle-aged and elderly population. Arch Genontol Geriatr. 1999;29:175–82.CrossRef Giansanti R, Rabini RA, Romagnoli F, Fumelli D, Sorichetti P, Boemi M, et al. Coronary heart disease, type 2 diabetes mellitus and cardiovascular disease risk factors: a study on a middle-aged and elderly population. Arch Genontol Geriatr. 1999;29:175–82.CrossRef
20.
go back to reference Yan Z, Liu Y, Huang H. Association of glycosylated hemoglobin level with lipid ratio and individual lipids in type 2 diabetic patients. Asian Pac J Trop Dis. 2012;5:469–71.CrossRef Yan Z, Liu Y, Huang H. Association of glycosylated hemoglobin level with lipid ratio and individual lipids in type 2 diabetic patients. Asian Pac J Trop Dis. 2012;5:469–71.CrossRef
21.
go back to reference Faulkner MS, Chao WH, Kamath SK, Quinn L, Fritschi C, Maggiore JA, et al. Total homocysteine, diet, and lipid profiles in type 1 and type 2 diabetic and nondiabetic adolescents. J Cardiovasc. 2006;21(1):47–55. Faulkner MS, Chao WH, Kamath SK, Quinn L, Fritschi C, Maggiore JA, et al. Total homocysteine, diet, and lipid profiles in type 1 and type 2 diabetic and nondiabetic adolescents. J Cardiovasc. 2006;21(1):47–55.
22.
go back to reference Cefalu WT, Rood J, Pinsonat P, Qin J, Sereda O, Levitan L, et al. Characterization of the metabolic and physiologic response to chromium supplementation in subjects with type 2 diabetes mellitus. Metab Clin Exp. 2010;59:755–62.CrossRefPubMed Cefalu WT, Rood J, Pinsonat P, Qin J, Sereda O, Levitan L, et al. Characterization of the metabolic and physiologic response to chromium supplementation in subjects with type 2 diabetes mellitus. Metab Clin Exp. 2010;59:755–62.CrossRefPubMed
23.
go back to reference Jain SK, Rains JL, Croad JL. Effect of chromium niacinate and chromium picolinate supplementation on lipid peroxidation, TNF-α, IL-6, CRP, glycated hemoglobin, triglycerides, and cholesterol levels in blood of streptozotocin-treated diabetic rats. Free Radic Biol Med. 2007;43(8):1124–31.CrossRefPubMedPubMedCentral Jain SK, Rains JL, Croad JL. Effect of chromium niacinate and chromium picolinate supplementation on lipid peroxidation, TNF-α, IL-6, CRP, glycated hemoglobin, triglycerides, and cholesterol levels in blood of streptozotocin-treated diabetic rats. Free Radic Biol Med. 2007;43(8):1124–31.CrossRefPubMedPubMedCentral
24.
go back to reference Vincent JB. Recent advances in the biochemistry of chromiumb [III]. J Trace Elements Exp Med. 2003;16:227–36.CrossRef Vincent JB. Recent advances in the biochemistry of chromiumb [III]. J Trace Elements Exp Med. 2003;16:227–36.CrossRef
25.
go back to reference Cefalu WT, Hu FB. Role of chromium in human health and in diabetes. Diabetes Care. 2004;27(11):2741–51.CrossRefPubMed Cefalu WT, Hu FB. Role of chromium in human health and in diabetes. Diabetes Care. 2004;27(11):2741–51.CrossRefPubMed
26.
27.
go back to reference Chen SH, Sun YP, Chen XS. Effect of jiangtangkang on blood glucose, sensitivity of insulin and blood viscosity in non-insulin dependent diabetes mellitus. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997;17(11):666–8.PubMed Chen SH, Sun YP, Chen XS. Effect of jiangtangkang on blood glucose, sensitivity of insulin and blood viscosity in non-insulin dependent diabetes mellitus. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997;17(11):666–8.PubMed
28.
go back to reference Ravina A, Slezak L, Rubal A, Mirsky N. Clinical use of the trace element chromium [III] in the treatment of diabetes mellitus. J Trace Elem Exp Med. 1995;8:183–90. Ravina A, Slezak L, Rubal A, Mirsky N. Clinical use of the trace element chromium [III] in the treatment of diabetes mellitus. J Trace Elem Exp Med. 1995;8:183–90.
29.
go back to reference Chen G, Liu P, Pattar GR, Tackett L, Bhonagiri P, Strawbridge AB, et al. Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism. Mol Endocrinol. 2006;20(4):857–70.CrossRefPubMed Chen G, Liu P, Pattar GR, Tackett L, Bhonagiri P, Strawbridge AB, et al. Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism. Mol Endocrinol. 2006;20(4):857–70.CrossRefPubMed
30.
go back to reference Puchowicz MA, Xu K, Magness D, Miller C, Lust WD, Kern TS, et al. Comparison of glucose influx and blood flow in retina and brain of diabetic rats. J Cereb Blood Flow Metab. 2004;24(4):449–57.CrossRefPubMed Puchowicz MA, Xu K, Magness D, Miller C, Lust WD, Kern TS, et al. Comparison of glucose influx and blood flow in retina and brain of diabetic rats. J Cereb Blood Flow Metab. 2004;24(4):449–57.CrossRefPubMed
31.
go back to reference Watanabe T, Matsushima S, Okazaki M, Nagamatsu S, Hirosawa K, Uchimura H, et al. Localization and ontogeny of GLUT3 expression in the rat retina. Brain Res Dev Brain Res. 1996;94(1):60–6.CrossRefPubMed Watanabe T, Matsushima S, Okazaki M, Nagamatsu S, Hirosawa K, Uchimura H, et al. Localization and ontogeny of GLUT3 expression in the rat retina. Brain Res Dev Brain Res. 1996;94(1):60–6.CrossRefPubMed
32.
go back to reference Kumagai AK. Glucose transport in brain and retina: ımplications in the management and complications of diabetes. Diabetes Metab Res Rev. 1999;15:261–73.CrossRefPubMed Kumagai AK. Glucose transport in brain and retina: ımplications in the management and complications of diabetes. Diabetes Metab Res Rev. 1999;15:261–73.CrossRefPubMed
33.
go back to reference Tserentsoodol N, Shin B-C, Suzuki T, Takata K. Colocalization of tight junction proteins, occludin and ZO-1, and glucose transporter GLUT1 in cells of the blood-ocular barrier in the mouse eye. Histochem Cell Biol. 1998;110:543–51.CrossRefPubMed Tserentsoodol N, Shin B-C, Suzuki T, Takata K. Colocalization of tight junction proteins, occludin and ZO-1, and glucose transporter GLUT1 in cells of the blood-ocular barrier in the mouse eye. Histochem Cell Biol. 1998;110:543–51.CrossRefPubMed
34.
go back to reference Klip A, Paquet MR. Glucose transport and glucose transporters in muscle and their metabolic regulation. Diabetes Care. 1990;13:228–43.CrossRefPubMed Klip A, Paquet MR. Glucose transport and glucose transporters in muscle and their metabolic regulation. Diabetes Care. 1990;13:228–43.CrossRefPubMed
35.
go back to reference Sreejayan N, Dong F, Kandadi MR, Yang X, Ren J. Chromium alleviates glucose intolerance, insulin resistance, and hepatic ER stress in obese mice. Obesity (Silver Spring). 2008;16(6):1331–7.CrossRef Sreejayan N, Dong F, Kandadi MR, Yang X, Ren J. Chromium alleviates glucose intolerance, insulin resistance, and hepatic ER stress in obese mice. Obesity (Silver Spring). 2008;16(6):1331–7.CrossRef
36.
go back to reference Mutuma S, Amuna P, Shukla H, Sumar S. Chromium in food, nutrition and health – an introduction. Nutri Food Sci. 1999;2:81–8.CrossRef Mutuma S, Amuna P, Shukla H, Sumar S. Chromium in food, nutrition and health – an introduction. Nutri Food Sci. 1999;2:81–8.CrossRef
37.
go back to reference Ueda Y, Kanazawa S, Gong H, Miyamura N, Kitaoka T, Amemiya T. The retinal pigment epithelium of Cr-deficient rats. Life Sci. 2002;71:1569–77.CrossRefPubMed Ueda Y, Kanazawa S, Gong H, Miyamura N, Kitaoka T, Amemiya T. The retinal pigment epithelium of Cr-deficient rats. Life Sci. 2002;71:1569–77.CrossRefPubMed
38.
go back to reference Mueckler M, Thorens B. The SLC2 [GLUT] family of membrane transporters. Mol Asp Med. 2013;34:121–38.CrossRef Mueckler M, Thorens B. The SLC2 [GLUT] family of membrane transporters. Mol Asp Med. 2013;34:121–38.CrossRef
39.
go back to reference Shinde UA, Goyal RK. Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats. J Cell Mol Med. 2003;7(3):322–9.CrossRefPubMed Shinde UA, Goyal RK. Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats. J Cell Mol Med. 2003;7(3):322–9.CrossRefPubMed
Metadata
Title
Anti-diabetic potential of chromium histidinate in diabetic retinopathy rats
Authors
Mustafa Ulas
Cemal Orhan
Mehmet Tuzcu
Ibrahim Hanifi Ozercan
Nurhan Sahin
Hasan Gencoglu
James R Komorowski
Kazim Sahin
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2015
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-015-0537-3

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