Abstract
This study was designed to investigate the susceptibility of liver and brain tissues, as insulin-independent tissues, of normal adult male rats to the oxidative challenge of subchronic supplementation with chromium picolinate (CrPic) at low (human equivalent) and high doses (2.90 and 13.20 μg Cr kg−1 day−1, respectively). Also, the modulative effect of CrPic administration on the enhanced oxidative stress in the liver and brain tissues of alloxan-diabetic rats was studied. Fasting serum glucose level was not modified in normal rats but significantly reduced in diabetic rats that had received CrPic supplement. A mild oxidative stress was observed in the liver and brain of CrPic-supplemented normal rats confirmed by the dose-dependent reductions in the levels of hepatic and cerebral free fatty acids, superoxide dismutase and glutathione peroxidase activities, and in contrast increased tissue malondialdehyde concentration. On the other hand, hepatic and cerebral catalase activity was reduced in the high dose group only. CrPic supplementation did not act as a peroxisome proliferator confirmed by the significant reductions in liver and brain peroxisomal palmitoyl CoA oxidase activity. The non significant alterations in liver protein/DNA and RNA/DNA ratios indicate that CrPic did not affect protein synthesis per cell, and that mild elevations in hepatic total protein and RNA concentrations might be due to block or decrease in the export rate of synthesized proteins from the liver to the plasma. In diabetic rats, elevated levels of hepatic and cerebral free fatty acids and malondialdehyde, and in contrast the overwhelmed antioxidant enzymes, were significantly modulated in the low dose group and near-normalized in the high dose group. The significant increases observed in liver total protein and RNA concentrations, as well as protein/DNA and RNA/DNA ratios in diabetic rats supplemented with the high dose of Cr, compared to untreated diabetics, may be related to the improvement in the glycemic status of the diabetic animals rather than the direct effect of CrPic on protein anabolism.
Similar content being viewed by others
References
Anderson RA (1993) Recent advances in the clinical and biochemical effects of chromium deficiency. In: Prasad AS (ed) Essential and toxic trace elements in human health and disease. Wiley Liss, New York, pp 221–234
Anderson RA (1998) Chromium, glucose intolerance and diabetes. J Am Coll Nutr 17:548–555
Anderson RA, Polansky MM, Bryden NA, Bhathena SJ, Canary J (1987) Effects of supplemental chromium on patients with symptoms of reactive hypoglycemia. Metabolism 36:351–355
Anderson RA, Cheng N, Bryden NA, Polansky MM, Chi J, Feng J (1997) Beneficial effects of chromium for people with diabetes. Diabetes 46:1786–1791
Anjuman G, Rahman MA, Jaleel A (2005) Changes in glycosylated proteins in type II diabetic patients with and without complications. J Ayub Med Coll Abbottabad 17:1–5
Bagchi D, Balmoori J, Bagchi M, Ye Xumein, Casey B, Williams J, Stohs SJ (2002) Comparative effects of TCDD, endrin, naphthalene and chromium (VI) on oxidative stress and tissue damage in the liver and brain tissues of mice. Toxicology 175:73–82
Bernao A, Meseguer I (2004) Effect of different doses of chromium picolinate on protein metabolism in infant rats. J Trace Elem Med Biol 1:33–39
Bissery MC, Guenard D, Gueritte-Voegelein F, Lavelle F (1991) Experimental antitumor activity of taxotere (RP56976, NSC 628503), a taxol analogue. Cancer Res 51:4845–4852
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Bukau B, Weissman J, Horwich A (2006) Molecular chaperones and protein quality control. Cell 125:443–451
Cefalu WT, Hu FB (2004) Role of chromium in human health and in diabetes. Diabetes Care 27:2742–2751
Cefalu WT, Bell-Farrow AD, Stegner J, Wang ZQ, King T, Morgan T, Terry JG (1999) Effect of chromium picolinate on insulin sensitivity in vivo. J Trace Elem Exp Med 12:71–83
Cefalu WT, Zhong Q, Wang XH, Zhang LC, Baldor F, Russell JC (2002) Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal Muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA Corpulent) rats. J Nutr 132:1107–1114
Chen G, Liu P, Guruprasad RP, Tacket L, Bhonagiri P, Strawbridg AB, Elemendorf JS (2006) Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3–L1 adipocytes via a cholesterol-dependent mechanism. Molec Endoc 20:857–870
Chu R, Varanasi U, Chu S, Lin Y, Usuda N, Rao M, Reddy J (1995) Overexpression and characterization of the human peroxisomal acyl CoA oxidase in insect cells. J Biol Chem 270:4908–4915
Davis CM, Sumall KH, Vincent JB (1996) A biologically active form of chromium may activate a membrane phosphotyrosine phosphatase (PTP). Biochemistry 35:12963–12969
Dische Z (1957) Determination of pentoses. In: Colourick SP, Kaplan NO (eds) Methods in enzymology. Academic Press, New York, p 88
Dische Z, Schwartz K (1954) Estimation of nucleic acids. In: Glick D (ed) Methods of biochemical analysis vol I. Interscience Publishers, New York, p 299
Duncombe WG (1963) The colorimetric micro-determination of long chain fatty acids. Biochem J 88:7–10
Esterbauer H, Cheesman KH (1990) Determination of aldehyde lipid peroxidation products: malondialdehyde and 4-hydroxynonenal. Methods Enzymol 186:407–410
Evans GW, Bowman TD (1992) Chromium picolinate increases membrane fluidity and rate of insulin internalization. J Inorg Biochem 46:243–250
Fridlyand LE, Philipson LH (2005) Oxidative reactive species in cell injury: mechanisms in diabetes mellitus and therapeutic approaches. Ann NY Acad Sci 1066:136–151
Fulop T Jr, Nagy JT, Worum I, Foris G, Mudri K, Varga P, Udvardy M (1987) Glucose intolerance and insulin resistance with aging: studies on insulin receptors and postreceptor events. Arch Gerontol Geriatr 6:107–115
Garg MC, Ojha S, Bansal DD (1996) Antioxidant status of streptozotocin- diabetic rats. Indian J Exp Biol 34:264–269
Giugliano D, Ceriello A, Paolisso G (1998) Oxidative stress and diabetic vascular complications. Diabetes Care 21:326–327
Gow A, Sharma R (2003) The unfolded protein response in protein aggregating diseases. Neuromolecular Med 4:73–94
Hepburn DD, Vincent JB (2002) In vivo distribution of chromium from chromium picolinate in rats and implications for the safety of the dietary supplement. Chem Res Toxicol 15:93–100
Hryb DJ, Hogg JF (1979) Chain length specificities of peroxisomal and mitochondrial β-oxidation in rat liver. Biochem Biophys Res Commun 87:1200–1206
Jefferson LS, Warren SLL, Daniel EP, Thomas BM, Micheal CA, John MT (1983) Diabetes-induced alterations in liver protein synthesis. J Biol Chem 228:1369–1375
Kesavulu M, Rao BK, Giri R, Vijya JS, Subramanyam A (2001) Lipid peroxidation and antioxidant enzymes status in type 2 diabetics with coronary heart disease. Diabetes Res Clin Pract 53:33–39
Mahboob M, McNeil L, Tolliver T, Ogden L (2002) Effects of chromium picolinate on antioxidant enzyme levels in rats. Toxicol Sci 66:32–37
Mertz W (1969) Chromium occurrence and function in biological systems. Physiol Rev 49:163–239
Nakatami Y, Kaneto H, Kawamori D, Yoshiuchi K, Hatazaki M, Matsuoka TA, Ozawa K, Ogawa S, Hori M, Yamasaki Y, Matsuhisa M (2005) Involvement of ER stress in insulin resistance and diabetes. J Biol Chem 280:847–851
Newsholme P, Haber EP, Hirabara SM, Rebelato EL, Procopio J, Morgan D, Oliveira-Emilio HC, Carpinelli AR, Curi R (2007) Diabetes associated cell stress and dysfunction: role of mitochondrial and non mitochondrial ROS production and activity. J Physiol 583:9–24
Ramalingam S, Leelavinothan P (2005) Antihyperlipidemic and antiperoxidative effect of diasulin, a polyherbal formulation in alloxan- induced hyperglycemic rats. BMC Complement Altern Med 5:14–19
Reddy JK, Azarnoff DL, Hignite CE (1980) Hypolipidemic hepatic peroxisome proliferators form a novel class of chemical carcinogens. Nature 283:397–3982
Refaie FM, Esmat AY, Abdel Gawad SM, Ibrahim AM, Mohamed MA (2005) The antihyperlipidemic activities of 4 (3H) quinazolinone and 2 halogenated derivatives in rats. Lipids Health Dis 4:22–33
Roth EF, Gilbert HS (1984) The pyrogallol assay for superoxide dismutase: absence of a glutathione artifact. Anal Biochem 137:90–95
Saxena AK, Srivastava P, Kale RK, Baquer NZ (1993) Impaired antioxidant status in diabetic rat liver: effect of vanadate. Biochem Pharmacol 45:539–543
Schneider WC, Hogeboom GN, Ross NE (1950) Intracellular distribution of enzymes, distribution of nucleic acids and adenosine triphosphate in normal mouse liver and mouse hepatoma. J Natl Cancer Inst 10:977–982
Schwarz K, Mertz W (1957) A glucose tolerance factor and its differentiation from factor 3. Arch Biochem Biophys 72:515–520
Schwarz K, Mertz W (1959) Chromium (III) and the glucose tolerance factor. Arch Biochem Biophys 85:292–295
Sellei C, Hardt E, Nemeth L (1970) Chemotherapy of neoplastic diseases. Akademiai Kiado. The Publishing House of the Hungarian, Budapest, pp 35–45
Sheweita SA, Newairy AA, Mansour HA, Youssef MI (2002) Effect of some hypoglycemic herbs on the activity of phase I and II drug- metabolizing enzymes in alloxan-induced diabetic rats. Toxicology 174:131–139
Shinde UA, Goyal RK (2002) Mechanism of anti-diabetic action of chromium. Indian J Pharmacol 34:142–147
Shinde UA, Goyal RK (2003) Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ-diabetic rats. J Cell Mol Med 7:322–329
Sies H, Sharov VS, Klotz LO, Briviba K (1997) Glutathione peroxidase protects against peroxynitrite-mediated oxidations: a new function for selenoproteins as peroxynitrite reductase. J Biol Chem 272:27812–27817
Sinha KA (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394
Stott W (1988) Chemically induced proliferation of peroxisomes: implications for risk assessment. Regul Toxicol Pharmacol 8:125–159
Striffler JS, Polansky MM, Anderson RA (1998) Dietary chromium decreases insulin resistance in rats fed a high fat, mineral-imbalanced diet. Metabolism 47:396–400
Striffler JS, Polansky MM, Anderson RA (1999) Overproduction of insulin in the chromium-deficient rat. Metabolism 48:1063–1068
Strydom C, Robinson C, Pretorius E, Whitcutt JM, Marx J, Bornman MS (2006) The effect of selected metals on the central metabolic pathways in biology: a review. Water SA 32:543–554
Trinder P (1969) Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 6:24–29
Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552:335–344
Ursini F, Maiorino M, Gregolin C (1985) The selenoenzyme phospholipids hydroperoxide glutathione peroxidase. Biochim Biophys Acta 839:62–70
Von Veldhoven PP, Vanhove G, Vanhoutte F, Dacremont G, Parmentier G, Eyssen HJ, Mannaerts GP (1991) Identification and purification of a peroxisomal branched chain fatty acyl-CoA oxidase. J Biol Chem 36:24676–24683
Warner DS, Huaxin S, Ines BH (2004) Oxidants, antioxidants and the ischemic brain. J Exp Biol 207:3221–3323
Williams MD, Van Remmen H, Conrad CC, Huang TT, Epstein CJ, Richardson A (1998) Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice. J Biol Chem 273:28510–28515
Wills ED (1969) Lipid peroxide formation in microsomes. General considerations. Biochem J 113:315–327
Wohaieb SA, Godin DV (1987) Alterations in free radicals tissue-defense mechanisms in streptozotocin-induced diabetes in rat: effects of insulin treatment. Diabetes Care 36:1014–1018
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Refaie, F.M., Esmat, A.Y., Mohamed, A.F. et al. Effect of chromium supplementation on the diabetes induced-oxidative stress in liver and brain of adult rats. Biometals 22, 1075–1087 (2009). https://doi.org/10.1007/s10534-009-9258-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10534-009-9258-8