Abstract
Oxidative stress in diabetes co-exists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Hyperlipidaemia is one of the major risk factors of cardiovascular complications in diabetes. A study was undertaken to evaluate the antioxidant and antihyperlipidaemic activity of protocatechuic acid (PCA) on streptozotocin (STZ)-induced diabetic rats. The levels of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH) were increased and the level of enzymatic and non-enzymatic antioxidants decreased except vitamin E. Lipid profile increased in diabetic rats, whereas HDL-C level decreased. These alterations reverted to near control levels after the diabetic rats were treated with PCA. Histopathological studies also revealed the protective effects of PCA on liver and kidney. These findings suggest that PCA treatment exerts a therapeutic property by decreasing the oxidative stress and lipid profile. The effect of PCA was comparable to glibenclamide, a well-known hypoglycaemic drug.
Keywords: DIABETES, ANTIOXIDANT, OXIDATIVE STRESS, HYPERLIPIDAEMIA, PROTOCATECHUIC ACID
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References
- 1.Halliwell B, Gutteridge JMC. Role of free radicals and catalytic metal ions in human disease. Methods Enzymol 1990; 186: 1–88. [DOI] [PubMed] [Google Scholar]
- 2.King GL, Loken MR. Hyperglycemia-induced oxidative stress in diabetic complications. Histochem Cell Biol 2004; 122: 333–338. [DOI] [PubMed] [Google Scholar]
- 3.Abu-seif MA, Youseef AA. Evaluation of some biochemical changes in diabetic patients. Clin Chim Acta 2004; 346: 161–170. [DOI] [PubMed] [Google Scholar]
- 4.Deedwania PC, Hunninghake DB, Bays H. Effects of lipid-altering treatment in diabetes mellitus and metabolic syndrome. Am J Cardiol 2004; 93: 18c-20c. [DOI] [PubMed] [Google Scholar]
- 5.Huang MT, Ferrano T. Phenolic compounds in food and cancer prevention. In: Huang MD, Ho CT, Lee CY. (eds). Phenolic Compounds in Food and Their Effects on Health: Antioxidants and Cancer Prevention Washington, DC: American Chemical Society, 1992. [Google Scholar]
- 6.Chan K, Chui SH, Wong DY et al. Protective effects of Danshensu from the aqueous extract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunction'. Life Sci 2004; 75: 3157–3171. [DOI] [PubMed] [Google Scholar]
- 7.Chuen-Lan L, Jin-Ming W, Chia-Yih C et al. In vivo protectiveeffect of protocatechuic acid on tert-butyl hydroperoxide-induced rat hepatotoxicity. Food Chem Toxicol 2002; 40: 635–641. [DOI] [PubMed] [Google Scholar]
- 8.Tanaka T, Kojima T, Kawamori T et al. Chemoprevention diethylnitrosamine-induced hepatocarcinogenesis by a simple phenolic acid protocatechuic acid in rats. Can Res 1993; 53: 2775–2779. [PubMed] [Google Scholar]
- 9.Niehaus WG, Samuelson B. Formation of malondialdehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968; 6: 126–130. [DOI] [PubMed] [Google Scholar]
- 10.Jiang ZY, Hunt JV, Wolff SP. Detection of lipid hydroperoxides using the ‘fox method’. Anal Biochem 1992; 202: 384–389. [DOI] [PubMed] [Google Scholar]
- 11.Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Ind J Biochem Biophys 1984; 21: 130–132. [PubMed] [Google Scholar]
- 12.Sinha KA, Colorimetric assay of catalase. Anal Biochem 1972; 47: 389–394. [DOI] [PubMed] [Google Scholar]
- 13.Rotruck JJ, Pope AL, Ganther HE et al. Selenium: biochemical rates as a component of glutathione peroxidase. Science 1973; 179: 588–590. [DOI] [PubMed] [Google Scholar]
- 14.Ellman GL. Tissue sulphydryl groups. Arch Biochem Biophys 1959; 82: 70–77. [DOI] [PubMed] [Google Scholar]
- 15.Roe JH, Kuether CA. Detection of ascorbic acid in whole blood and urine through 2,4-DNPH derivative of dehydroascorbic acid. J Biol Chem 1943; 47: 399–407. [Google Scholar]
- 16.Baker H. Plasma tocopherol in man at various times after ingesting free or acetylated tocopherol. Nutr Rep Int 1980; 21: 531–536. [Google Scholar]
- 17.Folch J, Lees M, Sloane Stanly GH. A simple method for isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 26: 497–509. [PubMed] [Google Scholar]
- 18.Allain CC, Poon LS, Chan CS et al. Enzymatic determination of total serum cholesterol. Clin Chem 1974; 20: 470–475. [PubMed] [Google Scholar]
- 19.Izzo C, Grillo F, Murador E. Improved method for the determination of high density lipoprotein cholesterol. Isolation of high-density lipoproteins by the use of polyethylene glycol 6000. Clin Chem 1981; 27: 371–374. [PubMed] [Google Scholar]
- 20.Friedewald WT, Levy RI, Fredrickson DS. Estimation of LDL-cholesterol in the plasma, without the use of preparative ultracentrifuge. Clin Chem 1972; 18: 449. [PubMed] [Google Scholar]
- 21.McGowan MW, Artiss JD, Strandbergh DR et al. A peroxidase-coupled method for the colorimetric determination of serum triglycerides. Clin Chem 1983; 29: 538–542. [PubMed] [Google Scholar]
- 22.Falholt K, Lund B, Falholt W An easy colorimetric method for routine determination of free fatty acids in the plasma. Clin Chim Acta 1973; 46: 105–111. [DOI] [PubMed] [Google Scholar]
- 23.Zilversmit DB, Davis AK. Micro-determination of plasma phospholipids by trichloroacetic acid precipitation. J Lab Clin Med 1950; 35: 155–159. [PubMed] [Google Scholar]
- 24.Papaccio G, Pisanti FA, Latronico MV, Ammendola E, Galdieri M. Multiple low-dose and single high-dose treatments with streptozotocin do not generate nitric oxide. J Cell Biochem 2000; 77: 82–91. [PubMed] [Google Scholar]
- 25.Mohamed AK, Bierhaus A, Schiekofer S. The role of oxidative stress and NF-kappaB activation in late diabetic complications. Biofactors 1999; 10: 157–167. [DOI] [PubMed] [Google Scholar]
- 26.Girotti MW Mechanisms of lipid peroxidation Free Radic Biol Med 1985; 1: 87–95. [DOI] [PubMed] [Google Scholar]
- 27.Zhang XF, Tan BK. Antihyperglycaemic and antioxidant properties of andrographis particulate in normal and diabetic rats. Clin Exp Pharmacol Physiol 2000; 27: 5–6. [DOI] [PubMed] [Google Scholar]
- 28.Yu BP. Cellular defenses against damage from reactive oxygen species. Physiol Rev 1994; 74: 136–162. [DOI] [PubMed] [Google Scholar]
- 29.Del Maestro RF. An approach to free radicals in medicine and biology. Acta Physiol Scand Suppl 1980; 492: 153–168. [PubMed] [Google Scholar]
- 30.Andallu B, Varadacharyulu NCh. Antioxidant role of mulberry (Morus indica L.) leaves in streptozotocin diabetic rats. Clin Chim Acta 2003; 338: 3–10. [DOI] [PubMed] [Google Scholar]
- 31.Yen GC, Hsieh CL. Inhibitory effects of Du-zhong (Eucommia olmoides oliv.) against low-density lipoprotein oxidative modification. Food Chem 2002; 77: 449–456. [Google Scholar]
- 32.Wefers H, Sies H. The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin E. Eur J Biochem 1998; 174: 353–357. [DOI] [PubMed] [Google Scholar]
- 33.Gary M, Bansal DD. Protective antioxidant effect of vitamin C and vitamin E in STZ-induced diabetic rats. Ind J Exp Biol 2000; 28: 101–104. [PubMed] [Google Scholar]
- 34.Jain SK, Levine SN. Elevated lipid peroxidation and vitamin E quinine levels in heart ventricles of streptozotocin treated diabetic rats. Free Radic Biol Med 1995; 18: 337–341. [DOI] [PubMed] [Google Scholar]
- 35.Asayama K, Nakane T, Uchida N, Hayashibe H, Dobashi K, Nakazawa S. Serum antioxidant status in streptozotocin induced diabetic rats. Horm Metab Res 1994; 26: 313–315. [DOI] [PubMed] [Google Scholar]
- 36.Yoshida K, Hirokawa J, Tagami S. Weakened cellular scavenging activity against oxidative stress in diabetes mellitus: regulation of glutathione synthesis and efflux. Diabetologia 1995; 38: 201–210. [DOI] [PubMed] [Google Scholar]
- 37.Halliwell B, Gutteridge JMC. Lipid peroxidation, oxygen radicals, cell damage and antioxidant therapy. Lancet 1994; 1: 1396–1397. [DOI] [PubMed] [Google Scholar]
- 38.Levine WG. Interaction of ascorbic acid and a-tocopherol. Ann Nutr Acad Sci 1990; 498: 186–199. [Google Scholar]
- 39.Darlin Quine S, Pamakanthan S. Effects of (—)-epicatechin, a flavonoid on lipid peroxidation and antioxidants in streptozotocin-induced diabetic liver, kidney and heart. Pharmacol Rep 2005; 57: 610–615. [PubMed] [Google Scholar]
- 40.Fontbonne A, Eschwege E, Cambien F et al. Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes. Diabetologia 1989; 32: 300–304. [DOI] [PubMed] [Google Scholar]
- 41.Grudy MS, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BY. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 1999; 100: 1134–1146. [DOI] [PubMed] [Google Scholar]
- 42.Lusis JA. Atheroscelerosis. Nature 2000; 407,233–241. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Kudchodkar BJ, Lee MJ, Lee SM, DiMarco NM, Lacko AG. Effect of dietary protein on cholesterol homeostasis in diabetic rats. J Lipid Res 1988; 10: 1272–1287. [PubMed] [Google Scholar]
- 44.Braun JE, Severson DL. Regulation of the synthesis, processing and translocation of lipoprotein lipase. Biochem J1992; 287: 337-347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Lopez-Virella MF, Wholtmann HJ, Mayfield RK, Loadholt CB, Colwell JA. Effect of metabolic control on lipid, lipoprotein, and apolipoprotein levels in 55 insulin-dependent diabetic patients: a longitudinal study. Diabetes 1983; 32: 20–25. [DOI] [PubMed] [Google Scholar]
- 46.Rhoads GG, Gulbrandse CL, Kagan A. Serum lipoproteins and coronary artery diseases in a population study of Hawaii, a Japanese man'. N Engl J Med 1976; 294: 293–298. [DOI] [PubMed] [Google Scholar]