Metilglioksal verilan ratlarda karnozinin antioksidan özelliklerinin araştırılması

Reaktif karbonil bileşiklerinden olan metilglioksal (MGO) 'in, ileri glikasyon son ürünleri (advanced glycation end products; AGE) için bir prekürsör olduğu düşünülmekte ve AGE oluşumu, diyabetes mellitus, ateroskleroz, yaşlanma ve Alzheimer gibi pek çok hastalığın etiyopatogenezinden sorumlu tutulmaktadır. Diğer taraftan endojen dipeptid olan karnozinin, anüoksidan ve antiglikasyon özelliklere sahip olduğu ve bu etkileriyle, yukarıda belirtilen hastalıkların önlenmesinde faydalı olabileceği ileri sürülmektedir. Oksidatif ve karbonil stres üzerine MGO'nun muhtemel etkilerini değerlendirmek ve karnozin varlığında, bu etkilerin ne şekilde değişebileceğini araştırmak amacıyla yapılan bu çalışmada; dört gruba ayrılan erkek ratlara 10 gün boyunca intraperitoneal olarak, her gün kg rat ağırlığı başına 1 mi serum fizyolojik (Kontrol grubu), 50 mg MGO (MGO grubu), 200 mg karnozin (Karnozin grubu) ve 50 mg MGO/200 mg karnozin (MGO-Karnozin grubu) uygulandı. Katlardan elde edilen plazma örneklerinde malondialdehit (MDA) ve protein karbonil bileşikleri (PCC) düzeyleri tayin edildi. MGO grubunda bulunan rafların zayıfladıkları ve MGO ile birlikte verilen karnozinin kilo kaybını önemli ölçüde önlediği tespit edildi (p

Investigation of antioxidant properties of carnosine in rats treated with methiglyoxal

Methylglyoxal (MGO), one of the reactive carbonyl compounds, is thought to be a precursor for advanced glycation end products (AGE) which are responsible for disorders such as diabetes mellitus and atherosclerosis. On the other hand carnosine, endogen dipeptid, has been suggested to be useful for preventing the disorders mentioned above due to its antioxidant and antiglycation properties. In this study, four groups of male rats were intraperitoneally treated with daily 1 ml serum physiologic (control group), 50 mg MGO (MGO group), 200 mg carnosine (carnosine group) and 50 mg MGO/200 mg carnosine (MGO-carnosine group), per kg of rat weight, for 10 days in order to investigate the effects of MGO on oxidative and carbonyl stress and also whether these effects may be influenced in the presence of carnosine. The levels of malondialdehyde (MDA) and protein carbonyl compounds (PCC) were measured in plasma samples obtained from these groups. Although weight-lose was observed in MGO given rats, it was prevented in the presence of carnosine (p

PDF

___

1.Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications. Diabetes 1999, 48: 1-8.
2.Dalle-Donne I, Scaloni A, 'Giustarini D, Cavarra E, Tell G, et al Proteins as biomarkers of oxidative/nitrojsative stress in diseases: The contribution of redox proteomics. Mass Spectrom Rev 2005, 24: 55-99.
3.Lyons TJ. Glycation, carbonyl stress, EAGLEs, and the vascular complications of diabetes. Semin Vase Med 2002, 2: 175-189.
4.Kyselova Z, Gajdosik A, Gajdosikova A, Ulicna O, Mihalova D, Karasu C, Stefek M. Effect of the pyridoindole antioxidant stobadine on development of experimental diabetic cataract and on lens protein oxidation in rats: comparison with vitamin E and BHT. Mol Vis. 2005, 11:56-65.
5.Miyata T, Ishikawa N, van Ypersele de Strihou C. Carbonyl stress and diabetic complications. Clin Chem Lab Med. 2003, 41:1150-1158.
6.Kalapos MP. Methylglyoxal in living organ isms. Chemistry, biochemistry, toxicology and biological implications. Toxicol Lett 1999; 110: 145-175.
7.Bonfanti L, Peretto P, De Marchis S, Fasolo A. Carnosine-related dipeptides in the mammal ian brain. Prog Neurobiol 1999, 59: 333-353.
8.Miyata T. Alterations of non-enzymatic bio chemistry in uremia, diabetes, and atheroscle rosis ("carbonyl stress"). Bull Mem Acad Med Belg 2002, 157: 189-196.
9.Hipkiss AR, Brownson C. A possible new role for the anti-ageing peptide carnosine. Cell Mol Life Sci2000;57 747-7 53.
10.Hipkiss AR, Chana H. Carnosine protects proteins against methylglyoxal-mediated modifications. Biochem Biophys Res Commun 1998,248:28-32.
11.Hipkiss AR, Bownson C, Carrier MJ. Carnosine the anti-agening, anti-oxidant dipeptide, may react with protein carbonyl groups. Mech Ageing Dev 2001, 122: 1431-1445.
12.Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1978, 95: 351-358.
13.Reznick AZ, Packer L. Oxidative damage to proteins: Spectrophotometric method for carbonyl assay. Methods Enzymol 1994, 233:357-363.
14.Thornalley PJ. The glyoxalase system: new developments towards functional characteriza tion of a metabolic pathway fundamental to biological life. Biochem J 1990, 269: 1-11.
15.Lo TW, Westwood ME, McLellan AC, Selwood T, Thornalley PJ. Binding and modification of proteins by methylglyoxal under physiological conditions. A kinetic and mechanistic study with N alpha-acetylarginine, N alphaacetylcysteine, and N alpha-acetyllysine, and bovine serum albumin. J Biol Chem 1994, 269:32299-32305.
16.Kalapos MP, Littauer A, de Groot H. Has reactive oxygen a role in methylglyoxal toxicity? A study on cultured rat hepatocytes. Arch Toxicol 1993, 67:369-372.
17.Argirova M, Breipohl W. Comparison between modifications of lens proteins resulted from glycation with methylglyoxal, glyoxal, ascorbic acid, and fructose. J Biochem Mol Toxicol 2002, 16: 140-145.
18.Kang JH. Modification and inactivation of human Cu,Zn-superoxide dismutase by methyl glyoxal Mol Cells 2003, 15: 194-199.
19.Choudhary D, Chandra D, Kale R.K. Influence of methylglyoxal on oxidant enzymes and oxidative damage. Toxicol Lett 1997, 93: 141-152.
20.Golej J, Hoeger H, Radner W, Unfried G, Lubec G. Oral administration of methylglyoxal leads to kidney collagen accumulation in the mouse. Life Sci 1998, 63: 801-807.
21.Thomalley PJ. The clinical significance of glycation. Clin Lab 1999, 45: 263-273.
22.Garibella SE, Sinclair AJ. Carnosine: physiological properties and therapeutic potential,Age Ageing 2000, 29: 207-210.
23.Munch G, Thome J, Foley P, Schinzel R, Riederer P. Advanced glycation endproducts in ageing and Alzheimer's disease. Brain Res Brain Res Rev 1997, 23:134-143.
24.Hipkiss AR, Brownson C, Bertani MF, Ruiz E, Ferro A. Reaction of carnosine with aged pro teins: another protective process? Ann NY Acad Sci 2002, 959: 285-294.
25.Nagaraj RH, Sarkar P, Mally A, Biemel KM, Lederer MO, et al Effect of pyridoxamine on chemical modification of proteins by carbonyls in diabetic rats: characterization of a major product from the reaction of pyridoxamine and methylglyoxal. Arch Biochem Biophys 2002, 402:110-119.
26.Gallant S, Semyonova M, Yuneva M. Carnosine as a potential anti-senescence drug. Biochemistry (Mosc) 2000, 65:866-868.
27.Bogardus SL, Boissonneault GA. Carnosine inhibits in vitro low-density lipoprotein oxidation. Nutr Res 2000, 20: 967-976.
28.Decker EA, Livisay SA, Zhou S.A reevaluation of the antioxidant of purified carnosine. Biochemistry (Mosc) 2000, 28: 1564-1570.
29.Hipkiss AR, Worthington VC, Himsworth DT, Herwig W. Protective effects of carnosine against protein modification mediated by malondialdehyde and hypochlorite. Biochim Biophys Acta 1998, 1380: 46-54.
30.Preston JE, Hipkiss AR, Himsworth DT, Romero IA, Abbott JN. Toxic effects of betaamyloid (25-35) on immortalised rat brain endothelial cell: protection by carnosine, homocarnosine and beta-alanine. Neurosci Lett 1998, 242: 105-108.