Effects of antioxidant stobadine on protein carbonylation, advanced oxidation protein products and reductive capacity of liver in streptozotocin-diabetic rats:: Role of oxidative/nitrosative stress

被引：30

作者：

Cumaoglu, Ahmet ^{[2
]}

Cevik, Cemal ^{[2
]}

Rackova, Lucia ^{[3
]}

Ari, Nuray ^{[4
]}

Karasu, Cimen ^{[1
]}

机构：

[1] Gazi Univ, Dept Med Pharmacol, Fac Med, TR-06500 Ankara, Turkey

[2] Gazi Univ, Dept Med Biochem, Fac Med, TR-06500 Ankara, Turkey

[3] Slovak Acad Sci, Dept Expt Pharmacol, Bratislava, Slovakia

[4] Ankara Univ, Dept Pharmacol, Fac Pharm, TR-06100 Ankara, Turkey

来源：

BIOFACTORS | 2007年 / 30卷 / 03期

关键词：

diabetes; protein oxidation; stobadine; carbonyl; thiol; oxidative stress; nitrosative stress; advanced oxidation protein products; nitrotyrosine; VITAMIN-E; LIPID-PEROXIDATION; PYRIDOINDOLE STOBADINE; CHEMICAL-MODIFICATION; IN-VITRO; COMPLICATIONS; GLYCATION; PEROXYNITRITE; MELLITUS; ALBUMIN;

D O I：

10.1002/biof.5520300304

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Increased oxidative/nitrosative stress is important in the pathogenesis of diabetic complications, and the protective effects of antioxidants are a topic of intense research. The purpose of this study was to investigate whether a pyridoindole antioxidant stobadine (STB) have a protective effect on tissue oxidative protein damage represented by the parameters such as protein carbonylation (PC), protein thiol (P-SH), total thiol (T-SH) and non-protein thiol (Np-SH), nitrotyrosine (3-NT), and advanced oxidation protein products (AOPP) in streptozotocin-diabetic rats. Methods: Diabetes was induced in male Wistar rats by intraperitonal injection of streptozotocin (55 mg/kg). Some of the non-diabetic (control) and diabetic rats treated with STB (24.7 mg/kg/day) during 16 weeks, and the effects on blood glucose, PC, AOPP, 3-NT, P-SH, T-SH and Np-SH were studied. Biomarkers were assayed by enzyme-linked immunosorbent assay (ELISA) or by colorimetric methods. Results: Administration of stobadine to diabetic animals lowered elevated blood glucose levels by similar to 16% relative to untreated diabetic rats. Although stobadine decreased blood glucose, poor glycemic control was maintained in stobadine treated diabetic rats during the treatment period. Biochemical analyses of liver proteins showed significant diminution of sulfhydryl groups, P-SH, T-SH, Np-SH, and elevation of carbonyl groups in diabetic animals in comparison to healthy controls. As a biomarker of nitrosative stress, 3-NT levels did not significantly change by diabetes induction or by stobadine treatment when compared to control animals. However, the treatment with stobadine resulted in a significant decrease in PC, AOPP levels and normalized P-SH, T-SH, Np-SH groups in liver of diabetic animals. Conclusions: The results are in accordance with the pro-oxidant role of chronic hyperglycemia, and the ability of stobadine to attenuate protein oxidation and improving tissue reductive capacity may account, at least partly, for its observed beneficial effects on tissue functions in diabetes.

引用

页码：171 / 178

页数：8

共 33 条

[11]

Kayali R, 2003, EUR J MED RES, V8, P307

[12]

Kyselova Z, 2005, MOL VIS, V11, P56

[13]

LOWRY OH, 1951, J BIOL CHEM, V193, P265

[14]

Mercuri F, 2000, Diabetes Technol Ther, V2, P589, DOI 10.1089/15209150050502014

[15] Pyridoxamine traps intermediates in lipid peroxidation reactions in vivo -: Evidence on the role of lipids in chemical modification of protein and development of diabetic complications [J].

Metz, TO ;

Alderson, NL ;

Chachich, ME ;

Thorpe, SR ;

Baynes, JW .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (43) :42012-42019

[16] Carbonyl stress and diabetic complications [J].

Miyata, T ;

Ishikawa, N ;

de Strihou, CV .

CLINICAL CHEMISTRY AND LABORATORY MEDICINE, 2003, 41 (09) :1150-1158

[17] Malondialdehyde modification of proteins in vitro is enhanced in the presence of acetaldehyde [J].

Mooradian, AD ;

Reinacher, D ;

Li, JP ;

Pinnas, JL .

NUTRITION, 2001, 17 (7-8) :619-622

[18] Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic complications.: Emerging new therapeutical strategies [J].

Pacher, P ;

Obrosova, IG ;

Mabley, JG ;

Szabó, C .

CURRENT MEDICINAL CHEMISTRY, 2005, 12 (03) :267-275

[19] In vivo treatment with stobadine prevents lipid peroxidation, protein glycation and calcium overload but does not ameliorate Ca2+-ATPase activity in heart and liver of streptozotocin-diabetic rats:: comparison with vitamin E [J].

Pekiner, B ;

Ulusu, NN ;

Das-Evcimen, N ;

Sahilli, M ;

Aktan, F ;

Stefek, M ;

Stolc, S ;

Karasu, Ç .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2002, 1588 (01) :71-78

[20] Mechanisms for oxidative stress in diabetic cardiovascular disease [J].

Pennathur, Subramaniam ;

Heinecke, Jay W. .

ANTIOXIDANTS & REDOX SIGNALING, 2007, 9 (07) :955-969

← 1 2 3 4 →