Effects of pioglitazone on hyperglycemia-induced alterations in antioxidative system in tissues of alloxan-treated diabetic animals.
Hyperglycemia not only generates reactive oxygen species but also attenuates antioxidant mechanisms creating a state of oxidative stress. Oxidative stress is thought to play a crucial role in pathogenesis of chronic diabetic complications. Pioglitazone is a new oral antidiabetic agent, a potent inhibitor of glycation and potent antioxidant. In the present study, normoglycemic and alloxan-induced diabetic rabbits were treated with pioglitazone (1 mg/kg daily) for 4 and 8 weeks. At the end, glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione (GSH) and protein carbonyl groups (PCG) were evaluated in homogenates of liver and kidney. Chronic hyperglycemia caused a marked increase in oxidative processes and some changes in activity of antioxidants. In liver, diabetic vs. control values (mean+/-S.E.M; P<0.05) for GSH-Px were 181.0+/-5.4 vs. 203.1+/-1.9 and 187.4+/-6.6 vs. 240.9+/-18.8mU/mg protein. Pioglitazone treatment for 8 weeks affected GSH-Px activity in diabetic liver (261.5+/-7.3 mU/mg protein). In diabetic kidney, GSSG-R activity (20.6+/-1.6 vs. 32.4+/-1.5 and 23.6+/-0.6 vs. 36.3+/-0.3 mU/mg protein) and GSH level (16.6+/-0.5 vs. 23.2+/-0.9 and 17.9+/-0.5 vs. 23.2+/-0.6 nmol/mg protein) were diminished, while PCG level (0.32+/-0.03 vs. 0.11+/-0.02 and 0.35+/-0.03 vs. 0.16+/-0.03 nmol/mg protein) was elevated. In diabetic kidney, pioglitazone restored to control values GSSG-R activity (34.4+/-1.4 and 30.6+/-0.1 mU/mg protein) as well as GSH (25.5+/-1.2 and 21.6+/-0.5 nmol/mg protein) and PCG (0.16+/-0.01 and 0.19+/-0.02 nmol/mg protein) levels. The present study showed that pioglitazone reduced to some extent the oxidative stress enhanced by chronic hyperglycemia.
Gumieniczek
Anna
A
Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, 20-093 Lublin, Poland. gumieni@asklepios.am.lublin.pl
D000496:Alloxan / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy* / Q000209:etiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D000077205:Pioglitazone; D011817:Rabbits; D045162:Thiazolidinediones / Q000627:therapeutic use*
D000975:Antioxidants; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000496:Alloxan; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; D000077205:Pioglitazone