cell biochemistry and function Cell Biochem Funct 2005; 23: 421–426. Published online 12 November 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1027/cbf.1168 Effects of simvastatin treatment on oxidant/antioxidant state and ultrastructure of streptozotocin-diabetic rat lung Gu ¨lgu ¨n Ozansoy* 1 , Cengiz Gu ¨ven 2 , Asl Ceylan 1 , Belgin Can 2 , Fu ¨gen Aktan 3 , Eser O ¨ z 4 and Bilge Go ¨nu ¨l 4 1 AnkaraUniversity, Faculty of Pharmacy, Department of Pharmacology, Tandog ˘an, Ankara, Turkey 2 Ankara University, Faculty of Medicine, Department of Histology–Embryology, Shhye, Ankara, Turkey 3 AnkaraUniversity, Faculty of Pharmacy, Department of Biochemistry, Tandog ˘an, Ankara, Turkey 4 Gazi University, Faculty of Medicine, Department of Physiology,Bes¸evler, Ankara,Turkey In the present study, we investigated the effects of simvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhi- bitor, on lipid metabolism, lipid peroxidation, antioxidant enzyme activities and ultrastructure of diabetic rat lung. Diabetes was induced by a single injection of streptozotocin (45 mg kg 1 , i.p.). After 8 weeks induction of diabetes, some control and diabetic rats were treated with simvastatin (10 mg kg 1 rat day 1 ; orally) for 4 weeks. Diabetes resulted in significantly high levels of blood glucose and plasma lipids. Malondialdehyde levels were unchanged after 12-week-old diabetic rats, whereas catalase activity significantly decreased in the lung. Glutathione peroxidase activity and nitric oxide level were significantly elevated in the diabetic lung. Histological analysis of the diabetic lung revealed some deterioration in the structure. Simvas- tatin treatment reduced plasma lipid levels and partially decreased the severity of hyperglycaemia. Catalase, glutathione peroxidase activities and nitric oxide levels were partially restored and accompanied by improved structure in diabetic lung by the simvastatin treatment. These results suggest that structural disturbances and alteration of antioxidative enzyme acti- vities occurred in diabetic lung. Simvastatin treatment may provide some benefits in the maintenance of antioxidant status and structural organization of diabetes-induced injury of lung. Copyright # 2004 John Wiley & Sons, Ltd. key words — catalase; glutathione peroxidase; lung; malondialdehyde; simvastatin; STZ-diabetes INTRODUCTION Reactive oxygen species (ROS) are well characterized mediators of cell and tissue injury. 1 Generally, cells defend themselves from ROS and other toxic oxygen species by a variety of mechanisms including none- nzymic and enzymic defence systems. 2 An ineffective scavenging capacity of antioxidant systems may play an important role in determining the degree of oxida- tive stress. 3 The diabetic state itself causes oxidative stress via autooxidation of glucose, protein glycation and due to increased lipid peroxidation through quan- titative and qualitative changes in lipid metabolism. 4,5 The lung contains a glucose transport system that is stimulated by insulin, so that diabetes may have effects on glucose utilization and lead to disturbances of the lung. 6 It is known that diabetes causes mild functional abnormalities and some structural modifications in pneumocytes but investigations of the role of diabetes- induced oxidative stress on the pulmonary system are few. 7,8 Simvastatin is a 3-hydroxy-3-methyl-glutaryl (HMG- CoA) reductase inhibitor which is widely used in cholesterol-lowering therapy including diabetic patients. 9 HMG-CoA reductase inhibitors inhibit both synthesis of cholesterol and the synthesis of isopre- noids from mevolanate, which have an essential role in proliferation, migration and signalling of cells. 10 Furthermore the possible antioxidant role of HMG- CoA reductase inhibitors has also been studied in the cardiovascular system but it is not clearly known in lung. Thus we designed experiments to examine (i) Received 13 August 2004 Revised 19 April 2004 Copyright # 2004 John Wiley & Sons, Ltd. Accepted 27 April 2004 * Correspondence to: Gu ¨lgu ¨n Ozansoy, Ankara University, Faculty of Pharmacy, Department of Pharmacology, 06100, Tandog ˘an, Ankara, Turkey. Tel: (90) 312 212 68 05 Ext. 2224. Fax: (90) 312 213 10 80. E-mail: ozansoy@pharmacy.ankara.edu.tr