JOURNAL OF MEDICINAL FOOD J Med Food 11 (3) 2008, 525–532 © Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition DOI: 10.1089/jmf.2006.0230 Therapeutic Effects of Teucrium polium Extract on Oxidative Stress in Pancreas of Streptozotocin-Induced Diabetic Rats A. Ardestani, R. Yazdanparast, and Sh. Jamshidi Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran ABSTRACT Increased oxidative stress is a widely accepted factor in the development and progression of diabetes and its complications. In this study, we evaluated the antioxidative potential of Teucrium polium (Family Lamiaceae) aqueous ex- tract for protecting rat pancreatic tissue against streptozotocin (STZ)-induced oxidative stress. Diabetes was induced in rats by intraperitoneal injections of at a single dose of STZ at 40 mg/kg. The crude extract (equivalent to 0.5 g of plant powder/kg of body weight) was administered orally (intragastrically) to a group of STZ diabetic rats for 30 consecutive days. Changes in antioxidant status were evaluated by determining catalase (CAT) and superoxide dismutase (SOD) activities and the level of reduced glutathione (GSH) in pancreatic tissue. In addition, serum nitric oxide (NO) concentration, pancreatic tissue mal- ondialdehyde (MDA) (an index of lipid peroxidation) level, and reliable markers of protein oxidation such as protein carbonyl content (PCO) and advanced oxidation protein products (AOPP) were also determined. Under diabetic conditions, blood glu- cose level, serum NO concentration, and pancreatic MDA, PCO, and AOPP levels were all increased. The diabetic rats also exhibited pancreatic GSH depletion along with significant reductions in activities of CAT and SOD. Rats treated with T. polium extract had significantly higher GSH levels along with enhanced CAT and SOD activities in pancreatic tissue. In ad- dition to suppressed blood glucose levels, serum NO, pancreatic MDA, PCO, and AOPP levels were all lower than in the di- abetic group. Our results strongly support the proposal that antioxidative activity of T. polium occurs by quenching the ex- tent of lipid and protein oxidation. Based on these observations, it is concluded that T. polium may have protective effect(s) on pancreatic tissue in STZ-induced oxidative stress due to its high antioxidative potential. KEY WORDS: • antioxidant • diabetes • oxidative stress • Teucrium polium 525 INTRODUCTION O XIDATIVE STRESS refers to the serious imbalance be- tween the production of free radicals and antioxidant defense system, which results in functional tissue damages. 1 There is growing evidence that in people with diabetes ex- cess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further ex- acerbates the development and progression of diabetes and its complication. 2,3 There is evidence to suggest that oxida- tive stress in the pathogenesis of diabetes is induced not only by oxygen free radical generation due to nonenzymatic pro- tein glycosylation, the polyol pathway, and autooxidation of glucose, but also by changes in the tissue content and ac- tivity of antioxidant defense systems. 3,4 Streptozotocin (STZ) is an agent widely applied to cause experimental diabetes because of its ability to selectively tar- get and destroy pancreatic islet -cells. The glucose moiety of STZ allows preferential uptake of the toxin into -cells via the glucose transporter, GLUT-2. 5 STZ is an alkylating agent that causes DNA strand breaks and activates poly(ADP-ribose) synthetase. Activation of poly(ADP-ribose) synthetase induces rapid and lethal depletion of NAD in -cells. 6 Its diabetogenic action has also been attributed to the production of nitric ox- ide (NO) 7 and reactive oxygen species (ROS). 8 Synergistic ac- tion of both NO and ROS may contribute to DNA fragmen- tation and other deleterious changes caused by STZ. NO and ROS can act separately or form the highly toxic peroxynitrite. Therefore, intracellular antioxidants or NO scavengers sub- stantially attenuate STZ toxicity. 6 Intracellular antioxidants in- clude low-molecular-weight scavengers of oxidizing species and enzymes that degrade superoxide and hydroperoxides. Such antioxidant systems prevent the uncontrolled formation of free radicals and activated oxygen species or inhibit their reaction with biological structures. 9 The efficiency of this de- fense mechanism is altered in diabetes, and therefore free rad- icals will accumulate in the system, finally producing de- structive effects in many vital tissues. 10 Protective effects of exogenously administered antioxidants have been extensively studied in diabetic animal models in recent years, and benefi- cial effects have demonstrated of numerous antioxidants, mainly from plant sources. 11 It has been documented that an- Manuscript received 6 December 2006. Revision accepted 8 February 2007. Address reprint requests to: R. Yazdanparast, Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran, E-mail: yazdan@ibb.ut.ac.ir