Research Article Resveratrol Ameliorates the Components of Hepatic Inflammation and Apoptosis in a Rat Model of Streptozotocin-Induced Diabetes Mehmet Bilgehan Pektas ¸, 1 G€ okhan Sadi, 2 * Halit Bugra Koca, 3 Yasemin Yuksel, 4 Ayhan Vurmaz, 3 Tulay Koca, 5 and Murat Tosun 4 1 Department of Medical Pharmacology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey 2 Department of Biology, K. € O. Science Faculty, Karamanoglu Mehmetbey University, Karaman, Turkey 3 Department of Medical Biochemistry, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey 4 Department of Histology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey 5 Department of Medical Laboratory, Ataturk Vocational School of Health Services, Afyon Kocatepe University, Afyonkarahisar and Karaman, Turkey Strategy, Management and Health Policy Enabling Technology, Genomics, Proteomics Preclinical Research Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Clinical Development Phases I-III Regulatory, Quality, Manufacturing Postmarketing Phase IV ABSTRACT Trans-resveratrol has a wide range of biological effects that reflect its antioxidant, anti- inflammatory, anticarcinogenic and cardioprotective properties. This study was conducted to elucidate the potential role of resveratrol on hepatic inflammation and the apoptotic pathway components Bcl-2, Bax and p53 in a streptozotocin (STZ)-induced rat model of diabetes mellitus. Inflammatory and apopto- tic biomarkers indicated a reduction in hepatic erythropoietin (1.26-fold) and increased asymmetric dime- thylarginine (3.9-fold), visfatin (1.6-fold), inflammatory interleukins and TNF–a contents (approximately twofold each) in the diabetic animals. Induction of inducible nitric oxide synthase gene (2.04-fold) and protein expression (1.24-fold) was also observed. Immunohistochemical studies showed enhancement of the apoptotic biomarkers Bax and p53 in diabetic animals. STZ-induced diabetic male Wistar rats were treated with resveratrol (20 mg/kg/day i.p.). Resveratrol succeeded to recover most of these inflammatory and apoptotic elements. Therefore, inflammatory and apoptotic pathways were proved to be affected by STZ-induced diabetes in several aspects and resveratrol might contribute hepatoprotective effects as evi- denced from this study. Drug Dev Res 77 : 12–19, 2016. V C 2016 Wiley Periodicals, Inc. Key words: Diabetes; resveratrol liver; inflammation; Bax; Bcl-2; p53 INTRODUCTION Diabetes mellitus (DM) is a state of hyperglycemia caused by either insulin deficiency or resistance. DM-related hyperglycemia induces oxidative stress which in turn affects inflammatory and apoptotic mech- anisms in several tissues [Omoruyi et al., 2013; Zheng et al., 2015]. Visfatin, a pro-inflammatory adipokine *Correspondence to: G€ okhan Sadi, Department of Biol- ogy, K. € O. Science Faculty, Karamanoglu Mehmetbey University, Karaman, Turkey. E-mail: sadi@kmu.edu.tr Conflict of interest: The authors declare no conflict of interest. Received 4 October 2015; Accepted 9 December 2015 Published online in Wiley Online Library (wileyonlinelibrary. com). DOI: 10.1002/ddr.21287 V C 2016 Wiley Periodicals, Inc. DRUG DEVELOPMENT RESEARCH 77 : 12–19 (2016) DDR