Research Article Open Access Salahuddin and Katary, J Appl Pharm 2017, 9:2 DOI: 10.21065/1920-4159.1000239 Research Article OMICS International Journal of Applied Pharmacy J o u r n a l o f A p p li e d P h a r m a c y ISSN: 1920-4159 Volume 9 • Issue 2 • 1000239 J Appl Pharm, an open access journal ISSN: 1920-4159 Effects of Grape Seed Proanthocyanidin Extract in Attenuating Diabetic Complications in Streptozotocin-Induced Diabetic Rats Ahmad Salahuddin 1 * and Mohamed Katary 2 1 Department of Biochemistry, Damanhour University, Egypt 2 Department of Pharmacology and Toxicology, Damanhour University, Egypt Abstract Oxidative stress is a major cause for development and progression of diabetic mediated peripheral and central complications. The aim of this work is to evaluate the role of Grape Seed Proanthocyanidin (GSPE) extract in attenuating diabetic complications. Forty-fve adult male Wistar rats were divided into three groups. Control, non-treated diabetic and diabetic rats treated with GSPE. Diabetes was induced by intraperitoneal injection of streptozotocin. After eight weeks; urine, blood and brain, heart, kidneys, liver tissue homogenate parameters were evaluated. The results showed a reduction in both renal and hepatic function in non-treated group as well as an elevated serum infammatory markers (TNF-α, hs-CRP and IL-6). In addition, there were an elevation in both serum and different tissue homogenate oxidative stress parameters (SOD, GPx, Catalase and MDA). Treatments with GSPE improve the oxidative stress status in different tissue and improve renal and kidney functions. These fnding suggested that GSPE is effective as adjuvant therapy for protection from diabetic complications as well as its potent antioxidant and anti-infammatory activity. Keywords: Proanthocyanidins; Oxidative stress; Infammatory markers; Glutathione peroxidase; Catalase; Malondialdehyde; Superoxide dismutase; TNF-α; hs-CRP; IL-6 Introduction Diabetes Mellitus (DM) is an important metabolic disorder with a global prevalence estimated to be 9% among adults [1] and 15.4% among adult Egyptian population [2]. In 2012, an estimated 1.5 million deaths were directly caused by diabetes. More than 80% of diabetes deaths occur in low- and middle-income countries [3]. Diabetes is the eleventh most important cause of premature mortality in Egypt, and is responsible for 2.4% of all years of life lost. Similarly, diabetes is the sixth most important cause of disability burden in Egypt [4]. Diabetic macrovascular complication is subjected to a high incidence of vascular diseases such as stroke, myocardial infarction, and peripheral vascular diseases [5]. Pathological changes in major blood vessels leading to functional and structural abnormalities in diabetic vessels include endothelial dysfunction, reduced vascular compliance, and atherosclerosis. Almost half of diabetic patients die of cardiovascular disease [6]. DM is conjoined with the presence of microvascular complications. Tis complications lead to nephropathy, retinopathy, and peripheral neuropathy [7]. Diabetic peripheral neuropathy is the major reason for loss of protective limb mechanical sensations, traumatic ulcerations and therefore amputations [8]. Diabetic retinopathy is an important cause of blindness, and occurs because of long-term accumulated damage to the small blood vessels in the retina. 1% of global blindness can be attributed to diabetes [9]. DM is the major cause of end-stage kidney diseases. About 67% of diabetic patients have nephropathy [10]. Oxidative stress is a widely accepted participant in the development of DM and progression of its complications [11]. Excessively high levels of free radicals cause damage to cellular proteins, membrane lipids and nucleic acids, and eventually cell death [12]. Moreover, DM is accompanied by elevated lipid peroxidation, reduced antioxidant enzymes activities, as well as, altered glutathione redox situation [13]. During diabetes, constant hyperglycemia stimulates glycosylation of circulating and cellular protein. It may start a chain of auto-oxidative *Corresponding author: Ahmad Salahuddin, Biochemistry Department, Faculty of Pharmacy, Damanhour University, Egypt, Tel: +20 45 3368069; E-mail: ahmad.dr@live.com Received: February 01, 2017; Accepted: March 02, 2017; Published: March 07, 2017 Citation: Salahuddin A, Katary M (2017) Effects of Grape Seed Proanthocyanidin Extract in Attenuating Diabetic Complications in Streptozotocin-Induced Diabetic Rats. J Appl Pharm 9: 239. doi: 10.21065/1920-4159.1000239 Copyright: © 2017 Salahuddin A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. reactions which in turn lead to formation and aggregation of advanced glycosylation end products (AGEs) in tissue proteins. AGEs can promote tissue damage by free radicals [14]. Grape Seed Proanthocyanidin Extract (GSPE) is a natural product containing a mixture of biologically active polyphenolic favonoids [15]. GSPE has marked properties against free radicals and oxidative stress [16]. Tis antioxidant activity is higher than that of vitamin E, C and β-carotene [17]. GSPE have been reported to possess a variety of potent properties, including anti-nonenzymatic glycation, anti- infammation, anti-atherosclerosis, anti-tumor, and so on immune function modulator, antithrombotic agent, and LDL oxidation inhibitor [18]. It has a protective efect on various forms of cardiac disorders, reduce hypoxic-ischemic brain injury, prevent diabetic nephropathy from progressing, and protect gastric mucosa [13]. Te aim of this study was to investigate the biochemical changes and the protective efects of GSPE against macrovascular and microvascular complications of DM induced in rats by STZ. Methods Chemicals GSPE was obtained as Gervital ® capsules, each containing 150 mg GSPE, (MEPACO, Egypt). STZ was obtained from Sigma-Aldrich Chemical Co. (St. Louis, USA).