ACTA SCIENTIFIC NUTRITIONAL HEALTH Volume 3 Issue 6 June 2019 Review Article Allicin as Antioxidant: Possible Mechanisms for the Control of Diabetes-Induced Atherosclerosis Lina N Tamimi1* and Hayder A.AL-Domi2 1Department of medicinal chemistry and pharmacology, Faculty of pharmacy, University of Petra, Amman, Jordan 2Professor of Dietetics, Department of Nutrition and Food Technology, Faculty of Agriculture, The University of Jordan, Amman, Jordan *Corresponding Author: Lina N Tamimi, Department of medicinal chemistry and pharmacology, Faculty of pharmacy, University of Petra, Amman, Jordan. Received: April 02, 2019; Published: May 09, 2019 Abstract mitochondrial reactive oxygen species production (ROS), intracellular advanced glycation end-products formation and activation Diabetic atherosclerosis is strongly developed by oxidative stress and inflammation. Intracellular hyperglycemia promotes density lipoprotein, and insulin resistance. In addition, they inhibit the activation of AMP-protein kinase and adiponectin, decrease of protein kinase C. ROS directly increase the expression of inflammatory and adhesion factors, the formation of oxidized-low endothelial nitric oxide synthase activity, which accumulatively accelerate and progress atherosclerosis. Allicin is one of the main active components in garlic and exerts several therapeutic and antioxidant activity effects via attenuating superoxide production considered as a natural component that may have a valuable preventive role in diabetes -induced atherosclerosis. and limiting inflammation and fibrogenesis. According to the role of oxidative stress within the diabetic complications, Allicin is Keywords: Diabetes; Reactive Oxygen Species; Allicin; Atherosclerosis Abbreviations disease is accelerated associated with worse outcomes as diabetes - DM: Diabetes Mellitus; ROS: Reactive Oxygen Species; AMP-Protein matory cells, and plaque necrosis [2]. Kinase: Adenosine Monophosphate-Activated Protein Kinase; CVD: mellitus increases the risk of atherosclerosis, infiltration of inflam Cardiovascular Disease; GDM: Gestational Diabetes Mellitus; ECM: There are several factors that play great role in pathogenesis - of diabetes such as oxidative stress and hyperlipidemia leading to Extracellular Matrix; NFκB: Nuclear Factor Kappa-Light-Chain-En high risk of complications [3]. Introductionhancer of Activated B Cells; RAS: Renin–Angiotensin-System. Classification of diabetes - - Diabetes mellitus (DM) is defined as a chronic endocrine het cemia, this is due to either insulin secretion impairment, defective Diabetes• Type can 1 be diabetes: classified into the following general categories: erogeneous metabolic disorder, DM is characterized by hypergly [1]. Due to autoimmune β-cell destruction, • usuallyType 2 leadingdiabetes: to absolute insulin deficiency. insulin efficiency or both The chronic hyperglycemia of diabetes is associated with long- secretion frequently on the background of insulin resistance. Due to a progressive loss of β-cell insulin term microvascular and macrovascular complications combined • Gestational diabetes mellitus (GDM): Diabetes diagnosed with a high risk of cardiovascular disease (CVD). Patients with in the second or third trimester of pregnancy that was not diabetes mellitus (DM) have an over tenfold risk for cardiovascu- clearly overt diabetes prior to gestation. lar disease during their lifetime, the progression of cardiovascular Citation: Lina N Tamimi and Hayder A.AL-Domi. “Allicin as Antioxidant: Possible Mechanisms for the Control of Diabetes-Induced Atherosclerosis". Acta Scientific Nutritional Health 3.6 (2019): 22-28. Allicin as Antioxidant: Possible Mechanisms for the Control of Diabetes-Induced Atherosclerosis 23 • been noted to contribute in oxidative stress promotion through monogenic diabetes syndromes such as neonatal diabetes free radical generation and suppression of the antioxidant defense Specific types of diabetes due to other causes, e.g., and maturity-onset diabetes of the young, diseases of the suppression in various tissues, which further exacerbate oxidative systems, via antioxidant enzymes and non-enzymatic antioxidants and drug- or chemical-induced diabetes such as with stress. This explains why diabetic persons tend to have more exocrine pancreas such as cystic fibrosis and pancreatitis, glucocorticoid use, in the treatment of HIV/AIDS, or after oxidative cell and organism environments than healthy individuals, organ transplantation (Table 1), [4]. oxidative stress plays important role in the development of vascular complications in diabetes particularly type 2 diabetes [6]. DM type DM type description According to epidemiological studies, diabetic mortalities can A result of pancreatic beta cell destruction combined with insulin be explained by progression of severed vascular diseases other Type 1 diabetes than hyperglycemia. Recently, evidences have supported the role of to an autoimmune process and beta cell oxidative stress in type 1 and type 2 diabetes pathogenesis, in dia- deficiency. This form includes cases due destruction with unknown epidemics. betes, free radicals are formed by: rapid lipid peroxidation, glucose Predominant insulin resistance with Type 2 diabetes oxidation and non-enzymatic glycation of proteins that leads to Gestational insulin deficiency and secretory defects. in insulin resistance [7]. In addition, apolipoprotein component of diabetes mellitus recognition during pregnancy. damage of enzymes, cellular metabolic pathways and also increase Glucose intolerance with onset or first to hydroxyl radical that controls and accelerate oxidative damage forms of diabetes or diabetes associated LDL spontaneously forms insoluble oxidized aggregates of fat due as one of diabetic complication. Uncommonwith other conditions, diseases genetically or drug use. defined It also includes latent autoimmune In diabetes mellitus, mitochondria are considered as main diabetes in adults (LADA); the term used to source of oxidative stress, during oxidative metabolism in mito- types describe the small number of people with Other specific apparent type 2 diabetes who appear to and the remaining oxygen is transformed to oxygen free radicals have immune-mediated loss of pancreatic chondria, a component of the utilized oxygen is reduced to water, beta cells. which is an important ROS that is converted to ONOO, OH and H2O2 [8]. Table 1 During the production of ATP by oxidative phosphorylation in Oxidative stress in diabetes: DM Milletus classification 2 is re- Similar to numerous other health conditions, oxidative stress duced to superoxide O2 - has been widely linked with the incidence of diabetes mellitus. the mitochondrial electron transport chain, 1–5% of the O – radicals, which can be converted by an Several studies have approved that oxidative stress is a key element or react with NO to form peroxynitrite. Excess ROS production or in diabetes development and its complications progression. In line tioxidant enzymes to hydrogen peroxide, hydroxyl free radicals, with this view, oxidative stress was proposed as a major participant stress, which occurs in various pathologies [9]. in the pathophysiology of diabetes and its complications. Oxidative insufficient antioxidant activity lead to mitochondrial oxidative stress occurs when there is an abnormal distortion in the redox Diabetes-induced excessive ROS production and balance of the cell, resulting in vital biomolecules and structures atherosclerosis incidence damage such as DNA, proteins and lipids, as it compromises in The development of diabetes-related atherosclerosis follows the both; insulin secretion and insulin action . same histologic course as atherosclerosis in nondiabetic patients, atherosclerosis is accelerated in both type 1 and type 2 diabetes. Reactive oxygen species (ROS) do not[5] only promote the onset The hallmark of diabetes is the presence of hyperglycemia. This of diabetes but also exacerbates its associated complications. includes endothelial injury, smooth muscle cell proliferation, Experimental evidence implicates the role of in impaired beta- cell function caused by autoimmune reactions, cytokines and foam cell development and infiltration, platelet activation, and increased inflammation. Increased endothelial permeability leads inflammatory proteins in type 1 diabetes. Also, hyperglycemia has Citation: Lina N Tamimi and Hayder A.AL-Domi. “Allicin as Antioxidant: Possible Mechanisms for the Control of Diabetes-Induced Atherosclerosis". Acta Scientific Nutritional Health 3.6 (2019): 22-28. Allicin as Antioxidant: Possible Mechanisms for the Control of Diabetes-Induced Atherosclerosis 24 to intensive low-density lipoproteins (LDL) retention that interact Diabetes mellitus and atherosclerosis share the same oxidative with the underlying extracellular matrix (ECM) which retains the stress and mitochondrial pathologies, hyperglycemia increases LDL in the vessel wall where oxidation by reactive oxygen species ROS production by driving mitochondria toward increased oxygen use and increased redox potential. the overlying endothelial cells to upregulate cellular adhesion (ROS) is spontaneously occurring. The oxidized LDL stimulates molecules, chemotactic proteins, growth factors, and inhibit nitric In addition, hyperglycemia increases the mutation rate of nu- oxide (NO) production. These processes activate monocytes and clear DNA because exposure to oxygen radicals is increased. The mechanism of ROS induced breaks in nuclear DNA strands may include an increase