Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia

Abstract

Hyperglycemia causes the autoxidation of glucose, glycation of proteins, and the activation of polyol metabolism. These changes accelerate generation of reactive oxygen species (ROS) and increases in oxidative chemical modification of lipids, DNA, and proteins in various tissues. Oxidative stress may play an important role in the development of complications in diabetes such as lens cataracts, nephropathy, and neuropathy. Glycation reactions, especially Maillard reactions, occur in vivo as well as in vitro and are associated with the chronic complications of diabetes mellitus and aging and age-related diseases by increases in oxidative chemical modification of lipids, DNA, and proteins. In particular, long-lived proteins such as lens crystallines, collagens, and hemoglobin may react with reducing sugars to form advanced glycation end products (AGEs). Recently, we found a novel type of AGE, named MRX, and we found that MRX is a good biomarker for detecting oxidative stress produced during Maillard reaction. We also examined in detail the role of lipid peroxidation reaction in hyperglycemia and found that hexanoyl modification formed by the reaction of oxidized lipids and proteins must be important for oxidative stress. Detailed analyses of the formation mechanism of hexanoyl lysine (HEL) moiety in proteins were conducted, and excretion of HEL into urine was quantified by using LC/MS/MS. Macrophages and neutrophils play an important role in oxidative stress during hyperglycemia, and we determined that oxidatively modified tyrosines are a good biomarker for formation of oxidative stress at an early stage. Immunochemical analyses by application of monoclonal antibodies specific to lipid hydroperoxide-modified proteins produced by polyunsaturated fatty acids including docosahexaenoic acid (DHA) in oxidative stress caused by hyperglycemia were conducted, and the relationship between glycation and lipid peroxidation reactions both by chemical and immunochemical approaches are discussed. Recently, we put much more focus on dietary antioxidants for prevention of diabetic complications. Curcuminoids, the main yellow pigments in Curcuma longa (turmeric), have been used widely and for a long time in the treatment of sprain and inflammation in indigenous medicine. Curcumin is the main component of turmeric, and two minor components are also present as the curcuminoids. Curcuminoids possess antioxidant activity. Protective effects of curcumin (U1) and one of its major metabolites, tetrahydrocurcumin (THU1), have been examined for development of diabetic cataract in 25% galactose-fed SD rats. Through detailed examination of protective mechanisms of THU1, it was found that THU1 showed that scavenger ROS not only formed during hyperglycemia, but also induced antioxidative enzymes including detoxification enzymes such as glutathine S-transferase. THU1 also showed significant increase of glutathione concentration in the cultured rat lens. Glutathione (gamma-glutamylcysteinyl glycine [GSH]) is thought to be an important factor in cellular function and defense against oxidative stress, and we found that dietary GSH suppresses oxidative stress in vivo in prevention of diabetic complications such as diabetic nephropathy and neuropathy.