Introduction
Diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, insulin action or both. Insulin deficiency in turn leads to chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism (Kumar et al., 2011).
During diabetes, failure of insulin-stimulated glucose uptake by fat and muscle cause glucose concentration in the blood to remain high, consequently glucose uptake by insulin-independent tissue increases. Increased glucose flux both enhances oxidant production and impairs antioxidant defenses by multiple interacting non-enzymatic, enzymatic and mitochondrial pathways (Klotz 2002; Mehta et al., 2006). These include activation of protein kinase C isoforms (Inoguchi et al., 2000), increased hexosamine pathway (Kaneto et al., 2001), glucose autoxidation (Brownlee, 2001), increased methylglyoxal and advanced glycation end-product (AGEs) formation (Thornalley, 1998) as well as increased polyol pathway flux ( Lee and Chung, 1999)
. These seemingly different mechanisms are the results of a single process-that is, overproduction of superoxide by the mitochondrial electron transport system (Tushuizen et al., 2005). This hyperglycaemia-induced oxidative stress ultimately results in modification of intracellular proteins resulting in an altered function and DNA damage, activation of the cellular transcription (NFK B), causing abnormal changes in gene expression, decreased production of nitric oxide, and increased expression of cytokines, growth factors and pro-coagulant and pro-inflammatory molecules (Palmer et al., 1988; Evans et al., 2002; Klotz, 2002; Taniyama and Griendling, 2003). Oxidative stress is responsible for molecular and cellular tissue damage in a wide spectrum of human diseases (Halliwell, 1994), amongst which is diabetes mellitus. Diabetes produces disturbances of lipid profiles, especially an increased susceptibility to lipid peroxidation (Lyons, 1991), which is responsible for increased incidence of atherosclerosis (Guigliano et al.,1996), a major complication of diabetes mellitus . An enhanced oxidative stress has been observed in these patients as indicated by increased free radical production, lipid peroxidation and diminished antioxidant status (Baynes, 1991).
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