Oxidative Stress Markers Regulating the Healing of Foot Ulcers in Patients With Type 2 Diabetes
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Abstract: Objective. This study was aimed at identifying factors that affect the healing of foot ulcers among patients with type 2 diabetes, focusing on the evaluation of oxidative stress—one marker of the inflammatory response. Methods. A cross sectional study comprised of 96 subjects who were divided into 6 groups (16 subjects in each group). The groups were classified as non-diabetic control (group I), diabetic subjects without foot ulcer (group II), diabetic subjects with foot ulcers were sub-divided as neuropathic ulcer-noninfected (group III), neuropathic ulcer-infected (group IV), neuroischemic ulcer-noninfected (group V), and neuroischemic ulcer-infected (group VI). Oxidative stress markers such as lipid peroxidation, thiobarbituric acid reactive substance (TBARS), superoxide dismutase (SOD), catalase, G-peroxidase, GS-peroxidase, and plasma total antioxidant status were assayed in the blood samples. Results. Lipid peroxidation increased progressively from group I to group VI subjects (P < 0.001). The TBARS in erythrocyte membrane was higher than in plasma. A progressive decrease of the total antioxidant status in plasma from group III to group VI (P < 0.01) was noted. There was a triggering increase in the antioxidative enzymes SOD and catalase in group V and group VI. Conclusion. There is a high level of lipid peroxidation with insufficient antioxidant enzymes and decreased total antioxidant status in plasma that leads to chronic ulceration and an extended inflammatory reaction. Thus, oxidative stress may be regarded as an important factor in nonhealing diabetic foot ulcers among patients with type 2 diabetes.
Address correspondence to:
Vijay Viswanathan, MD, PhD
M.V. Hospital for Diabetes & Diabetes Research Centre
5 Main Rd., Royapuram
Chennai 600013
India
Phone: +91 44 25954913-15
Email: dr_vijay@vsnl.com
Oxidative damage due to the endogenous production of oxidative reactive oxygen species (ROS) or toxic oxygen free radicals by mitochondria is a common and ubiquitous form of oxidative stress in most mammalian cells. It is one of the classic events in the pathogenesis of diabetes and its complications. Intracellular hyperglycemia is the primary initiating event in the formation of both intracellular and extracellular advanced glycation end products (AGE).1 Plasma proteins modified by AGE precursors bind to AGE receptors on endothelial cells, mesangial cells, and macrophages, which induces receptor-mediated production of reactive oxygen species.
One of the most common complications of diabetes in the lower extremity is the diabetic foot ulcer.2 Diabetic foot infection is a common cause for hospital admission among patients with diabetes in India.3 Several studies have compared the oxidative stress between diabetic4,5 and nondiabetic subjects and among diabetic patients with and without complications.6,7 The present study was undertaken to assess the peroxidative damage due to secondary complications in diabetes, namely foot ulcers, in comparison with diabetic and nondiabetic controls. This study focuses on the Asian-Indian ethnic group for which there are very little data available.
The main focus of this study was to evaluate the biochemical and molecular markers of the inflammatory response by evaluating free radical production and the scavenging antioxidant status in blood, and to analyze whether neuropathy, ischemia, ulcer, and infection contribute to the reactive oxygen species production and indicate oxidative stress.
Methods
Study subjects and characteristics. A total of 96 subjects (59 male, 37 female) from M.V. Hospital for Diabetes and Diabetes Research Center (Royapuram, Chennai), a large referral center for diabetes in southern India, were categorized into 6 groups of 16 members each.
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