Oxidative Stress and Antioxidant Defense in Relation to the Severity of Diabetic Polyneuropathy and Cardiovascular Autonomic Neuropathy

Abstract

OBJECTIVE—Oxidative stress resulting from enhanced free-radical formation and/or a defect in antioxidant defenses has been implicated in the pathogenesis of experimental diabetic neuropathy. The objective of this study was to evaluate plasma levels of various biomarkers of oxidative stress in diabetic subjects in relation to the presence or absence of polyneuropathy (PN) and/or cardiovascular autonomic neuropathy (CAN). RESEARCH DESIGN AND METHODS—Plasma 8-iso-prostaglandin F2α (8-iso-PGF2α), superoxide anion (O2·−) generation, lag phase to peroxidation by peroxynitrite (ONOO−), vitamin E-to-lipid ratio, and vitamin C were measured in nonsmoking diabetic patients without PN and CAN (PN−/CAN− group; n = 62), in a group with PN but without CAN (PN+/CAN− group; n = 105), in those with both PN and CAN (PN+/CAN+ group; n = 22), and in healthy control subjects (n = 85). RESULTS—All three markers of oxidative stress were significantly increased, and both markers of antioxidant defense were decreased in the PN+/CAN− group compared with the control group (all P < 0.05). PN−/CAN− subjects showed a significant increase compared with control subjects for 8-iso-PGF2α, O2·−, and ONOO− and a decrease for the vitamin E-to-lipid ratio (all P < 0.05). In the PN+/CAN− group, a significant increase compared with the PN−/CAN− group was noted for O2·−, whereas the vitamin E-to-lipid ratio and vitamin C were reduced (all P < 0.05). No significant differences were noted between the PN+/CAN− and PN+/CAN+ groups for each of the five markers of oxidative stress. In multivariate models, O2·− and ONOO− were independently associated with neuropathic deficits, but diabetes duration and triglyceride levels were also independent determinants. CONCLUSIONS—Oxidative stress is enhanced in diabetic patients before the development of PN but to an even higher degree in those with PN, without further significant increase in relation to superimposed autonomic neuropathy. However, apart from oxidative stress, diabetes duration and triglyceride levels are also related to the severity of PN.

Vitamin C in Disease Prevention and Cure: An Overview

“…Some studies report that the role of vitamin C in diabetic neuropathy is not as well pronounced as other antioxidants [175]. Some suggest that the AA levels are significantly low in diabetic polyneuropathy patients [176]. Role of vitamin C and other dietary antioxidants have been reviewed by several authors with controversial findings [177].…”

Hippocampal Neuronal Apoptosis in Rat Offspring Due to Gestational Diabetes

“…Diabetes mellitus is a chronic endogenous stressor that is associated with increased oxidative stress in central nervous system (Ahmadpour et al, 2010;Grillo et al). CNS complications of diabetes mellitus could be mediated through excessive free radicals generation Ahmadpour et al, 2008;Okouchi et al, 2005;Ziegler et al, 2004). Free radicals cause mitochondrial alterations and activated apoptosis by caspase pathways (Russell & Feldman).…”

Alterations of the Giant Pyramidal Neurons (Betz Cells) in Brain Cortex of Rat Offspring Born from Gestational Diabetic Dams: A Morphometric Study

“…CNS complications of diabetes mellitus could be mediated through excessive free radicals generation Okouchi et al, 2005;Ziegler et al, 2004). Free radicals by oxidizing proteins, damaging DNA, and inducing the lipoperoxidation of cellular membranes contribute to increased neuronal death (Hawkins & Davies, 2001).…”