Evaluation of oxidative stress markers in pathogenesis of diabetic neuropathy

Abstract

Experimental evidences suggest that hyperglycaemia-induced overproduction of reactive oxygen species and subsequent damage to proteins, lipids and DNA may play a key role in the development of distal symmetric polyneuropathy (DSPN)—the most common complication of diabetes mellitus. The study population consisted of 51 individuals aged 52–82 years classified into 3 groups: 16 patients diagnosed with type 2 diabetes mellitus (T2DM) with DSPN, 16 T2DM patients without DSPN and 19 control subjects without diabetes and neuropathy. The study was conducted to determine the activity of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant status (TAS) in the examined groups. An alkaline comet assay was used to determine the extent of DNA damage of oxidized purines as glicosylo-formamidoglicosylase (Fpg) sites, and oxidized pyrimidines as endonuclease III (Nth) sites. A significant decrease of SOD (P < 0.05), GPX (P < 0.05) and nonsignificant decrease of CAT (P > 0.05), and TAS status (P > 0.05) were seen in T2DM patients with neuropathy compared to T2DM patients as well as controls. T2DM patients with or without neuropathy revealed significantly lower (P < 0.05) plasma concentration of nitrous oxide compared to the control subjects. Endogenous level of oxidative DNA damage in T2DM patients with DSPN was significantly higher compared both to the controls and T2DM patients without DSPN (P < 0.001). Moreover, lymphocytes isolated from T2DM patients with DSPN were more susceptible to oxidative DNA lesions induced by hydrogen peroxide than from T2DM patients without DSPN (P < 0.001). Our results confirm hypothesis that oxidative stress may play a substantial role in the development and progression of diabetic distal symmetric polyneuropathy.

Risk Factors and Comorbidities in Diabetic Neuropathy: An Update 2015

“…Secondary risk factors are smoking and prediabetes [1,21,60,63]. Platelet activation [79][80][81][82], oxidative stress [65][66][67][68][69][70][71][72][73][74], low vitamin D [83,84], insulin resistance [58], and genetic factors [100][101][102][103][104][105][106] play another supplementary role, but, for the time being, there are limited options for intervention. A suggestion for targeting insulin resistance originates from the study by Pop-Busui et al, showing that reduced incident DSPN is less frequent in T2D patients receiving insulin-sensitizing oral agents (66%) than in those receiving insulinproviding treatment (66% vs. 72%, respectively, p = 0.02) [155].…”

“…For example, lower values of reduced glutathione and reduced glutathione/oxidized glutathione ratio in association with DSPN have been reported [69]. Lower plasma concentrations of nitric oxide and higher endogenous oxidative DNA damage in T2D patients with DSPN have also been observed [70]. Bierhaus et al have reported increased plasma methylglyoxal concentrations in association with painful DSPN [71].…”

Antioxidant defenses in diabetes mellitus: a clinical and molecular approach

“…However, in a recent clinical study, TAC was not significantly decreased even in the presence of SOD and GPX depletion [63]. It is possible that this discrepancy could be due to different clinical stages of the patients from the two studies.…”

Dysfunction of the lower gastrointestinal tract as a complication of diabetes — a problematic issue in the diabetic care

“…In research conducted by Takuma et al it was shown that blocking RAGE receptors in mice resulted in reduced frequency of nerve complications [21]. Oxidative stress, which is greatly increased in diabetes, is currently considered an important factor in pathogenesis of gastrointestinal complications [9,22]. Disorders in hexosamine and protein kinase C (PKC) transformation pathways also play an important role in RONS production [7].…”