Alterations in enzymatic antioxidant defence in diabetes mellitus − a rational approach

Szaleczky, Erika; Prechl, József; Fehér, János; Somogyi, Anikó

doi:10.1136/pgmj.75.879.13

Cited by 85 publications

(59 citation statements)

References 38 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Results of other studies concerning GPx activity in HT subjects are contradictory showing both increased and decreased activity of the enzyme [23]. The same conclusion can be made regarding review of diabetes mellitus studies [ 24,25]. Although GPx1 remained unchanged, GR activity increased significantly in HT group.…”

Section: Discussionsupporting

confidence: 62%

Glutathione concentration, glutathione peroxidase and glutathione reductase activity in elderly patients with type II diabetes compared to hypertensives

Rybka

Kupczyk

Kędziora–Kornatowska

et al. 2010

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 62%

Glutathione concentration, glutathione peroxidase and glutathione reductase activity in elderly patients with type II diabetes compared to hypertensives

Rybka

Kupczyk

Kędziora–Kornatowska

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Intracellular antioxidative defense is primarily enabled by the antioxidative enzymes, most significant of which are SOD, CAT and GSH-Px (Andrea et al,2004;Maritim et al, 2003;Szaleczky et al, 1999;. These three antioxidant enzymes differ in their structure, tissue distribution and cofactors required for functioning.…”

Section: Antioxidant Protectionmentioning

confidence: 99%

The Role of Oxidative Stress in Pathogenesis of Diabetic Neuropathy: Erythrocyte Superoxide Dismutase, Catalase and Glutathione Peroxidase Level in Relation to Peripheral Nerve Conduction in Diabetic Neuropathy Patients

Djordjević¹,

Djuric²,

Djordjević³

et al. 2011

Role of the Adipocyte in Development of Type 2 Diabetes

View full text Add to dashboard Cite

The Role of Oxidative Stress in Pathogenesis of Diabetic Neuropathy: Erythrocyte Superoxide Dismutase, Catalase and Glutathione Peroxidase Level in Relation to.... 155In hyperglicemia there is enhanced metabolism of glucose through the polyol (sorbitol) pathway, which also results in inhanced productions of O 2 -. Glucose is a poor substrate for aldose reductase, but at high concentrations this enzyme converts glucose to sorbitole, initiating the polyol pathway of glucose conversion to fructose. This pathway of glucose metabolism implies the participation of aldosoreductase enzyme, which using the NADPH cofactor, catalyzes the reduction of glucose into sorbitol, which can be further transformed into fructose. Aldosoreductase is widespread in the mammalian tissues such as peripheral nerves, retina, renal glomeruli, eye lenses. Stimulation of this pathway in hyperglycemic conditions is one of the pathogenetic mechanisms responsible for the development of diabetic neuropathy, nephropathy, and cataract. Activation of this pathway leads to structural changes in the tissues via several mechanisms, out of which most significant are increased osmotic pressure in the cell, depletion of myoinositol, and disordered redox potential of the cell due to reduced NADPH concentration, on the account of which the activity of NADPH dependent enzymes (including glutathione reductase and NO synthase) is diminished. Reduced production of NO leads to vasoconstriction, and impossibility of reduced glutathione regeneration in the so called glutathione redox cycle leads to depletion of reduced glutathione, since it is regenerated by the action of NADPHdependent glutathione reductase (Garlberg & Mannervik, 1975), ultimately producing a permanent oxidative stress. Change of redox status of the cell, as determined by the cellular content of thiol compounds, glutathione above all, is a significant factor in the regulation of signal transduction to appropriate genes. This signal transduction pathway is effectuated via so called redox sensors which react to any change of concentration of intracellular thiols responsible for upkeeping of the cellular redox status. Numerous regulatory transcription factors supress transcription if bound in reduced state to regulatory sequences of certain genes. In the absence of GSH in the cell and in the state of intensified polyol metabolic pathway, the oxidized form of regulatory nuclear transcription factors loses the affinity for regulatory gene sequence, which results in increased transcription and synthesis of appropriate functional and structural proteins responsible for complications in diabetes and dysregulation of glucose metabolism homeostasis. Disturbed redox potential initiates the activation of stress-signaling cascade, resulting in direct activation of other kinases and transcription factors and/or indirect modulation (oxidation) of cysteine-rich redox-sensitive proteins, such as thioredoxin and glutathione S-transferase (Adler et al., 1999). Modulation of cell signal transductionResults of recent...

show abstract

“…Previous studies (8,9) have suggested that diabetic patients are under a state of oxidative stress characterized by a relative overload of oxidants. In these patients, free oxygen radicals, especially superoxide (O 2 -), are aberrantly accumulated in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…Such coordination is largely dependent on the nitric oxide (NO) released from nerve endings of parasympathetic nerves, which serves as a major neurotransmitter (5,6). NO can diffuse into the smooth musculature of the urethra, in which it stimulates the synthesis of cyclic guanosine monophosphate (cGMP) and finally induces smooth muscle cell relaxation (7).Previous studies (8,9) …”

mentioning

confidence: 99%

Grape seed proanthocyanidin extract alleviates urethral dysfunction in diabetic rats through modulating the NO‑cGMP pathway

Zhang

et al. 2017

Exp Ther Med

View full text Add to dashboard Cite

Abstract.Oxidative stress is closely associated with the onset of diabetes mellitus (DM). Diabetic urethropathy is one of the most common complications of DM, but few studies have been conducted to investigate the role of oxidative stress in diabetic urethropathy. Grape seed proanthocyanidin extract (GSPE) has been previously reported to reduce oxidative injury. The present study aimed to investigate the role of oxidative stress and the protective effects of GSPE on urethral dysfunction using a streptozotocin-induced DM rat model. Female Wistar rats were divided into a control group (n=36), a DM group (n=36) and a DM + GSPE group (n=36). Urodynamic testing was performed using a PowerLab data acquisition device. The expression of neuronal nitric oxide synthase (nNOS), 3-nitrotyrosine and nuclear factor erythroid 2-related factor 2 (Nrf2) was determined using western blot analysis. The expression of 3-nitrotyrosine was also determined using immunohistochemistry. Nitric oxide (NO), cyclic guanosine monophosphate (cGMP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured using commercial ELISA kits. A significant increase was observed in the intravesical pressure thresholds for inducing urethral relaxation and the urethral perfusion pressure nadir in DM rats compared with the control group. GSPE was observed to reverse the increase of these parameters compared with the DM group. In addition, GSPE could reverse the downregulation of nNOS, NO and cGMP expression, and the decreased activities of antioxidant enzymes (SOD and GSH-Px). GSPE reversed the upregulation of 3-nitrotyrosine and MDA in DM rats. GSPE also activated Nrf2, which is a key antioxidative transcription factor. The findings of the present study demonstrated that GSPE protects urethra function in DM rats through modulating the NO-cGMP signaling pathway. The protective roles of GSPE may be associated with activation of the Nrf2 defense pathway. IntroductionDiabetes mellitus (DM) refers to a group of metabolic disorders characterized by hyperglycemia, which have a severe impact on public health. To date, the majority of studies examining DM complications have focused on the pathogenesis and management of diabetic cystopathy, one of the most common complications of DM (1,2). Diabetic cystopathy is considered to be a manifestation of polyneuropathy, involving sensory and autonomic nerve fibers 1 (3). A previous study reported that DM induces damage to the innervation of the urethra, together with reduction of urethral relaxation during micturition reflex (4). DM may also induce impairment of urethral smooth muscle, which is closely associated with urethral dysfunction. However, few studies have been conducted to investigate the mechanism of urethral dysfunction in DM, so this remains unclear.Precise coordination between smooth muscle in the urethra and bladder is crucial for the balance between urine storage and bladder emptying (4). Such coordination is largely dependent on the nitric oxide (NO) released from...

show abstract

Alterations in enzymatic antioxidant defence in diabetes mellitus − a rational approach

Cited by 85 publications

References 38 publications

Glutathione concentration, glutathione peroxidase and glutathione reductase activity in elderly patients with type II diabetes compared to hypertensives

Glutathione concentration, glutathione peroxidase and glutathione reductase activity in elderly patients with type II diabetes compared to hypertensives

The Role of Oxidative Stress in Pathogenesis of Diabetic Neuropathy: Erythrocyte Superoxide Dismutase, Catalase and Glutathione Peroxidase Level in Relation to Peripheral Nerve Conduction in Diabetic Neuropathy Patients

Grape seed proanthocyanidin extract alleviates urethral dysfunction in diabetic rats through modulating the NO‑cGMP pathway

Contact Info

Product

Resources

About