Antioxidant therapy in diabetic complications: What is new?

Roberto Da Ros, Roberta Assaloni, Antonio Ceriello

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

In diabetes oxidative stress plays a key role in the pathogenesis of vascular complications, and an early step of such damage is considered the development of an endothelial dysfunction. Hyperglycemia directly promotes an endothelial dysfunction inducing process of overproduction of superoxide and consequently peroxynitrite that damages DNA and activates the nuclear enzyme poly(ADP-ribose) polymerase. This process, depleting NAD+, slowing glycolysis, ATP formation and electron transport, results in acute endothelial dysfunction in diabetic blood vessels and contributes to the development of diabetic complications. Classic antioxidants, like vitamin E, failed to show beneficial effects on diabetic complications probably due to their only "symptomatic" action. It is now evident that, statins, ACE inhibitors, AT-1 blockers, calcium channel blockers and thiazolinediones have a strong intracellular antioxidant activity, and it has been suggested that many of their beneficial ancillary effects are due to this property. Statins increase NO bioavailability and decrease superoxide production, probably interfering with NAD(P)H activity and modulating eNOS expression. ACE inhibitors and AT-1 blockers prevent hyperglycemia-derived oxidative stress modulating angiotensin action and production. This effect is of particular interest because hyperglycemia is able to directly modulate cellular angiotensin generation. Calcium channel blockers inhibit the peroxidation of cell membrane lipids and their subsequent intracellular translocation. Thiazolinediones bind and activate the nuclear peroxisome proliferator-activated receptor gamma, a nuclear receptor of ligand-dependent transcription factors. The inhibition of this receptors lead to inhibition of the inducible nitric oxide synthase and consequently reduction of peroxynitrite generation. This preventive activity against oxidative stress generation can justify a large utilization and association of this compound for preventing complications in diabetic patients, where antioxidant defences have been shown to be defective.

Original languageEnglish
Pages (from-to)335-341
Number of pages7
JournalCurrent Vascular Pharmacology
Volume2
Issue number4
DOIs
Publication statusPublished - Oct 2004

Fingerprint

Diabetes Complications
Hyperglycemia
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Oxidative Stress
Peroxynitrous Acid
Antioxidants
Angiotensins
Calcium Channel Blockers
Angiotensin-Converting Enzyme Inhibitors
Superoxides
NAD
Blood Vessels
Poly(ADP-ribose) Polymerases
PPAR gamma
Nitric Oxide Synthase Type II
Glycolysis
Membrane Lipids
Cytoplasmic and Nuclear Receptors
Electron Transport
Vitamin E

Keywords

  • ACE inhibitors
  • AT1 receptor inhibitors
  • Calcium channel blockers
  • Diabetic complications
  • Oxidative stress
  • Statins
  • Thiazolidinediones

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Antioxidant therapy in diabetic complications : What is new? / Da Ros, Roberto; Assaloni, Roberta; Ceriello, Antonio.

In: Current Vascular Pharmacology, Vol. 2, No. 4, 10.2004, p. 335-341.

Research output: Contribution to journalArticle

Da Ros, Roberto ; Assaloni, Roberta ; Ceriello, Antonio. / Antioxidant therapy in diabetic complications : What is new?. In: Current Vascular Pharmacology. 2004 ; Vol. 2, No. 4. pp. 335-341.
@article{581e88451f9f4edb92c82e24fc7214fa,
title = "Antioxidant therapy in diabetic complications: What is new?",
abstract = "In diabetes oxidative stress plays a key role in the pathogenesis of vascular complications, and an early step of such damage is considered the development of an endothelial dysfunction. Hyperglycemia directly promotes an endothelial dysfunction inducing process of overproduction of superoxide and consequently peroxynitrite that damages DNA and activates the nuclear enzyme poly(ADP-ribose) polymerase. This process, depleting NAD+, slowing glycolysis, ATP formation and electron transport, results in acute endothelial dysfunction in diabetic blood vessels and contributes to the development of diabetic complications. Classic antioxidants, like vitamin E, failed to show beneficial effects on diabetic complications probably due to their only {"}symptomatic{"} action. It is now evident that, statins, ACE inhibitors, AT-1 blockers, calcium channel blockers and thiazolinediones have a strong intracellular antioxidant activity, and it has been suggested that many of their beneficial ancillary effects are due to this property. Statins increase NO bioavailability and decrease superoxide production, probably interfering with NAD(P)H activity and modulating eNOS expression. ACE inhibitors and AT-1 blockers prevent hyperglycemia-derived oxidative stress modulating angiotensin action and production. This effect is of particular interest because hyperglycemia is able to directly modulate cellular angiotensin generation. Calcium channel blockers inhibit the peroxidation of cell membrane lipids and their subsequent intracellular translocation. Thiazolinediones bind and activate the nuclear peroxisome proliferator-activated receptor gamma, a nuclear receptor of ligand-dependent transcription factors. The inhibition of this receptors lead to inhibition of the inducible nitric oxide synthase and consequently reduction of peroxynitrite generation. This preventive activity against oxidative stress generation can justify a large utilization and association of this compound for preventing complications in diabetic patients, where antioxidant defences have been shown to be defective.",
keywords = "ACE inhibitors, AT1 receptor inhibitors, Calcium channel blockers, Diabetic complications, Oxidative stress, Statins, Thiazolidinediones",
author = "{Da Ros}, Roberto and Roberta Assaloni and Antonio Ceriello",
year = "2004",
month = "10",
doi = "10.2174/1570161043385538",
language = "English",
volume = "2",
pages = "335--341",
journal = "Current Vascular Pharmacology",
issn = "1570-1611",
publisher = "Bentham Science Publishers B.V.",
number = "4",

}

TY - JOUR

T1 - Antioxidant therapy in diabetic complications

T2 - What is new?

AU - Da Ros, Roberto

AU - Assaloni, Roberta

AU - Ceriello, Antonio

PY - 2004/10

Y1 - 2004/10

N2 - In diabetes oxidative stress plays a key role in the pathogenesis of vascular complications, and an early step of such damage is considered the development of an endothelial dysfunction. Hyperglycemia directly promotes an endothelial dysfunction inducing process of overproduction of superoxide and consequently peroxynitrite that damages DNA and activates the nuclear enzyme poly(ADP-ribose) polymerase. This process, depleting NAD+, slowing glycolysis, ATP formation and electron transport, results in acute endothelial dysfunction in diabetic blood vessels and contributes to the development of diabetic complications. Classic antioxidants, like vitamin E, failed to show beneficial effects on diabetic complications probably due to their only "symptomatic" action. It is now evident that, statins, ACE inhibitors, AT-1 blockers, calcium channel blockers and thiazolinediones have a strong intracellular antioxidant activity, and it has been suggested that many of their beneficial ancillary effects are due to this property. Statins increase NO bioavailability and decrease superoxide production, probably interfering with NAD(P)H activity and modulating eNOS expression. ACE inhibitors and AT-1 blockers prevent hyperglycemia-derived oxidative stress modulating angiotensin action and production. This effect is of particular interest because hyperglycemia is able to directly modulate cellular angiotensin generation. Calcium channel blockers inhibit the peroxidation of cell membrane lipids and their subsequent intracellular translocation. Thiazolinediones bind and activate the nuclear peroxisome proliferator-activated receptor gamma, a nuclear receptor of ligand-dependent transcription factors. The inhibition of this receptors lead to inhibition of the inducible nitric oxide synthase and consequently reduction of peroxynitrite generation. This preventive activity against oxidative stress generation can justify a large utilization and association of this compound for preventing complications in diabetic patients, where antioxidant defences have been shown to be defective.

AB - In diabetes oxidative stress plays a key role in the pathogenesis of vascular complications, and an early step of such damage is considered the development of an endothelial dysfunction. Hyperglycemia directly promotes an endothelial dysfunction inducing process of overproduction of superoxide and consequently peroxynitrite that damages DNA and activates the nuclear enzyme poly(ADP-ribose) polymerase. This process, depleting NAD+, slowing glycolysis, ATP formation and electron transport, results in acute endothelial dysfunction in diabetic blood vessels and contributes to the development of diabetic complications. Classic antioxidants, like vitamin E, failed to show beneficial effects on diabetic complications probably due to their only "symptomatic" action. It is now evident that, statins, ACE inhibitors, AT-1 blockers, calcium channel blockers and thiazolinediones have a strong intracellular antioxidant activity, and it has been suggested that many of their beneficial ancillary effects are due to this property. Statins increase NO bioavailability and decrease superoxide production, probably interfering with NAD(P)H activity and modulating eNOS expression. ACE inhibitors and AT-1 blockers prevent hyperglycemia-derived oxidative stress modulating angiotensin action and production. This effect is of particular interest because hyperglycemia is able to directly modulate cellular angiotensin generation. Calcium channel blockers inhibit the peroxidation of cell membrane lipids and their subsequent intracellular translocation. Thiazolinediones bind and activate the nuclear peroxisome proliferator-activated receptor gamma, a nuclear receptor of ligand-dependent transcription factors. The inhibition of this receptors lead to inhibition of the inducible nitric oxide synthase and consequently reduction of peroxynitrite generation. This preventive activity against oxidative stress generation can justify a large utilization and association of this compound for preventing complications in diabetic patients, where antioxidant defences have been shown to be defective.

KW - ACE inhibitors

KW - AT1 receptor inhibitors

KW - Calcium channel blockers

KW - Diabetic complications

KW - Oxidative stress

KW - Statins

KW - Thiazolidinediones

UR - http://www.scopus.com/inward/record.url?scp=4444265474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444265474&partnerID=8YFLogxK

U2 - 10.2174/1570161043385538

DO - 10.2174/1570161043385538

M3 - Article

C2 - 15320813

AN - SCOPUS:4444265474

VL - 2

SP - 335

EP - 341

JO - Current Vascular Pharmacology

JF - Current Vascular Pharmacology

SN - 1570-1611

IS - 4

ER -