Synthetic antioxidants as potential medical remedies: An update of the past decade of pyridoindols


KARASU Ç. , Stefek M.

Turkiye Klinikleri Journal of Medical Sciences, vol.29, no.SUPPL., 2009 (Journal Indexed in SCI Expanded) identifier

  • Publication Type: Article / Abstract
  • Volume: 29 Issue: SUPPL.
  • Publication Date: 2009
  • Title of Journal : Turkiye Klinikleri Journal of Medical Sciences
  • Keywords: Aging, Antioxidant, Experimental diabetes, Glycation, Oxidative stress, Pyridoindol, Stobadine

Abstract

Diabetes mellitus, has long been recognized as a cause of accelerated aging, is a heterogeneous metabolic disorder characterized by hyperglycemia, which is often associated with complications such as cardiovascular disease, retinopathy, nephropathy and peripheral and autonomic neuropathy. In fact, aging and age-related diseases such as diabetes are accompanied by increased Oxidative Stress (OS) and accumulation of Advanced Glycation End products (AGEs). Unmitigated OS can lead to diminished cellular longevity, accelerated aging, and accumulated toxic effects for an organism. Consequences of oxidative stress are damage to DNA, lipids, proteins, accumulation of damaged molecules and disruption in cellular homeostasis. These damaged molecules also impair endothelial integrity and destroy membrane calcium current, leading to endothelial dysfunction, vascular smooth muscle proliferation and abnormal cardiovascular reactivity. Diabetes-induced oxidative stress increases AGEs formation. AGE modification of proteins leads to alterations in their normal functions by binding to intracellular or extracellular cell components, or through receptor binding. These interactions consequently can initiate a cascade of signal transduction pathways, which activate inflammatory responses, causing tissue injury. Such tissue injury contributes to the development of cardiovascular and other serious complications responsible for morbidity and mortality in diabetes. The increased amount of evidence on the harmful effects of hyperglycemia-induced oxidative stress on organ functions, the recent interest has focused on strategies to prevent, reverse or retard firstly oxidative stress and then its triggered harmful signaling. In this regard, stobadine, a synthetic and efficient antioxidant pyridoindole, has been studied largely, and found that it inhibits glyco-oxidative damage, decreases albuminuria, enzymuria, lipid peroxidation, matrix collagen cross-linking, plasma cholesterol, triglycerides, protein carbonylation and protein AGEs formation, and lead to a normalization in protein thiol, total thiol and non-protein thiol groups in different tissues of diabetic animals. Stobadine treatment of diabetic rats is characterized by retarded calcium accumulation in hearth. Stobadine is able to control mean arterial blood pressure, to prevent endothelial disturbances and to restore vascular reactivity abnormalities. This antioxidant protects metabolism, function and/or structure of heart, aorta, kidney, brain, liver, peripheral nerves, vas deferens and retina in streptozotocin-diabetic rats. Accumulating experimental evidence suggest that stobadine is a promising agent to prevent, delay or treat late diabetic complications. Copyright © 2009 by Türkiye Klinikleri.