Recycling processes of cellular ascorbate generate oxidative stress in pancreatic tissues in in vitro system.
Ascorbate is a reducing agent, which is also known to oxidize cellular components. Our proposed mechanism of the oxidative action is as follows: Ascorbate is concentrated in the pancreas and is leaked in adverse conditions, and oxidized to dehydroascorbate. The dehydroascorbate is carried into cells by a glucose transporter (GLUT) and reduced back to ascorbate. The reduction processes take electrons from other cellular components. Ascorbate or dehydroascorbate treatment elevated thiobarbituric acid-reactive substance (TBARS) concentrations in pancreas. The elevations in TBARS concentrations were blocked by cytochalasin B, a GLUT inhibitor. To confirm further the prooxidative action, changes in glutathione content were quantified. Glutathione concentrations were lower in ascorbate- or dehydroascorbate-treated groups. The ascorbate-induced decrease in glutathione was blocked by cytochalasin B. To prevent oxidation of ascorbate to dehydroascorbate, glutathione was added to the medium. The ascorbate plus glutathione and dehydroascorbate plus glutathione groups showed lower TBARS concentrations than those of the ascorbate and dehydroascorbate groups, respectively. There were changes in the morphology of Langerhans islets following ascorbate treatment, which disappeared following treatment with ascorbate plus cyto-chalasin B. The observations indicate that ascorbate generates oxidative stress and affects the structure of islets.
Brown
Shelley
S
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Georgatos
Maria
M
Reifel
Conrad
C
Song
Jih H
JH
Shin
Seon H
SH
Hong
Murray
M
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism* / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003683:Dehydroascorbic Acid / Q000378:metabolism / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010179:Pancreas / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D009004:Monosaccharide Transport Proteins; D017392:Thiobarbituric Acid Reactive Substances; D003571:Cytochalasin B; D005978:Glutathione; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid