Brain and liver mitochondria isolated from diabeticGoto‐Kakizaki rats show different susceptibility to induced oxidative stress

MS Santos, DL Santos, CM Palmeira… - Diabetes/metabolism …, 2001 - Wiley Online Library
MS Santos, DL Santos, CM Palmeira, R Seiça, AJ Moreno, CR Oliveira
Diabetes/metabolism research and reviews, 2001Wiley Online Library
Background Increased oxidative stress and changes in antioxidant capacity observed in
both clinical and experimental diabetes mellitus have been implicated in the etiology of
chronic diabetic complications. Many authors have shown that hyperglycemia leads to an
increase in lipid peroxidation in diabetic patients and animals reflecting a rise in reactive
oxygen species production. The aim of the study was to compare the susceptibility of
mitochondria from brain and liver of Goto‐Kakizaki (12‐month‐old diabetic) rats (GK rats), a …
Background
Increased oxidative stress and changes in antioxidant capacity observed in both clinical and experimental diabetes mellitus have been implicated in the etiology of chronic diabetic complications. Many authors have shown that hyperglycemia leads to an increase in lipid peroxidation in diabetic patients and animals reflecting a rise in reactive oxygen species production. The aim of the study was to compare the susceptibility of mitochondria from brain and liver of Goto‐Kakizaki (12‐month‐old diabetic) rats (GK rats), a model of non‐insulin dependent diabetes mellitus, to oxidative stress and antioxidant defenses.
Methods
Brain and liver mitochondrial preparations were obtained by differential centrifugation. Oxidative damage injury was induced in vitro by the oxidant pair ADP/Fe2+ and the extent of membrane oxidation was assessed by oxygen consumption, malondialdehyde (MDA) and thiobarbituric acid reactive substances (TBARS) formation. Coenzyme Q and α‐tocopherol contents were measured by high‐performance liquid chromatography (HPLC).
Results
Brain mitochondria isolated from 12‐month‐old control rats displayed a higher susceptibility to lipid peroxidation, as assessed by oxygen consumption and formation of MDA and TBARS, compared to liver mitochondria. In GK rats, mitochondria isolated from brain were more susceptible to invitro oxidative damage than brain mitochondria from normal rats. In contrast, liver mitochondria from diabetic rats were less susceptible to oxidative damage than mitochondria from normal rats. This decreased susceptibility was inversely related to their α‐tocopherol and coenzyme Q (CoQ) content.
Conclusions
The present results indicate that the diabetic state can result in an elevation of both α‐tocopherol and CoQ content in liver, which may be involved in the elimination of mitochondrially generated reactive oxygen species. The difference in the antioxidant defense mechanisms in the brain and liver mitochondrial preparations of moderately hyperglycemic diabetic GK rats may correspond to a different adaptive response of the cells to the increased oxidative damage in diabetes. Copyright © 2001 John Wiley & Sons, Ltd.
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