Brain and liver mitochondria isolated from diabetic Goto-Kakizaki rats show different susceptibility to induced oxidative stress

Background Increased oxidative stress and changes in antioxidant capacity o bserved in both clinical and experimental diabetes mellitus have been impli cated in the etiology of chronic diabetic complications. Many authors have shown that hyperglycemia leads to an increase in lipid peroxidation in diab etic patients and animals reflecting a rise in reactive oxygen species prod uction. The aim of the study was to compare the susceptibility of mitochond ria from brain and liver of Goto-Kakizaki (12-month-old diabetic) rats (GK rats), a model of non-insulin dependent diabetes mellitus, to oxidative str ess and antioxidant defenses. Methods Brain and liver mitochondrial preparations were obtained by differe ntial centrifugation. Oxidative damage injury was induced in vitro by the o xidant pair ADP/Fe2+ and the extent of membrane oxidation was assessed by o xygen consumption, malondialdehyde (MDA) and thiobarbituric acid reactive s ubstances (TBARS) formation. Coenzyme Q and alpha -tocopherol contents were measured by high-performance liquid chromatography (HPLC). Results Brain mitochondria isolated from 12-month-old control rats displaye d a higher susceptibility to lipid peroxidation, as assessed by oxygen cons umption and formation of MDA and TEARS, compared to liver mitochondria. In GK rats, mitochondria isolated from brain were more susceptible to in vitro oxidative damage than brain mitochondria from normal rats. In contrast, li ver mitochondria from diabetic rats were less susceptible to oxidative dama ge than mitochondria from normal rats. This decreased susceptibility was in versely related to their alpha -tocopherol and coenzyme Q (CoQ) content. Conclusions The present results indicate that the diabetic state can result in an elevation of both alpha -tocopherol and CoQ content in liver, which may be involved in the elimination of mitochondrially generated reactive ox ygen species. The difference in the antioxidant defense mechanisms in the b rain and liver mitochondrial preparations of moderately hyperglycemic diabe tic GK rats may correspond to a different adaptive response of the cells to the increased oxidative damage in diabetes. Copyright (C) 2001 John Wiley & Sons, Ltd.