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 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/Fe(2+) and the extent of membrane oxidation was assessed by oxygen consumption, malondialdehyde (MDA) and thiobarbituric acid reactive substances (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 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 in vitro 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 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 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.
Santos
M S
MS
Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology, University of Coimbra, Coimbra, Portugal.
Santos
D L
DL
Palmeira
C M
CM
Seiça
R
R
Moreno
A J
AJ
Oliveira
C R
CR
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012402:Rotenone / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D012402:Rotenone; D014451:Ubiquinone; D014810:Vitamin E; D008315:Malondialdehyde; D011189:Potassium Chloride