Effects of hypoxia reoxygenation in brain slices from rats with type 1-like diabetes mellitus.
BACKGROUND
The aim of this study was to determine whether the brain tissue of type 1 diabetic animals is more susceptible to damage by hypoxia reoxygenation than healthy animals.


METHODS
This study used rats with diabetes of 1, 2 and 3 months (N = 15 rats/group). Brain slices were subjected to hypoxia and reoxygenation for 180 min in vitro. We measured oxidative stress (lipid peroxidation, glutathione concentration and enzyme activities related to glutathione), concentration of prostaglandin E(2) (PGE(2)) and nitric oxide (NO) pathway (nitrite + nitrate, activities of constitutive (cNOS) and inducible (iNOS) nitric oxide synthase). As a parameter of cell death we measured the efflux of lactate dehydrogenase (LDH).


RESULTS
After reoxygenation LDH activity increased in comparison to nondiabetic animals by 40, 40.6 and 68.9% in animals with diabetes of 1, 2 and 3 months duration, respectively. These changes were accompanied by greater increases in lipid peroxides (25.4, 93.7 and 92.8%). PGE(2) accumulated in significantly larger amounts in diabetic animals (62.5, 85.5 and 114%), and nitrite + nitrate accumulation was significantly greater in rats with diabetes of 2 (40.2%) and 3 months duration (24.0%). iNOS activity increased significantly in all the groups of diabetic animals, with the largest increases in rats with diabetes of 2 (18.6%) and 3 months duration (21.1%).


CONCLUSIONS
The biochemical pathways involved in oxidative stress and neuronal death are more sensitive to hypoxia reoxygenation in type 1-like diabetic, as compared to normal, rats.
González-Correa
J A
JA
Laboratorio de Investigaciones Antitrombóticas e Isquemia Tisular, Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, 29071 Málaga, Spain.
Arrebola
M M
MM
Cansino
A L
AL
Muñoz-Marín
J
J
Ruiz-Villafranca
D
D
Guerrero
A
A
de la Cuesta
F Sánchez
FS
De La Cruz
J P
JP
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D000860:Hypoxia; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D009566:Nitrates; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D007770:L-Lactate Dehydrogenase