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Effects of hypoxia reoxygenation in brain slices from rats with type 1‐like diabetes mellitus
Author(s) -
GonzálezCorrea J. A.,
Arrebola M. M.,
Cansino A. L.,
MuñozMarín J.,
RuizVillafranca D.,
Guerrero A.,
Sánchez de la Cuesta F.,
De La Cruz J. P.
Publication year - 2006
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.650
Subject(s) - endocrinology , medicine , hypoxia (environmental) , oxidative stress , diabetes mellitus , lipid peroxidation , glutathione , lactate dehydrogenase , nitric oxide , nitric oxide synthase , nitrite , chemistry , enzyme , biochemistry , oxygen , nitrate , organic chemistry
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. Copyright © 2006 John Wiley & Sons, Ltd.