The peroxidase-dependent degradation of H202 in human umbilical vein endothelial cells (ECs) cultured in the presence of 16.5 mM and 33 mM glucose was significantly impaired, by 12%(p< 0.01) and 36%(p<0.001), respectively, as compared to the 5.5 mM glucose control. Furthermore, non-metabolizable L-glucose and D-raffinose had no effect on the degradation of H202 in cultured ECs.The high glucose effect was completely reversed in the presence of 1, uM SNK 860, an aldose reductase inhibitor.In contrast, there was no effect of high glucose on the catalase-dependent degradation of H
20
2 in ECs. The EC number per dish decreased by 11%(p<0.05) and H
20
2-induced
51Cr release from ECs increased by 50%, as compared with the control values, after the cells were cultured for 4-5 days in 33 mM glucose media.These results indicate that impairment of peroxidase-dependent degradation of H
20
2 in ECs cultured in high glucose media, is associated with activation of the sorbitol pathway and that ECs consequently become more susceptible to H202-induced cell injury
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