Fructose-1,6-biphosphate in rat intestinal preconditioning: involvement ofnitric oxide

Background and aims-Inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by nitric oxide (NO) in intestinal preconditioning could modify the rate of formation of glycolytic intermediates. Fructose-1,6-biphosphate (F 16BP) is a glycolytic intermediate that protects tissue from ischaemia/repe rfusion injury. We evaluated if F16BP may be endogenously accumulated as a consequence of GAPDH inhibition by NO during intestinal preconditioning in rats. Methods-We assessed: (1) effect of preconditioning on F16BP content; (2) ef fect of NO on GAPDH activity before and during sustained ischaemia; and (3) protective effect of F16BP in control, ischaemic, and preconditioned anima ls with or without administration of N-nitro-L-arginine methyl ester (L-NAM E), NO donor, or F16BP. Results-Preconditioned rats showed a significant transient decrease in GAPD H activity and also maintained basal F16BP levels longer than ischaemic rat s. L-NAME administration to preconditioned rats reversed these effects. F16 BP administration to ischaemic rats decreased protein release in the perfus ate. Administration of F16BP to L-NAME treated rats attenuated the harmful effect of L-NAME. Conclusions-Our study indicates that F16BP may be endogenously accumulated in preconditioned rats as a consequence of inhibition of GAPDH by NO, and t his may contribute to the protection observed in intestinal preconditioning .