Influence of Diethyl Maleate-Induced Loss of Thiols on Cefmetazole Uptake into Isolated Epithelial Cells and on Cefmetazole Absorption from Ileal Loop of Rats(Pharmaceutical)

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Uptake of cefmetazole into isolated rat intestinal epithelial cells increased with increasing nonprotein thiol loss induced by diethyl maleate(DEM) at concentrations up to 1 mM. However, 5 mM DEM decreased cefmetazole uptake, accompanied with a loss of protein thiol, despite the loss of nonprotein thiol. The coaddition of calmodulin inhibitors such as trifluoperazine(TFPZ) and chlorpromazine(CPZ) with 5 mM DEM restored cefmetazole uptake and inhibited protein thiol loss. The administration of DEM at 0.75 mM into the lumen of a rat ileal loop increased cefmetazole absorption along with loss of nonprotein thiol in the tissue. However, significant protein thiol loss occurred on administration of 7.5 mM DEM, and cefmetazole absorption was decreased. The appearance of cefmetazole in plasma after an injection of cefmetazole into connective tissue of the ileal loop was also inhibited by preadministration of 7.5 mM DEM into the loop. Coadministration of calmodulin inhibitors at a concentration of less than 100/m with 7.5 mM DEM inhibited protein thiol loss but not nonprotein thiol loss. Coadministration of calmodulin inhibitors with 7.5 mM DEM increased cefmetazole absorption from the ileal lumen, and restored cefmetazole appearance in the plasma after injection into connective tissue. Thus, nonprotein thiol loss in cells and tissue of the intestine increased cefmetazole absorption from the mucosal lumen into the blood circulation, but protein thiol loss inhibited it.
1987-07-25

Influence of Diethyl Maleate-Induced Loss of Thiols on Cefmetazole Uptake into Isolated Epithelial Cells and on Cefmetazole Absorption from Ileal Loop of Rats(Pharmaceutical)

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