Inhibitory effect of salicylate on 2,4-dinitrophenol and diethyl maleate in isolated rat intestinal epithelial cells.
Studies on the mechanism of chemically induced intestinal epithelial injury were carried out using isolated, rat small intestinal epithelial cells. Compounds such as 2,4-dinitrophenol (DNP) and diethyl maleate (DEM), caused NADH loss, an increase in cytosolic Ca2+ concentration and protein thiol loss. Further, these compounds accelerated cell aggregation and decreased cell viability. Calmodulin antagonists inhibited protein thiol loss induced by either of the compound, inhibited cell aggregation and prolonged cell viability, but did not influence NADH loss. It has been reported that the calmodulin-binding protein may regulate cytoskeletal activity. Therefore, the inhibition of protein thiol loss by calmodulin antagonist may be due to a dissociation of calmodulin-binding proteins from cytoskeletal elements. Salicylate also inhibited protein thiol loss induced by DNP and DEM, and inhibited cell aggregation. However, salicylate may have a direct effect in reducing the cytosolic free Ca2+ concentration by complexation and subsequent facilitated release of Ca2+ from cells. Further, in the present study, the induction of cell aggregation may be caused by the appearance of specific sites on the cell membrane surface to which arsenazo III could adsorb, since adsorption of arsenazo III to the isolated epithelial cells seemed to correlate with increased cell aggregation.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002449:Cell Aggregation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects*; D007700:Kinetics; D008298:Maleates / Q000494:pharmacology*; D009243:NAD / Q000378:metabolism; D051381:Rats; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid; D012995:Solubility; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D004140:Dinitrophenols; D008298:Maleates; D012459:Salicylates; D013438:Sulfhydryl Compounds; D013449:Sulfonamides; D009243:NAD; D000001:Calcimycin; C017967:W 7; C014476:diethyl maleate; D020156:Salicylic Acid; D002118:Calcium; D004229:Dithiothreitol; D002746:Chlorpromazine