Protection by Polaprezinc, an Anti-ulcer Drug, Against Indomethacin-Induced Apoptosis in Rat Gastric Mucosal Cells

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Abstract
Polaprezinc [N−(3−aminopropionyl)−L−histidinato zinc](PZ), an anti−ulcer drug, is a chelate compound consisting of zinc and L−carnosine.PZ has been shown to prevent gastric mucosal injury.In the present study, we investigated the inhibitory effect of PZ on indomethacin(IND)−induced apoptosis in a rat gastric mucosal cell line, RGM1.Pretreatment with PZ suppressed caspase−3 activation and subsequent apoptosis in the cells exposed to 500 μM IND in a dose−dependent manner, and 50 μM PZ exhibited the maximum inhibitory effect.Among PZ subcomponents, zinc but not L−carnosine played a pivotal role in this anti−apoptotic function.PZ did not affect mitochondrial cytochrome c release upstream of caspase−3 activation in the IND−induced apoptotic signal pathway.Treatment with 500 μM IND evidently produced reactive oxygen species(ROS)in RGM1 cells.However, PZ did not scavenge ROS in IND−treated cells.Moreover, N−acetyl−L−cysteine, a potent antioxidant, inhibited ROS generation but did not suppress apoptosis in RGM1 cells exposed to IND.These observations demonstrate a novel pharmacological action of PZ;i.e., that PZ, and in particular its zinc subcomponent, inhibits apoptosis via inhibition of caspase−3 activation but not antioxidant activity.