Jpn. J. Pharmacol. 84 (1), 63-70 (2000)

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

Yasuyoshi Fujii1,2, Tatsuya Matsura1,*, Masachika Kai1, Hironaka Kawasaki2 and Kazuo Yamada1

1Department╩of Biochemistry and 2Second Department of Internal Medicine, Faculty of Medicine, Tottori University,
86 Nishi-cho, Yonago 683-8503, Japan
*╩To whom correspondence should be addressed.

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╩mM IND in a dose-dependent manner, and 50╩mM 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╩mM 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.

Keywords: Polaprezinc, Indomethacin, Apoptosis, Caspase-3, Reactive oxygen species

Copyrightę The Japanese Pharmacological Society 2000

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