Inhibitory Effects of Polaprezine on the Inflammatory Response toHelicobacter pylori

Abstract

Helicobacter pylori-infected gastrointestinal mucosa is frequently infiltrated by polymorphonuclear leukocytes (PMN) and monocytes, and these invading cells have been implicated in gastrointestinal mucosal inflammation. To clarify the efficacy of polaprezinc, a chelate compound consisting of zinc and L-carnosine, against H pylori-induced inflammation including PMN infiltration, the in vitro effects of this drug on interleukin (IL)-8 production by an established gastric cancer cell line (MKN 45 cells) and on PMN-endothelial cell adhesive interactions was investigated. Polaprezinc and zinc sulphate inhibited IL-8 production by MKN 45 cells in response to stimulation with H pylori water extract (HPE) in a dose-dependent manner from 10(-7) M to 10(-5) M. In addition, the expression of CD11b and CD18 on PMN and PMN-dependent adhesion to endothelial cells elicited by HPE was inhibited by polaprezinc and zinc sulphate in a concentration-dependent manner. L-carnosine did not have any effects on IL-8 production or PMN-endothelial cell interactions. These results suggest that polaprezinc, mainly the zinc component, may inhibit H pylori-induced PMN-mediated gastric inflammation by attenuating CD11b/CD18 expression on PMN and IL-8 production from gastric epithelial cells.

Reactive oxygen species-quenching and anti-apoptotic effect of polaprezinc on indomethacin-induced small intestinal epithelial cell injury

“…Because PZ has been shown to exhibit potent ROSquenching effects [11,12], we employed PZ, a gastric muco-protective drug, as a candidate drug for the prevention of indomethacin-induced small intestinal mucosal damage. Besides its ROS-quenching effect, PZ has various other pharmacological actions, such as induction of the expression of heat shock protein 27 (HSP-27), HSP-72 [39], and heme oxygenase-1 (HO-1) [40], molecules which exhibit cytoprotective effects or an anti-inflammatory effect via the inhibition of adhesion molecules on polymorphonuclear leukocytes or the inhibition of cytokine production by gastric epithelial cells [41]. In the present study, we found that PZ significantly inhibited the indomethacin-induced apoptosis of RIE-1 cells (Figs.…”

Effectiveness of polaprezinc for low-dose aspirin-induced small-bowel mucosal injuries as evaluated by capsule endoscopy: a pilot randomized controlled study

“…In Japan, polaprezinc is commonly used for the treatment of gastric ulcer. Polaprezinc is a chelate compound consisting of zinc and L-carnosine that is thought to function in protecting intercellular tight junctions [11,12], as an anti-oxidant [13], in preventing apoptosis [14-16], and in reducing inflammation [17]. Omatsu et al [14] speculated that polaprezinc protects rat intestinal epithelial (RIE-1) cells from indomethacin-induced apoptosis via its reactive oxygen species (ROS)-quenching effect.…”

Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells

“…(20) Consequently, several studies have indicated that PZ can protect gastric mucosa against various stimuli in vivo (21,22) and in vitro . (15,23) In this study, we examined whether PZ can protect small intestinal epithelial cells from ASA-induced apoptosis, and determined the involvement of HSP70, induced by PZ, in this process.…”