title: Polaprezinc Protects Mice against Endotoxin Shock.
abstract: Polaprezinc (PZ), a chelate compound consisting of zinc and l-carnosine (Car), is an anti-ulcer drug developed in Japan. In the present study, we investigated whether PZ suppresses mortality, pulmonary inflammation, and plasma nitric oxide (NO) and tumor necrosis factor (TNF)-alpha levels in endotoxin shock mice after peritoneal injection of lipopolysaccharide (LPS), and how PZ protects against LPS-induced endotoxin shock. PZ pretreatment inhibited the decrease in the survival rate of mice after LPS injection. PZ inhibited the increases in plasma NO as well as TNF-alpha after LPS. Compatibly, PZ suppressed LPS-induced inducible NO synthase mRNA transcription in the mouse lungs. PZ also improved LPS-induced lung injury. However, PZ did not enhance the induction of heat shock protein (HSP) 70 in the mouse lungs after LPS. Pretreatment of RAW264 cells with PZ suppressed the production of NO and TNF-alpha after LPS addition. This inhibition likely resulted from the inhibitory effect of PZ on LPS-mediated nuclear factor-kappaB (NF-kappaB) activation. Zinc sulfate, but not Car, suppressed NO production after LPS. These results indicate that PZ, in particular its zinc subcomponent, inhibits LPS-induced endotoxin shock via the inhibition of NF-kappaB activation and subsequent induction of proinflammatory products such as NO and TNF-alpha, but not HSP induction.
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Ohata
authors.forename: Chihiro
authors.initials: C
authors.lastname: Moriyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamashita
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nishida
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kusumoto
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Mochida
authors.forename: Yukari
authors.initials: Y
authors.lastname: Minami
authors.forename: Junya
authors.initials: J
authors.lastname: Nakada
authors.forename: Kohei
authors.initials: K
authors.lastname: Shomori
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Inagaki
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Ohta
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Matsura