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Polaprezinc Protects Mice against Endotoxin Shock.

Ohata S, Moriyama C, Yamashita A, Nishida T, Kusumoto C, Mochida S, Minami Y, Nakada J, Shomori K, Inagaki Y, Ohta Y, Matsura T - J Clin Biochem Nutr (2010)

Bottom Line: PZ also improved LPS-induced lung injury.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of PZ on the expression of iNOS mRNA in the mouse lung 6 h after LPS. PZ (100 mg/kg) was given to mice 2 h before LPS (40 mg/kg, i.p.) administration. The level of iNOS mRNA in the mouse lung was measured as described in Materials and Methods. Data points represent the means ± SE (n = 5). *p<0.05 vs LPS alone.
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Figure 6: Effect of PZ on the expression of iNOS mRNA in the mouse lung 6 h after LPS. PZ (100 mg/kg) was given to mice 2 h before LPS (40 mg/kg, i.p.) administration. The level of iNOS mRNA in the mouse lung was measured as described in Materials and Methods. Data points represent the means ± SE (n = 5). *p<0.05 vs LPS alone.

Mentions: We determined the effect of PZ on expression of iNOS mRNA 6 h after LPS injection (Fig. 6). LPS treatment increased iNOS mRNA level in the lung approximately 20-fold of normal level. PZ administration 2 h before LPS significantly reduced the increase in iNOS mRNA gene expression by around 50%. In contrast, there was no difference of metallothionein-I (MT-I) and metallothionein-II (MT-II) mRNA levels between treatment with LPS alone and pretreatment with PZ at 2 h before LPS although MT-I and MT-II gene expressions increased remarkably in both groups (data not shown).


Polaprezinc Protects Mice against Endotoxin Shock.

Ohata S, Moriyama C, Yamashita A, Nishida T, Kusumoto C, Mochida S, Minami Y, Nakada J, Shomori K, Inagaki Y, Ohta Y, Matsura T - J Clin Biochem Nutr (2010)

Effect of PZ on the expression of iNOS mRNA in the mouse lung 6 h after LPS. PZ (100 mg/kg) was given to mice 2 h before LPS (40 mg/kg, i.p.) administration. The level of iNOS mRNA in the mouse lung was measured as described in Materials and Methods. Data points represent the means ± SE (n = 5). *p<0.05 vs LPS alone.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2872229&req=5

Figure 6: Effect of PZ on the expression of iNOS mRNA in the mouse lung 6 h after LPS. PZ (100 mg/kg) was given to mice 2 h before LPS (40 mg/kg, i.p.) administration. The level of iNOS mRNA in the mouse lung was measured as described in Materials and Methods. Data points represent the means ± SE (n = 5). *p<0.05 vs LPS alone.
Mentions: We determined the effect of PZ on expression of iNOS mRNA 6 h after LPS injection (Fig. 6). LPS treatment increased iNOS mRNA level in the lung approximately 20-fold of normal level. PZ administration 2 h before LPS significantly reduced the increase in iNOS mRNA gene expression by around 50%. In contrast, there was no difference of metallothionein-I (MT-I) and metallothionein-II (MT-II) mRNA levels between treatment with LPS alone and pretreatment with PZ at 2 h before LPS although MT-I and MT-II gene expressions increased remarkably in both groups (data not shown).

Bottom Line: PZ also improved LPS-induced lung injury.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.

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.

No MeSH data available.


Related in: MedlinePlus