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Published on: May 2, 2018
Polaprezinc Protects Mice against Endotoxin Shock
Shuzo Ohata1, Chihiro Moriyama, Atsushi Yamashita
1Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
Journal of Clinical Biochemistry and Nutrition
|May 22, 2010
Summary
Polaprezinc (PZ), an anti-ulcer drug, effectively reduces mortality and inflammation in endotoxin shock by inhibiting nitric oxide and TNF-alpha production. Its zinc component plays a key role in this protective effect.
Area of Science:
- Pharmacology
- Immunology
- Biochemistry
Background:
- Polaprezinc (PZ) is a Japanese anti-ulcer drug composed of zinc and l-carnosine.
- Endotoxin shock, induced by lipopolysaccharide (LPS), causes significant mortality and inflammation.
- Understanding the protective mechanisms of drugs like PZ against endotoxin shock is crucial.
Purpose of the Study:
- To investigate the efficacy of Polaprezinc (PZ) in suppressing mortality and pulmonary inflammation in a mouse model of endotoxin shock.
- To elucidate the mechanisms by which PZ protects against LPS-induced endotoxin shock, focusing on nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) pathways.
- To determine the role of zinc and l-carnosine components of PZ in its protective effects.
Main Methods:
- Mice were pretreated with PZ before LPS injection to assess survival rates and pulmonary injury.
- Plasma levels of NO and TNF-alpha were measured post-LPS injection.
- Inducible NO synthase (iNOS) mRNA expression and heat shock protein 70 (HSP70) induction in lung tissue were analyzed.
- RAW264 cells were used to investigate the effect of PZ on LPS-mediated inflammatory responses and nuclear factor-kappaB (NF-kappaB) activation.
- The effects of zinc sulfate and l-carnosine alone were also evaluated.
Main Results:
- PZ pretreatment significantly improved survival rates in LPS-injected mice.
- PZ suppressed the increase in plasma NO and TNF-alpha levels following LPS administration.
- PZ inhibited LPS-induced iNOS mRNA transcription and improved lung injury.
- PZ pretreatment suppressed NO and TNF-alpha production in RAW264 cells by inhibiting NF-kappaB activation.
- Zinc sulfate, but not l-carnosine, reduced NO production, suggesting zinc is the active component.
Conclusions:
- Polaprezinc (PZ) demonstrates significant protective effects against LPS-induced endotoxin shock in mice.
- The anti-inflammatory and survival-promoting effects of PZ are mediated through the inhibition of NF-kappaB activation, leading to reduced production of NO and TNF-alpha.
- The zinc component of PZ is primarily responsible for its beneficial effects in endotoxin shock.
