Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes Against Acetaminophen-Induced Toxicity Via Induction of Heat Shock Protein 70

Overview

Journal J Clin Biochem Nutr

Specialty Biochemistry

Date 2010 Jan 28

PMID 20104264

Citations 6

Authors

Tadashi Nishida

Shuzo Ohata

Chiaki Kusumoto

Shinsuke Mochida

Junya Nakada

Yoshimi Inagaki

Yoshiji Ohta

Tatsuya Matsura

Affiliations

Soon will be listed here.

Abstract

Polaprezinc, a chelate compound consisting of zinc and l-carnosine, is clinically used as a medicine for gastric ulcers. It has been shown that induction of heat shock protein (HSP) is involved in protective effects of polaprezinc against gastric mucosal injury. In the present study, we investigated whether polaprezinc and its components could induce HSP70 and prevent acetaminophen (APAP) toxicity in mouse primary cultured hepatocytes. Hepatocytes were treated with polaprezinc, zinc sulfate or l-carnosine at the concentration of 100 microM for 9 h, and then exposed to 10 mM APAP. Polaprezinc or zinc sulfate increased cellular HSP70 expression. However, l-carnosine had no influence on it. Pretreatment of the cells with polaprezinc or zinc sulfate significantly suppressed cell death as well as cellular lipid peroxidation after APAP treatment. In contrast, pretreatment with polaprezinc did not affect decrease in intracellular glutathione after APAP. Furthermore, treatment with KNK437, an HSP inhibitor, attenuated increase in HSP70 expression induced by polaprezinc, and abolished protective effect of polaprezinc on cell death after APAP. These results suggested that polaprezinc, in particular its zinc component, induces HSP70 expression in mouse primary cultured hepatocytes, and inhibits lipid peroxidation after APAP treatment, resulting in protection against APAP toxicity.

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