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Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes against Acetaminophen-Induced Toxicity via Induction of Heat Shock Protein 70.

Nishida T, Ohata S, Kusumoto C, Mochida S, Nakada J, Inagaki Y, Ohta Y, Matsura T - J Clin Biochem Nutr (2009)

Bottom Line: 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.

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, 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.

No MeSH data available.


Related in: MedlinePlus

Effect of polaprezinc, zinc sulfate or l-carnosine on cell viability after APAP exposure. The cell viability was analyzed using WST-8 assay. Cells were treated with polaprezinc, zinc sulfate or l-carnosine at a concentration of 100 µM at 9 h before APAP (10 mM) treatment. The cell viability was measured 0, 6 or 12 h after APAP. The data are expressed as means ± SE of 7 separate experiments. PZ; polaprezinc, ZS; zinc sulfate, LC; l-carnosine. **p<0.01 vs APAP alone.
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Figure 3: Effect of polaprezinc, zinc sulfate or l-carnosine on cell viability after APAP exposure. The cell viability was analyzed using WST-8 assay. Cells were treated with polaprezinc, zinc sulfate or l-carnosine at a concentration of 100 µM at 9 h before APAP (10 mM) treatment. The cell viability was measured 0, 6 or 12 h after APAP. The data are expressed as means ± SE of 7 separate experiments. PZ; polaprezinc, ZS; zinc sulfate, LC; l-carnosine. **p<0.01 vs APAP alone.

Mentions: While APAP overdoses cause liver damage in vivo and in vitro, it has been reported that overexpression of HSP70 protects APAP toxicity [13, 34, 35]. We next investigated whether polaprezinc, zinc sulfate or l-carnosine improves cell viability in mouse hepatocytes after APAP treatment (Fig. 3). The cell viability after APAP decreased in a time-dependent manner and was 55% of normal level after 12 h. Treatments of mouse hepatocytes with polaprezinc and zinc sulfate 9 h before APAP improved cell viability to 89% and 83% of normal level at 12 h, respectively, while l-carnosine treatment failed to improve the cell viability (62%).


Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes against Acetaminophen-Induced Toxicity via Induction of Heat Shock Protein 70.

Nishida T, Ohata S, Kusumoto C, Mochida S, Nakada J, Inagaki Y, Ohta Y, Matsura T - J Clin Biochem Nutr (2009)

Effect of polaprezinc, zinc sulfate or l-carnosine on cell viability after APAP exposure. The cell viability was analyzed using WST-8 assay. Cells were treated with polaprezinc, zinc sulfate or l-carnosine at a concentration of 100 µM at 9 h before APAP (10 mM) treatment. The cell viability was measured 0, 6 or 12 h after APAP. The data are expressed as means ± SE of 7 separate experiments. PZ; polaprezinc, ZS; zinc sulfate, LC; l-carnosine. **p<0.01 vs APAP alone.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2803132&req=5

Figure 3: Effect of polaprezinc, zinc sulfate or l-carnosine on cell viability after APAP exposure. The cell viability was analyzed using WST-8 assay. Cells were treated with polaprezinc, zinc sulfate or l-carnosine at a concentration of 100 µM at 9 h before APAP (10 mM) treatment. The cell viability was measured 0, 6 or 12 h after APAP. The data are expressed as means ± SE of 7 separate experiments. PZ; polaprezinc, ZS; zinc sulfate, LC; l-carnosine. **p<0.01 vs APAP alone.
Mentions: While APAP overdoses cause liver damage in vivo and in vitro, it has been reported that overexpression of HSP70 protects APAP toxicity [13, 34, 35]. We next investigated whether polaprezinc, zinc sulfate or l-carnosine improves cell viability in mouse hepatocytes after APAP treatment (Fig. 3). The cell viability after APAP decreased in a time-dependent manner and was 55% of normal level after 12 h. Treatments of mouse hepatocytes with polaprezinc and zinc sulfate 9 h before APAP improved cell viability to 89% and 83% of normal level at 12 h, respectively, while l-carnosine treatment failed to improve the cell viability (62%).

Bottom Line: 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.

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, 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.

No MeSH data available.


Related in: MedlinePlus