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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

Inhibition by KNK437 against HSP70 induction and prevention of APAP toxicity by polaprezinc. Cells were treated with KNK437 of 50 µM at 6 h before polaprezinc (PZ) treatment. (A) After 6 h, cells were incubated in the presence of 100 µM polaprezinc for 9 h. HSP70 expression was analyzed by Western blot. (B) After incubation with KNK437 for 6 h followed by polaprezinc for 9 h, cells were treated with 10 mM APAP. The cell viability was measured at 12 h after APAP. The data are expressed as means ± SE of 3–7 separate experiments. *p<0.05 vs PZ alone (in A), #p<0.05 vs PZ + APAP (in B).
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Figure 6: Inhibition by KNK437 against HSP70 induction and prevention of APAP toxicity by polaprezinc. Cells were treated with KNK437 of 50 µM at 6 h before polaprezinc (PZ) treatment. (A) After 6 h, cells were incubated in the presence of 100 µM polaprezinc for 9 h. HSP70 expression was analyzed by Western blot. (B) After incubation with KNK437 for 6 h followed by polaprezinc for 9 h, cells were treated with 10 mM APAP. The cell viability was measured at 12 h after APAP. The data are expressed as means ± SE of 3–7 separate experiments. *p<0.05 vs PZ alone (in A), #p<0.05 vs PZ + APAP (in B).

Mentions: To confirm that increase of HSP70 expression by polaprezinc exerts a protective effect against APAP toxicity, we investigated whether KNK437 inhibits HSP70 expression in mouse hepatocytes following polaprezinc treatment and abrogates the protective effect of polaprezinc on APAP toxicity. Treatment with KNK437 at 6 h before polaprezinc suppressed the polaprezinc-induced HSP70 expression by 58% (Fig. 6A). Furthermore, the protective effect of polaprezinc on the cell viability at 12 h after APAP treatment was completely suppressed by KNK437 pretreatment (Fig. 6B).


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)

Inhibition by KNK437 against HSP70 induction and prevention of APAP toxicity by polaprezinc. Cells were treated with KNK437 of 50 µM at 6 h before polaprezinc (PZ) treatment. (A) After 6 h, cells were incubated in the presence of 100 µM polaprezinc for 9 h. HSP70 expression was analyzed by Western blot. (B) After incubation with KNK437 for 6 h followed by polaprezinc for 9 h, cells were treated with 10 mM APAP. The cell viability was measured at 12 h after APAP. The data are expressed as means ± SE of 3–7 separate experiments. *p<0.05 vs PZ alone (in A), #p<0.05 vs PZ + APAP (in B).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 6: Inhibition by KNK437 against HSP70 induction and prevention of APAP toxicity by polaprezinc. Cells were treated with KNK437 of 50 µM at 6 h before polaprezinc (PZ) treatment. (A) After 6 h, cells were incubated in the presence of 100 µM polaprezinc for 9 h. HSP70 expression was analyzed by Western blot. (B) After incubation with KNK437 for 6 h followed by polaprezinc for 9 h, cells were treated with 10 mM APAP. The cell viability was measured at 12 h after APAP. The data are expressed as means ± SE of 3–7 separate experiments. *p<0.05 vs PZ alone (in A), #p<0.05 vs PZ + APAP (in B).
Mentions: To confirm that increase of HSP70 expression by polaprezinc exerts a protective effect against APAP toxicity, we investigated whether KNK437 inhibits HSP70 expression in mouse hepatocytes following polaprezinc treatment and abrogates the protective effect of polaprezinc on APAP toxicity. Treatment with KNK437 at 6 h before polaprezinc suppressed the polaprezinc-induced HSP70 expression by 58% (Fig. 6A). Furthermore, the protective effect of polaprezinc on the cell viability at 12 h after APAP treatment was completely suppressed by KNK437 pretreatment (Fig. 6B).

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