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Polaprezinc attenuates liver fibrosis in a mouse model of non-alcoholic steatohepatitis.
J Gastroenterol Hepatol. 2008 Dec; 23(12):1909-16.JG

Abstract

BACKGROUND AND AIM

The effect of polaprezinc, a zinc-carnosine chelate compound, on the development of non-alcoholic steatohepatitis (NASH) was investigated in dietary methionine and choline deficient (MCD) mice.

METHODS

Mice were fed the MCD diet with or without polaprezinc (2.2 g/kg diet) for 10 weeks. Liver histopathology, triglyceride and lipid peroxide levels, and the expression of genes linked to fibrosis were then assessed.

RESULTS

MCD mice developed steatohepatitis accompanied by mild fibrosis with an increase in lipid peroxidation, hepatic stellate cell (HSC) activation, and the augmented mRNA expression of tumor necrosis factor-alpha, transforming growth factor-beta1 and procollagen alpha1(I). The mRNA expression levels of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were also enhanced. Histopathologically, polaprezinc supplementation did not influence the development of steatosis but it apparently attenuated fibrosis. Polaprezinc slightly reduced lipid peroxidation and suppressed HSC activation as well as the mRNA expression of pro-inflammatory cytokines. Polaprezinc affected the MCD diet-enhanced expression of TIMP-1 even when administered relatively late.

CONCLUSION

These results suggest that polaprezinc attenuates fibrosis in NASH by reducing inflammation and lipid peroxidation and, during a later phase, promoting fibrolysis via the inhibition of TIMP expression in the liver. Further investigation is required to clarify the clinical efficacy of polaprezinc in patients with NASH.

Authors+Show Affiliations

Division of Pathophysiology, Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. suginoh@pharm.kitasato-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18422963

Citation

Sugino, Haruko, et al. "Polaprezinc Attenuates Liver Fibrosis in a Mouse Model of Non-alcoholic Steatohepatitis." Journal of Gastroenterology and Hepatology, vol. 23, no. 12, 2008, pp. 1909-16.
Sugino H, Kumagai N, Watanabe S, et al. Polaprezinc attenuates liver fibrosis in a mouse model of non-alcoholic steatohepatitis. J Gastroenterol Hepatol. 2008;23(12):1909-16.
Sugino, H., Kumagai, N., Watanabe, S., Toda, K., Takeuchi, O., Tsunematsu, S., Morinaga, S., & Tsuchimoto, K. (2008). Polaprezinc attenuates liver fibrosis in a mouse model of non-alcoholic steatohepatitis. Journal of Gastroenterology and Hepatology, 23(12), 1909-16. https://doi.org/10.1111/j.1440-1746.2008.05393.x
Sugino H, et al. Polaprezinc Attenuates Liver Fibrosis in a Mouse Model of Non-alcoholic Steatohepatitis. J Gastroenterol Hepatol. 2008;23(12):1909-16. PubMed PMID: 18422963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polaprezinc attenuates liver fibrosis in a mouse model of non-alcoholic steatohepatitis. AU - Sugino,Haruko, AU - Kumagai,Naoki, AU - Watanabe,Sakiko, AU - Toda,Kyoko, AU - Takeuchi,Osamu, AU - Tsunematsu,Satoshi, AU - Morinaga,Shojiroh, AU - Tsuchimoto,Kanji, Y1 - 2008/04/19/ PY - 2008/4/22/pubmed PY - 2009/4/10/medline PY - 2008/4/22/entrez SP - 1909 EP - 16 JF - Journal of gastroenterology and hepatology JO - J. Gastroenterol. Hepatol. VL - 23 IS - 12 N2 - BACKGROUND AND AIM: The effect of polaprezinc, a zinc-carnosine chelate compound, on the development of non-alcoholic steatohepatitis (NASH) was investigated in dietary methionine and choline deficient (MCD) mice. METHODS: Mice were fed the MCD diet with or without polaprezinc (2.2 g/kg diet) for 10 weeks. Liver histopathology, triglyceride and lipid peroxide levels, and the expression of genes linked to fibrosis were then assessed. RESULTS: MCD mice developed steatohepatitis accompanied by mild fibrosis with an increase in lipid peroxidation, hepatic stellate cell (HSC) activation, and the augmented mRNA expression of tumor necrosis factor-alpha, transforming growth factor-beta1 and procollagen alpha1(I). The mRNA expression levels of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were also enhanced. Histopathologically, polaprezinc supplementation did not influence the development of steatosis but it apparently attenuated fibrosis. Polaprezinc slightly reduced lipid peroxidation and suppressed HSC activation as well as the mRNA expression of pro-inflammatory cytokines. Polaprezinc affected the MCD diet-enhanced expression of TIMP-1 even when administered relatively late. CONCLUSION: These results suggest that polaprezinc attenuates fibrosis in NASH by reducing inflammation and lipid peroxidation and, during a later phase, promoting fibrolysis via the inhibition of TIMP expression in the liver. Further investigation is required to clarify the clinical efficacy of polaprezinc in patients with NASH. SN - 1440-1746 UR - https://www.unboundmedicine.com/medline/citation/18422963/Polaprezinc_attenuates_liver_fibrosis_in_a_mouse_model_of_non_alcoholic_steatohepatitis_ L2 - https://doi.org/10.1111/j.1440-1746.2008.05393.x DB - PRIME DP - Unbound Medicine ER -