Polaprezinc prevents ongoing thioacetamide-induced liver fibrosis in rats
Autor: | Toshiyuki Asama, Masashi Yoneda, Hiroyuki Furukawa, Taishi Okayama, Yoshiaki Ebisawa, Kouji Imai, Toru Kono, Hidenori Karasaki, Naoyuki Chisato |
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Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Liver Cirrhosis
Male medicine.medical_specialty Cirrhosis Carnosine chemistry.chemical_element Zinc Thioacetamide Polaprezinc Antioxidants General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Fibrosis Internal medicine Organometallic Compounds medicine Animals Rats Wistar General Pharmacology Toxicology and Pharmaceutics General Medicine medicine.disease Rats Amino acid complex Oxidative Stress Endocrinology Biochemistry chemistry Zinc Compounds Zinc deficiency Hepatic fibrosis |
Zdroj: | Life Sciences. 90(3-4):122-130 |
ISSN: | 0024-3205 |
Popis: | Author Aims: Cirrhotic patients commonly have a liver zinc deficiency, which may aggravate liver fibrosis due to the lack of antioxidative effects of zinc. This study examined the ability of polaprezinc, N-(3-aminopropionyl)-Lhistidinato zinc, to prevent fibrosis in a rat model of thioacetamide (TAA)-induced hepatic fibrosis. Main methods: Liver cirrhosis was induced by orally administering TAA for 20 weeks. The rats were cotreated with one of the following for the last 10 weeks of TAA treatment: (1) polaprezinc (50 or 200 mg/kg/day); (2) L-carnosine (155 mg/kg/day),which contained equal amounts of L-carnosine as 200 mg/kg/day polaprezinc; (3) zinc sulfate (112 mg/kg/day) or (4) zinc-L-aspartic complex (317.8 mg/kg/day). Both zinc supplementations contained equal amounts of zinc as high-dose polaprezinc. Key findings: Hepatic zinc levels fell significantly in rats treated with TAA for 20 weeks. Cotreating with high-dose polaprezinc and zinc-L-aspartic complex for 10 weeks prevented hepatic zinc loss. Hepatic hydroxyproline and tissue inhibitor of metalloproteinases-1 (TIMP-1) were significantly higher in rats treated with TAA for 20 weeks than 10 weeks, whereas polaprezinc prevented changes in these fibrosis markers and reduced hepatic transforming growth factor-β1 protein concentration, macroscopic and histologic changes. TAA caused oxidative stress-related changes in the liver that were prevented by high-dose polaprezinc and partially by zinc-L-aspartic complex. Treatment with L-carnosine, low-dose polaprezinc or zinc sulfate for 10 weeks did not affect liver fibrosis progression or oxidative stress-related changes. Significance: Polaprezincmay prevent ongoing fibrosis by preventing zinc depletion, oxidative stress and fibrosis markers in cirrhotic livers. |
Databáze: | OpenAIRE |
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