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J Physiol Pharmacol. 2015 Aug;66(4):567-79.

Protective effects of melatonin against thioacetamide-induced liver fibrosis in rats.

Author information

1
Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Lublin, Poland.
2
Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Lublin, Poland. celinski.krzysztof@gmail.com.
3
Chair and Department of Clinical Pathomorphology, Medical University of Lublin, Lublin, Poland.
4
Chair and Department of Clinical Pathophysiology, Medical University of Lublin, Lublin, Poland.
5
Independent Laboratory of Medical Biology, Medical University of Lublin, Lublin, Poland.
6
Chair and Department of Clinical Immunology, Medical University of Lublin, Lublin, Poland.
7
Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, USA.

Abstract

The aim of this study was to determine the effect of melatonin on thioacetamide (TAA) induced liver fibrosis in rats. The antifibrotic effects of melatonin were assessed by determining activity indirect markers of fibrosis: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and proinflammatory cytokines: interleukin 6 (IL-6), interleukin-1beta (IL-1β), tumour necrosis factor alpha (TNF-α), transforming growth factor-beta (TGF-β) and platelet-derived growth factor (PDGF). Parameters of oxidative stress: oxidised glutathione (GSSG), reduced glutathione (GSH) and presaged activity of paraoxonase 1 (PON-1), an antioxidative enzyme were determined. Inflammatory changes and fibrosis extent were evaluated histologically. Experiments were carried out in Wistar rats. Animals were divided into 4 groups: I - controls, water ad libitum for 12 weeks, group II - TAA, 300 mg/L ad libitum for 12 weeks, III - melatonin, 10 mg/kg b.w. intraperitoneally (i.p.) daily for 4 weeks, IV - TAA, 300 mg/L ad libitum for 12 weeks followed by melatonin, 10 mg/kg/b.w. i.p. daily for 4 weeks. Results of serum determinations demonstrated significantly lower activity of AST, ALT and AP in the group receiving TAA followed by melatonin compared to the group receiving only TAA. Immunoenzymatic findings on effect of melatonin on concentration of proinflammatory cytokines confirmed these data. Biochemical examinations in liver homogenates revealed statistically significant improvement (concentration of GSH increases and concentration of GSSG decreases) in animals with TAA-induced liver damage receiving melatonin. Moreover, the activity of PON-1 toward phenyl acetate and paraoxon was increased in liver homogenates and serum in the group receiving TAA followed by melatonin compared to the TAA group without melatonin treatment. Microscopic evaluation disclosed inhibitory effects of melatonin on inflammatory changes and extent of liver fibrosis.

PMID:
26348081
[Indexed for MEDLINE]
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