By:Lebda, MA (Lebda, Mohamed A.)1 ] Sadek, KM (Sadek, Kadry M.)2 ] Abouzed, TK (Abouzed, Tarek K.)3 ] Tohamy, HG (Tohamy, Hossam G.)4 ] El-Sayed, YS (El-Sayed, Yasser S.)5 ]

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Volume: 192


Pages: 136-143

DOI: 10.1016/j.lfs.2017.11.036

Published: JAN 1 2018

Document Type:Article

http://0810oh5mq.1104.y.http.apps.webofknowledge.com.mplbci.ekb.eg/openoverlay.do?action=JCRoverlayIF&product=WOS&SID=F4SdJ3kXgRSJsYlQLhK&cacheurl=no&excludeEventConfig=ExcludeIfFromFullRecPage');" tabindex="0" oncontextmenu="javascript:return IsAllowedRightClick(this);" hasautosubmit="true" style="margin: 0px; list-style: none; padding: 0px; color: rgb(0, 90, 132); text-decoration: none; outline: rgb(248, 248, 248) solid 2px !important; border: 1px solid rgb(248, 248, 248) !important;">View Journal Impact


Aims: The potential antifibrotic effects of melatonin against induced hepatic fibrosis were explored. 

Main methods: Rats were allocated into four groups: placebo; thioacetamide (TAA) (200 mg/kg bwt, i.p twice weekly for two months); melatonin (5 mg/kg bwt, i.p daily for a week before TAA and continued for an additional two months); and melatonin plus TAA. Hepatic fibrotic changes were evaluated biochemically and histopathologically. Hepatic oxidative/antioxidative indices were assessed. The expression of hepatic proinflammatory cytokines (tumor necrosis factor-alpha, and interleukin-1 beta), fibrogenic-related genes (transforming growth factor-1 beta, collagen I, collagen, III, laminin, and autotaxin) and an antioxidant-related gene (thioredoxin-1) were detected by qRT-PCR. 

Key findings: In fibrotic rats, melatonin lowered serum aspartate aminotransferase, alanine aminotransferase, and autotaxin activities, bilirubin, hepatic hydroxyproline and plasma ammonia levels. Melatonin displayed hepatoprotective and antifibrotic potential as indicated by mild hydropic degeneration of some hepatocytes and mild fibroplasia. In addition, TAA induced the depletion of glutathione, glutathione s-transferase, glutathione peroxidase, superoxide dismutase, catalase, and paraoxonase-1 (PON-1), while inducing the accumulation of malondialdehyde, protein carbonyl (C = O) and nitric oxide (NO), and DNA fragmentation. These effects were restored by melatonin pretreatment. Furthermore, melatonin markedly attenuated the expression of proinflammatory cytokines and fibrogenic genes via the upregulation of thioredoxin-1 mRNA transcripts. 

Significance: Melatonin exhibits potent anti-inflammatory, antioxidant and fibrosuppressive activities against TAA-induced hepatic fibrogenesis via the suppression of oxidative stress, DNA damage, proinflammatory cytokines and fibrogenic gene transcripts. In addition, we demonstrate that the antifibrotic activity of melatonin is mediated by the induction of thioredoxin-1 with attenuation of autotaxin expressions.

Author Information

Reprint Address: El-Sayed, YS (reprint author)

Show more Damanhur Univ, Fac Vet Med, Dept Forens Med & Toxicol, Damanhour 22511, Egypt.


Show more [ 1 ] Alexandria Univ, Fac Vet Med, Dept Biochem, Alexandria, Egypt
Show more [ 2 ] Damanhur Univ, Fac Vet Med, Dept Biochem, Damanhour, Egypt
Show more [ 3 ] Kafr Elsheikh Univ, Fac Vet Med, Dept Biochem, Kafr Al Sheikh, Egypt
Show more [ 4 ] Alexandria Univ, Fac Vet Med, Dept Pathol, Alexandria, Egypt
Show more [ 5 ] Damanhur Univ, Fac Vet Med, Dept Forens Med & Toxicol, Damanhour 22511, Egypt

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Funding AgencyGrant Number
Egyptian Knowledge Bank (EKB)   
Egyptian Specialized Presidential Council for Education and Scientific Research   
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Categories / Classification

Research Areas:Research & Experimental Medicine; Pharmacology & Pharmacy

Web of Science Categories:Medicine, Research & Experimental; Pharmacology & Pharmacy