Therapeutic Value of Melatonin Post-Treatment on Ccl4-Induced Fibrotic Rat Liver Publisher



Mortezaee K¹ ; Sabbaghziarani F¹ ; Omidi A¹ ; Dehpour AR² ; Omidi N³ ; Ghasemi S¹ ; Pasbakhsh P¹ ; Kashani IR¹ Show Affiliations
Source: Canadian Journal of Physiology and Pharmacology Published:2016

Abstract

Melatonin is known for being beneficial in targeting liver diseases. This study aimed to investigate whether melatonin post-treatment is capable of rat carbon tetrachloride (CCl4)– induced liver fibrosis reduction. 32 male Sprague-Dawley rats were divided into four groups: normal; fibrosis with CCl4 injection (1ml/kg) twice weekly for eight weeks; phosphatebuffered saline (PBS); and melatonin (20 mg/kg) for the further four weeks once CCl4 cessation. At the beginning of week thirteen, liver tissue samples were used for hematoxylineosin (H&E), Periodic acid-Schiff (PAS), Masson’s trichrome (MT), and Oil Red O staining, quantitative real-time PCR (qRT-PCR) analysis of the matrix metalloproteinase-9 (MMP-9), MMP-13, transforming growth factor-β1 (TGF-β1), Bcl-2, and Bax genes as well as immunofluorescence (IF) of the first three, and sera for measurement of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and hydroxyproline. Chronic administration of CCl4 followed by considerable increase in tissue disruption, macroand micro-vesicles, collagen, lipid droplets (LDs), AST, ALT, hydroxyproline, TGF-β1, and Bax, and decrease in glycogen depository, albumin, Bcl-2, MMP-9, and MMP-13; however, the pattern was reverse when it comes to melatonin treatment (for all p < 0.05). Our results reveal the beneficial aspects of melatonin in treatment of liver fibrosis probably via inhibition of TGF-β1expression. © 2016, Canadian Science Publishing. All rights reserved.