Therapeutic value of melatonin post-treatment on CCl4-induced fibrotic rat liver.

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. Thirty-two male Sprague-Dawley rats were divided into 4 groups: normal; fibrosis with CCl4 injection (1 mL/kg) twice weekly for 8 weeks; phosphate-buffered saline (PBS); and melatonin (20 mg/kg) for a further 4 weeks on cessation of CCl4. At the beginning of week 13, liver tissue samples were used for hematoxylin-eosin (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 3, 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, macro- and 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.