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

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 (CCl)-induced liver fibrosis reduction. Thirty-two male Sprague-Dawley rats were divided into 4 groups: normal; fibrosis with CCl 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 CCl. 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 CCl 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.

Effects of Melatonin on Liver Injuries and Diseases

“…In a study, it was demonstrated that melatonin attenuated CCl 4 -induced liver fibrosis through preventing necroptosis-associated inflammatory signaling. Melatonin reduced hepatic hydroxyproline content, hepatocellular damage, and transforming growth factor β1 and α-smooth muscle actin expression [145,146]. Moreover, melatonin significantly attenuated RIP1 expression, RIP1 and RIP3 necrosome complex formation, and mixed lineage kinase domain-like protein level in the liver [145].…”

Human hepatocellular carcinoma: Protection by melatonin

“…Melatonin is a secretory product of the pineal gland and gastrointestinal tract during night and daytime, respectively (Margheri et al, ). Melatonin is responsible for a variety of physiological functions (Mortezaee, Khanlarkhani, Sabbaghziarani et al, ; Mortezaee, Sabbaghziarani et al, ), including antioxidant (Mortezaee & Khanlarkhani, ; Mortezaee et al, ; Mortezaee, Khanlarkhani, Beyer, & Zendedel, ), anti‐apoptotic (Mortezaee, Majidpoor, Daneshi, Abouzaripour, & Abdi, ), and pro‐apoptotic (Lin et al, ) activities. Melatonin is the only known chronobotic hormone for regulation of neoplastic cell growth (Blask, Sauer, & Dauchy, ).…”

Melatonin application in targeting oxidative‐induced liver injuries: A review

“…CCl 4 has been used as the most common experimental model of chemically induced liver fibrosis (Ogeturk et al, ) and cirrhosis (Oliveira‐Junior et al, ) in rodents causing damages resemble those seen in human subjects (Mortezaee, Sabbaghziarani, et al, ). Metabolization of CCl 4 produces • CCl 3 that reacts with O 2 to form CCl 3 (Shaker et al, ).…”