RETRACTED: Post‐treatment of melatonin with CCl₄ better reduces fibrogenic and oxidative changes in liver than melatonin co‐treatment

Abstract

Therapeutic effects of melatonin (MEL) in targeting CCl -induced liver fibrosis has been widely known, but there is no study comparing oxidative and fibrogenic changes in co- and post-treatment of MEL with CCl , which was further aimed in this experiment. Male SD rats were injected with CCl (1 mL/kg/i.p./daily) dissolved 1:1 in olive oil for 1 month. Some animals received MEL (20 mg/kg/i.p./daily) diluted in 1 mL PBS in combination with CCl (co-treatment), and some rats were treated with MEL, beginning with injection of the last dose of CCl for one month (post-treatment). The groups were control, CCl , CCl -co vehicle, CCl -post vehicle, post-CCl , MEL co-treatment, and MEL post-treatment. MEL post-treatment group showed significantly lower lipid deposition, serum malondialdehyde (MDA), serum alanine aminotransferase (ALT), and liver hydroxyproline. This group also had low expressions of Bax and transforming growth factor-β1 (TGF-β1). MEL post-treatment group revealed higher sera levels of albumin, superoxide dismutase (SOD) and glutathione peroxidase (GPx). Expression levels of metalloproteinase-13 (MMP-13) and Bcl2 was also higher in this group (P ≤ 0.05 vs co-treatment). Results of the present study indicated that MEL post-treatment is more powerful in reduction of CCl -induced liver fibrosis through reduction of oxidative stress and maintenance of matrix balance.

Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies

“…injection) for CCl 4 ‐administered rats decreased serum ALT and AST levels, as well as liver fibrosis by inhibiting expression of TGF‐β1 and VEGF‐A in the liver . Although both melatonin treatments before or after CCl 4 administration have protective effects on CCl 4 ‐induced liver injury, a study demonstrated that post‐treatment had better therapeutic effects compared to co‐treatment in CCl 4 ‐administered rats . Another study demonstrated therapeutic effects of melatonin administration (5 or 10 mg/kg per day, i.p.…”

“…67,68 Although both melatonin treatments before or after CCl 4 administration have protective effects on CCl 4 -induced liver injury, 69 a study demonstrated that post-treatment had better therapeutic effects compared to co-treatment in CCl 4 -administered rats. 70 Another study demonstrated therapeutic effects of melatonin administration (5 or 10 mg/kg per day, i.p. injection) against CCl 4 -induced liver injury in mice with decreased liver fibrosis levels.…”

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, ).…”

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and liver fibrosis: A review

“…Carbon tetrachloride (CCl 4 ) and bile duct ligation (BDL) are common models for induction of liver fibrosis . NOX1, NOX2, and probably NOX4 play a role in the two models .…”

“…10 Unlike the other types of NOXs, activation of NOX4 does not require additional cytosolic modulators, indicating constitutive activation of this isoform primarily at the transcriptional level during fibrogenesis. 24 Carbon tetrachloride (CCl 4 ) [25][26][27][28][29] and bile duct ligation (BDL) are common models for induction of liver fibrosis. 15 NOX1, NOX2, and probably NOX4 play a role in the two models.…”