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

Therapeutic effects of melatonin (MEL) in targeting CCl4-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 CCl4, which was further aimed in this experiment. Male SD rats were injected with CCl4 (1mL/kg/i.p./daily) dissolved 1:1 in olive oil for 1 month. Some animals received MEL (20mg/kg/i.p./daily) diluted in 1mL PBS in combination with CCl4 (co-treatment), and some rats were treated with MEL, beginning with injection of the last dose of CCl4 for one month (post-treatment). The groups were control, CCl4, CCl4-co vehicle, CCl4-post vehicle, post-CCl4, 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-1 (TGF-1). 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 (P0.05 vs co-treatment). Results of the present study indicated that MEL post-treatment is more powerful in reduction of CCl4-induced liver fibrosis through reduction of oxidative stress and maintenance of matrix balance. In this paper the two types of therapeutic approaches has been compared in targeting liver fibrosis induced by CCl4, and we noticed that post melatonin treatment exert better therapeutic outcomes in targeting oxidative and fibrogenic mediators in the fibrotic liver.