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 (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 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-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 CCl4 -induced liver fibrosis through reduction of oxidative stress and maintenance of matrix balance.