Effect of melatonin on oxidative stress indicators in animal models of fibrosis: A systematic review and meta-analysis

Background and objective: Imbalance of oxidative stress has been detected in a range of fibrotic diseases. Melatonin as an indoleamine hormone plays an important role in regulating the circadian rhythm of human, while in recent years, its antioxidant effect has also attracted increasing attention. This study aimed to perform a systematic review and meta-analysis to comprehensively evaluate the antioxidant effect of melatonin in animal models of fibrosis.Methods: The PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang database, China Science and Technology Journal Database (VIP), and SinoMed databases were searched from inception to March 1st, 2022 to retrieve eligible studies that evaluated the effect of melatonin supplementation on the levels of malondialdehyde (MDA), lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) in animal models of fibrosis.Results: A total of 64 studies were included in this meta-analysis. The results showed that melatonin supplementation significantly reduced the levels of oxidative indicators including MDA (P < 0.00001), LPO (P < 0.00001) and NO (P < 0.0001), and elevated the levels of antioxidant indicators including GSH (P < 0.00001), GPx (P < 0.00001) and SOD (P < 0.00001) in fibrotic diseases.Conclusions: Our research findings showed that melatonin supplementation could significantly reduce the levels of oxidative indicators including MDA, LPO and NO and elevate the levels of antioxidant indicators including GSH, GPx and SOD so as to correct oxidative stress in animal models of fibrosis. However, no significant changes were observed in CAT level. More clinical studies are needed to further confirm the beneficial role of melatonin in fibrotic diseases.