Antioxidant and Analgesic Effect of Melatonin Involving Sirtuin 1: A Randomised Pilot Clinical Study

Melatonin is a potent antioxidant molecule, and its analgesic effects have been observed in children. However, the underlying mechanisms of these effects have not yet been fully explored in clinical studies. We tested the hypothesis that melatonin reduces pain and oxidative stress involving the sirtuin pathway. Forty-four children were randomly assigned to oral supplementation with melatonin or placebo before induction of anaesthesia for surgery. Plasma levels of 4-hydroxynonenal (4-HNE), melatonin, sirtuin 1 (SIRT1) and circulating miR-34 and miR-124a were analysed at T0 (pre-hospitalisation), T1 (before surgery) and T2 (1 h after the end of the surgery). Melatonin decreased 4-HNE and increased SIRT1 concentrations at T2 in supplemented children. Significant correlations were found between melatonin and pain score (R = −0.404), 4-HNE and pain score (R = 0.44), melatonin and 4-HNE (R = 0.42), 4-HNE and SIRT1 (R = −0.43) and melatonin and SIRT1 (R = 0.41) at T2. Circulating miR-34 and miR-124a modulation were also observed. The reduction of oxidative stress and the modulation of circulating miR-34 and miR-124a, which target SIRT1 activity, suggest a novel pathway underlying melatonin's antioxidant and analgesic effects. Trial Registration: ClinicalTrials.gov identifier: NCT06724432.