The Effect of Preoperative Melatonin on Nuclear Erythroid 2-Related Factor 2 Activation in Patients Undergoing Coronary Artery Bypass Grafting Surgery

Abstract

During and after coronary artery bypass grafting (CABG), oxidative stress occurs. Finding an effective way to improve antioxidant response is important in CABG surgery. It has been shown that patients with coronary heart disease have a low Melatonin production rate. The present study aimed to investigate the effects of Melatoninon nuclear erythroid 2-related factor 2(Nrf2) activity in patients undergoing CABG surgery. Thirty volunteers undergoing CABG were randomized to receive 10 mg oral Melatonin (Melatonin group, n = 15) or placebo (placebo group, n = 15) before sleeping for 1 month before surgery. The activated Nrf2 was measured twice by DNA-based ELISA method in the nuclear extract of peripheral blood mononuclear cells of patients before aortic clumps and 45 minutes after CABG operation. Melatonin administration was associated with a significant increase in both plasma levels of Melatonin and Nrf2 concentration in Melatonin group compared to placebo group, respectively (15.2 ± 4.6 pmol/L, 0.28 ± 0.01 versus 1.1 ± 0.59 pmol/L, 0.20 ± 0.07, P < 0.05). The findings of the present study provide preliminary data suggesting that Melatonin may play a significant role in the potentiation of the antioxidant defense and attenuate cellular damages resulting from CABG surgery via theNrf2 pathway.

A systematic review of peri‐operative melatonin

“…Most studies gave melatonin 30-100 min before surgery [4, 12, 14, 17-24, 27, 29-31]. One study gave melatonin daily for one month pre-operatively [28], whereas four studies gave melatonin the night before surgery, in addition to the immediate pre-operative dose [5,6,13,15]. Three studies gave melatonin at surgical incision [25,26] or after intubation [32].…”

“…Participants had various operations: abdominal [15][16][17]25, Full-text studies excluded (n = 17) -10 studies did not investigate surgical patients -3 studies were protocol studies -2 studies were not randomised -2 studies used melatonin only in combination with other drug interventions 32]; dental [27]; gynaecological [5,6,18,19,30]; ophthalmological [4,14]; orthopaedic [12]; thoracic [28,29]; urological [13]; vascular [26]; and mixed [20][21][22][23][24]31]. The anaesthetic techniques included: general anaesthesia [13,[15][16][17][18][19][20][21][22][23][24][25][26][28][29][30][31][32]; intravenous regional anaesthesia [12]; neuraxial block [5,6,20,26,31]; sedation …”

“…Melatonin had no effect on malondialdehyde, ascorbic acid, dehydroascorbic acid or C-reactive protein [25,26]. Melatonin increased intra-operative levels of nuclear factor erythroid 2-related factor 2, suggesting potentiation of the anti-oxidative response [28].…”

“…Only one out of 24 RCTs reported adequate limitation of risk of bias in all methodological domains [32]. Sample size calculations were inadequately documented in 7/24 RCTs, increasing the risk of false negative findings (type-2 errors) [4,17,23,24,28,30,32]. A primary outcome was not documented in 14/24 RCTs [12, 14, 15, 17-20, 22-24, 27-30].…”

“…pulmonary oedema [45,46]. Haghjooy et al demonstrated that prolonged melatonin treatment induces anti-oxidant enzyme activity in patients undergoing coronary artery bypass grafts [28]. In infants, anti-oxidative effects of high-dose melatonin administration (up to 10 repeated administrations of 10 mg.kg À1 bodyweight over 72 h) have been correlated to clinical outcomes [8,[47][48][49].…”