Protective Effects of Melatonin against Severe Burn-Induced Distant Organ Injury: A Systematic Review and Meta-Analysis of Experimental Studies

Dewan Md Sumsuzzman,Jeonghyun Choi,Yonggeun Hong,Zeeshan Ahmad Khan

doi:10.3390/antiox9121196

Dewan Md Sumsuzzman, Jeonghyun Choi + Show 2 more

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https://doi.org/10.3390/antiox9121196

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Abstract

Extensive burns result in a local wound response and distant-organ injury (DOI) caused by oxidative-stress and inflammation. Melatonin (MT) shows promise in alleviating oxidative-stress and inflammation, but its role in thermal injury is largely unexplored. The present systematic review and meta-analysis were designed to assess the effects of MT on oxidative-stress and inflammatory markers against severe burn-induced DOI. Mean difference (MD)/standard mean difference (SMD) with 95% confidence interval (CI) were estimated using fixed-effect/random-effects models. Eighteen experimental studies met the inclusion criteria. Compared with the control group, MT significantly decreased the levels of malondialdehyde (SMD, −1.03; 95% CI, −1.30, −0.76, p < 0.00001) and 4-hydroxynonenal (MD, −1.06; 95% CI, −1.57, −0.56, p < 0.0001). Additionally, MT increased the levels of glutathione (SMD, 1.94; 95% CI, 1.27, 2.61, p < 0.00001) and superoxide-dismutase (SMD, 0.76; 95% CI, 0.08, 1.45, p = 0.03). Finally, MT significantly decreased the levels of tumor necrosis factor-α (SMD, −1.34; 95% CI, −1.92 to −0.77; p < 0.00001) and C-reactive protein (MD, −12.67; 95% CI, −16.72 to −8.62; p < 0.00001). Meta-analysis indicates that severe burn followed by immediate MT (10 mg/kg) intervention shows significant beneficial effects after 24-h against DOI by regulating oxidative-stress and the inflammatory response.

Highlights

Burns represent complex traumatic skin injuries caused mainly by heat, radiation, electricity, abrasion, or exposure to chemicals [1]
Accumulating evidence demonstrates that the inflammatory response and oxidative stress contribute to the progression of distant organ injury (DOI) following severe burns [8,11,12,13]
Because the oxidizing agent may originate from neutrophils sequestered in systemic organs as a systemic inflammatory reaction to a local burn insult [28], agents that suppress neutrophil activation and adherence might protect against thermal injury [29]

Summary

Introduction

Burns represent complex traumatic skin injuries caused mainly by heat, radiation, electricity, abrasion, or exposure to chemicals [1]. Accumulating evidence demonstrates that the inflammatory response and oxidative stress contribute to the progression of distant organ injury (DOI) following severe burns [8,11,12,13]. Antioxidants are administered during the post-burn period to restore the oxidant-antioxidant balance and attenuate the inflammatory response, blood coagulation, and tissue injury [15,31,32]. Despite this knowledge, it is surprising that still, the clinical application of anti-oxidant therapy as an adjunct to burn care is limited [33]. Evidence synthesis is urgently required to study the role of anti-oxidants in burn injury, including potent antioxidants with anti-inflammatory, and immunomodulatory biomolecule like melatonin [36,37,38]

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