Melatonin can be, more effective than N-acetylcysteine, protecting acute lung injury induced by intestinal ischemia-reperfusion in rat model

Alberto Andrade Leite,Russel Joseph Reiter,Julio Cezar Mendes Brandão,Thiago Mamoru Sakae,Marcia Marinho,Celia Regina Camargo,Itamar Souza Oliveira-Junior

doi:10.6061/clinics/2021/e2513

Abstract

OBJECTIVES:The current study compared the impact of pretreatment with melatonin and N-acetylcysteine (NAC) on the prevention of rat lung damage following intestinal ischemia-reperfusion (iIR).METHODS:Twenty-eight Wistar rats were subjected to intestinal ischemia induced by a 60 min occlusion of the superior mesenteric artery, followed by reperfusion for 120 min. Animals were divided into the following groups (n=7 per group): sham, only abdominal incision; SS+iIR, pretreated with saline solution and iIR; NAC+iIR, pretreated with NAC (20 mg/kg) and iIR; MEL+iIR, pretreated with melatonin (20 mg/kg) and iIR. Oxidative stress and inflammatory mediators were measured and histological analyses were performed in the lung tissues.RESULTS:Data showed a reduction in malondialdehyde (MDA), myeloperoxidase (MPO), and TNF-alpha in the animals pretreated with NAC or MEL when compared to those treated with SS+iIR (p<0.05). An increase in superoxide dismutase (SOD) levels in the NAC- and MEL-pretreated animals as compared to the SS+iIR group (34±8 U/g of tissue; p<0.05) was also observed. TNF-α levels were lower in the MEL+iIR group (91±5 pg/mL) than in the NAC+iIR group (101±6 pg/mL). Histological analysis demonstrated a higher lung lesion score in the SS+iIR group than in the pretreated groups.CONCLUSION:Both agents individually provided tissue protective effect against intestinal IR-induced lung injury, but melatonin was more effective in ameliorating the parameters analyzed in this study.

Highlights

Intestinal ischemia-reperfusion occurs in many clinical situations, including ischemic colitis, acute mesenteric ischemia, septic shock, hemorrhagic or traumatic shock, small bowel transplantation, severe burns, and other conditions that contribute to organ failure with high mortality rates of up to 60% [1,2,3,4]
Lungs are highly susceptible to such injuries and the resulting condition is clinically defined as acute respiratory distress syndrome (ARDS) and is a primary component of multiple organ dysfunction syndrome (MODS)
Blood gas analysis (Figure 1) demonstrated a reduction in the oxygen index (PaO2/FiO2) in the SS+iIR group when compared with the NAC and MEL-pretreated groups

Summary

Introduction

Intestinal ischemia-reperfusion (iIR) occurs in many clinical situations, including ischemic colitis, acute mesenteric ischemia, septic shock, hemorrhagic or traumatic shock, small bowel transplantation, severe burns, and other conditions that contribute to organ failure with high mortality rates of up to 60% [1,2,3,4]. Received for publication on October 12, 2020. Accepted for publication on March 18, 2021. In iIR, the inflammatory response can occur in organs remote from the point of insult [5], resulting in multiple organ dysfunction syndrome (MODS) [6]. Lungs are highly susceptible to such injuries and the resulting condition is clinically defined as acute respiratory distress syndrome (ARDS) and is a primary component of MODS. It is important to develop therapies and strategies for the prevention and treatment of ARDS after iIR

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Conclusion