Evelyn Thais Fantozzi1, Sara Rodrigues-Garbin1, Fernanda Yamamoto Ricardo-da-Silva2, Ricardo Martins Oliveira-Filho1, Domenico Spina3, Wothan Tavares-de-Lima1, Yanira Riffo-Vasquez4. 1. Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. 2. Laboratory of Cardiovascular Surgery and Physiopathology of Circulation (LIM-11), Heart Institute (InCor), Medicine School, University of Sao Paulo, Brazil. 3. Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, UK. 4. Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, UK. Electronic address: yanira.vasquez@kcl.ac.uk.
Abstract
RATIONAL: Acute lung injury (ALI) is a common complication after intestinal ischemia and reperfusion (I/R) injury that can lead to acute respiratory distress syndrome (ARDS). We have previously demonstrated that females are protected against lung damage induced by intestinal I/R through an estrogen mediated mechanism. OBJECTIVES: To investigate the effect of obesity on ALI induced by intestinal I/R in female mice. METHODS: C57Bl/6 female mice were fed with a standard low-fat diet (SD) or a high-fat diet (HFD) for 9 weeks. Intestinal I/R injury was induced by a 45 min occlusion of the mesenteric artery followed by 2 and 24 h of reperfusion. RESULTS: Significant increase in lung myeloperoxidase expression (MPO) and neutrophil numbers of SD and HFD mice occurred at 2 h and 24 h of reperfusion. Furthermore, HFD mice presented a significant increase in lung eosinophil peroxidase (EPO) expression and eosinophil numbers compared to SD mice. Lung wet/dry weight ratio was significantly greater in HFD mice at 2 and 24 h of reperfusion, accompanied by a significant increase in the expression of inducible NO in the lung tissue and a significant decrease in arterial oxygen saturation at 24 h of reperfusion relative to SD mice. CONCLUSION: Obesity predisposes female mice to increased pulmonary oedema and deterioration in gas exchange, which is accompanied by an increase in iNOS expression in the lung.
RATIONAL: Acute lung injury (ALI) is a common complication after intestinal ischemia and reperfusion (I/R) injury that can lead to acute respiratory distress syndrome (ARDS). We have previously demonstrated that females are protected against lung damage induced by intestinal I/R through an estrogen mediated mechanism. OBJECTIVES: To investigate the effect of obesity on ALI induced by intestinal I/R in female mice. METHODS: C57Bl/6 female mice were fed with a standard low-fat diet (SD) or a high-fat diet (HFD) for 9 weeks. Intestinal I/R injury was induced by a 45 min occlusion of the mesenteric artery followed by 2 and 24 h of reperfusion. RESULTS: Significant increase in lung myeloperoxidase expression (MPO) and neutrophil numbers of SD and HFD mice occurred at 2 h and 24 h of reperfusion. Furthermore, HFD mice presented a significant increase in lung eosinophil peroxidase (EPO) expression and eosinophil numbers compared to SDmice. Lung wet/dry weight ratio was significantly greater in HFD mice at 2 and 24 h of reperfusion, accompanied by a significant increase in the expression of inducible NO in the lung tissue and a significant decrease in arterial oxygen saturation at 24 h of reperfusion relative to SDmice. CONCLUSION:Obesity predisposes female mice to increased pulmonary oedema and deterioration in gas exchange, which is accompanied by an increase in iNOS expression in the lung.