Tomatidine Improves Pulmonary Inflammation in Mice with Acute Lung Injury.

Wen-Chung Huang,Chwan-Fwu Lin,Chian-Jiun Liou,Shu-Ju Wu,Ya-Ling Chen,Eduardo Dalmarco

doi:10.1155/2021/4544294

Abstract

Tomatidine, which is isolated from green tomato, can ameliorate inflammation and oxidative stress in cells and animal experiments and has been shown to improve airway inflammation in a murine model of asthma. Here, we investigated whether tomatidine can ameliorate acute lung injury in mice. Mice were given tomatidine by intraperitoneal injection for 7 consecutive days, and then, lung injury was induced via intratracheal instillation of lipopolysaccharide (LPS). Tomatidine reduced inflammatory cytokine expressions in bronchoalveolar lavage fluid (BALF), attenuated neutrophil infiltration in the BALF and lung tissue, increased superoxide dismutase activity and glutathione levels, and alleviated myeloperoxidase expression in the lung tissue of mice with lung injury. Tomatidine also decreased inflammatory cytokine and chemokine gene expression in inflammatory lungs and attenuated the phosphorylation of mitogen-activated protein kinase and nuclear factor kappa B. Furthermore, tomatidine enhanced the production of heme oxygenase-1, decreased the secretion of inflammatory cytokines and chemokines in LPS-stimulated lung epithelial cells, and attenuated THP-1 monocyte adhesion. Our findings suggest that tomatidine attenuates oxidative stress and inflammation, improving acute lung injury in mice.

Highlights

Acute lung injury (ALI) is a serious respiratory disease that can cause severe clinical complications and high mortality and can lead to acute respiratory distress syndrome [1]
We have found that tomatidine can suppress mucin production, airway inflammation, and airway hyperresponsiveness in ovalbumin-induced asthma mouse model through suppression of Th2 cell activity [13]
Tomatidine effectively decreased neutrophil numbers in the bronchoalveolar lavage fluid (BALF) compared to LPS (T5: 4:1 × 105 ± 6:4 × cells/ml, p < 0:05; T10: 3:1 × ± 4:8 × cells/ml, p < 0:01 vs. LPS: 6:4 × ± 5:0 × 104 cells/ml) (Figure 1(a))

Summary

Introduction

Acute lung injury (ALI) is a serious respiratory disease that can cause severe clinical complications and high mortality and can lead to acute respiratory distress syndrome [1]. The main clinical features of ALI are excessive lung inflammation and neutrophil infiltration of the lungs, as well as excessive inflammatory cytokine and chemokine secretions, which induce lung cell damage, causing severe diffuse pulmonary infiltrates, increased vascular permeability, pulmonary edema, and reduced respiratory gas exchange [2, 3]. When the lungs are infected with bacteria, LPS stimulates TLR4 activation and inflammatory mediator overproduction mainly through the activation of the MYD88-dependent TLR4 pathway, leading to lung damage and ALI development [7]. We have found that tomatidine can suppress mucin production, airway inflammation, and airway hyperresponsiveness in ovalbumin-induced asthma mouse model through suppression of Th2 cell activity [13]. We evaluated whether tomatidine alleviates acute lung injury and investigated the molecular mechanisms underlying inflammation and oxidative stress in mice

Materials and Methods

Results

Discussion

Conflicts of Interest