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Diet-Induced Pulmonary Inflammation and Incipient Fibrosis in Mice: a Possible Role of Neutrophilic Inflammation

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Abstract

Chicken fat and fructose are added into food-processing to reduce costs and enhance acceptability; however, these additives turn food into unhealthy and hypercaloric meals. Herein we have hypothesized that chronic feeding with chicken fat and fructose, together or by separate, can cause pulmonary redox and inflammatory changes. These changes are particularly related to neutrophils and myeloperoxidase, with consequent changes in the organ histophysiology. To test this hypothesis, we fed mice for 16 weeks with either control food (low-fat diet, LFD) or control food supplemented with 22% chicken fat and with or without 10% fructose in the drinking water. At the end of the feeding regimen, we measured redox and inflammatory changes in the lung with particular emphasis on neutrophil accumulation/activation and molecular-histological markers of fibrosis. Our results suggest that a diet supplemented with chicken fat and fructose causes additive effects on pulmonary oxidative stress, inflammation, and a pro-fibrotic status. Neutrophilic inflammation may play a critical role in pulmonary pathology associated with metabolic syndrome.

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Abbreviations

BALF:

Bronchoalveolar lavage fluid

ECM:

Extracellular matrix

HFD:

High-fat diet

iNOS:

Inducible nitric oxide synthase

ICAM-1:

Intercellular adhesion molecule-1

LFD:

Low-fat diet

NOX:

NAPDH-dependent oxido-reductase

MDA:

Malondialdehyde

TBARS:

Tiobarbituric acid-reactive substances

GSH:

Reduced glutathione

GSSG:

Oxidized glutathione

SOD:

Superoxide dismutase

CAT:

Catalase

GPx:

Glutathione peroxidase

MMP:

Metalloproteinase

MPO:

Myeloperoxidase

MS:

Metabolic syndrome

RT-PCR:

Reverse transcriptase-polymerase chain reaction

TAC:

Total antioxidant capacity.

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Acknowledgments

The authors are deeply grateful to the members of the Laboratory of Diabetes, School of Chemistry, Biochemistry and Pharmacy, led by Dr. Susana E. Siewert for helping with gene expression analysis.

Funding

This research was supported by the following grants: FONCYT, Argentina (PICT3369, to DCR and SEGM), CONICET, Argentina (PIP916, to DCR and SEGM), and Universidad Nacional de San Luis, Argentina (PROICO2-3418 to DCR; and PROICO, 10-0218 to SEGM).

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Correspondence to Sandra E. Gomez Mejiba or Dario C. Ramirez.

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Supplementary Table 1

(PPT 190 kb)

Supplementary Figure 1

Effects of diet on the expression of antioxidant enzymes in lung parenchyma. The measurement of the mRNA encoding for A) superoxide dismutase (SOD); B) catalase (CAT); C) Glutathione peroxidase (GPx) and β-actin (housekeeping gene) were measured by RT-PCR. Primer sequences are shown in Supplementary Table 1. Band intensities were measured using the ImageJ software and expressed as the gene of interest/β-actin intensity ratios. Results are shown as mean values ± SEM (n = 6). Data were analyzed by using the one-way ANOVA followed by the Bonferroni post-test. Statistic symbols (p < 0.05): a, LFD vs LFD + F; b, LFD + F vs HFD; c, LFD vs HFD + F; d, LFD + F vs HFD; e, LFD + F vs HFD + F; and f, HFD vs HFD + F. (PPT 338 kb)

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Vedova, M.C.D., Soler Garcia, F.M., Muñoz, M.D. et al. Diet-Induced Pulmonary Inflammation and Incipient Fibrosis in Mice: a Possible Role of Neutrophilic Inflammation. Inflammation 42, 1886–1900 (2019). https://doi.org/10.1007/s10753-019-01051-9

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