Methylglyoxal Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via RAGE-Induced ROS Generation: Protective Effects of Metformin

Matheus L Medeiros, Akila L Oliveira, Mariana G de Oliveira, Fabíola Z Mónica, Edson Antunes Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Sao Paulo, BrazilCorrespondence: Edson AntunesDepartment of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP)...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Medeiros ML, Oliveira AL, de Oliveira MG, Monica FZ, Antunes E
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	advanced glycated end products neutrophil airways immunohistochemistry Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/e4491834f4ec44e08cfc19a3357a5891
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e4491834f4ec44e08cfc19a3357a5891
record_format	dspace
spelling	oai:doaj.org-article:e4491834f4ec44e08cfc19a3357a58912021-12-02T19:17:36ZMethylglyoxal Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via RAGE-Induced ROS Generation: Protective Effects of Metformin1178-7031https://doaj.org/article/e4491834f4ec44e08cfc19a3357a58912021-12-01T00:00:00Zhttps://www.dovepress.com/methylglyoxal-exacerbates-lipopolysaccharide-induced-acute-lung-injury-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Matheus L Medeiros, Akila L Oliveira, Mariana G de Oliveira, Fabíola Z Mónica, Edson Antunes Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Sao Paulo, BrazilCorrespondence: Edson AntunesDepartment of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, Sao Paulo, 13084-971, BrazilTel +55 19-9-9601-1516Email eantunes@unicamp.br; edson.antunes@uol.com.brPurpose: Methylglyoxal (MGO) is a highly reactive dicarbonyl species implicated in diabetic-associated diseases. Acute lung injury (ALI) symptoms and prognosis are worsened by diabetes and obesity. Here, we hypothesized that elevated MGO levels aggravate ALI, which can be prevented by metformin. Therefore, this study evaluated the lung inflammation in lipopolysaccharide (LPS)-exposed mice pretreated with MGO.Methods: C57Bl/6 male mice treated or not with MGO for 12 weeks were intranasally instilled with LPS (30 μg) to induce ALI, and metformin (300 mg/kg) was given as gavage in the last two weeks of treatment. After 6 h, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to quantify the cell infiltration, cytokine levels, reactive-oxygen species (ROS) production, and RAGE expression.Results: LPS exposure markedly increased the neutrophil infiltration in BALF and lung tissue, which was accompanied by higher levels of IFN-γ, TNF-α and IL-1β compared with untreated group. MGO treatment significantly increased the airways neutrophil infiltration and mRNA expressions of TNF-α and IL-1β, whereas COX-2 expression remained unchanged. In lung tissues of LPS-exposed mice, MGO treatment significantly increased the immunostaining and mRNA expression of RAGE, and the ROS levels. Serum MGO concentration achieved after 12-week intake was 9.2-fold higher than control mice, which was normalized by metformin treatment. Metformin also reduced the inflammatory markers in response to MGO.Conclusion: MGO intake potentiates the LPS-induced ALI, increases RAGE expression and ROS generation, which is normalized by metformin. MGO scavengers may be a good adjuvant therapy to reduce ALI in patients with cardiometabolic diseases.Keywords: advanced glycated end products, neutrophil, airways, immunohistochemistryMedeiros MLOliveira ALde Oliveira MGMonica FZAntunes EDove Medical Pressarticleadvanced glycated end productsneutrophilairwaysimmunohistochemistryPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 6477-6489 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	advanced glycated end products neutrophil airways immunohistochemistry Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	advanced glycated end products neutrophil airways immunohistochemistry Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Medeiros ML Oliveira AL de Oliveira MG Monica FZ Antunes E Methylglyoxal Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via RAGE-Induced ROS Generation: Protective Effects of Metformin
description	Matheus L Medeiros, Akila L Oliveira, Mariana G de Oliveira, Fabíola Z Mónica, Edson Antunes Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Sao Paulo, BrazilCorrespondence: Edson AntunesDepartment of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, Sao Paulo, 13084-971, BrazilTel +55 19-9-9601-1516Email eantunes@unicamp.br; edson.antunes@uol.com.brPurpose: Methylglyoxal (MGO) is a highly reactive dicarbonyl species implicated in diabetic-associated diseases. Acute lung injury (ALI) symptoms and prognosis are worsened by diabetes and obesity. Here, we hypothesized that elevated MGO levels aggravate ALI, which can be prevented by metformin. Therefore, this study evaluated the lung inflammation in lipopolysaccharide (LPS)-exposed mice pretreated with MGO.Methods: C57Bl/6 male mice treated or not with MGO for 12 weeks were intranasally instilled with LPS (30 μg) to induce ALI, and metformin (300 mg/kg) was given as gavage in the last two weeks of treatment. After 6 h, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to quantify the cell infiltration, cytokine levels, reactive-oxygen species (ROS) production, and RAGE expression.Results: LPS exposure markedly increased the neutrophil infiltration in BALF and lung tissue, which was accompanied by higher levels of IFN-γ, TNF-α and IL-1β compared with untreated group. MGO treatment significantly increased the airways neutrophil infiltration and mRNA expressions of TNF-α and IL-1β, whereas COX-2 expression remained unchanged. In lung tissues of LPS-exposed mice, MGO treatment significantly increased the immunostaining and mRNA expression of RAGE, and the ROS levels. Serum MGO concentration achieved after 12-week intake was 9.2-fold higher than control mice, which was normalized by metformin treatment. Metformin also reduced the inflammatory markers in response to MGO.Conclusion: MGO intake potentiates the LPS-induced ALI, increases RAGE expression and ROS generation, which is normalized by metformin. MGO scavengers may be a good adjuvant therapy to reduce ALI in patients with cardiometabolic diseases.Keywords: advanced glycated end products, neutrophil, airways, immunohistochemistry
format	article
author	Medeiros ML Oliveira AL de Oliveira MG Monica FZ Antunes E
author_facet	Medeiros ML Oliveira AL de Oliveira MG Monica FZ Antunes E
author_sort	Medeiros ML
title	Methylglyoxal Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via RAGE-Induced ROS Generation: Protective Effects of Metformin
title_short	Methylglyoxal Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via RAGE-Induced ROS Generation: Protective Effects of Metformin
title_full	Methylglyoxal Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via RAGE-Induced ROS Generation: Protective Effects of Metformin
title_fullStr	Methylglyoxal Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via RAGE-Induced ROS Generation: Protective Effects of Metformin
title_full_unstemmed	Methylglyoxal Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via RAGE-Induced ROS Generation: Protective Effects of Metformin
title_sort	methylglyoxal exacerbates lipopolysaccharide-induced acute lung injury via rage-induced ros generation: protective effects of metformin
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/e4491834f4ec44e08cfc19a3357a5891
work_keys_str_mv	AT medeirosml methylglyoxalexacerbateslipopolysaccharideinducedacutelunginjuryviarageinducedrosgenerationprotectiveeffectsofmetformin AT oliveiraal methylglyoxalexacerbateslipopolysaccharideinducedacutelunginjuryviarageinducedrosgenerationprotectiveeffectsofmetformin AT deoliveiramg methylglyoxalexacerbateslipopolysaccharideinducedacutelunginjuryviarageinducedrosgenerationprotectiveeffectsofmetformin AT monicafz methylglyoxalexacerbateslipopolysaccharideinducedacutelunginjuryviarageinducedrosgenerationprotectiveeffectsofmetformin AT antunese methylglyoxalexacerbateslipopolysaccharideinducedacutelunginjuryviarageinducedrosgenerationprotectiveeffectsofmetformin
_version_	1718376886118121472

Methylglyoxal Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via RAGE-Induced ROS Generation: Protective Effects of Metformin

Ejemplares similares