Aminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury

Oxidative stress produces macromolecules dysfunction and cellular damage. Renal ischemia-reperfusion injury (IRI) induces oxidative stress, inflammation, epithelium and endothelium damage, and cessation of renal function. The IRI is an inevitable process during kidney transplantation. Preliminary st...

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Autores principales:	Consuelo Pasten, Mauricio Lozano, Jocelyn Rocco, Flavio Carrión, Cristobal Alvarado, Jéssica Liberona, Luis Michea, Carlos E. Irarrázabal
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	aminoguanidine antioxidants oxidative stress ischemia-reperfusion injury renal protection Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/fee9d9f49e0143bd846d5ad3c90ca4e8
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spelling	oai:doaj.org-article:fee9d9f49e0143bd846d5ad3c90ca4e82021-11-25T16:27:15ZAminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury10.3390/antiox101117242076-3921https://doaj.org/article/fee9d9f49e0143bd846d5ad3c90ca4e82021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1724https://doaj.org/toc/2076-3921Oxidative stress produces macromolecules dysfunction and cellular damage. Renal ischemia-reperfusion injury (IRI) induces oxidative stress, inflammation, epithelium and endothelium damage, and cessation of renal function. The IRI is an inevitable process during kidney transplantation. Preliminary studies suggest that aminoguanidine (AG) is an antioxidant compound. In this study, we investigated the antioxidant effects of AG (50 mg/kg, intraperitoneal) and its association with molecular pathways activated by IRI (30 min/48 h) in the kidney. The antioxidant effect of AG was studied measuring GSSH/GSSG ratio, GST activity, lipoperoxidation, iNOS, and Hsp27 levels. In addition, we examined the effect of AG on elements associated with cell survival, inflammation, endothelium, and mesenchymal transition during IRI. AG prevented lipid peroxidation, increased GSH levels, and recovered the GST activity impaired by IRI. AG was associated with inhibition of iNOS, Hsp27, endothelial activation (VE-cadherin, PECAM), mesenchymal markers (vimentin, fascin, and HSP47), and inflammation (IL-1β, IL-6, Foxp3, and IL-10) upregulation. In addition, AG reduced kidney injury (NGAL, clusterin, Arg-2, and TFG-β1) and improved kidney function (glomerular filtration rate) during IRI. In conclusion, we found new evidence of the antioxidant properties of AG as a renoprotective compound during IRI. Therefore, AG is a promising compound to treat the deleterious effect of renal IRI.Consuelo PastenMauricio LozanoJocelyn RoccoFlavio CarriónCristobal AlvaradoJéssica LiberonaLuis MicheaCarlos E. IrarrázabalMDPI AGarticleaminoguanidineantioxidantsoxidative stressischemia-reperfusion injuryrenal protectionTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1724, p 1724 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aminoguanidine antioxidants oxidative stress ischemia-reperfusion injury renal protection Therapeutics. Pharmacology RM1-950
spellingShingle	aminoguanidine antioxidants oxidative stress ischemia-reperfusion injury renal protection Therapeutics. Pharmacology RM1-950 Consuelo Pasten Mauricio Lozano Jocelyn Rocco Flavio Carrión Cristobal Alvarado Jéssica Liberona Luis Michea Carlos E. Irarrázabal Aminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury
description	Oxidative stress produces macromolecules dysfunction and cellular damage. Renal ischemia-reperfusion injury (IRI) induces oxidative stress, inflammation, epithelium and endothelium damage, and cessation of renal function. The IRI is an inevitable process during kidney transplantation. Preliminary studies suggest that aminoguanidine (AG) is an antioxidant compound. In this study, we investigated the antioxidant effects of AG (50 mg/kg, intraperitoneal) and its association with molecular pathways activated by IRI (30 min/48 h) in the kidney. The antioxidant effect of AG was studied measuring GSSH/GSSG ratio, GST activity, lipoperoxidation, iNOS, and Hsp27 levels. In addition, we examined the effect of AG on elements associated with cell survival, inflammation, endothelium, and mesenchymal transition during IRI. AG prevented lipid peroxidation, increased GSH levels, and recovered the GST activity impaired by IRI. AG was associated with inhibition of iNOS, Hsp27, endothelial activation (VE-cadherin, PECAM), mesenchymal markers (vimentin, fascin, and HSP47), and inflammation (IL-1β, IL-6, Foxp3, and IL-10) upregulation. In addition, AG reduced kidney injury (NGAL, clusterin, Arg-2, and TFG-β1) and improved kidney function (glomerular filtration rate) during IRI. In conclusion, we found new evidence of the antioxidant properties of AG as a renoprotective compound during IRI. Therefore, AG is a promising compound to treat the deleterious effect of renal IRI.
format	article
author	Consuelo Pasten Mauricio Lozano Jocelyn Rocco Flavio Carrión Cristobal Alvarado Jéssica Liberona Luis Michea Carlos E. Irarrázabal
author_facet	Consuelo Pasten Mauricio Lozano Jocelyn Rocco Flavio Carrión Cristobal Alvarado Jéssica Liberona Luis Michea Carlos E. Irarrázabal
author_sort	Consuelo Pasten
title	Aminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury
title_short	Aminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury
title_full	Aminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury
title_fullStr	Aminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury
title_full_unstemmed	Aminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury
title_sort	aminoguanidine prevents the oxidative stress, inhibiting elements of inflammation, endothelial activation, mesenchymal markers, and confers a renoprotective effect in renal ischemia and reperfusion injury
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fee9d9f49e0143bd846d5ad3c90ca4e8
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Aminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury

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