Aminoguanidine prevents the oxidative stress, inhibiting elements of inflammation, endothelial activation, mesenchymal markers, and confers a renoprotective effect in renal ischemia and reperfusion injury

Consuelo Pasten, Mauricio Lozano, Jocelyn Rocco, Flavio Carrión, Cristobal Alvarado, Jéssica Liberona, Luis Michea, Carlos E. Irarrázabal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Oxidative stress produces macromolecules dysfunction and cellular damage. Renal ische-mia‐reperfusion injury (IRI) induces oxidative stress, inflammation, epithelium and endothelium damage, and cessation of renal function. The IRI is an inevitable process during kidney transplan-tation. 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, fas-cin, 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 (glo-merular 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.

Original languageEnglish
Article number1724
JournalAntioxidants
Volume10
Issue number11
DOIs
StatePublished - Nov 2021

Bibliographical note

Funding Information:
This research was funded by: FONDECYT?1151157, FONDECYT?21150304 and FOND? ECYT?1211949 (supported by ANID, Agencia Nacional de Investigaci?n y Desarrollo, Chile); and FAI?2019 and FAI?Puente 2019 (supported by Fondo de Ayuda a la Investigaci?n, Universidad de los Andes, Chile).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Aminoguanidine
  • Antioxidants
  • Ischemia‐reperfusion injury
  • Oxidative stress
  • Renal protection

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