ACE2 activator diminazene aceturate exerts renoprotective effects in gentamicin-induced acute renal injury in rats

Clin Sci (Lond). 2020 Dec 11;134(23):3093-3106. doi: 10.1042/CS20201022.

Abstract

Acute Kidney Injury (AKI) comprises a rapidly developed renal failure and is associated with high mortality rates. The Renin-Angiotensin System (RAS) plays a pivotal role in AKI, as the over-active RAS axis exerts major deleterious effects in disease progression. In this sense, the conversion of Angiotensin II (Ang II) into Angiotensin-(1-7) (Ang-(1-7)) by the Angiotensin-converting enzyme 2 (ACE2) is of utmost importance to prevent worse clinical outcomes. Previous studies reported the beneficial effects of oral diminazene aceturate (DIZE) administration, an ACE2 activator, in renal diseases models. In the present study, we aimed to evaluate the therapeutic effects of DIZE administration in experimental AKI induced by gentamicin (GM) in rats. Our findings showed that treatment with DIZE improved renal function and tissue damage by increasing Ang-(1-7) and ACE2 activity, and reducing TNF-α. These results corroborate with a raising potential of ACE2 activation as a strategy for treating AKI.

Keywords: Angiotensin-Converting Enzyme 2; Renin Angiotensin System; acute kidney injury; diminazene aceturate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / enzymology*
  • Acute Kidney Injury / physiopathology
  • Acute Kidney Injury / urine
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Animals
  • Biomarkers / metabolism
  • Body Weight / drug effects
  • Cytokines / metabolism
  • Diminazene / analogs & derivatives*
  • Diminazene / pharmacology
  • Diminazene / therapeutic use
  • Enzyme Activators / pharmacology*
  • Gentamicins / adverse effects*
  • Inflammation / pathology
  • Kidney / drug effects
  • Kidney / pathology*
  • Kidney / physiopathology
  • Male
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Rats, Wistar
  • Renin-Angiotensin System

Substances

  • Biomarkers
  • Cytokines
  • Enzyme Activators
  • Gentamicins
  • Protective Agents
  • Angiotensin-Converting Enzyme 2
  • diminazene aceturate
  • Diminazene