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Perindopril Dampens Cd-induced Nephrotoxicity by Suppressing Inflammatory Burden, Ang II/Ang 1-7, and Apoptosis

Zuhair M Mohammedsaleh1, Emad H M Hassanein2, Fares E M Ali3

  • 1Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, 71491, Kingdom of Saudi Arabia.

Biological Trace Element Research
|October 17, 2023
PubMed

Insights

Perindopril (PER) protects kidneys from cadmium (Cd) toxicity by reducing inflammation and apoptosis. This study shows PER modulates the renin-angiotensin system (RAS) and key inflammatory pathways, offering potential therapeutic benefits for heavy metal-induced kidney damage.

Area of Science:

  • Toxicology
  • Nephrology
  • Pharmacology

Background:

  • Cadmium (Cd) exposure causes significant kidney damage, with inflammation being a key factor in its toxicity.
  • The renin-angiotensin system (RAS) plays a role in inflammatory processes and cardiovascular health.
  • Perindopril (PER), an angiotensin-converting enzyme inhibitor, is used for hypertension and cardiovascular conditions.

Purpose of the Study:

  • To investigate the renoprotective effects of Perindopril (PER) against cadmium (Cd)-induced nephrotoxicity.
  • To elucidate the impact of PER on inflammation and the underlying molecular mechanisms in Cd-intoxicated rats.
  • To examine PER's modulation of the Angiotensin II (Ang II)/Ang-(1-7) axis and apoptotic pathways.

Main Methods:

  • Rats were administered Perindopril (PER) at 1 mg/kg/day and exposed to a single dose of Cadmium (Cd) at 1.2 mg/kg.
  • Evaluated serum markers of kidney function (urea, creatinine, uric acid) and albuminuria.
  • Assessed inflammatory markers (MPO, NO, IL-1β, IL-6, INF-γ), NF-κB, JAK-1/STAT3 signaling, Ang II/Ang-(1-7) axis, and apoptosis-related proteins (Bax, Bcl-2, cytochrome c, cleaved caspase 3).

Main Results:

  • PER treatment significantly reduced serum urea, creatinine, uric acid, and the urine albumin/creatinine ratio.
  • PER mitigated inflammation by decreasing MPO, NO, IL-1β, IL-6, and INF-γ, through downregulation of NF-κB and suppression of JAK-1/STAT3 phosphorylation.
  • PER modulated the Ang II/Ang-(1-7) axis, inhibited Cd-induced apoptosis by altering Bax, Bcl-2, cytochrome c, and cleaved caspase 3 levels.

Conclusions:

  • Perindopril (PER) demonstrates significant renoprotective effects against cadmium (Cd)-induced nephrotoxicity.
  • PER exerts its protective action by suppressing inflammation via the NF-κB and JAK-1/STAT3 pathways, and modulating the Ang II/Ang-(1-7) axis.
  • PER inhibits apoptosis, highlighting its potential as a therapeutic agent for heavy metal-induced kidney injury.
Keywords:
Ang II/Ang 1-7ApoptosisCadmiumInflammatory burdenNephroprotectivePerindopril

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