Alda-1, an aldehyde dehydrogenase-2 agonist, causes deterioration in renal functions following ischemia–reperfusion injury due to crystalline nephropathy

Fayez T. Hammad, Suhail Al-Salam, Priya Yuvaraju, Loay Lubbad

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Renal ischemia–reperfusion injury (IRI) induces the production of aldehydes which are detoxified by aldehyde dehydrogenases (ALDHs). Alda-1 is a selective ALDH2 agonist and its protective effect was demonstrated in several conditions. The effect of Alda-1 on the kidney or on renal IRI was not investigated. We investigated the effect of Alda-1 on the renal dysfunction following IRI. Wistar rats underwent left IRI for 40 min. Group-Alda (n = 11) received Alda-1 starting 24 h before IRI and continued for 7 days thereafter when renal functions were measured. Group-Vx (n = 11) underwent similar protocol but received the dissolvent. Alda-1 did not affect renal blood flow or glomerular filtration rate in the left ischemic kidney in Group-Alda compared to Group-Vx (3.05 ± 0.50 vs. 3.53 ± 0.70, and 0.40 ± 0.06 vs. 0.51 ± 0.08, respectively, p >.05 for both). However, left renal fractional sodium excretion was higher in Group-Alda (2.80 ± 0.43 vs. 1.37 ± 0.36, p =.02). Alda-1 also adversely affected the gene expressions of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin (217 ± 38 vs. 99 ± 13 and 49 ± 13 vs. 20 ± 5, respectively, p <.05 for both) and the alterations in tumor necrosis factor-α, transforming growth factor-β1, plasminogen activator inhibitor-1, fibronectin 1 and p53 (4.4 ± 0.9 vs. 2.1 ± 0.3, 1.5 ± 0.1 vs. 1.1 ± 0.1, 30.0 ± 2.7 vs. 11.7 ± 2.3, 3.6 ± 0.4 vs. 2.1 ± 0.2 and 1.3 ± 0.1 vs. 0.9 ± 0.07, respectively, p ≤.05 for all). This was associated with intratubular crystal deposition suggestive of crystalline nephropathy. Alda-1 exacerbated the IRI-induced renal tubular dysfunction and alterations in markers of acute kidney injury, biomarkers of inflammation, fibrosis and apoptosis and this was associated with intratubular crystal deposition suggestive of crystalline nephropathy.

Original languageEnglish
Pages (from-to)315-323
Number of pages9
JournalDrug Development Research
Volume79
Issue number7
DOIs
Publication statusPublished - Nov 2018

Keywords

  • Alda-1
  • crystalline nephropathy
  • ischemia–reperfusion injury
  • renal functions

ASJC Scopus subject areas

  • Drug Discovery

Fingerprint

Dive into the research topics of 'Alda-1, an aldehyde dehydrogenase-2 agonist, causes deterioration in renal functions following ischemia–reperfusion injury due to crystalline nephropathy'. Together they form a unique fingerprint.

Cite this