The effect of diminazene, an angiotensin-converting enzyme 2 activator, on adenine-induced chronic kidney disease in rats

Aly M. Abdelrahman*, Badreldin H. Ali, Haytham Ali, Priyadarsini Manoj, Yousuf Al-Suleimani

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The present study investigated the effect of diminazene, lisinopril, or valsartan on adenine-induced chronic kidney disease (CKD) in rats. The animals were divided into five groups (n = 6). The first and second groups received normal diet and adenine in the feed at a dose of 0.25% w/w for 35 days, respectively. The third, fourth, and fifth groups were treated as the second group but also received diminazene (15 mg/kg/day), lisinopril (10 mg/kg/day), and valsartan (30 mg/kg/day), respectively, for 35 days. Adenine significantly increased plasma urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), calcium, phosphorus, and uric acid. In addition, adenine increased urinary albumin/creatinine ratio and N-Acetyl-β-D-glucosaminidase (NAG)/creatinine ratio and reduced creatinine clearance. Adenine also significantly increased the plasma concentrations of inflammatory cytokines (plasma tumor necrosis factor–alpha [TNF-α] and interleukin-1beta [IL-1β]) and significantly reduced antioxidant indices (catalase, glutathione reductase [GR], and superoxide dismutase [SOD]). Histopathologically, renal tissue from adenine-treated rats showed necrosis of renal tubules, tubular casts, shrunken glomeruli, and increased renal fibrosis. All drugs ameliorated adenine-induced biochemical and histopathological changes. The protective effect of the three drugs used is, at least partially, due to their anti-inflammatory and antioxidant effects. Our results show that administration of diminazene, lisinopril, or valsartan had a comparable effect on the reversal of the biochemical and histopathological indices of adenine-induced CKD in rats.

Original languageEnglish
Pages (from-to)235-244
Number of pages10
JournalFundamental and Clinical Pharmacology
Volume37
Issue number2
DOIs
Publication statusPublished - Nov 7 2022

Keywords

  • ACE2 activator
  • adenine
  • chronic kidney disease
  • diminazene
  • lisinopril
  • valsartan

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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