BMC Veterinary Research (Oct 2024)

The clinical efficacy of cGMP-specific sildenafil on mitochondrial biogenesis induction and renal damage in cats with acute on chronic kidney disease

  • Mehmet Maden,
  • Merve Ider,
  • Mehmet Erman Or,
  • Banu Dokuzeylül,
  • Erdem Gülersoy,
  • Merve Cansu Kılıçkaya,
  • Bengü Bilgiç,
  • Murat Kaan Durgut,
  • Semih İzmirli,
  • Suleyman Serhat Iyigün,
  • Deniz Zeynep Telci,
  • Amir Naseri

DOI
https://doi.org/10.1186/s12917-024-04345-9
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 13

Abstract

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Abstract Background Mitochondrial biogenesis (MB) induction has recently emerged as potential therapeutic approaches in kidney pathology and the mitochondria-targeted therapies should be investigated to improve treatment of animals with kidney diseases. This study aimed to investigate the effects of MB induction with sildenafil citrate on the cGMP/NO pathway, glomerular filtration, and reduction of kidney damage and fibrosis (TGF-β/SMAD pathway) in cats with acute on chronic kidney disease (ACKD). Thirty-three cats were divided into the non-azotemic (healthy) group (n:8) and the ACKD group (n:25), comprising different breeds, sexes, and ages. Sildenafil citrate was administered to the non-azotemic and ACKD groups (2.5 mg/kg, PO, q12 hours) for 30 days. Serum and urine NO, MDA, NGAL, KIM-1, TGF-β1, IL-18, FGF 23, PGC-1α and cGMP concentrations were measured. Results Serum cGMP concentrations increased (P < 0.05) in the non-azotemic group during the 2nd (median 475.99 pmol/mL) and 3rd (median 405.01 pmol/mL) weeks of the study, whereas serum cGMP concentrations decreased in the ACKD group during the 4th(median 188.52 pmol/mL) week compared to the non-azotemic group (P < 0.05). No difference was observed in serum biomarker concentrations except NO, which increased in the 4th week (P < 0.05). The urinary concentrations of NO, MDA, PGC-1α, TGF-β1, NGAL, KIM-1, IL-18, and FGF 23 in the ACKD group were found to be higher compared to those in the non-azotemic group from the 1st to the 4th week (P < 0.05). In the ACKD group, the urine PGC-1α concentration in the 2nd (median 6.10 ng/mL) week was lower compared to that in the 0 and 1st (median 7.65 and 7.21 ng/mL, respectively) week, and the NO concentration in the 3rd (median 28.94 µmol/mL) week was lower than that in the 0th (median 37.43 µmol/mL) week (P < 0.05). Conclusions While sildenafil citrate has been determined to induce a low level of MB and to have a beneficial effect on glomerular filtration, it is observed to be ineffective in mitigating renal damage and fibrosis via the TGF-β/SMAD pathway in cats with ACKD.

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