The Clinical Efficacy of CGMP-specific Sildenafil on Mitochondrial Biogenesis Induction and Renal Damage in Cats with Acute on Chronic Kidney Disease

Overview

Journal BMC Vet Res

Publisher Biomed Central

Specialty Veterinary Medicine

Date 2024 Oct 31

PMID 39478527

Authors

Mehmet Maden

Merve Ider

Mehmet Erman Or

Banu Dokuzeylul

Erdem Gulersoy

Merve Cansu Kilickaya

Bengu Bilgic

Murat Kaan Durgut

Semih Izmirli

Suleyman Serhat Iyigun

Deniz Zeynep Telci

Amir Naseri

Affiliations

Soon will be listed here.

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 2 (median 475.99 pmol/mL) and 3 (median 405.01 pmol/mL) weeks of the study, whereas serum cGMP concentrations decreased in the ACKD group during the 4(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 4 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 1 to the 4 week (P < 0.05). In the ACKD group, the urine PGC-1α concentration in the 2 (median 6.10 ng/mL) week was lower compared to that in the 0 and 1 (median 7.65 and 7.21 ng/mL, respectively) week, and the NO concentration in the 3 (median 28.94 µmol/mL) week was lower than that in the 0 (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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