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
{"title":"cGMP 特异性西地那非对急慢性肾病猫线粒体生物生成诱导和肾损伤的临床疗效。","authors":"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":"10.1186/s12917-024-04345-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>Serum cGMP concentrations increased (P < 0.05) in the non-azotemic group during the 2<sup>nd</sup> (median 475.99 pmol/mL) and 3<sup>rd</sup> (median 405.01 pmol/mL) weeks of the study, whereas serum cGMP concentrations decreased in the ACKD group during the 4<sup>th</sup>(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<sup>th</sup> 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<sup>st</sup> to the 4<sup>th</sup> week (P < 0.05). In the ACKD group, the urine PGC-1α concentration in the 2<sup>nd</sup> (median 6.10 ng/mL) week was lower compared to that in the 0 and 1<sup>st</sup> (median 7.65 and 7.21 ng/mL, respectively) week, and the NO concentration in the 3<sup>rd</sup> (median 28.94 µmol/mL) week was lower than that in the 0<sup>th</sup> (median 37.43 µmol/mL) week (P < 0.05).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9041,"journal":{"name":"BMC Veterinary Research","volume":"20 1","pages":"499"},"PeriodicalIF":2.3000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526613/pdf/","citationCount":"0","resultStr":"{\"title\":\"The clinical efficacy of cGMP-specific sildenafil on mitochondrial biogenesis induction and renal damage in cats with acute on chronic kidney disease.\",\"authors\":\"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\":\"10.1186/s12917-024-04345-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>Serum cGMP concentrations increased (P < 0.05) in the non-azotemic group during the 2<sup>nd</sup> (median 475.99 pmol/mL) and 3<sup>rd</sup> (median 405.01 pmol/mL) weeks of the study, whereas serum cGMP concentrations decreased in the ACKD group during the 4<sup>th</sup>(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<sup>th</sup> 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<sup>st</sup> to the 4<sup>th</sup> week (P < 0.05). In the ACKD group, the urine PGC-1α concentration in the 2<sup>nd</sup> (median 6.10 ng/mL) week was lower compared to that in the 0 and 1<sup>st</sup> (median 7.65 and 7.21 ng/mL, respectively) week, and the NO concentration in the 3<sup>rd</sup> (median 28.94 µmol/mL) week was lower than that in the 0<sup>th</sup> (median 37.43 µmol/mL) week (P < 0.05).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":9041,\"journal\":{\"name\":\"BMC Veterinary Research\",\"volume\":\"20 1\",\"pages\":\"499\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-10-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526613/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Veterinary Research\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1186/s12917-024-04345-9\",\"RegionNum\":2,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Veterinary Research","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1186/s12917-024-04345-9","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
The clinical efficacy of cGMP-specific sildenafil on mitochondrial biogenesis induction and renal damage in cats with acute on chronic kidney disease.
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.
期刊介绍：
BMC Veterinary Research is an open access, peer-reviewed journal that considers articles on all aspects of veterinary science and medicine, including the epidemiology, diagnosis, prevention and treatment of medical conditions of domestic, companion, farm and wild animals, as well as the biomedical processes that underlie their health.
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