Perioperative treatment with cilostazol reverses steatosis and improves liver regeneration after major hepatectomy in a steatotic rat model
Abstract Cilostazol has previously been shown to reduce liver steatosis and enhance hepatic perfusion. We investigated the effects of cilostazol after major hepatectomy in a steatotic rat model. Six weeks prior to surgery, Sprague–Dawley rats were fed with a high-fructose diet. The treatment group r...
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2025-01-01
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| author | Sebastian Holländer Maximilian von Heesen Gereon Gäbelein Julie Mercier Matthias W. Laschke Michael D. Menger Matthias Glanemann Antonios E. Spiliotis |
| author_facet | Sebastian Holländer Maximilian von Heesen Gereon Gäbelein Julie Mercier Matthias W. Laschke Michael D. Menger Matthias Glanemann Antonios E. Spiliotis |
| author_sort | Sebastian Holländer |
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| description | Abstract Cilostazol has previously been shown to reduce liver steatosis and enhance hepatic perfusion. We investigated the effects of cilostazol after major hepatectomy in a steatotic rat model. Six weeks prior to surgery, Sprague–Dawley rats were fed with a high-fructose diet. The treatment group received daily 5 mg/kg cilostazol. Seven days following the cilostazol treatment, all animals underwent 70% liver resection (PHX). Analysis of hepatic blood flow and microcirculation and immunohistochemical examinations were conducted 30 min after PHX (postoperative day [POD] 0) as well as on POD 1, POD 3 and POD 7. The weight of cilostazol-treated animals was significantly reduced compared to untreated controls after completion of the 6-week high-FRC diet. Furthermore, 41% macrovesicular steatosis was found in the control group compared to 8% in the cilostazol group. Hepatic arterial and portal venous perfusion were increased in the cilostazol group on POD 7. Lower liver enzyme release was found postoperatively in cilostazol-treated animals. Moreover, apoptosis and neutrophil infiltration were reduced after cilostazol treatment. Proliferation of hepatocytes and liver regeneration after PHX were significantly increased in the cilostazol group. Consequently, cilostazol should be evaluated as a novel strategy to reduce the rate of liver failure after PHX in steatotic liver. |
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| institution | Kabale University |
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| language | English |
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| spelling | doaj-art-6facd203b5a24b52bf51325aa9968efc2025-01-26T12:34:31ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-87135-zPerioperative treatment with cilostazol reverses steatosis and improves liver regeneration after major hepatectomy in a steatotic rat modelSebastian Holländer0Maximilian von Heesen1Gereon Gäbelein2Julie Mercier3Matthias W. Laschke4Michael D. Menger5Matthias Glanemann6Antonios E. Spiliotis7Department of General Surgery, Vascular-, Visceral- and Pediatric Surgery, Saarland University Medical CenterDepartment of General- and Visceral Surgery, University Hospital GöttingenDepartment of General Surgery, Vascular-, Visceral- and Pediatric Surgery, Saarland University Medical CenterDepartment of General Surgery, Vascular-, Visceral- and Pediatric Surgery, Saarland University Medical CenterInstitute for Clinical and Experimental Surgery, Saarland UniversityInstitute for Clinical and Experimental Surgery, Saarland UniversityDepartment of General Surgery, Vascular-, Visceral- and Pediatric Surgery, Saarland University Medical CenterInstitute for Clinical and Experimental Surgery, Saarland UniversityAbstract Cilostazol has previously been shown to reduce liver steatosis and enhance hepatic perfusion. We investigated the effects of cilostazol after major hepatectomy in a steatotic rat model. Six weeks prior to surgery, Sprague–Dawley rats were fed with a high-fructose diet. The treatment group received daily 5 mg/kg cilostazol. Seven days following the cilostazol treatment, all animals underwent 70% liver resection (PHX). Analysis of hepatic blood flow and microcirculation and immunohistochemical examinations were conducted 30 min after PHX (postoperative day [POD] 0) as well as on POD 1, POD 3 and POD 7. The weight of cilostazol-treated animals was significantly reduced compared to untreated controls after completion of the 6-week high-FRC diet. Furthermore, 41% macrovesicular steatosis was found in the control group compared to 8% in the cilostazol group. Hepatic arterial and portal venous perfusion were increased in the cilostazol group on POD 7. Lower liver enzyme release was found postoperatively in cilostazol-treated animals. Moreover, apoptosis and neutrophil infiltration were reduced after cilostazol treatment. Proliferation of hepatocytes and liver regeneration after PHX were significantly increased in the cilostazol group. Consequently, cilostazol should be evaluated as a novel strategy to reduce the rate of liver failure after PHX in steatotic liver.https://doi.org/10.1038/s41598-025-87135-zObesityNon-alcoholic fatty liver diseaseHepatectomyCilostazolLiver regeneration |
| spellingShingle | Sebastian Holländer Maximilian von Heesen Gereon Gäbelein Julie Mercier Matthias W. Laschke Michael D. Menger Matthias Glanemann Antonios E. Spiliotis Perioperative treatment with cilostazol reverses steatosis and improves liver regeneration after major hepatectomy in a steatotic rat model Scientific Reports Obesity Non-alcoholic fatty liver disease Hepatectomy Cilostazol Liver regeneration |
| title | Perioperative treatment with cilostazol reverses steatosis and improves liver regeneration after major hepatectomy in a steatotic rat model |
| title_full | Perioperative treatment with cilostazol reverses steatosis and improves liver regeneration after major hepatectomy in a steatotic rat model |
| title_fullStr | Perioperative treatment with cilostazol reverses steatosis and improves liver regeneration after major hepatectomy in a steatotic rat model |
| title_full_unstemmed | Perioperative treatment with cilostazol reverses steatosis and improves liver regeneration after major hepatectomy in a steatotic rat model |
| title_short | Perioperative treatment with cilostazol reverses steatosis and improves liver regeneration after major hepatectomy in a steatotic rat model |
| title_sort | perioperative treatment with cilostazol reverses steatosis and improves liver regeneration after major hepatectomy in a steatotic rat model |
| topic | Obesity Non-alcoholic fatty liver disease Hepatectomy Cilostazol Liver regeneration |
| url | https://doi.org/10.1038/s41598-025-87135-z |
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