{"title":"Ursodeoxycholic acid ameliorates paclitaxel-induced hepatic injury in rats: Evaluation of oxidative and DNA damage, apoptosis and autophagy.","authors":"Mehmet Eki Ci, Mustafa Özkaraca, Hilmi Ataseven","doi":"10.1556/004.2025.01155","DOIUrl":null,"url":null,"abstract":"<p><p>Paclitaxel (PTX), widely used in chemotherapy, can cause serious side effects such as hepatotoxicity. This study aimed to investigate the therapeutic effects of ursodeoxycholic acid (UDCA) - a secondary bile acid, a byproduct of intestinal bacteria with potent antioxidant properties - against PTX-induced liver injury. PTX was administered intraperitoneally at 2 mg*kg-1 for 5 days to induce liver damage. Rats in the first treatment group received UDCA orally at 60 mg*kg-1 for fifteen days, while the second group received the same dose for ten days. Serum levels of AST, ALT, ALP, LDH, total protein, and albumin were analysed using an autoanalyzer. Liver tissue was assessed for total oxidative status (TOS), oxidative stress index (OSI) and total antioxidant status (TAS). Histopathological and immunohistochemical analyses were also conducted. UDCA administration ameliorated PTX-induced changes in bodyweight and liver enzymes. It reduced necrosis, hydropic degeneration and mononuclear cell infiltration in liver tissue. UDCA also significantly decreased TOS and OSI levels, alleviating oxidative stress, and increased TAS. Furthermore, UDCA reduced DNA damage, evidenced by lower 8-OHdG immunoreactivity, and regulated autophagy and apoptosis by reversing elevated LC3B and cleaved caspase-3 levels. These findings suggest that UDCA may offer therapeutic benefits against PTX-induced hepatotoxicity.</p>","PeriodicalId":7247,"journal":{"name":"Acta veterinaria Hungarica","volume":" ","pages":""},"PeriodicalIF":0.7000,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta veterinaria Hungarica","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1556/004.2025.01155","RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Paclitaxel (PTX), widely used in chemotherapy, can cause serious side effects such as hepatotoxicity. This study aimed to investigate the therapeutic effects of ursodeoxycholic acid (UDCA) - a secondary bile acid, a byproduct of intestinal bacteria with potent antioxidant properties - against PTX-induced liver injury. PTX was administered intraperitoneally at 2 mg*kg-1 for 5 days to induce liver damage. Rats in the first treatment group received UDCA orally at 60 mg*kg-1 for fifteen days, while the second group received the same dose for ten days. Serum levels of AST, ALT, ALP, LDH, total protein, and albumin were analysed using an autoanalyzer. Liver tissue was assessed for total oxidative status (TOS), oxidative stress index (OSI) and total antioxidant status (TAS). Histopathological and immunohistochemical analyses were also conducted. UDCA administration ameliorated PTX-induced changes in bodyweight and liver enzymes. It reduced necrosis, hydropic degeneration and mononuclear cell infiltration in liver tissue. UDCA also significantly decreased TOS and OSI levels, alleviating oxidative stress, and increased TAS. Furthermore, UDCA reduced DNA damage, evidenced by lower 8-OHdG immunoreactivity, and regulated autophagy and apoptosis by reversing elevated LC3B and cleaved caspase-3 levels. These findings suggest that UDCA may offer therapeutic benefits against PTX-induced hepatotoxicity.
期刊介绍:
Acta Veterinaria Hungarica publishes original research papers presenting new scientific results of international interest, and to a limited extent also review articles and clinical case reports, on veterinary physiology (physiological chemistry and metabolism), veterinary microbiology (bacteriology, virology, immunology, molecular biology), on the infectious diseases of domestic animals, on veterinary parasitology, pathology, clinical veterinary science and reproduction.