Mohd Wasim, Mansoor Ali Syed, Syed Ehtaishamul Haque
{"title":"马鞭草酮对瑞士白化病小鼠抗环磷酰胺诱导的氧化应激、炎症、凋亡和纤维化的肝保护作用:NF-κB、caspase-3和TGF-β信号通路的参与","authors":"Mohd Wasim, Mansoor Ali Syed, Syed Ehtaishamul Haque","doi":"10.1007/s13205-025-04496-y","DOIUrl":null,"url":null,"abstract":"<p><p>Cyclophosphamide (CP), an anti-cancer drug, causes oxidative stress, inflammation, apoptosis and fibrosis in liver. Verbenone (VRB), a bicyclic monoterpene ketone, having antioxidant, anti-inflammatory and anti-apoptotic properties, was selected to investigate its efficiency in reversing CP-induced hepatotoxicity. We hypothesized that VRB having good antioxidant, anti-inflammatory and anti-apoptotic properties, might neutralize the CP-induced toxicity and offer liver protection. Seven groups of mice were formed (<i>n</i> = 6): Vehicle Control, CP 200, VRB 200 + CP, VRB 300 + CP, FF 80 + CP, FF 80 per se, and VRB 300 per se. CP (200 mg/kg, i.p.) was injected once on the seventh day, while VRB (200 and 300 mg/kg, p.o.) and fenofibrate (FF, 80 mg/kg, p.o.) were given daily for 14 days. On 15th day, they were sacrificed and samples for biochemical and histological investigation were taken. CP-treated mice showed an increase in malondialdehyde levels, liver enzymes (AST, ALT, ALP, GGT), inflammatory markers (NF-κB, TNF-α, IL-1β, IL-6), and apoptotic markers (cleaved caspase-3), with a decrease in IL-10 and antioxidant enzymes (SOD, catalase, and glutathione). VRB administration significantly improved the liver function by reducing inflammation, oxidative stress, fibrosis and apoptosis. It restored antioxidant enzymes and hepatocyte structure as confirmed by histopathological and immunohistochemical analyses. Thus, these findings clearly supported our hypothesis and proved that VRB has a strong hepatoprotective effect that counteracts CP-induced liver toxicity through antioxidative, anti-inflammatory, anti-apoptotic, and anti-fibrotic mechanisms. However, further research is needed to be done involving animal cancer models to confirm its potential role and efficiency in reducing CP-induced hepatotoxicity.</p>","PeriodicalId":7067,"journal":{"name":"3 Biotech","volume":"15 10","pages":"326"},"PeriodicalIF":2.9000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408882/pdf/","citationCount":"0","resultStr":"{\"title\":\"Hepatoprotective role of verbenone against cyclophosphamide-induced oxidative stress, inflammation, apoptosis, and fibrosis in Swiss albino mice: insights into the involvement of NF-κB, caspase-3, and TGF-β signaling pathways.\",\"authors\":\"Mohd Wasim, Mansoor Ali Syed, Syed Ehtaishamul Haque\",\"doi\":\"10.1007/s13205-025-04496-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cyclophosphamide (CP), an anti-cancer drug, causes oxidative stress, inflammation, apoptosis and fibrosis in liver. Verbenone (VRB), a bicyclic monoterpene ketone, having antioxidant, anti-inflammatory and anti-apoptotic properties, was selected to investigate its efficiency in reversing CP-induced hepatotoxicity. We hypothesized that VRB having good antioxidant, anti-inflammatory and anti-apoptotic properties, might neutralize the CP-induced toxicity and offer liver protection. Seven groups of mice were formed (<i>n</i> = 6): Vehicle Control, CP 200, VRB 200 + CP, VRB 300 + CP, FF 80 + CP, FF 80 per se, and VRB 300 per se. CP (200 mg/kg, i.p.) was injected once on the seventh day, while VRB (200 and 300 mg/kg, p.o.) and fenofibrate (FF, 80 mg/kg, p.o.) were given daily for 14 days. On 15th day, they were sacrificed and samples for biochemical and histological investigation were taken. CP-treated mice showed an increase in malondialdehyde levels, liver enzymes (AST, ALT, ALP, GGT), inflammatory markers (NF-κB, TNF-α, IL-1β, IL-6), and apoptotic markers (cleaved caspase-3), with a decrease in IL-10 and antioxidant enzymes (SOD, catalase, and glutathione). VRB administration significantly improved the liver function by reducing inflammation, oxidative stress, fibrosis and apoptosis. It restored antioxidant enzymes and hepatocyte structure as confirmed by histopathological and immunohistochemical analyses. Thus, these findings clearly supported our hypothesis and proved that VRB has a strong hepatoprotective effect that counteracts CP-induced liver toxicity through antioxidative, anti-inflammatory, anti-apoptotic, and anti-fibrotic mechanisms. However, further research is needed to be done involving animal cancer models to confirm its potential role and efficiency in reducing CP-induced hepatotoxicity.</p>\",\"PeriodicalId\":7067,\"journal\":{\"name\":\"3 Biotech\",\"volume\":\"15 10\",\"pages\":\"326\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408882/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"3 Biotech\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1007/s13205-025-04496-y\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"3 Biotech","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s13205-025-04496-y","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/3 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Hepatoprotective role of verbenone against cyclophosphamide-induced oxidative stress, inflammation, apoptosis, and fibrosis in Swiss albino mice: insights into the involvement of NF-κB, caspase-3, and TGF-β signaling pathways.
Cyclophosphamide (CP), an anti-cancer drug, causes oxidative stress, inflammation, apoptosis and fibrosis in liver. Verbenone (VRB), a bicyclic monoterpene ketone, having antioxidant, anti-inflammatory and anti-apoptotic properties, was selected to investigate its efficiency in reversing CP-induced hepatotoxicity. We hypothesized that VRB having good antioxidant, anti-inflammatory and anti-apoptotic properties, might neutralize the CP-induced toxicity and offer liver protection. Seven groups of mice were formed (n = 6): Vehicle Control, CP 200, VRB 200 + CP, VRB 300 + CP, FF 80 + CP, FF 80 per se, and VRB 300 per se. CP (200 mg/kg, i.p.) was injected once on the seventh day, while VRB (200 and 300 mg/kg, p.o.) and fenofibrate (FF, 80 mg/kg, p.o.) were given daily for 14 days. On 15th day, they were sacrificed and samples for biochemical and histological investigation were taken. CP-treated mice showed an increase in malondialdehyde levels, liver enzymes (AST, ALT, ALP, GGT), inflammatory markers (NF-κB, TNF-α, IL-1β, IL-6), and apoptotic markers (cleaved caspase-3), with a decrease in IL-10 and antioxidant enzymes (SOD, catalase, and glutathione). VRB administration significantly improved the liver function by reducing inflammation, oxidative stress, fibrosis and apoptosis. It restored antioxidant enzymes and hepatocyte structure as confirmed by histopathological and immunohistochemical analyses. Thus, these findings clearly supported our hypothesis and proved that VRB has a strong hepatoprotective effect that counteracts CP-induced liver toxicity through antioxidative, anti-inflammatory, anti-apoptotic, and anti-fibrotic mechanisms. However, further research is needed to be done involving animal cancer models to confirm its potential role and efficiency in reducing CP-induced hepatotoxicity.
3 BiotechAgricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)
CiteScore
6.00
自引率
0.00%
发文量
314
期刊介绍:
3 Biotech publishes the results of the latest research related to the study and application of biotechnology to:
- Medicine and Biomedical Sciences
- Agriculture
- The Environment
The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.