Mohammad Hady Khosravi, Khairollah Asadollahi, Bahareh Ghiasi, Amir Adibi, Somayeh Heidarizadi, Monireh Azizi
{"title":"Anti-inflammatory and Antioxidant Effects of Silibinin on Valproate-Induced Pancreatitis in Male Wistar Rats.","authors":"Mohammad Hady Khosravi, Khairollah Asadollahi, Bahareh Ghiasi, Amir Adibi, Somayeh Heidarizadi, Monireh Azizi","doi":"10.2174/0118715303411821250914094338","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Valproic acid (VPA), a widely used antiepileptic drug, is associated with pancreatic toxicity. Silibinin, the active component of silymarin, exhibits antioxidant/anti-inflammatory properties. This study investigated silibinin's protective effects against VPA-induced pancreatitis.</p><p><strong>Methods: </strong>48 male Wistar rats (250-280 g) were divided into 8 groups (n=6): control, VPA-only (150,300 and 450 mg/kg), silibinin-only (150 mg/kg), and co-treatment groups. After 3 weeks, biochemical markers (amylase, lipase, SOD, CAT, TNF-α, IL-6) and histopathology (H&E staining) were analyzed. Data were compared using ANOVA/Tukey's test (p<0.05 significant).</p><p><strong>Results: </strong>VPA dose-dependently increased pancreatic enzymes and inflammatory markers, while reducing antioxidants. Silibinin co-treatment significantly attenuated these effects: Reduced amylase (642.8→375.6 U/L at 450 mg/kg VPA) and TNF-α (61.0→31.6 pg/mL) and restored SOD (10.9→18.3 U/mg) and CAT (5.3→366.2 U/mg). Histopathology confirmed reduced inflammation/ necrosis in co-treatment groups (p<0.01).</p><p><strong>Discussion: </strong>Silibinin mitigated VPA-induced pancreatitis via antioxidant (SOD/CAT upregulation) and anti-inflammatory (TNF-α/IL-6 reduction) mechanisms. The effect was dose-dependent, with optimal protection at lower VPA doses (150 and 300 mg/kg).</p><p><strong>Conclusion: </strong>Silibinin shows promise as an adjunct therapy to reduce VPA-associated pancreatic damage. Further clinical studies are warranted.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine, metabolic & immune disorders drug targets","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0118715303411821250914094338","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Valproic acid (VPA), a widely used antiepileptic drug, is associated with pancreatic toxicity. Silibinin, the active component of silymarin, exhibits antioxidant/anti-inflammatory properties. This study investigated silibinin's protective effects against VPA-induced pancreatitis.
Methods: 48 male Wistar rats (250-280 g) were divided into 8 groups (n=6): control, VPA-only (150,300 and 450 mg/kg), silibinin-only (150 mg/kg), and co-treatment groups. After 3 weeks, biochemical markers (amylase, lipase, SOD, CAT, TNF-α, IL-6) and histopathology (H&E staining) were analyzed. Data were compared using ANOVA/Tukey's test (p<0.05 significant).
Results: VPA dose-dependently increased pancreatic enzymes and inflammatory markers, while reducing antioxidants. Silibinin co-treatment significantly attenuated these effects: Reduced amylase (642.8→375.6 U/L at 450 mg/kg VPA) and TNF-α (61.0→31.6 pg/mL) and restored SOD (10.9→18.3 U/mg) and CAT (5.3→366.2 U/mg). Histopathology confirmed reduced inflammation/ necrosis in co-treatment groups (p<0.01).
Discussion: Silibinin mitigated VPA-induced pancreatitis via antioxidant (SOD/CAT upregulation) and anti-inflammatory (TNF-α/IL-6 reduction) mechanisms. The effect was dose-dependent, with optimal protection at lower VPA doses (150 and 300 mg/kg).
Conclusion: Silibinin shows promise as an adjunct therapy to reduce VPA-associated pancreatic damage. Further clinical studies are warranted.