Anti-inflammatory and Antioxidant Effects of Silibinin on Valproate-Induced Pancreatitis in Male Wistar Rats

Mohammad Hady Khosravi; Khairollah Asadollahi; Bahareh Ghiasi; Amir Adibi; Somayeh Heidarizadi; Monireh Azizi

doi:10.2174/0118715303411821250914094338

Anti-inflammatory and Antioxidant Effects of Silibinin on Valproate-Induced Pancreatitis in Male Wistar Rats

Endocr Metab Immune Disord Drug Targets. 2025 Oct 2. doi: 10.2174/0118715303411821250914094338. Online ahead of print.

Authors

Mohammad Hady Khosravi¹, Khairollah Asadollahi², Bahareh Ghiasi³, Amir Adibi⁴, Somayeh Heidarizadi⁵, Monireh Azizi^{5

6}

Affiliations

¹ Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
² Department of Social Medicine, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
³ Psychosocial Injuries Research Center, Ilam University of Medical Sciences, Ilam, Iran.
⁴ Department of Psychiatry, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
⁵ Department of Anatomy, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
⁶ Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam, Iran.

PMID: 41047694
DOI: 10.2174/0118715303411821250914094338

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.

Keywords: Valproate; inflammatory factors; oxidative stress; pancreatitis; wistar rats..