Effect of thymoquinone on ameliorating valproic acid-induced damage in pancreatic tissue of rats

Purpose: The aim of this study was to evaluate the potential effect of thymoquinone (TQ) in preventing or treating valproic acid (VPA)-induced pancreatic injury, gene expressions and histopathological changes in pancreatic tissue of rats.. Materials and Methods: 21 male Spraque-Dawley rats were divided into 3 groups (n = 7): Control, VPA, VPA + TQ. Rats were treated orally with VPA (500 mg/kg/day) and TQ (50 mg/kg/day) for 14 days. On the 15th day of treatment, pancreatic tissue was resected for the analysis of the expression levels of histone deacetylase (HDAC1 and HDAC2) genes. Structural changes in pancreatic tissues were examined Results: It was observed that VPA + TQ group had significantly higher HDAC1 and HDAC2 genes expression compared to the VPA group. Furthermore, the findings show that TQ therapy can protect pancreatic tissue against the negative effects of VPA on HDAC1 and HDAC2 gene expression. It also decreased the levels of NADPH oxidase-4 (NOX-4) and caspase-3 (CAS-3). Oxidative stress decreased, antioxidant activity increased and histopathological changes decreased in the VPA + TQ group compared to the VPA group. Pancreatic damage caused by VPA was attenuated due to TQ's antioxidative and antiapoptotic effects. Conclusion: TQ may be useful for reducing the severity of VPA-induced pancreatic damage.