The effects of a Cilostazol, a selective phosphodiesterase III inhibitor, on liver ischemic-reperfusion injury and liver regeneration; In vitro experimental study

Abstract

Objective: Hepatectomy and transplantation cause liver damage through ischemic reperfusion and oxidative stress. There is no treatment available to improve liver regeneration and reduce ischemic-reperfusion injury. The present study aimed to investigate whether a selective phosphodiesterase III inhibitor, Cilostazol, improves ischemic reperfusion injury and liver regeneration following extended hepatectomy. Material and Methods: Wistar albino rats (n=40) were randomized and divided into 4 equal groups. All rats underwent 60% hepatectomy, and Cilostazol (5 mg/kg per day) was administered to the experimental group. The subjects were sacrificed on the 4th and 7th days following the resection. Blood samples were taken to evaluate liver enzymes (ALT, AST) and liver tissue samples were taken to analyze morphology. Biochemical, morphological, and histopathological parameters were compared between Groups. Results: No statistically significant differences were detected in ALT, AST values , and relative liver weights in rats treated with Cilostazol compared to the control group without Cilostazol. Although not statistically significant, a significant increase was detected in relative liver weight and a decrease in AST value in rats treated with Cilostazol. SOD activity was found to be significantly higher and GSH levels, MPO and AOPPs levels were significantly lower in Cilostazol applied Groups. It is seen in these findings that selective inhibition of PDE3 by Cilostazol improves hepatic circulation. It was also found that ischemic reperfusion injury decreased and regeneration markers such as mitosis index, even nucleus, and proliferating cell nuclear antigen ratio increased in rats treated with Cilostazol. Conclusion: The present study found that selective PDE3 inhibitor Cilostazol positively affected the histopathological parameters following extended liver resection and significantly increased hepatocellular proliferation.