Effect of tipiracil hydrochloride (5-chloro-6- (2-iminopyrrolidin-1-yl) methyl-2,4 (1H, 3H) - pyrimidinedione hydrochloride), thymidine phosphorylase inhibitor on the ischemia/reperfusion (I/R) process of brain tissue in rats

Abstract Background Thymidine phosphorylase (TP) plays a significant role in platelet activation and thrombosis. Its expression is increased in neurons under IR conditions.Aim The study aims to evaluate the effect of tipiracil hydrochloride (TPI), a selective TP inhibitor, on the brain tissue subjected to IR in rats.Methods Under anesthesia, common carotid arteries were isolated and occluded (BCCAO) for 30 min in groups of rats, CIR(n = 9), TIR25(n = 10), and TIR50(n = 9). In group C(n = 12) arteries were isolated but not ligated. During ischemia and after 8h of IR, rats received TPI i.p. (25 or 50mg/kg). After 24h of IR brain tissue was isolated for histopathological evaluation and the visualization of TP expression in immunohistochemical reaction (IHC). In serum levels of metalloproteinases (MMP-2 and − 9), and their inhibitor (TIMP-1) were determinedResults TP expression in brain tissue was the highest in CIR and TIR25 compared to the C and TIR50. After 3 h of IR, a significant increase in TP activity in CIR and TIR25 was noticed compared to the C. In the TIR50, the TP value was not significantly different from the C group at both time points of IR. After 24 h there was a significant decrease in MMP-9 level in TIR25 compared to the CIR and TIR50, also MMP-2 values decreased significantly in all groups compared to group C, which correlated with an increase in TIMP-1 activity in the TIR25 and TIR50.Conclusion The inhibition of TP activity in the group receiving TPI suggests its protective effect on brain tissue under IR conditions The decrease in MMPs activities in treated groups suggests a protective effect of TPI on the development of neuroinflammation caused by local brain tissue ischemia