A study published in the journal Brain Research investigated the effect of tipiracil hydrochloride (TPI), a selective inhibitor of thymidine phosphorylase (TP), on brain tissue damage in rats subjected to ischemia/reperfusion (I/R) injury. The research, conducted by scientists at the University of Tokyo, found that TP expression is increased in neurons under I/R conditions.
The study involved 40 adult male Sprague-Dawley rats, divided into four groups: sham, I/R control, I/R treated with low-dose TPI (10 mg/kg), and I/R treated with high-dose TPI (30 mg/kg). TPI was administered intraperitoneally 30 minutes before the induction of I/R injury via middle cerebral artery occlusion for 2 hours, followed by 24 hours of reperfusion.
Results showed that TPI treatment significantly reduced infarct volume and improved neurological deficit scores compared to the I/R control group. The high-dose TPI group exhibited a 45% reduction in infarct volume (p < 0.01) and a 38% improvement in neurological scores (p < 0.05). Additionally, TPI decreased oxidative stress markers (malondialdehyde levels) and increased antioxidant enzyme activity (superoxide dismutase and glutathione peroxidase).
The researchers concluded that TPI exerts neuroprotective effects against I/R injury by inhibiting TP activity, reducing oxidative stress, and suppressing apoptosis. These findings suggest that TPI could be a potential therapeutic agent for stroke treatment, though further studies are needed to confirm its efficacy in humans.
