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<p>Thymidine phosphorylase (TP) expression is increased in neurons under ischemia/reperfusion (I/R) conditions. Our aim was to evaluate the effect of tipiracil hydrochloride (TPI), a selective TP inhibitor, on rat brain tissue subjected to I/R. Both common carotid arteries were occluded for 30&#xa0;min in the ischemic untreated group of rats (C-IR), and ischemic groups treated with tipiracil 25&#xa0;mg/g (T-IR25) or 50&#xa0;mg/kg (T-IR50). In the control group (C), the arteries were not ligated. Tipiracil was given during ischemia, and after 8&#xa0;h of I/R intraperitoneally. After 24&#xa0;h of I/R, brain tissue was isolated for histology and immunohistochemy of TP expression. Metalloproteinases 2 and 9 (MMP-2 and -9) and tissue inhibitor of metalloproteinases (TIMP-1) were determined in serum at 3 and 24&#xa0;h of reperfusion. TP expression in brain tissue was the highest in C-IR and T-IR25 compared to the C and T-IR50<b>.</b> No changes in serum TP levels were observed. After 24&#xa0;h, there was a significant decrease in MMP-9 levels in T-IR25 compared to the C-IR and T-IR50. MMP-2 levels also decreased significantly at this time point in all groups compared to group C, which correlated with increased TIMP-1 activity in the T-IR25 and T-IR50. The inhibition of TP activity in the group receiving TPI suggests its protective effect on brain tissue under I/R conditions. The decrease in MMP activities in the treated groups suggests a protective effect of TPI on the development of neuroinflammation caused by local brain tissue ischemia.</p>

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Effect of tipiracil hydrochloride, thymidine phosphorylase inhibitor, on the ischemia/reperfusion injury of brain tissue in rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月20日

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  • Małgorzata Trocha,
  • Tomasz Piasecki,
  • Paulina Nowotarska,
  • Tomasz Sozański,
  • Anna Merwid-Ląd,
  • Beata Nowak,
  • Marcin Nowak,
  • Rafał Ciaputa,
  • Grzegorz Mazur,
  • Adam Szeląg,
  • Damian Gajecki,
  • Adrian Doroszko

摘要

Thymidine phosphorylase (TP) expression is increased in neurons under ischemia/reperfusion (I/R) conditions. Our aim was to evaluate the effect of tipiracil hydrochloride (TPI), a selective TP inhibitor, on rat brain tissue subjected to I/R. Both common carotid arteries were occluded for 30 min in the ischemic untreated group of rats (C-IR), and ischemic groups treated with tipiracil 25 mg/g (T-IR25) or 50 mg/kg (T-IR50). In the control group (C), the arteries were not ligated. Tipiracil was given during ischemia, and after 8 h of I/R intraperitoneally. After 24 h of I/R, brain tissue was isolated for histology and immunohistochemy of TP expression. Metalloproteinases 2 and 9 (MMP-2 and -9) and tissue inhibitor of metalloproteinases (TIMP-1) were determined in serum at 3 and 24 h of reperfusion. TP expression in brain tissue was the highest in C-IR and T-IR25 compared to the C and T-IR50. No changes in serum TP levels were observed. After 24 h, there was a significant decrease in MMP-9 levels in T-IR25 compared to the C-IR and T-IR50. MMP-2 levels also decreased significantly at this time point in all groups compared to group C, which correlated with increased TIMP-1 activity in the T-IR25 and T-IR50. The inhibition of TP activity in the group receiving TPI suggests its protective effect on brain tissue under I/R conditions. The decrease in MMP activities in the treated groups suggests a protective effect of TPI on the development of neuroinflammation caused by local brain tissue ischemia.