TNPN2-m-Trifluorobenzyl N6-p-nitrobenzylpurine Composition for preventing and treating acetaminophen inducing hepatotoxicity containing TNPN2-m-Trifluorobenzyl N6-p-nitrobenzylpurine as an effective ingredient
The present invention relates to a composition for prevention and treatment of hepatotoxicity derived from acetaminophen (AP) containing TNP (N2- (m-Trifluorobenzyl), N6- (p-nitrobenzyl) purine) TNP, which is known as an inhibitor of inositol pyrophosphate, inhibits apoptosis by acetaminophen in human embryonic stem cell-derived hepatocytes, mouse-derived hepatocytes and human liver cancer cell lines, and the concentration of reduced glutathione (GSH) in hepatocytes , Confirming that it inhibits phosphorylated JNK, which is an increased stress response by acetaminophen, and confirmed that it has the same protective effect of acetaminophen-induced hepatocellular toxicity as in the animal model, Can be effectively used as an active ingredient of a composition for preventing and treating liver toxicity by aminophen.본 발명은 TNP(N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine)를 유효성분으로 함유하는 아세트아미노펜(Acetaminophen, AP) 유래 간 독성 예방 및 치료용 조성물에 관한 것으로, 5-이노시톨 파이로인산(inositol pyrophosphate)의 저해제로 알려진 TNP가 인간 배아 줄기세포 유래 간세포, 생쥐 유래 간세포 및 인간 간암 세포주에서 아세트아미노펜에 의한 세포 사멸을 억제하고, 간세포 내 환원된 글루타치온(glutathione, GSH)의 농도를 증가시켰으며, 아세트아미노펜에 의해 증가하는 스트레스 반응인 인산화된 JNK를 억제하는 것을 확인하고, 동물 모델에서 상기와 동일한 아세트아미노펜-유발성 간세포독성의 보호효과를 갖는 것을 확인함으로써, 상기 TNP를 아세트아미노펜에 의한 간 독성 예방 및 치료용 조성물의 유효성분으로 유용하게 사용할 수 있다.
