Inhibiting poly (ADP-ribose) polymerase 1 activation alleviates acetaminophen-induced acute liver injury in mice

作者全名："Tang, Jiarui; Liao, Cuiting; Hu, Kai; Li, Longhui; Yang, Yongqiang; Huang, Jiayi; Tang, Li; Zhang, Li; Li, Longjiang"

作者地址："[Tang, Jiarui; Liao, Cuiting; Yang, Yongqiang; Huang, Jiayi; Tang, Li; Zhang, Li; Li, Longjiang] Chongqing Med Univ, Sch Basic Med Coll, Dept Pathophysiol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Tang, Jiarui; Liao, Cuiting; Hu, Kai; Yang, Yongqiang; Huang, Jiayi; Tang, Li; Zhang, Li; Li, Longjiang] Chongqing Med Univ, Lab Stem Cell & Tissue Engn, Chongqing 400016, Peoples R China; [Li, Longhui] Univ Chinese Acad Sci, Chongqing Gen Hosp, Ctr Hlth Management, Chongqing 400000, Peoples R China"

通信作者："Zhang, L; Li, LJ (通讯作者)，Chongqing Med Univ, Sch Basic Med Coll, Dept Pathophysiol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Zhang, L; Li, LJ (通讯作者)，Chongqing Med Univ, Lab Stem Cell & Tissue Engn, Chongqing 400016, Peoples R China."

来源：MOLECULAR & CELLULAR TOXICOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001077790800001

JCR分区：Q4

影响因子：1.7

年份：2024

卷号：20

期号：4

开始页：929

结束页：937

文献类型：Article

关键词：Acetaminophen; Acute liver injury; Poly (ADP-ribose) polymerase 1; Sirtuin 1

摘要："BackgroundAcetaminophen (APAP) overdose can cause severe acute liver injury. Poly (ADP-ribose) polymerase 1 (PARP1) is a nuclear protease that senses DNA breaks and repairs damaged DNA. The role PARP1 plays in APAP-induced hepatotoxicity is still unclear.Materials and methodsThe study was designed in two parts. First, the relationship between PARP1 expression and hepatotoxicity was investigated. Then, the inhibitor PJ34 was used to inhibit the activity of PARP1 and examined its effects. In particular, APAP, vehicle or PJ34 was intraperitoneally administered to mice. Serum transaminase levels were measured with commercial kits. Hematoxylin & eosin staining was used for histopathological observation of the liver. The protein levels of PARP1, poly (ADP-ribose), Sirtuin1 (Sirt1) and gamma-H2AX were detected by western blotting.ResultsIn a dose- and time-dependent manner, APAP exposure resulted in the overactivation of PARP1 in the livers of mice. Posttreatment with PJ34 ameliorated changes in serum transaminase levels, and histopathological abnormalities. The protein expression of Sirt1 was elevated by PJ34, while that of PARP1, poly (ADP-ribose), and gamma-H2AX was reduced due to PJ34 administration.ConclusionExcessive APAP administration results in PARP1 overactivation, and its inhibition sheds light on the treatment of APAP-induced liver injury."

基金机构："The authors thank the Chongqing Yike Tianya Biotechnology Co., Ltd for the assistance in Hamp;E and PAS staining."

基金资助正文："The authors thank the Chongqing Yike Tianya Biotechnology Co., Ltd for the assistance in H&E and PAS staining."