title: Cisplatin protects against acute liver failure by inhibiting nuclear HMGB1 release.
abstract: Cisplatin is one of the most widely used chemical drugs for anticancer treatment. Recent studies have focused on the ability of cisplatin to retain the high mobility group box 1 (HMGB1) protein in cisplatin-DNA adducts, thereby preventing its release from the nucleus. Because HMGB1 is a powerful inflammatory mediator in many diseases, the aim of this study is to evaluate the therapeutic effect of cisplatin acute liver failure. In this study, low-dose cisplatin was administered to treat PMA-induced macrophage-like cells induced by PMA and rats with acute liver failure. We found that cell viability and liver injury were greatly improved by cisplatin treatment. The extracellular levels of HMGB1, TNF-α and IFN-γ were also significantly decreased by the administration of cisplatin. During inflammation, nuclear HMGB1 translocates from the nucleus to the cytoplasm. The administration of cisplatin reduced the cytoplasmic levels of HMGB1 and increased nuclear HMGB1 levels in vitro and in vivo. In conclusion, cisplatin can protect against acute liver failure by retaining HMGB1 in the nucleus and preventing its release into the extracellular milieu.
authors.affiliation: Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, China. zjgong@163.com.
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.forename: Li-Kun
authors.initials: LK
authors.lastname: Wang
authors.forename: Lu-Wen
authors.initials: LW
authors.lastname: Wang
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Han
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Zuo-Jiong
authors.initials: ZJ
authors.lastname: Gong
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis; D019610:Cytoprotection / Q000187:drug effects*; D024243:HMGB1 Protein / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017208:Rats, Wistar; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; D000410:Alanine Transaminase; D002945:Cisplatin