Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury - PubMed (original) (raw)

Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury

Jon Cardinal et al. Hepatology. 2009 Aug.

Abstract

The nuclear protein high mobility group box 1 (HMGB1) is an important inflammatory mediator involved in the pathogenesis of liver ischemia/reperfusion (I/R) injury. Strategies aimed at preventing its release from stressed or damaged cells may be beneficial in preventing inflammation after I/R. Cisplatin is a member of the platinating chemotherapeutic agents and can induce DNA lesions that are capable of retaining high mobility group proteins inside the nucleus of cells. In vitro studies in primary cultured rat hepatocytes show that nontoxic concentrations of cisplatin can sequester HMGB1 inside the nucleus of hypoxic cells. Similarly, the in vivo administration of nontoxic doses of cisplatin prevents liver damage associated with a well-established murine model of hepatic I/R as measured by lower circulating serum aminotransferase levels, lower hepatic inflammatory cytokine levels including tumor necrosis factor alpha and interleukin-6, lower inducible NO synthase expression, and fewer I/R-associated histopathologic changes. The mechanism of action in vivo appears to involve the capacity of cisplatin to prevent the I/R-induced release of HMGB1 as well as to alter cell survival and stress signaling in the form of autophagy and mitogen-activated protein kinase activation, respectively.

Conclusion: Low, nontoxic doses of cisplatin can sequester HMGB1 inside the nucleus of redox-stressed hepatocytes in vitro and prevent its release in vivo in a murine model of hepatic I/R. Furthermore, cell survival and stress signaling pathways are altered by low-dose cisplatin. Therefore, platinating agents may provide a novel approach to mitigating the deleterious effects of I/R-mediated disease processes.

PubMed Disclaimer

Cited by

Identification and validation of potential diagnostic signature and immune cell infiltration for HIRI based on cuproptosis-related genes through bioinformatics analysis and machine learning.
Xiao F, Huang G, Yuan G, Li S, Wang Y, Tan Z, Liu Z, Tomlinson S, He S, Ouyang G, Zeng Y. Xiao F, et al. Front Immunol. 2024 Apr 16;15:1372441. doi: 10.3389/fimmu.2024.1372441. eCollection 2024. Front Immunol. 2024. PMID: 38690269 Free PMC article.
Inhibition of the HMGB1/RAGE axis protects against cisplatin-induced ototoxicity via suppression of inflammation and oxidative stress.
Qiao X, Li W, Zheng Z, Liu C, Zhao L, He Y, Li H. Qiao X, et al. Int J Biol Sci. 2024 Jan 1;20(2):784-800. doi: 10.7150/ijbs.82003. eCollection 2024. Int J Biol Sci. 2024. PMID: 38169643 Free PMC article.
Autophagy in hepatic ischemia-reperfusion injury.
Mao B, Yuan W, Wu F, Yan Y, Wang B. Mao B, et al. Cell Death Discov. 2023 Apr 5;9(1):115. doi: 10.1038/s41420-023-01387-0. Cell Death Discov. 2023. PMID: 37019879 Free PMC article. Review.
Mitochondrial Autophagy in Ischemic Aged Livers.
Kim JS, Chapman WC, Lin Y. Kim JS, et al. Cells. 2022 Dec 16;11(24):4083. doi: 10.3390/cells11244083. Cells. 2022. PMID: 36552847 Free PMC article. Review.
Regulation of autophagy protects against liver injury in liver surgery-induced ischaemia/reperfusion.
Hu C, Zhao L, Zhang F, Li L. Hu C, et al. J Cell Mol Med. 2021 Nov;25(21):9905-9917. doi: 10.1111/jcmm.16943. Epub 2021 Oct 8. J Cell Mol Med. 2021. PMID: 34626066 Free PMC article. Review.

Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury - PubMed (original) (raw)