Surgery, Gastroenterology and Oncology
Vol. 25, Nr. 4, Sept 2020
Is PARP-1 Inhibitor (Nutlin3a) Effective on Hepatic Ischemia-Reperfusion Injury?
Daisuke Kawahara, Kosho Yamanouchi, Naoyuki Okita, Yoshikazu Higami, Yusuke Inoue, Shinichiro Ito, Masaaki Hidaka, Kengo Kanetaka, Fumihiko Fujita, Susumu Eguchi
Article DOI: 10.21614/sgo-25-4-189
Background Aims: Nutlin3a is known to have effects of stabilization of p53 and degradation of Poly(ADP-ribose) polymerase 1 (PARP1) in cell-specific manner. It was demonstrated that nutrlin3a decrease tissue damage caused by ischemia reperfusion (I R) in transplant settings such as lung. We aimed to evaluate if the reagent would still alleviate hepatic I R injury.

Methodology: First, to evaluate an efficacy of nutlin3a in normal liver, we administered it to male C57Bl 6 mice intraperitoneally at doses of 0 (vehicle only), 5, and 20 mg kg of body-weight. The animals were killed at 4, 8, and 12 hours after administration and proteins of p53 and PARP1 in the liver were evaluated. Next, we assessed the effects of nutlin3a on the liver after I R. Twenty-four hours after administration of nutlin3a, the mice suffered from hepatic ischemia, and then were sacrificed at 8 and 24 hours after reperfusion.

Results: No changes were observed in proteins of p53 and PARP1 in both the normal and I R liver by administration of nutlin3a. Nutilin3a did not only show the effect of alleviation of hepatic I R injury, but also seemed to have cytotoxicity to hepatocyte in dose-dependent manner.

Conclusion: A protective effect of nutilin3a was not evident in hepatic I R model.

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Surgery, Gastroenterology and Oncology is indexed in Scopus, CrossRef (DOI: 10.21614/sgo)

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