Ischemia-reperfusion injury in fatty liver is mediated by activated NADPH oxidase 2 in rats

Koichi Kimura, Ken Shirabe, Tomoharu Yoshizumi, Kazuki Takeishi, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Hideaki Uchiyama, Shinji Okano, Yoshihiko Maehara

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Background. Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery, and steatosis is a risk factor for liver damage. Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate oxidase (NOX) contribute to liver dysfunction. Here we examined the role of NOX in I/R injury of fatty livers. Methods. Rats were fed a methionine and cholinedeficient diet to induce a fatty liver. Rats then underwent surgically induced partial hepatic ischemia followed by reperfusion. Results. The overall survival rate after I/R was lower in rats with fatty livers than with normal livers (P < 0.01). Necrotic area and the concentrations of 8-hydroxy-2α-deoxyguanosine (8-OHdG), TNFÁ, and IL-6 were higher in fatty liver tissue than in normal liver tissue (P < 0.01). The number of p47phox-positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 24 hours after reperfusion. The number of TLR-4 positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 4 and 24 hours after reperfusion coupled with a decreased number of high-mobility group box 1-positive hepatocytes. Apocynin significantly improved the survival rate, necrotic area, and concentrations of 8-hydroxy-2α-deoxyguanosine, TNFα, and IL-6 (P < 0.01). The protective effect of apocynin on fatty livers was greater than on normal livers. Conclusions. Ischemia-reperfusion injury was associated with increased high-mobility group box 1, TLR4, and NOX2. Inhibition of NOX activity improved oxidative stress and may prevent I/R injury in fatty liver.

Original languageEnglish
Pages (from-to)791-800
Number of pages10
JournalTransplantation
Volume100
Issue number4
DOIs
Publication statusPublished - 2016

All Science Journal Classification (ASJC) codes

  • Transplantation

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