Abstract
The role of ferroptosis in steatohepatitis development is largely unknown. We investigated (1) whether hepatocyte ferroptosis occurs in a gene-modified steatohepatitis model without modifying dietary components, (2) whether ferroptosis occurs at an early stage of steatohepatitis, and (3) whether apomorphine, recently reported as a ferroptosis inhibitor, can ameliorate steatohepatitis. Hepatocyte-specific PTEN KO mice were used. Huh 7 and primary cultured hepatocytes isolated from the mice were used in this study. The number of dead cells increased in 10-week-old PTEN KO mice. This cell death was suppressed by the administration of ferroptosis inhibitor ferrostatin-1 for 2 weeks. Apomorphine also ameliorated the severity of steatohepatitis. Treatment with ferroptosis inhibitors, including apomorphine, decreases the level of lipid peroxidase. Apomorphine suppressed cell death induced by RSL-3 (a ferroptosis inducer), which was not suppressed by apoptosis or necroptosis inhibitors. Apomorphine showed a radical trapping capacity with much more potent activity than ferrostatin-1 and Trolox, a soluble form of vitamin E. In addition, apomorphine activated nrf2 and its downstream genes, including HO-1 and xCT. In conclusion, ferroptosis occurs in steatohepatitis from an early stage in PTEN KO mice. In addition, apomorphine ameliorates the severity of steatohepatitis by inhibiting ferroptosis.
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MDPI and ACS Style
Maeda, H.; Miura, K.; Aizawa, K.; Bat-Erdene, O.; Sashikawa-Kimura, M.; Noguchi, E.; Watanabe, M.; Yamada, N.; Osaka, H.; Morimoto, N.;
et al. Apomorphine Suppresses the Progression of Steatohepatitis by Inhibiting Ferroptosis. Antioxidants 2024, 13, 805.
https://doi.org/10.3390/antiox13070805
AMA Style
Maeda H, Miura K, Aizawa K, Bat-Erdene O, Sashikawa-Kimura M, Noguchi E, Watanabe M, Yamada N, Osaka H, Morimoto N,
et al. Apomorphine Suppresses the Progression of Steatohepatitis by Inhibiting Ferroptosis. Antioxidants. 2024; 13(7):805.
https://doi.org/10.3390/antiox13070805
Chicago/Turabian Style
Maeda, Hiroshi, Kouichi Miura, Kenichi Aizawa, Oyunjargal Bat-Erdene, Miho Sashikawa-Kimura, Eri Noguchi, Masako Watanabe, Naoya Yamada, Hitoshi Osaka, Naoki Morimoto,
and et al. 2024. "Apomorphine Suppresses the Progression of Steatohepatitis by Inhibiting Ferroptosis" Antioxidants 13, no. 7: 805.
https://doi.org/10.3390/antiox13070805
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