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The Proton Pump Inhibitor Lansoprazole Has Hepatoprotective Effects in In Vitro and In Vivo Rat Models of Acute Liver Injury

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Abstract

Background/Aims

The proton pump inhibitor lansoprazole (LPZ) is clinically used to reduce gastric acid secretion, but little is known about its possible hepatoprotective effects. This study aimed to investigate the hepatoprotective effects of LPZ and its potential mechanisms using in vitro and in vivo rat models of liver injury.

Methods

For the in vitro model of liver injury, primary cultured rat hepatocytes were treated with interleukin-1β in the presence or absence of LPZ. The influence of LPZ on inducible nitric oxide synthase (iNOS) induction and nitric oxide (NO) production and on the associated signaling pathways was analyzed. For the in vivo model, rats were treated with D-galactosamine (GalN) and lipopolysaccharide (LPS). The effects of LPZ on survival and proinflammatory mediator expression (including iNOS and tumor necrosis factor-α) in these rats were examined.

Results

LPZ inhibited iNOS induction partially through suppression of the nuclear factor-kappa B signaling pathway in hepatocytes, thereby reducing potential liver injury from excessive NO levels. Additionally, LPZ increased survival by 50% and decreased iNOS, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 mRNA expression in the livers of GalN/LPS-treated rats. LPZ also inhibited nuclear factor-kappa B activation by GalN/LPS.

Conclusions

LPZ inhibits the induction of several inflammatory mediators (including cytokines, chemokines, and NO) partially through suppression of nuclear factor-kappa B, resulting in the prevention of fulminant liver failure. The therapeutic potential of LPZ for liver injuries warrants further investigation.

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Acknowledgments

This work was supported in part by grants from the Science Research Promotion Fund of the Japan Private School Promotion Foundation.

Funding

This work was supported in part by grants from the Science Research Promotion Fund of the Japan Private School Promotion Foundation.

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Author notes

  1. Richi Nakatake and Hidehiko Hishikawa contributed equally to this study.

Authors and Affiliations

  1. Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan

    Richi Nakatake, Hidehiko Hishikawa, Masaya Kotsuka, Morihiko Ishizaki, Kosuke Matsui, Masaki Kaibori & Tadayoshi Okumura

  2. Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

    Mikio Nishizawa

  3. Laboratory of Environmental Sciences, Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Mukogawa Women’s University, 6-46 Ikebiraki-cho, Nishinomiya, Hyogo, 663-8558, Japan

    Katsuhiko Yoshizawa

  4. Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

    Tadayoshi Okumura

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  1. Richi Nakatake
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Correspondence to Richi Nakatake.

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Nakatake, R., Hishikawa, H., Kotsuka, M. et al. The Proton Pump Inhibitor Lansoprazole Has Hepatoprotective Effects in In Vitro and In Vivo Rat Models of Acute Liver Injury. Dig Dis Sci 64, 2854–2866 (2019). https://doi.org/10.1007/s10620-019-05622-6

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