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The administration of hepatocyte growth factor prevents total parenteral nutrition-induced hepatocellular injury in a rat model

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Abstract

Purpose

Total parenteral nutrition (TPN) sometimes induces parenteral nutrition-associated liver disease (PNALD). Hepatocyte growth factor (HGF) acts as a potent hepatocyte mitogen anti-inflammatory and antioxidant actions. We aimed to evaluate the effect of HGF on PNALD in a rat model of TPN.

Methods

A catheter was placed in the right jugular vein for 7-day continuous TPN. All rats were divided into three groups: TPN alone (TPN group), TPN plus intravenous HGF at 0.3 mg/kg/day [TPN + HGF (low) group], and TPN plus HGF at 1.0 mg/kg/day [TPN + HGF (high) group]. On day 7, livers were harvested and the histology, inflammatory cytokines and apoptosis were evaluated.

Results

Histologically, lipid droplets were apparent in the TPN group, but decreased in the TPN + HGF (low) and TPN + HGF (high) groups. The histological nonalcoholic fatty liver disease activity scores in the TPN + HGF (low) and TPN + HGF (high) groups were significantly lower than that in the TPN group (p < 0.01). There were no significant differences in the inflammatory cytokine levels of the three groups. The caspase-9 expression levels in the TPN + HGF (low) and TPN + HGF (high) groups were significantly decreased in comparison to that in the control group (p < 0.05).

Conclusion

The intravenous administration of HGF attenuated hepatic steatosis induced by 7-day TPN dose dependently.

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Acknowledgements

We thank Mr. Brain Quinn for his comments and help with the manuscript. This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS: 20K08934, 20K17558, 20K22958, 19K10485, 19K09150, 19K09078, 19K03084, 19K18061, 19K17304, 19K18032, 18K08578, 18K16262 17K10555, 17K11514, 17K10183, 17K11515, 16K10466, 16K10094, 16K10095, 16K10434, 16H07090), a Grant for Experimental Research in the Japanese Society for Parenteral & Enteral Nutrition, research grant from Kagoshima Prefecture Medical Association, research grant from The Mother and Child Health Foundation and research grant from Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics.

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Author notes

  1. Makoto Matsukubo and Keisuke Yano contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan

    Makoto Matsukubo, Keisuke Yano, Tatsuru Kaji, Koshiro Sugita, Shun Onishi, Toshio Harumatsu, Ayaka Nagano, Mayu Matsui, Masakazu Murakami, Koji Yamada, Waka Yamada, Mitsuru Muto & Satoshi Ieiri

  2. Clinical Training Center, Kagoshima University Hospital, Kagoshima, Japan

    Tatsuru Kaji & Waka Yamada

  3. Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, School of Medical and Dental Sciences, Kagoshima University Graduate, Kagoshima, Japan

    Kotaro Kumagai & Akio Ido

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  1. Makoto Matsukubo
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  2. Keisuke Yano
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Correspondence to Satoshi Ieiri.

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Matsukubo, M., Yano, K., Kaji, T. et al. The administration of hepatocyte growth factor prevents total parenteral nutrition-induced hepatocellular injury in a rat model. Pediatr Surg Int 37, 353–361 (2021). https://doi.org/10.1007/s00383-020-04823-9

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  • DOI: https://doi.org/10.1007/s00383-020-04823-9

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