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Nitric oxide facilitates the targeting Kupffer cells of a nano-antioxidant for the treatment of NASH.
Maeda, Hitoshi; Ishima, Yu; Saruwatari, Junji; Mizuta, Yuki; Minayoshi, Yuki; Ichimizu, Shota; Yanagisawa, Hiroki; Nagasaki, Taisei; Yasuda, Kengo; Oshiro, Shun; Taura, Manabu; McConnell, Matthew J; Oniki, Kentaro; Sonoda, Kayoko; Wakayama, Tomohiko; Kinoshita, Manabu; Shuto, Tsuyoshi; Kai, Hirofumi; Tanaka, Motohiko; Sasaki, Yutaka; Iwakiri, Yasuko; Otagiri, Masaki; Watanabe, Hiroshi; Maruyama, Toru.
Afiliación
  • Maeda H; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; Department of Internal Medicine, Sections of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.
  • Ishima Y; Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.
  • Saruwatari J; Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Mizuta Y; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Minayoshi Y; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Ichimizu S; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Yanagisawa H; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Nagasaki T; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Yasuda K; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Oshiro S; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Taura M; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA; Laboratory of Bioresponse Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
  • McConnell MJ; Department of Internal Medicine, Sections of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.
  • Oniki K; Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Sonoda K; Department of Histology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Wakayama T; Department of Histology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Kinoshita M; Department of Immunology and Microbiology, National Defense Medical College, Saitama, Japan.
  • Shuto T; Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Kai H; Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Tanaka M; Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Sasaki Y; Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Iwakiri Y; Department of Internal Medicine, Sections of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.
  • Otagiri M; Faculty of Pharmaceutical Sciences and DDS Research Institute, Sojo University, Kumamoto, Japan.
  • Watanabe H; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: hnabe@kumamoto-u.ac.jp.
  • Maruyama T; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: tomaru@gpo.kumamoto-u.ac.jp.
J Control Release ; 341: 457-474, 2022 01.
Article en En | MEDLINE | ID: mdl-34856227
Kupffer cells are a key source of reactive oxygen species (ROS) and are implicated in the development of steatohepatitis and fibrosis in nonalcoholic steatohepatitis (NASH). We recently developed a polythiolated and mannosylated human serum albumin (SH-Man-HSA), a nano-antioxidant that targets Kupffer cells, in which the mannosyl units on albumin allows their specific uptake by Kupffer cells via the mannose receptor C type 1 (MRC1), and in which the polythiolation confers antioxidant activity. The aim of this study was to investigate the therapeutic potential of SH-Man-HSA in NASH model mice. In livers from mice and/or patients with NASH, we observed a reduced blood flow in the liver lobes and the down-regulation in MRC1 expression in Kupffer cells, and SH-Man-HSA alone failed to improve the pathological phenotype in NASH. However, the administration of a nitric oxide (NO) donor restored hepatic blood flow and increased the expression of the mannose receptor C type 2 (MRC2) instead of MRC1. Consequently, treatment with a combination of SH-Man-HSA and an NO donor improved oxidative stress-associated pathology. Finally, we developed a hybrid type of nano-antioxidant (SNO-Man-HSA) via the S-nitrosation of SH-Man-HSA. This nanomedicine efficiently delivered both NO and thiol groups to the liver, with a hepatoprotective effect that was comparable to the combination therapy of SH-Man-HSA and an NO donor. These findings suggest that SNO-Man-HSA has the potential for functioning as a novel nano-therapy for the treatment of NASH.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad del Hígado Graso no Alcohólico Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad del Hígado Graso no Alcohólico Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos