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Susceptibility of Asialoglycoprotein Receptor-Deficient Mice to Lps/Galactosamine Liver Injury and Protection by Betaine Administration.
Rasineni, Karuna; Lee, Serene M L; McVicker, Benita L; Osna, Natalia A; Casey, Carol A; Kharbanda, Kusum K.
Afiliação
  • Rasineni K; Research Service, Veterans' Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.
  • Lee SML; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • McVicker BL; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Osna NA; Research Service, Veterans' Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.
  • Casey CA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Kharbanda KK; Research Service, Veterans' Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.
Biology (Basel) ; 10(1)2020 Dec 31.
Article em En | MEDLINE | ID: mdl-33396223
ABSTRACT

BACKGROUND:

Work from our laboratory has shown that the ethanol-induced increase in apoptotic hepatocellular death is closely related to the impairment in the ability of the asialoglycoprotein receptor (ASGP-R) to remove neighboring apoptotic cells. In this study, we assessed the role of ASGP-R in fulminant liver failure and investigated whether prior treatment with betaine (a naturally occurring tertiary amine) is protective.

METHODS:

Lipopolysaccharide (LPS; 50 µg/kg BW) and galactosamine (GalN; 350 mg/kg BW) were injected together to wild-type and ASGP-R-deficient mice that were treated for two weeks prior with or without 2% betaine in drinking water. The mice were sacrificed 1.5, 3, or 4.5 h post-injection, and tissue samples were collected.

RESULTS:

LPS/GalN injection generate distinct molecular processes, which includes increased production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), thus causing apoptosis as evident by increased caspase-3 activity. ASGP-R deficient animals showed increased liver caspase activities, serum TNF-α and IL-6 levels, as well as more pronounced liver damage compared with the wild-type control animals after intraperitoneal injection of LPS/GalN. In addition, prior administration of betaine was found to significantly attenuate the LPS/GalN-induced increases in liver injury parameters.

CONCLUSION:

Our work underscores the importance of normal functioning of ASGP-R in preventing severe liver damage and signifies a therapeutic role of betaine in prevention of liver injuries from toxin-induced fulminant liver failure.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article