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Tumor necrosis factor-alpha-induced reduction of glomerular filtration rate in rats with fulminant hepatic failure.
Wang, Jing-Bo; Wang, Dong-Lei; Wang, Hai-Tao; Wang, Zhao-Han; Wen, Ying; Sun, Cui-Ming; Zhao, Yi-Tong; Wu, Jian; Liu, Pei.
Afiliación
  • Wang JB; 1] Department of Infectious Diseases, The First Affiliated Hospital, China Medical University, Shenyang City, People's Republic of China [2] Division of Gastroenterology, Department of Internal Medicine, The Sixth People's Hospital of Shenyang, Shenyang City, People's Republic of China.
  • Wang DL; Department of Infectious Diseases, The First Affiliated Hospital, China Medical University, Shenyang City, People's Republic of China.
  • Wang HT; Division of Hepatobiliary Diseases, Department of Surgery, The Affiliated Shenzhou Hospital of Shenyang Medical College, Shenyang City, People's Republic of China.
  • Wang ZH; Department of Infectious Diseases, The First Affiliated Hospital, China Medical University, Shenyang City, People's Republic of China.
  • Wen Y; Department of Infectious Diseases, The First Affiliated Hospital, China Medical University, Shenyang City, People's Republic of China.
  • Sun CM; Department of Infectious Diseases, The First Affiliated Hospital, China Medical University, Shenyang City, People's Republic of China.
  • Zhao YT; Division of Gastroenterology, Department of Internal Medicine, The Sixth People's Hospital of Shenyang, Shenyang City, People's Republic of China.
  • Wu J; 1] Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of California, Davis Medical Center, Sacramento, CA, USA [2] Key Laboratory of Molecular Virology, Fudan University College of Basic Medical Sciences, Shanghai, People's Republic of China.
  • Liu P; Department of Infectious Diseases, The First Affiliated Hospital, China Medical University, Shenyang City, People's Republic of China.
Lab Invest ; 94(7): 740-51, 2014 Jul.
Article en En | MEDLINE | ID: mdl-24887412
The mechanism of renal failure during fulminant hepatic failure (FHF) or end-stage of liver disease is not fully understood. The present study aims to delineate the mechanisms of decreased glomerular filtration rate (GFR) in acute hepatic failure. A rat model of renal insufficiency in severe liver injury was established by lipopolysaccharide (LPS) plus D-galactosamine (GalN) exposure. GFR was evaluated by continuous infusion of fluorescein isothiocyanate-inulin with implanted micro-osmotic pumps. GalN/LPS intoxication resulted in severe hepatocyte toxicity as evidenced by liver histology and biochemical tests, whereas renal morphology remained normal. GFR was reduced by 33% of the controls 12 h after GalN/LPS exposure, accompanied with a decreased serum sodium levels, a marked increase in serum TNF-α and ET-1 levels as well as significantly upregulated renal type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) expression. The upregulated IP3R1 expression was abrogated by the treatment of anti-TNF-α antibodies, but not by 2-aminoethoxydiphenylborate (2-APB), which blocks the inositol 1,4,5-trisphosphate signaling pathway. Treatments with either TNF-α antibodies or 2-APB also significantly improved the compromised GFR, elevated serum urea nitrogen and creatinine levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. The extent of acute liver injury as reflected by serum ALT levels was much more attenuated by anti-TNF-α antibodies than by 2-APB. Liver histology further confirmed that anti-TNF-α antibodies conferred better protection than 2-APB in GalN/LPS-exposed rats. LPS-elicited TNF-α over-production is responsible for decreased GFR through IP3R1 overexpression, and the compromised GFR resulted in the development of acute renal failure in rats with FHF.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Necrosis Tumoral alfa / Fallo Hepático Agudo / Tasa de Filtración Glomerular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Lab Invest Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Necrosis Tumoral alfa / Fallo Hepático Agudo / Tasa de Filtración Glomerular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Lab Invest Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos