Effects of insulin-like growth factor-type 1 on weight gain and hepatic glycogen during early development in a surfactant/virus mouse model of acute liver failure: Correlation with mortality

Philip D. Acott, John F.S. Crocker, Spencer H.S. Lee, Joanne Evans, Patrick O'Regan, Mustafa Al-Khalidi, Laurette Geldenhuys, Mary G. Murphy

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

2 Citas (Scopus)

Resumen

Acute liver failure (ALF) was reproduced in young mice exposed daily for 12 days to the industrial surfactant, Toximul 3409F (Tox), and infected on postnatal day (P) 14 with sublethal doses of mouse-adapted human influenza B (Lee) virus (FluB). Combined Tox + FluB treatment potentiated mortality due to non-necrotic ALF. This study tested the hypothesis that mortality would decline if the known losses in energy production due to compromised fatty-acid β-oxidation were compensated by pharmacological manipulation of hepatic glycogen stores. Glycogen levels, body weights, and mortality were determined without and with injections of insulin-like growth factor-1 (IGF-1). On P25, 13 days after Tox exposure ceased, glycogen levels (mg/100 mg) were: 4.0 (control), 1.7 (Tox), 4.3 (FluB), and 2.9 (Tox + FluB). Corresponding cumulative mortalities were 0, 14, 2, and 38%. Following daily IGF-1 injections from P12 to P17, liver glycogen levels on P25 were: 3.5 (IGF-1), 3.9 (IGF-1 + Tox), 12.3 (IGF-1 + FluB), and 5.6 (IGF-1 + Tox + FluB). Unexpectedly, IGF-1 treatment increased mortality to 67% (IGF-1), 89% (IGF-1 + Tox), 63% (IGF-1 + FluB), and 81% (IGF-1 + Tox + FluB). For all groups there was a significant correlation between mortality and poor weight gain. This is the first report of persistent glycogen reductions after surfactant exposure and withdrawal. Their role in potentiating FluB-induced mortality remains to be established.

Idioma originalEnglish
Páginas (desde-hasta)42-50
Número de páginas9
PublicaciónHepatology Research
Volumen29
N.º1
DOI
EstadoPublished - may. 2004

Nota bibliográfica

Funding Information:
The authors would like to thank Dr. R. Clark, Genetech, Inc., for providing the IGF-1, Mr. J. Warren for the statistical analyses and Dr. K. Peltekian for his critical review of the manuscript. This investigation was supported by a Grant-in-Aid from the Natural Sciences and Engineering Research Council of Canada. MA was supported by the Nova Scotia Health Research Foundation.

ASJC Scopus Subject Areas

  • Hepatology
  • Infectious Diseases

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