Acute Liver Failure: A Critical Appraisal of Available Animal Models

Abstract

The availability of adequate experimental models of acute liver failure (ALF) is of prime importance to provide a better understanding of this condition and allow the development and testing of new therapeutic approaches for patients with ALF. However, the numerous etiologies and complications of ALF contribute to the complexity of this condition and render the development of an ideal experimental model of ALF more difficult than expected. Instead, a number of different models that may be used for the study of specific aspects of ALF have been developed. The most common approaches used to induce ALFin experimental animals are surgical procedures, toxic liver injury,or a combination of both. Despite the high prevalence of viral hepatitis worldwide, very few satisfactory viral models of ALF are available. Established and newly developed models of ALF are reviewed.

Hepatoprotective effect of germanium-containingSpirulinain rats withd-galactosamine- and lipopolysaccharide-induced hepatitis

“…This phenomenon is observed in patients with acute hepatic failure (1) . GalN/LPS-induced liver injury is also known to cause cytokine release (TNF-a is the main mediator) that contributes to increased oxidative stress and the formation of reactive oxygen species, followed by hepatocyte death (2,3) .…”

Evaluating the best time to intervene acute liver failure in rat models induced by d-galactosamine

“…D-galactosamine is an amino sugar metabolized in the liver via galactose, which leads to depletion of uridine nucleotides and blocks the liver transition, thus resulting in massive diffuse necrosis of the liver 11 . Studies using radio labeled d-galactosamine have established the specific hepatotoxicity of this drug: virtually 100% of the drug is metabolized by the liver 12 .…”

L-carnitine in Hyperammonemia and Hepatic Encephalopathy

“…A model of ammonia-precipitated encephalopathy is the portacaval-shunted rat receiving ammonium acetate (Belanger and Butterworth, 2005). In this model, Therrien et al (1997) examined the effect of L-carnitine (16 mmol/kg, intraperitoneally), given 1 hour before ammonium acetate (8.5 mmol/kg, subcutaneously) to portacaval shunted rats.…”

“…As mentioned above, experimental HA is not a model of human liver disease and rather serves to investigate the neurotoxicity of acute or chronic ammonia exposure or to study specific aspects of liver failure (Belanger & Butterworth, 2005). Therefore, very few studies that investigate the effects of L-carnitine in appropriate animal models of HE have been published.…”