Abstract
D-galactosamine (GalN) is a highly selective hepatotoxin that causes liver damage similar to human viral hepatitis via depletion of uridine nucleotides, which subsequently diminishes synthesis of RNA and proteins. Model of galactosamine hepatotoxicity is frequently used in animal experiments in vitro. The purpose of our study was to establish the model of GalN-induced hepatocyte injury in in vitro conditions using primocultures of rat hepatocytes as an important pre-requisite for further experiments in which we would like to study potential hepatoprotective effect of various substances. Rate of hepatocyte injury was evaluated by morphological changes, changes in cell viability, albumin production, mitochondrial membrane potential, activity of mitochondrial dehydrogenases and glutathione content. Marked dose dependent hepatocyte injury was found after 24-hour incubation with GalN. Based on the results we suggest as an optimal model for short-term toxicity test exposure to GalN for 24 hours in dose of 40 mM.
Highlights
D-galactosamine (GalN) is frequently used as a model hepatotoxin in animal experiments
Siendones et al [17] reported that GalN induces cell death by enhancing the production of NO in hepatocyte culture and PGE1 pretreatment reduces GalNinduced cell death through its capacity to reduce inducible nitric oxide synthase (iNOS) expression and NO production caused by hepatotoxin
We did not find any significant change in lactate dehydrogenase activity (LDH) activity in hepatocyte cultures exposed to GalN for 0.5 and 4 hours respectively
Summary
D-galactosamine (GalN) is frequently used as a model hepatotoxin in animal experiments. Stachlewitz et al [18] documented the role of Kupffer cell activation and production of TNF-α as an important event in the mechanism of GalN-induced hepatotoxicity in the rat. They detected apoptosis to occur early after GalN administration before necrosis is developed. GalN decreases NO production in hepatocyte culture by suppressing of inducible nitric oxide synthase (iNOS). This suppression seems to be a consequence of GalN-induced depletion of uridine nucleotides and subsequent general inhibition of total cellular RNA and protein synthesis rather than a specific inhibition of iNOS protein synthesis [15]. Some authors emphasize participation of oxidative stress in pathogenesis of GalN toxicity in vivo [16,19] and in vitro [20]
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