Liver galactosamine hepatitis

Zang et al [140] reported the liver protective effects of the saponins isolated from A. membranaceus and A. sieversianus against chemical injury induced by CCU, D-galactosamine and acetaminophen in mice. In all cases there were positive activities and the saponins inhibited the rise in SGPT levels, decreased the malondialdehyde (MDA) content and increased the glutathione reduced (GSH) concentration in mouse liver. The same compounds were also evaluated in cultured rat hepatocytes, and the results indicated that the activity may be due to to the antioxidative activity of the saponins, since the content of liver protein in treated mice was more than the control. Moreover, in all treated mice, the level of hepatic microsomal cytochrome P-450 was increased. The liver metabolism and immunoregulating action produced by saponins may be also involved in their hepato-protective effects. Similar results were obtained by Zhang et al [141] when they studied the activity in vitro and... 

Fig. 6. The role of endogenous tumor necrosis factor TNF) in D-galactosamine (GalN)-induced liver damage. All mice were injected with 2.1 g/kg GalN. Serum transaminases ALT) and hepatic DNA fragmentation were determined after 24 h. Animals pretreated with neutralizing anti-TNF antibodies or mice lacking TNF receptor-1 tnf-rl°) were protected...

Charcoal hemoperfusion can also remove the toxin in hepatic failure. A model of galactosamine-induced fulminant hepatic failure in a rat with grade 3 hepatic encephalopathy, demonstrated the potential utility of multisorbent plasma perfusion over uncoated spherical charcoal, and an endotoxin removing adsorbent (polymyxin B-sepharose). Timing, duration and frequency of treatment impacted liver cell proliferative response as compared to untreated fulminant hepatic failure paired controls (Ryan et al., 2001). 

Orotic acid prevents experimental hepatitis induced by D-galactosamine. The experimental hepatitis paralleled by the accumulation of UDP derivatives of D-galactosamine was studied by Decker and co-workers [382-384]. On the basis of ultrastructural and biochemical analyses it was concluded that the liver damage observed after D-galactosamine treatment differs from that seen in human hepatitis in that the former leads to accumulation of liver triglycerides, hyperplasia of the smooth endoplasmic reticulum, and cell necrosis [385,386]. 

In earlier work we showed that the toxic effect of D-galactosamine on the liver can be inhibited by tryptophan and methionine (5). Furthermore, we found that D-galactosamine influences ADP-ribose metabolism (6). On the other hand it was reported that galactosamine enhances the effect of endotoxin (7). As already mentioned in the introduction, inhibitors of ADP-ribosylation reduce markedly the effect of endotoxin (1). These results stimulated us to study the effect of MDP on the ADP-ribose metabolism and we found indications for the interference of MDP with this metabolism (2). The induction of viral hepatitis by MHV3 in mice can be inhibited to a large extent by MDP and by benzamide. These are indications that the ADP-ribose metabolism plays a key role in the development of the hepatitis. 

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