Prevention of lethal hepatic injury in Long-Evans Cinnamon (LEC) rats by D-galactosamine hydrochloride

Abstract

: Repeated injections of D-galactosamine hydrochloride (GalN) increase the survival rate of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. The aim of the present study was to investigate the mechanism of GalN for prevention of spontaneous lethal hepatic injury in LEC rats. Male LEC rats were given a single subcutaneous injection of 300 mg/kg of GalN or vehicle (0.9% NaCl) at 14 weeks, and killed at 28 weeks of age. Next, 6-week-old male LEC rats were given weekly subcutaneous injections of 300 mg/kg of GalN or vehicle for 3 or 12 weeks, and their hepatic 8-hydroxydeoxy-2'-guanosine (8-OHdG), glutathione peroxidase (GPX), and catalase activities were measured. None of GalN-treated rats died of hepatic injury (0/12), whereas the mortality rate of control rats given 0.9% NaCl was 17% (2/12). GalN administration for 12 weeks decreased the hepatic 8-OHdG, and GalN administration for either 3 or 12 weeks increased the glutathione peroxidase activity. GalN administration increased the serum level of alanine aminotransferase, and accelerated megalocytic degeneration of the hepatocytes. GalN treatment is effective in preventing lethal hepatitis in LEC rats and decrease of oxidative DNA damage by GalN plays an important role in increase of the survival rate. 53:81-86, February, 2006

Protective effect of sulfated polysaccharide isolated fromUlva fasciataagainst galactosamine-induced liver injury in rats

“…d ‐Galactosamine (GalN) induces liver cell injury in rodents, which closely resembles human acute viral hepatitis in its morphological and functional features (Keppler & Decker, ). Its conversion to UDP‐ N ‐acetylgalactosamine depletes the uridine nucleotide pool with subsequent inhibition of RNA and protein syntheses that leads to necrosis of liver cells and hepatotoxicity (Decker & Keppler, ; Otsuka et al, ). Another possible mechanism for hepatotoxicity is based on the mediation of extrahepatic factor(s) triggered by GalN where bacterial endotoxins (such as lipopolysaccharide) from the gut might induce proinflammatory cytokines production from macrophages, including Kupffer cells, which participate in the pathogenesis of GalN‐induced liver injury (Kume, Okazaki, & Sasaki, ; Nagakawa et al, ).…”

Animal models of Wilson disease

“…Experimental treatments beneficial in the prevention of hepatitis in LEC rats through protection against free-radicals include D-mannitol, N-acetylcysteine, D-galactosaminehydrochloride, proline solution, ascorbic acid, alpha-lipoic acid and thioredoxin (Hawkins et al 1995;Yamamoto et al 2001;Otsuka et al 2006;Fu et al 2014). Combined treatment with proline and ascorbic acid have an additive protective effect in the prevention of hepatitis (Hawkins et al 1995).…”