Prevention of galactosamine-induced hepatotoxicity in rats with fructose-1,6-diphosphate.
Galactosamine (GalN) administration produces hepatitis-like liver injury in animals. The hepatotoxicity of GalN is attenuated by several interventions, including activation of the reticuloendothelial system (RES). Fructose-1,6-diphosphate (FDP) administration significantly increases the phagocytic activity of the RES in animals. Thus, investigations were designed to determine whether FDP affords protection against GalN toxicity. Rats were injected with GalN (375 mg/kg) and treated with 0.9% NaCl (n = 8) or FDP (n = 9). Eight rats were sham-operated. Serum glutamic oxaloacetic transaminase was 40 times higher in the saline group as compared to the FDP-treated rats (p less than 0.0001). Glutamic pyruvic transaminase, gamma-glutamyltranspeptidase and bilirubin were similarly elevated (saline vs. FDP, p less than 0.005, p less than 0.01 and p less than 0.05, respectively). These values were not different between FDP-treated and sham-operated rats. Extensive hepatic necrosis was observed in all saline-treated rats, whereas in the FDP group only isolated foci of hepatocellular necrosis were noted. The hepatoprotective effect of FDP in this model is attributed to its ability to enhance the phagocytic activity of RES and to suppress release of oxyradicals by the leukocytes during the inflammatory phase.
Markov
A K
AK
Department of Medicine, University of Mississippi Medical Center, Jackson.
Farias
L A
LA
Bennett
W S
WS
Subramony
C
C
Mihas
A A
AA
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D005635:Fructosediphosphates / Q000008:administration & dosage / Q000494:pharmacology*; D005688:Galactosamine / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000097:blood
D001786:Blood Glucose; D005635:Fructosediphosphates; D005688:Galactosamine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; C029063:fructose-1,6-diphosphate; D001663:Bilirubin