The effect of cyclic adenosine monophosphate (cAMP) on acute liver toxicity in mice induced by D-galactosamine and lipopolysaccharide.
The aim of this study was to examine the effect of cyclic adenosine monophosphate (cAMP) and its possible interference/synergism with calcium channel blocker in mice with acute liver injury induced with D-galactosamine (D-GalN) and lipopolysaccharide (LPS). C57Bl/6 mice were given i.p. simultaneously 300 mg/kg D-GalN and LPS 0.01 mg/kg. This treatment induced severe hepatitis, as evidenced by high mortality (80-90%) of control mice and large increase in concentration of aminotransferases in plasma (AST, ALT). Injection of stabile analogue of cAMP (dibutyryl-cAMP, db-cAMP) one hour before hepatotoxic agents increased survival of mice in dose-dependent manner and in medium dose significantly decreased plasma ALT level. Similar (protective) effect had also verapamil, calcium channel blocker, when given in non toxic doses and at the same time schedule as db-cAMP Combination of db-cAMP and verapamil had not synergistic effect in protection from D-GalN+LPS hepatotoxicity; the survival of mice was similar to that seen in protection caused by each agent alone.
Erceg
Damir
D
Childrens Hospital Srebrnjak, Srebrenjak 100, Zagreb, Croatia.
Kelava
Tomislav
T
Cavar
Ivan
I
Pasalić
Marijan
M
Culo
Filip
F
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D005260:Female; D005688:Galactosamine / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014700:Verapamil / Q000494:pharmacology
D008070:Lipopolysaccharides; D003994:Bucladesine; D005688:Galactosamine; D014700:Verapamil; D000410:Alanine Transaminase