Protection of mice against endotoxin-induced liver damage by anti-inflammatory drugs.

Mice were injected with Corynebacterium parvum, which induces multiple granulomas in liver and renders animals hyper-reactive to the lethal effect of bacterial lipopolysaccharide (LPS). Such animals when challenged with LPS developed also extensive liver parenchymal cell damage as estimated by elevated blood asparate transaminase levels and a hypoglycaemia. Treatment with indomethacin, hydrocortisone, dexamethasone, promethazine, metiazinic acid and (+)-catechin ameliorated the liver damage. Hydrocortisone, dexamethasone, promethazine and metiazinic acid also reduced the mortality rate in mice challenged with LPS. Diarrhoea, accompanying the LPS-induced shock, was prevented by the drugs used. Possible agents mediating the hepatotoxic and shock effects of LPS are discussed.