<Original Article> Reduction of Mortality in Endotoxemic Rats Pretreated with Gadolinium Chloride: Relationship to Suppression of Superoxide Production in Liver Macrophages
Possible causes of reductions in mortality in severely endotoxemic rats, brought about by gadolinium chloride (GdCl3) treatment, was analyzed in terms of the superoxide (O2-)-producing capacity of isolated liver imcrophages (M0s) and in terms of their morphological changes. T he addition of GdCl3 to the culture medium of isolated M0s from normal rats suppressed their O2--producing capacity in a dose-dependent manner. The cytoplasm of the M0s in medium containing more than 1×10^-3 mg/ml of GdCl3 was not spread or swollen, compared with that of M0s without GdCl3. Changes in the O2-producing capacity of M0s obtained from endotoxemic rats pretreated with or without GdCl3 were then analyzed. After two injections of GdCl3 (5 mg/kg at -24 and -48 hours), sublethal d mg/kg) or lethal (10 mg/kg) doses of lipopolysaccharide (LPS) were injected intravenously at 0 h. Without GdCl3, O2--production capacity in the sublethal, but not in the lethal dose group, was enhanced. Pretreatment with GdCl3 reduced the mortality of the endotoxemic rats from 100% to 0%; however, the O2--production capacity in both the sublethal and lethal groups was suppressed to the same extent. These results suggest that the suppression of O2--production by GdCl3 administration in vivo induced reductions in htpatotoxity and mortality in endotoxemia. Thus, Gdcl3 may be useful for the prevention of severe liver dysfunction induced by postoperative infection.journal articl
