Liver Damage in Rabbits from Administration of a Single Dose of Gram-negative Endotoxin

Abstract

Summary: The present experiments were undertaken to study the effect of a preparatory dose of gram-negative endotoxin on the liver. Sixteen adult male New Zealand rabbits bad initial liver biopsies, blood chemistries, and coagulation studies and were then divided into two groups: group I, consisting of 10 animals, received 50 μg/kg endotoxin from Escherichia coli OlllB4; group 11, consisting of six animals, served as controls and received no endotoxin. In group I all animals developed increased levels of lactic dehydrogenase (LDH) isoenzyme 5 and SGOT and decreased serum albumin levels. A rise in the level of SGPT and 5′-nucleotidase occurred in most rabbits. LDH isoenzyme 5 values increased from 3.6 ± 5.83 mU/ml before to 180.4 ± 142.11 mU/d after endotoxin (P < 0.005). SGOT rose from 28.90 ± 8.87 mU/ml to 241.10 ± 104.76 mU/ml (P < 0.001). Serum albumin levels decreased from 3.78 ± 0.31 g/dl to 3.21 ± 0.32 g/dl (P < 0.001). SGPT initially showed a level of 41.00 ± 6.97 mU/ml and this rose to 94.40 ± 19.60 mU/ml (P < 0.001). 5′-Nucleotidase rose from 1.48 ± 0.69 mU/ml to 6.01 ± 4.51 mU/d (P < 0.01). The animals also had changes in coagulation tests with a decrease in factors I1 and V. Factor I1 was 77.4 ± 11.82% before and decreased to 38.70 ± 7.47% after endotoxin (P < 0.001). Factor V values were 95.00 ± 9.04% before and 50.6 ± 7.5% after endotoxin (P < 0.001). Changes in fibrinogen and factor VIII were not significant. Split products of fibrinogen showed a slight increase. Definite hepatic necrosis consisting of scattered patchy areas of variable size and severity was found in 7 of the 10 animals. In many of these areas of necrosis a polymorphonuclear leukocyte reaction and few small thrombi were detectable. The Liver biopsies performed before endotoxin administration failed to show any evidence of hepatic involvement. Group I1 control animals showed no indications of abnormal liver function and no evidence of hepatic necrosis. These studies indicate that significant hepatic changes occur after the administration of a single dose of endotoxin given in preparation for the Shwartzman reaction.