Hepatic cellular injury following lethal Escherichia coli bacteremia in rats
Sato, T.; Tanaka, J.; Kono, Y.; Jones, R.T.; Cowley, R.A.; Trump, B.F.
Laboratory Investigation; A Journal of Technical Methods and Pathology 47(3): 304-310
1982
ISSN/ISBN: 0023-6837 PMID: 7050533 Document Number: 184695
Hepatic cellular injury after lethal E. coli bacteremia was evaluated by determining serum ornithine carbamoyltransferase (SOCT) and serum glutamic pyruvic transaminase (SGPT) activities and arterial blood ammonia level, along with ultrastructural changes in the liver. A lethal dose of E. coli (1.3-2.0 .times. 109 organisms in 0.5 ml. of saline/100 g body weight) was injected into conscious rats. Animals were sacrificed at 3, 6 and 12 h after treatment. After E. coli treatment, SOCT activity at 3, 6 and 12 h (42.9 .+-. 19.9 [SD], 124.2 .+-. 57.5 and 215.3 .+-. 110.2 IU/l, respectively), SGPT activity at 6 and 12 h (79.0 .+-. 52.9 and 130.0 .+-. 57.9 Wroblewski-LaDue U/ml), and blood ammonia level at 12 h (214.8 .+-. 68.2 .mu.g/dl) were significantly higher than those in controls (5.6 .+-. 2.6 IU/l of SOCT activity, 25.8 .+-. 8.1 U/ml of SGPT activity, and 101.1 .+-. 17.2 .mu.g/dl of ammonia). Progressive migration of leukocytes, fibrinoid deposits in sinusoids and Kupffer cell enlargement were observed. Rare hepatocytes revealed endoplasmic reticular cisternal dilation with mild mitochondrial swelling at 3 h. There were increased numbers of autophagic vacuoles containing sequestered cytoplasmic organelles including mitochondria at 6 h. At 12 h, occasional hepatocytes showed marked matrical swelling of mitochondria, varying degrees of loss of cristae and an increased number of autophagic vacuoles. No evidence of rupture of mitochondrial membranes or flocculent densities was noted. Since OCT is specifically located in the liver mitochondria, estimation of SOCT activity is a specific and sensitive indicator for hepatic cellular injury, even prior to development of structural damage in bacteremic shock.