Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on indocyanine green blood clearance in rhesus monkeys

Abstract

To assess effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on liver function adult male rhesus monkeys were treated with a single oral dose of acetone/corn oil (control) or 5, 25, or 75 micrograms/kg TCDD. Each monkey was used as its own control and indocyanine green (ICG) blood clearance and the following serum enzymes: glutamic pyruvate transaminase (SGPT), sorbitol dehydrogenase (SDH) and gamma glutamyl transpeptidase (gamma GTP), were measured at regular intervals for 4 weeks before and 17 weeks after treatment. In control monkeys ICG blood clearance and serum enzymes were similar before and after treatment. However, in the monkey that received 5 micrograms/kg TCDD there was a mild increase in ICG blood clearance followed by a slight decrease. The magnitude of this biphasic change was greater in monkeys that received 25 and 75 micrograms/kg TCDD and the decrease in clearance was invariably associated with a 1--2-week period before the monkeys died. SDH and SGPT activities were elevated at some time during the course of intoxication in all TCDD-treated monkeys but gamma GTP activity was not altered. The monkey treated with 5 micrograms/kg TCDD survived but monkeys treated with 25 and 75 micrograms/kg died 4--6 weeks after treatment. Light microscopy of the livers of TCDD-treated monkeys that died revealed fatty infiltration with minimal hepatocellular necrosis.