TOXICOLOGY AND APPLIED PHARMACOLOGY 47,431-440 (1979) Diethanolamine-Induced Alteration of Hepatic Mitochondrial Function and Structure’

amine (DEA) has been shown to interfere with phospholipid metabolism. It was hypothe-sized that DEA may alter membrane-bound biochemical processes which are dependent upon phospholipids. DEA was investigated for its effect on hepatic mitochondrial function and structure in the male Sprague-Dawley rat. DEA did not produce mitochondrial alterations in in vitro preparations from liver tissue. Similarly, acute treatment in vivo was without effect. However, a loss of mitochondrial integrity developed after subacute adminis-tration of DEA. Rats were given 0.25 (42 mg/kg/day), 1.0 (160 mg/kg/day), or 3.0 (490 mg/ kg/day) mg/mI in their drinking water for varying periods up to 5 weeks. The effects on mitochondria were dose- and time dependent. Significant alterations appeared after 3 days at 3.0 mg/ml and after 1 week at 1.O mg/ml. Mitochondrial State 4 acitivity was significantly elevated at all three dose levels following 2 weeks of DEA treatment. Concomitantly, an increase was noted in the Mg2+-dependent ATPase activity from rats treated with DEA at 2.0 mg/ml for 3 weeks. Electron micrographs indicated that treated animals had swollen hepatic mitochondria. The changes in the organelle may be related to alteration of phospho-lipid metabolism by DEA