Hepatic
necrosis is produced rapidly by 0.1 mmol/kg
diquat in male Fischer-344 rats but not Sprague-Dawley rats, yet massive
oxidant stress is caused by
diquat in both strains of rat. Liver plasma membrane
calcium uptake was unaltered by
diquat treatment in either strain. However,
diquat inhibited
ATP-dependent
calcium sequestration by hepatic microsomes from Fischer rats by 33% (33 +/- 2 versus 50 +/- 2 nmol/mg/20 min), whereas liver microsomal
calcium uptake in Sprague-Dawley rats was not decreased by
diquat treatment. Microsomes of
diquat-treated Fischer rats showed marked increases in
calcium efflux versus controls (k efflux = 0.115 +/- 0.027 versus 0.051 +/- 0.005 min-1; p less than 0.025), but microsomes of
diquat-treated Sprague-Dawley rats exhibited no significant change in efflux rate.
Calcium uptake by the endoplasmic reticulum of
saponin-permeabilized isolated hepatocytes was diminished in parallel with
diquat cytotoxicity. Significant increases in 11-, 12-, and 15-hydroxy 20:4
fatty acids were found in liver microsomes isolated after
diquat treatment in vivo and administration of
desferrioxamine (0.24 mmol/kg, intraperitoneally) administered before
diquat significantly protected against the inhibition of microsomal
calcium uptake. These data suggest a possible role for Fenton chemistry and lipid peroxidation in this feature of
diquat-generated hepatic damage in vivo.