Liver membrane calcium transport in diquat-induced oxidative stress in vivo.
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.
Tsokos-Kuhn
J O
JO
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Smith
C V
CV
Hughes
H
H
Mitchell
J R
JR
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D056486:Chemical and Drug Induced Liver Injury / Q000139:chemically induced; D004178:Diquat / Q000633:toxicity*; D006880:Hydroxy Acids / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D011726:Pyridinium Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D006880:Hydroxy Acids; D008054:Lipid Peroxides; D011726:Pyridinium Compounds; D004178:Diquat; D007501:Iron; D002118:Calcium