Ca(2+)-related hepatocellular alterations during intra-abdominal sepsis.
Intra-abdominal sepsis was induced in rats by implanting into their abdominal cavities fecal-agar pellets impregnated with Escherichia coli and Bacteroides fragilis. Sham-operated rats received sterile pellets. A group of sterile- and septic-implanted rats was treated intraperitoneally with diltiazem (1.2 mg/kg) 8 h after implantations. Septic- and sterile-implanted rat hepatocytes were loaded with 1) the fluorescent dye indo-1 to quantify hepatocyte basal and vasopressin (100 nM)-elevated cytosolic Ca2+ concentration and 2) 45Ca to quantify Ca2+ flux and cellular content of exchangeable Ca2+. Lipid peroxidation was determined by measuring conjugated dienes (CD) and thiobarbiturate-reactive substances (TBA-RS) in liver homogenates. In septic-implanted rats, the basal cytosolic [Ca2+], cellular exchangeable Ca2+, Ca2+ flux, CD, and TBA-RS were significantly higher than in sterile-implanted rats. Although vasopressin caused a significant elevation in cytosolic [Ca2+] in septic rat hepatocytes, the magnitude of this elevation was significantly smaller than that found in the sterile group. Diltiazem treatment of septic rats significantly decreased basal cytosolic [Ca2+], cellular exchangeable Ca2+ content, Ca2+ flux, CD, and TBA-RS. Also, vasopressin-induced increase in hepatocyte cytosolic [Ca2+] in diltiazem-treated septic rats was significantly greater than that observed in untreated septic rats. Both Ca2+ and membrane lipid alterations were attenuated with diltiazem treatment of septic rats. These results suggest that prevention or attenuation of Ca2+ channel-mediated Ca2+ influx restores both Ca2+ homeostasis and membrane lipid alteration.
Rose
S
S
Department of Physiology, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
Thompson
K D
KD
Sayeed
M M
MM
D000005:Abdomen / Q000382:microbiology*; D000818:Animals; D001424:Bacterial Infections / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013858:Thiobarbiturates; D014667:Vasopressins / Q000494:pharmacology
D013858:Thiobarbiturates; D014667:Vasopressins; D004110:Diltiazem; C029684:thiobarbituric acid; D002118:Calcium