RT Journal Article
SR Electronic
T1 Level of cytosolic free calcium during acetaminophen toxicity in mouse hepatocytes.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 665
OP 670
VO 41
IS 4
A1 A W Harman
A1 S O Mahar
A1 P C Burcham
A1 B W Madsen
YR 1992
UL http://molpharm.aspetjournals.org/content/41/4/665.abstract
AB It has been suggested that elevated cytosolic free calcium plays a key role in acetaminophen-induced cell death. The present study has examined the effect of a toxic concentration of acetaminophen on cytosolic free calcium in single mouse hepatocytes, using the dye fura-2 and video imaging fluorescence microscopy. Cytosolic free calcium was calculated from the ratio of emitted fluorescence at greater than 475 nm produced by excitation at 340 and 380 nm, using a double-intensified silicon target camera and digital image processing. In the presence of 5 mM acetaminophen, cell death did not occur for 2 hr, but the toxic lesion that ultimately killed the cells occurred as early as 1 hr. If cytosolic free calcium plays an important role in these toxic events, it would be expected to increase during this period. However, during a 2-hr exposure, cytosolic free calcium concentration in cells exposed to acetaminophen was not different from control. In hepatocytes incubated for longer than 2 hr, the calcium concentration increased shortly before loss of cell viability (i.e., as a late event), consistent with an influx of calcium through a damaged cell membrane. This late increase in calcium occurred well after the appearance of cell surface blebs. The data suggest that there is no sustained change in cytosolic free calcium in acetaminophen injury either before or during the time when irreversible toxic events occur in hepatocytes.