Le. Rikans et al., ALLYL ALCOHOL CYTOTOXICITY IN ISOLATED RAT HEPATOCYTES - MECHANISM OFCELL-DEATH DOES NOT INVOLVE AN EARLY RISE IN CYTOSOLIC-FREE CALCIUM, Archives of toxicology, 69(1), 1994, pp. 24-29
We examined the effect of a toxic concentration of allyl alcohol (0.5
mM) on intracellular calcium concentrations in isolated rat hepatocyte
s. An increase in phosphorylase a activity was evident in the hepatocy
tes after 30 min of incubation with allyl alcohol, suggesting that the
toxicant may produce an early rise in cytosolic free calcium. The inc
rease in phosphorylase a activity was not reversed by the addition of
dithiothreitol (DTT), a sulfhydryl compound that reverses the events t
hat initiate cell killing by allyl alcohol. When intracellular calcium
concentrations were measured directly, using fura-2 as the calcium in
dicator, there was no effect of allyl alcohol on cytosolic free calciu
m during the first 60 min of exposure, a critical period for developme
nt of irreversible damage. Incubation with allyl alcohol did not inter
fere with the measurement of intracellular calcium. The increases in c
ytosolic free calcium produced by phenylephrine or ATP were similar to
those reported by others and not affected by the presence of allyl al
cohol. The results from this study demonstrate that increased cytosoli
c free calcium is not essential for allyl alcohol-induced cytotoxicity
to isolated rat hepatocytes.