H. Kinugawa et al., LEAKAGE OF MITOCHONDRIAL AND CYTOSOLIC GOT IN ISOLATED RAT HEPATOCYTES EXPOSED TO HALOTHANE - AN IMMUNOHISTOCHEMICAL STUDY, Journal of applied toxicology, 13(5), 1993, pp. 327-336
The leakage of mitochondrial (m-) and cytosolic (s-) aspartate aminotr
ansferases (glutamic-oxaloacetic transaminase: GOT) from isolated hepa
tocytes exposed to halothane was investigated immunohistochemically. I
n control isolated hepatocytes, a large number of cells were immunopos
itive (m-GOT, 85%; S-GOT, 98.5%) at various intensities. Reaction prod
ucts of m-GOT-immunohistochemistry (m-GOT-I) were seen exclusively in
mitochondria, while those of s-GOT (s-GOT-I) were seen in the cytoplas
m. When treated with low concentrations of halothane (up to 0.75%), th
e number of strongly m-GOT-I-immunopositive cells was reduced to half,
while that of s-GOT-I showed no noticeable change. The number of m-GO
T-I-immunonegative cells showed a negligible increase, while that of s
-GOT-I increased gradually. At higher concentrations of halothane (1%
or more), strongly immunopositive cells in both m- and s-GOT-I almost
disappeared, while immunonegative cell numbers predominantly increased
. This study showed that the isolated hepatocyte system was not homoge
neous with regard to the quantity of GOT isozymes, and that halothane
could induce the leakage of these isozymes from hepatocytes, along wit
h inducing ultrastructural abnormalities, even at the lowest concentra
tion used (0.5%). Furthermore, the data appear to indicate that the se
nsitivity of isolated hepatocytes to halothane is dependent on the nat
ure of the hepatocyte itself and on the nature of both types of GOT is
ozymes.