Bromotrichloromethane (CBrCl3)-induced hepatic lipid peroxidation and cell
necrosis were studied histologically and biochemically, using isolated perfused livers from
phenobarbital-pretreated rats. Lipid peroxidation was assessed by
fuchsin staining of the liver slices and release of
thiobarbituric acid reactive substances (
TBARS) into the perfusate;
necrosis was assessed by
trypan blue uptake and
lactate dehydrogenase (LDH) leakage. A good correlation was observed between the Schiff-positive reaction and
TBARS release under various experimental conditions, supporting the validity of the
fuchsin staining method for histological detection of lipid peroxidation. Lobular localization of lipid peroxidation and
necrosis was as follows: Under high
oxygen supply (95% O2-saturated
buffer), infusion of CBrCl3 caused the Schiff-positive reaction in the pericentral to midzonal hepatocytes, irrespective of the direction of perfusion, but did not produce
necrosis. Under low
oxygen supply (20% O2) with retrograde perfusion, dissociation of lipid peroxidation and
necrosis was observed, i.e.,
trypan blue uptake in the periportal zones and Schiff-positive staining in the pericentral hepatocytes. Thus, lipid peroxidation by itself may have a relatively minor role in the development of CBrCl3-induced acute hepatic cell death.