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Effects of oxygen deficiency and calcium omission on carbon tetrachloride hepatotoxicity in isolated perfused livers from phenobarbital-pretreated rats.

Abstract：

:The effect of oxygen concentration and Ca2+ omission on CCl4-induced hepatotoxicity was studied in a non-recirculating and hemoglobin-free liver perfusion system using phenobarbital-pretreated rats. With 95% O2-saturated perfusate, infusion of 0.5 mM CCl4 caused an instantaneous increase of thiobarbituric acid reactive substances (TBA-RS) in the effluent perfusate, accompanied by only a slight leakage of K+ and lactate dehydrogenase (LDH). CBrCl3 produced a far greater increase in the TBA-RS level, but again with slight K+ and LDH leakage. With 20% O2-saturated perfusate, CCl4 caused a marked LDH leakage, which was preceded by an early and considerable increase in K+ leakage coupled with Na+ uptake, Ca2+ uptake was initially slight, being enhanced concurrently with the LDH leakage. The TBA-RS level changed biphasically with an initial moderate and a succeeding greater increase coupled with LDH leakage. N,N"-Diphenyl-p-phenylenediamine and promethazine suppressed the TBA-RS production, but improved neither K+ nor LDH leakage. Omission of the Ca2+ from the perfusate reduced the initial K+ leakage as well as the later TBA-RS release, and markedly delayed the LDH leakage. In retrograde perfusion under low oxygen supply with Ca2+, CCl4 produced essentially the same toxic manifestations as those observed in the anterograde perfusion. Hepatocytes of the periportal and pericentral areas were not stained with trypan blue in the antero- and retrograde perfusion systems respectively. Thus, oxygen deficiency, rather than lipid peroxidation by itself, and the essential role of extracellular Ca2+ may be important for CCl4-induced hepatic cell necrosis, in which plasma membrane permeability change may be an early and critical event.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Masuda Y,Nakamura Y

doi

10.1016/0006-2952(90)90368-u

subject

Has Abstract

pub_date

1990-10-15 00:00:00

pages

1865-76

issue

eissn

0006-2952

issn

1873-2968

pii

0006-2952(90)90368-U

journal_volume

pub_type

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Effects of oxygen deficiency and calcium omission on carbon tetrachloride hepatotoxicity in isolated perfused livers from phenobarbital-pretreated rats.