Effects of oxygen deficiency and calcium omission on carbon tetrachloride hepatotoxicity in isolated perfused livers from phenobarbital-pretreated rats
| Autor: | Masuda Yasusuke, Nakamura Yumi |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Male
medicine.medical_specialty Thiobarbituric acid chemistry.chemical_element Calcium In Vitro Techniques Phenylenediamines Biochemistry Oxygen Promethazine Lipid peroxidation chemistry.chemical_compound Internal medicine Lactate dehydrogenase medicine Retrograde perfusion Animals Carbon Tetrachloride Pharmacology Carbon Tetrachloride Poisoning Liver Diseases Rats Inbred Strains Rats Perfusion Endocrinology chemistry Liver Phenobarbital Carbon tetrachloride Chemical and Drug Induced Liver Injury |
| Zdroj: | Biochemical pharmacology. 40(8) |
| ISSN: | 0006-2952 |
| Popis: | The effect of oxygen concentration and Ca 2+ omission on CCl 4 -induced hepatotoxicity was studied in a non-recirculating and hemoglobin-free liver perfusion system using phenobarbital-pretreated rats. With 95% O 2 -saturated perfusate, infusion of 0.5 mM CCl 4 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). CBrCl 3 produced a far greater increase in the TBA-RS level, but again with slight K + and LDH leakage. With 20% O 2 -saturated perfusate, CCl 4 caused a marked LDH leakage, which was preceded by an early and considerable increase in K + leakage coupled with Na + uptake. Ca 2+ 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 Ca 2+ 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 Ca 2+ , CCl 4 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 Ca 2+ may be important for CCl 4 -induced hepatic cell necrosis, in which plasma membrane permeability change may be an early and critical event. |
| Databáze: | OpenAIRE |
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