In the Tsukamoto-French model, ethanol causes an important 10-20-fold induction of ethanol-inducible cytochrome P4502E1 (CYP2E1), mediated through enzyme stabilization and increased rate of gene transcription. The CYP2E1 induction results in a pronounced increase in the rate of NADPH-dependent microsomal lipid peroxidation, an elevation which is not seen after simultaneous administration of the CYP2E1 inhibitor diallylsulfide. Increased amounts of lipid peroxides are seen in plasma and red blood cells of both rats and humans during high ethanol intake. A mechanism for ethanol-dependent liver damage is proposed which involves the CYP2E1-dependent lipid peroxide formation, either directly by its capability to induce NADPH-dependent peroxidation in the microsomal membranes or indirectly by a hypoxia-mediated transformation of xanthine dehydrogenase to xanthine oxidase, in activation of Ito cells and Kupffer cells to yield cytokine and collagen production. The CYP2E1 gene is polymorphic among Caucasians. Four different unrelated or partially linked polymorphisms have been observed. One polymorphism in the 5'-flanking region has been described to be associated with altered enzyme expression in vitro, and the rare allele was found to be less frequent among Swedish patients having lung cancer when compared to two different control groups. Another polymorphism, detectable with Dra I restriction endonuclease fragment length polymorphism (RFLP), was localized to intron 6, and the rare allele was less common among Italian alcoholics with clinical signs of liver cirrhosis, as compared to controls. Several other mutations in the CYP2E1 gene were found to be associated with this allele. However, further research is needed to relate the CYP2E1 gene polymorphism with incidence of liver cirrhosis.

Animals↗

PubMedDate not supplied

Possible role of free radical intermediates in hepatotoxicity of hydrazine derivatives.

Hydrazine derivatives constitute a wide group of compounds and have found application in industry, agriculture, and (as therapeutical agents) medicine. In spite of their widely spread use, several hydrazine derivatives are known to exert hepatotoxic effects and are carcinogenic. Free radical species are produced during the hepatic biotransformation of alkylhydrazines by both rat and humans liver microsomes. Cytochrome P-450 dependent monoxygenase system is responsible for the production of these reactive species and specific cytochrome P-450 isoenzymes appear to catalyze the formation of free radical intermediates. Free radicals generated during the metabolism of alkylhydrazines are capable of inducing oxidative stress in isolated hepatocytes and might contribute to the development of cell injury.

Animals↗

PubMedDate not supplied

[Value of total gastrectomy for treatment of cancers of the stomach. Study of 482 radical operations].

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Evaluation Studies as Topic↗

PubMedDate not supplied

[Retro-peritoneal tumors. Report of 21 cases (author's transl)].

The authors report their experience about 21 cases of retroperitoneal tumors. They emphasise their often late revelation, the frequent malignity and the involvement of the surroundings organs. They insist on the interest of the opacification of urinary tract and angiography and the value of echo-ranging and total body scanner to evaluate the characteristics of these tumors and theirs extensions. Recurrents are frequents and must be operated each time necessary.

Adult↗