Cytochromes P450 2A6, 2E1, and 3A and production of protein-aldehyde adducts in the liver of patients with alcoholic and non-alcoholic liver diseases
Section snippets
Patients
The present study protocol and the use of human tissue samples was approved by the Ethics Committee of the University of Oulu, and the study was carried out according to the principles of the Declaration of Helsinki. The study subjects were patients undergoing surgery or liver biopsy. In all of them a liver biopsy was necessary for routine diagnostic purposes. Prior to the study, informed consent was obtained from each subject.
Liver biopsies were obtained from 12 patients with a history of
Results
The present sample of alcoholic patients consisted of 12 patients with either early-phase (n=7) or advanced liver disease (n=5), and of nine patients with non-alcoholic fatty liver (n=4) or hepatitis (n=5). The relevant clinical and biochemical data of the study subjects are summarized in Table 1.
The cellular distribution and the amount of various CYP forms was found to vary between the different study groups. Results of the immunohistochemical stainings for CYP2E1, CYP2A, and CYP3A in the
Discussion
A major finding that emerged from this study is the increase of multiple CYPs, CYP2E1, CYP2A and CYP3A, in human alcoholic liver disease (ALD). Increased expression of the different CYP forms occurred concomitantly with the formation of protein adducts with acetaldehyde, the first metabolite of ethanol, and malondialdehyde, a product of lipid peroxidation. The acinar distributions of CYP2E1 and CYP2A were also found to follow those of the protein adducts and steatosis, suggesting that the
Acknowledgements
We are indebted to Prof. Seppo Ylä-Herttuala, University of Kuopio for providing the anti-MDA-adduct antibodies. The expert technical assistance of Mrs. Lissu Hukkanen is gratefully acknowledged. The study was supported by the Finnish Foundation for Alcohol Studies, The Academy of Finland grants no. 34555, 29456, and by the European Council, Biomed 2 Program (EUROCYP).
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