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Baliharová, V. et al.

Baliharová, Skálová, Maas, De Vrieze, Bull, Fink-Gremmels,

The effects of benzimidazole anthelmintics on P4501A in rat hepatocytes and HepG2 cells.

Benzimidazole anthelmintics including albendazole, fenbendazole, and mebendazole are widely used in veterinary medicine. The effects of these benzimidazoles on cytochrome P4501A were investigated in primary cultures of rat hepatocytes and in the HepG2 cell line. After incubation of rat hepatocytes and HepG2 for 24-, 48-, and 72-h cells with drugs at various concentrations (0.1-50 microM), the enzyme activities associated with P4501A1/2 (7-ethoxyresorufin O-deethylation and 7-methoxyresorufin O-demethylation) were measured. The P4501A1/2 protein levels in both model systems were determined by Western blotting. Although all benzimidazoles provoked a significant increase of P4501A1/2 protein levels and P4501A activities, large differences in the induction response were found which was dependent on drug structure, concentration, and model system used. Based on the results, relationships between induction potency and structure of drug were demonstrated, as well as differences between the in vitro systems used. Therefore, pharmacological and toxicological consequences of cytochrome P4501A induction by benzimidazole drugs should be taken into account in veterinary therapy.[1]

References

The effects of benzimidazole anthelmintics on P4501A in rat hepatocytes and HepG2 cells. Baliharová, V., Skálová, L., Maas, R.F., De Vrieze, G., Bull, S., Fink-Gremmels, J. Res. Vet. Sci. (2003) [Pubmed]

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