Summary
Male Wistar rats were divided into 4 groups, receiving water, propylene glycol (PG), sodium phenobarbital (PB) and PB + PG, respectively.
After oral administration of these materials for 7 days, various enzymes in hepatic microsomes and the binding capacity of Y and Z fractions in the cytosol were assayed. As compared with the water group, the aniline hydroxylase activity, the cytochrome b5 content and the amount of Z fraction increased in the PG group. As compared with the PB group, the microsomal protein increased but the activities of paranitrophenol-UDP-glucuronyltransferase (pNP-GT) and aminopyrine demethylase (AD) decreased in the PB + PG group. When the PB + PG group and the PG group were compared with the PB group and the water group respectively, there was no parallel change. Even though PG added to hepatic microsomes of untreated ratsin vitro, there was no change in the difference spectrum produced by binding of cytochrome p-450 and aniline and also in the activities of AH and pNP-GT.
Based on these observations, it can be concluded that PG affected thein vitro assay data of drugmetabolizing enzyme without changing the cytochrome P-450 content by its certainin vivo action rather than by its direct interaction with microsomes, and modified the effect of PB on the microsomal enzymes and the cytosol proteins. Therefore, it is not appropriate to investigate the effect of the drugs on enzymes and proteins of the liver cell by the use of PG as a solvent.
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A part of this work was preliminarily reported at the 61st Annual Meeting of the Japanese Society of Gastroenterology on March 31, 1975.
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Yamamoto, T., Adachi, Y. Effect of oral administration of propylene glycol on the induction of enzymes and proteins in microsomes and cytosol of the rat liver. Gastroenterol Jpn 13, 359–365 (1978). https://doi.org/10.1007/BF02776012
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DOI: https://doi.org/10.1007/BF02776012