Alteration of hepatic drug metabolizing activities and contents of cytochrome P-450 isozymes by neonatal monosodium glutamate treatment.
By the treatment of newborn male rats with monosodium glutamate (MSG), microsomal benzo[a]pyrene hydroxylation, propoxycoumarin O-depropylation, and testosterone (T) 6 beta- and 2 beta-hydroxylations in the adult rats were decreased significantly, while microsomal aniline and T 7 alpha-hydroxylations were increased. However, the treatment of newborn female rats did not significantly alter any of the drug-metabolizing activities examined, except that T 6 beta-hydroxylation and androstenedione formation were slightly increased. The hepatic contents of male-specific cyt. P-450, P-450-male and P-4506 beta, which show high catalytic activities on respective T 16 alpha/2 alpha-, and T 6 beta/2 beta-hydroxylations, decreased in MSG-treated male rats. The level of the female specific enzyme, P-450-female, slightly decreased in the MSG-treated female rats, whereas higher phenobarbital (PB)-induction of PB-inducible isozymes, P-450b and P-450e, was observed in MSG-treated than in control female rats. These results are consistent with the idea that disruption of a pulsatile secretion of growth hormone, which is induced by the neonatal MSG treatment, leads to changes in drug metabolizing activities through the alteration of the levels of sex-specific cyt. P-450s, but also indicate that MSG-treated rats are not an animal model equivalent to hypophysectomized rats.
Yamazoe
Y
Y
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
Shimada
M
M
Murayama
N
N
Yamauchi
K
K
Kato
R
R
D000818:Animals; D000831:Animals, Newborn; D001711:Biotransformation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005971:Glutamates / Q000494:pharmacology*; D013006:Growth Hormone / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects; D051381:Rats; D012970:Sodium Glutamate / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism
D003573:Cytochrome b Group; D005971:Glutamates; D007527:Isoenzymes; D013739:Testosterone; D013006:Growth Hormone; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D012970:Sodium Glutamate; D010634:Phenobarbital