The effect of food restriction on the specific activities of the drug metab
olizing enzymes (DME) system was studied in Holtzman male rats by comparing
DME activities in 90-day-old control rats fed ad libitum (CO), rats fed 40
% restricted food (RF) from the gestation period to the day of sacrifice, a
nd recovered mts (rRF) fed 40% restricted food from period of gestation to
45 days of age and then fed ad libitum until the day of sacrifice. In liver
, total cytochrome P450 (CYP) of the RF and rRF groups was higher by approx
imately 50% and 28%, respectively, than in CO rats. Specific activities of
individual CYP monooxygenases (MO) such as CYP2B [7-methoxycoumarin demethy
lase (MOCD)] CYPIA [aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin
deethylase (EORD)], and CYP2E [nitrosodimethylamine demethylase (NDMAd)] we
re 31, 61, 43, and 56% in RF and 16, 36, 26, and 32 % in rRF groups, respec
tively, mo re than the CO values. Conjugases such as UDP- glucuronosyltrans
ferases with substrates 3-OH benzo(a)pyrene (UGTI) and 4-hydroxybiphenyl (U
GT2) and glutathione S-transferase (GST) with substrate 1-chloro-2,4-dinitr
obenzene were higher by 72, 69, and 33% in RF and 28, 38, and 24% in rRF gr
oups, respectively MO activities (MOCD and EORD) were significantly higher
in lung, kidney, and intestine: MOCD by 82, 48, and 45% in RF and 40, 25, a
nd 22% in rRF, respectively; and EORD by 84, 77 and 67% in RF and 40, 33, a
nd 28% in I-RF, respectively. However activity of conjugases (UGTI and GST)
were significantly lower (approximately 35-45%) in RF and rRF mts (approxi
mately 20-30%) than in the CO group in above mentioned extrahepatic tissues
. These studies indicate that undernourishment during the period of gestati
on, weanling, and growth and development of microsomal enzymes produces a s
equela of events on the DME in hepatic and extrahepatic tissues that cannot
return to the control values even when fed ad libitum. (C) Elsevier Scienc
e Inc. 1999. All rights reserved.