Malnutrition sequela on the drug metabolizing enzymes in male Holtzman rats

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.