Abstract
In the present study, we administered two low protein diets (LPDs) to rats during pregnancy and lactation and determined their effect on the ontogeny of select hepatic cytochrome P450 (P450) isoforms in their offspring. The L93 and LM76 LPDs were derived from the American Society of Nutrition recommended AIN93G and a modified version of the AIN76A purified control diets, respectively. The LPDs contained 8% crude protein in the form of casein, whereas the purified control diets contained 19% casein. A regular cereal-based diet (NP) was also included, and, therefore, a total of five groups were tested. Pups in all five groups were weaned onto a regular NP diet on postnatal day 28. Perinatal LPD altered the activities of a number of P450 isoforms in 28-day-old male and female offspring. However, nutritional rehabilitation abolished most of these changes as evidenced by lack of differences between the five groups in the activities of P450 isoforms in either 65- or 150-day-old offspring. Interestingly, 58-day-old female offspring in the LM76 group but not those in the L93 group exhibited shorter hexobarbital sleep time than the purified control group. However, hexobarbital hydroxylase activity and the amount of CYP2C12 protein, an important P450 isoform involved in hexobarbital metabolism in females, were unchanged. This suggests that the decrease in hexobarbital sleep time in this group is not due to an increase in the activity of hexobarbital-metabolizing enzymes. In summary, perinatal LPDs produced transient alterations in activities of select hepatic P450s and resulted in a gender- and diet-dependent long-term alteration in hexobarbital pharmacodynamics.
Footnotes
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.106.013748.
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ABBREVIATIONS: P450, cytochrome P450; EROD, ethoxyresorufin O-dealkylase; PROD, pentoxyresorufin O-dealkylase; CPR, cytochrome P450 reductase; LPD, low protein diet; NP, nonpurified diet; C93, AIN93G purified control diet; L93, low protein diet based on the AIN93G purified diet; LM76, low protein diet based on the modified version of the AIN76A purified diet; M76, Modified version of the AIN76A purified control diet; HST, hexobarbital sleep time
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↵ The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.
- Received November 7, 2006.
- Accepted March 27, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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