Results from both hepatic and renal

Results from both hepatic and renal microsomal catalytic activity and Western immunoblotting showed no significant difference between retinol and the control groups for CYP2E1. The liver displayed approximately double the CYP2E1 catalytic activity when compared to the kidney. Differential CYP2E1 activity has been demonstrated in mice, rats, rabbits and hamsters (Arubc et al., 1991, Guengerich and Mason, 1979, Liu et al., 1993, Ueng et al., 1991, Villard et al., 1998). The lack of induction of hepatic CYP2E1 by retinol is supported by previous work from our laboratory that showed no change in CYP2E1 catalytic activity or polypeptide levels in male Swiss Webster mice following 3 days of retinol treatment (75 mg/kg/day) (Inder et al., 1999). Therefore, it appears that this response is not altered by different durations of retinol or different strains of mice. However, in other Levodopa mg retinol and derivatives have been shown to induce CYP2E1. Miranda and Chhabra (1981) showed an increase in hepatic aniline hydroxylation in guinea pigs fed a retinol-supplemented (500 IU retinyl palmitate/g) diet. Furthermore, retinol (75 mg/kg) induced hepatic CYP2E1 polypeptide levels and catalytic activities in the rat (Badger et al., 1996). Interestingly, in this study 7 days of retinol treatment resulted in less CYP2E1 induction than 1 day of retinol. Therefore, any relevance of this finding to our design, utilising a 4-day treatment regimen and a different species, is unlikely. In the mouse, renal CYP2E1 is induced by inhalation of cigarette smoke, which indicates that xenobiotics modulate the activity of this enzyme in the kidney (Seree et al., 1996, Villard et al., 1998). However, our results indicate that retinol does not display this activity in the mouse. The hepatic constitutive levels of CYP1A2 were minimal and were below detectable limits in the kidney, indicating an organ-specific trend which has been reported by other groups (Hawke and Welch, 1985, Paolini et al., 1997, Parkinson, 1996, Villard et al., 1998). Retinol administration did not have an inductive effect on the this isoform, since both the catalytic activity and polypeptide levels were not increased from untreated or vehicle control. There has been some evidence demonstrating that retinoids may be involved in the regulation of the CYP1A gene. Vecchini et al. (1994) reported the presence of a retinoic acid response element on the human CYP1A1 gene in normal human keratinocytes. In vivo studies demonstrated that the metabolism of benzo[a]pyrene (BaP) was inhibited following 7 days of retinyl acetate, 13-cis-retinoic acid and N-(4-hydroxyphenyl)-retinamide administration in the Sprague–Dawley rat (McCarthy et al., 1987). Conversely, Miranda et al. (1981) failed to show any significant change in BaP metabolism following dietary supplementation with retinyl palmitate (500 IU/g) in either the guinea pig or rabbit. Therefore, it appears that retinol\'s effect on CYP1A is dependent on both the species and specific retinoid administered.