Dietary Fish Oil and Cytochrome P-450 Monooxygenase Activity in Rat Liver and Kidney Elena Valdes, Patricio Vega, Nicolas Avalos and Myriam Orellana* Departamento de Bioquimica, Facultad de Medicina, Universidad de Chile, Casilla 70086, Santiago 7, Chile ABSTRACT: Lauric acid hydroxylation and aminopyrine N-demethylation were studied in kidney and liver microsomes from rats treated with fish oil. Different doses of fish oil contain- ing 20% eicosapentaenoic acid and 10% docosahexaenoic acid were provided daily to the rats for seven days. In all the groups studied, the lauric acid metabolism was higher in kidney micro- somes and the aminopyrine metabolism in the liver micro- somes. Although no effect on the renal cytochrome P-450 con- centration was detectable, all four fish oil doses increased the hepatic concentration of cytochrome P-450 by a mean 27%. The higher fish oil doses used increased the renal and hepatic microsomal metabolism of aminopyrine. The lauric acid metab- olism was increased by fish oil only in the liver. Fish oil, a known inducer of fatty acid peroxisomal l]-oxidation, also in- duced microsomal activity. These results show that liver and kidney respond in different ways to dietary factors such as fish oil. In addition, our study would suggest that fish oil increased the activity of two different families of liver cytochrome P-450. The activity of kidney lauric acid 1 I- and 12-hydroxylation, however, was not modulated by fish oil. Lipids 30, 955-958 (I 995). Microsomal cytochrome P-450 catalyzes the oxidative me- tabolism of a wide variety of lipophilic compounds, such as drugs, carcinogens, endogenous steroids (1), and fatty acids (2). Cytochrome P-450s are found predominantly in the liver, but are also present in many other tissues, such as the kidney. Marine oils are rich in polyunsaturated fatty acids of n-3 family, especially eicosapentaenoic acid (20:5) (EPA) and do- cosahexaenoic acid (22:6) (DHA). There are several cy- tochrome P-450 isoenzymes from the family 4A that oxidize fatty acids. The CYP4AI purified from liver of clofibrate- treated rats catalyzes the to-hydroxylation of arachidonic and lauric acids (3). The physiological role of these isoenzymes P-450 has not been identified. It has been reported that clofibrate and other peroxisomal proliferators simultaneously enhance the cellular content and activity of liver cytochrome P-450 (3). In previous studies with starved rats, we showed an increase in the microsomal *To whom correspondence should be addressed at Departamentode Bio- quimica, Faeultadde Medicina, Universidad de Chile, Independencia 1027, Casilla 70086, Santiago7, Chile. Abbreviations: ANOVA, analysis of variance; EPA, eicosapentaenoic acid; DHA,docosahexaenoic acid. lauric acid (o-hydroxylation, which was correlated w!th an in- crease in peroxisomal fatty acid I~-oxidation in liver and in kidney (4,5). The liver microsomal activity has been studied exten- sively. Meanwhile, our knowledge of both the constitutive and inducible content and activity of kidney cytochrome P-450 remains very limited. The levels of cytochrome P-450 in kidney previously have been shown to be much lower than those seen in liver, and the renal cortex presents the highest levels of cytochrome P-450 (6,7). It has been reported that fish oil or diets enriched in EPA and DHA induce liver fatty acid microsomal and peroxisomal oxidation (8-11). The extent of the increase of microsomal activity or peroxisomal ~-oxidation depends on the type of dietary fish oil (10). However, the effect of fish oil on kidney microsomal activity has not been reported. In this work, we study the effect of fish oil consumption on microsomal lauric acid hydroxylation and aminopyrine N-demethylation to investigate the possible induction of the microsomal activity by this factor. We carded out a compara- tive study using liver and kidney microsomes in order to de- termine how these tissues respond to a diet enriched with polyunsaturated fatty acids EPA and DHA. MATERIALS AND METHODS Chemicals. Fish oil was provided by Maver Laboratory (San- tiago, Chile). According to the manufacturers, the fish oil was encapsulated under vacuum using anerobic conditions. The capsules were stored at room temperature upon arrival and opened just prior to the rat gavages. The fish oil was a sardine oil concentrate containing 36.5% polyunsaturated fatty acids [20.4% EPA, 10.3% DHA, 1.4% linoleic, 0.8% linolenic, 1.6% octadecatetraenoic (18:4n-3), 0.4% eicosadienoic (20:2n-9), 1. 1% arachidonic, and 0.5% docosatetraenoic acids (22:4n-6)]; 32.8% monounsaturated fatty acids [12.4% palmi- toleic, 16% oleic, 2.5% eicosanoic (20: ln-9), and 1.9% ce- toleic acids], and 30.7% saturated fatty acids (0.7% pentade- canoic, 20.1% palmitic, 1.0% heptadecanoic, 4.1% tetra- cosanoic, and 4.8% stearic acids). The corn oil used in our control rats was provided by Mazola (Inducoen, Santiago, Chile), and contained 60% total polyunsaturated fatty acids (57.7% linoleic and 2.3% linolenic acids); 26.1% of the too- Copyright 1995 by AOCS Press 955 Lipids, Vol. 30, no. 10 (1995)