Use of antioxidants for gene modulation

A method of treating oxidative stress in a canine in need thereof, the method comprising:

• treating the oxidative stress in the canine by administering to the canine in need thereof a pet food composition comprising:
• two or more antioxidants selected from a first group consisting of vitamin E, vitamin C, lipoic acid, and L-carnitine;
• one or more antioxidants selected from a second group consisting of astaxanthin, rice bran, algae, curcumin, marine oil, and yeast;
• and
• one or more antioxidants selected from a third group consisting of coenzyme Q10, lutein, lycopene, polyphenol(s), tocotrienol(s), selenium, and green tea;
• wherein a total amount of the two or more antioxidants in the first group, the one or more antioxidants in the second group, and the one or more antioxidants in the third group in the composition are sufficient to treat the oxidative stress in the canine in need thereof, and
• measuring a decrease in a ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) in a sample from a canine in need thereof relative to a control value for the ratio of GSH to GSSG in a sample from a normal canine or population of canines, and/or relative to a previous individual baseline value from the canine,
• measuring a down-regulation or an up-regulation of one or more genes selected from the group consisting of:
• cytochrome P450 genes, apolipoprotein genes, genes regulating hemodynamic properties, heat shock protein genes, genes regulating DNA damage, genes regulating cell cycle pathways, pro-inflammatory genes, chromaffin secretory genes, genes regulating gene transcription, NK-kB genes, genes encoding glycolytic or mitochondrial oxidative enzymes, genes encoding ribosomal protein to indicate treatment,
• wherein the ratio of GSH to GSSG is an indicator of oxidative stress,
• wherein the one or more genes includes cytochrome P450 genes,
• wherein measuring the down-regulation or the up-regulation of the one of more genes comprises measuring an up-regulation of the cytochrome P450 genes, and
• wherein the cytochrome P450 genes are selected from the group consisting of:
• P450, family 2, subfamily b, polypeptide 10 (Cyp2b10);
• P450, family 2, subfamily c, polypeptide 70 (Cyp2c70);
• P450, family 2, subfamily c, polypeptide 37 (Cyp2c37);
• P450, family 2, subfamily a, polypeptide 12 (Cyp2a12);
• P450, family 2, subfamily c, polypeptide 40 (Cyp2c40);
• P450, family 3, subfamily a, polypeptide 11 (Cyp3a11);
• P450, family 3, subfamily a, polypeptide 13 (Cyp3a15);
• P450, family 3, subfamily a, polypeptide 16 (Cyp3a16);
• P450, family 3, subfamily a, polypeptide 25 (Cyp3a25);
• P450, family 2, subfamily a, polypeptide 4 (Cyp2a4);
• P450, family 4, subfamily a, polypeptide 10 (Cyp4a10), and combinations thereof.