The antioxidant response mechanism by which phenolic phytochemicals show their positive benefits in animal systems is not very well understood. The ability of cranberry juice powder (CP), ellagic acid (EA), rosmarinic acid (RA) and their synergies to mediate a cellular antioxidant response in oxidatively stressed porcine muscle tissue was investigated. Results indicated that treatment with CP, EA, RA and their synergies reduced or helped counter oxidative stress as indicated by the formation of malondialdehyde (MDA). It was also observed that CP, EA, RA and their synergies stimulated the pentose phosphate pathway (PPP) linked to the accumulation of free proline suggesting a possible coupling of proline biosynthesis with PPP. This coupling of proline-linked pentose phosphate pathway could be involved in the stimulation of cellular antioxidant enzymic response by replenishing the cellular needs for NADPH(2). As a consequence these exogenous phenolic treatments resulted in the stimulation of cellular antioxidant enzyme systems involving superoxide dismutase (SOD), catalase (CAT) and peroxidase, which correlated well with the decreased MDA formation. This suggested that exogenously treated phenolic phytochemicals could be reducing the oxidative stress in porcine muscle by stimulating the PPP linked to proline biosynthesis and by the activation of the cellular antioxidant enzyme system. The results also suggest that pure exogenous phenolics, EA and RA appeared to be effective when they were present in a cranberry phenolic background, suggesting a possible synergistic mode of action between EA, RA and cranberry phenolics in mediating a cellular antioxidant enzyme response. (c) 2004 Elsevier Ltd. All rights reserved.