INDUCTION OF ANTIOXIDANT/DETOXIFYING SYSTEM IN PRIMARY RAT HEPATOCYTES BY LISOSAN G, A FERMENTED POWDER OF WHEAT

Experimental data indicates that certain vegetables may offer an indirect protection against oxidative stress by activating endogenous cellular defense systems at genetic and protein levels. In recent years a number of studies have shown that whole grain products have strong antioxidant activity and may reduce the risk of coronary heart disease (1). It has been recently shown that Lisosan G, a fermented power of grain of Triticum Sativum has a protective effect against the cisplatin induced toxicity. The authors suggested that the protective effect of Lisosan G could be associated mainly with the attenuation of the oxidative stress and the preservation in antioxidant enzymes (2). Further, Lisosan G does not interfer with drug metabolizing system and protects against CCl4-induced hepatotoxicity (3). Several antioxidant agents trigger Nrf2 signaling with a concomitant repression of NF-kB and its target genes. In this study, primary cultures of rat hepatocytes were used to investigate whether and how Lisosan G is able to modulate antioxidant/detoxifying enzymes, and whether or not it can activate the Nrf2 transcription factor or inhibit the NF-kB activation. All of the antioxidant/detoxifying enzymes studied were significantly up-regulated by 0.7mg/ml Lisosan G treatment. In particular, NAD(P)H:quinone oxidoreductase and heme oxygenase-1 were induced, although to different degrees, at transcriptional, protein and/or activity levels by treatment. As for the Nrf2 transcription factor, a partial translocation of its protein from the cytosol to the nucleus after 1h of Lisosan G treatment was revealed by immunoblotting. Lisosan G was also observed to decrease H2O2-induced toxicity. Taken together, these results show that this powder of wheat is an effective inducer of ARE/Nrf2-regulated antioxidant/detoxifying genes and has the potential to inhibit the translocation of NF-kB into the nucleus. References 1.Truswell, A.S., 2002. Cereal grains and coronary heart disease. Eur. J. Clin. Nutr. 56, 1-14 2.Longo, V., et al., 2011. Cisplatin induced toxicity in rat tissues: the protective effect of Lisosan G. Food and chemical toxicology 49, 233-237 3.Longo, V., et al. 2007. Lisosan G, a powder of grain, does not interfer with thw drug metabolizing enzymes and has a protective role on carbon tetrachloride-induced hepatotoxicity. Biotech. Letter 29, 1155-1159