Natural heme oxygenase-1 inducers in hepatobiliary function

Many physiological effects of natural antioxidants,their extracts or their major active components,have been reported in recent decades.Most of these compounds are characterized by a phenolic structure,similar to that of α-tocopherol,and present antioxidant proper-ties that have been demonstrated both in vitro and in vivo.Polyphenols may increase the capacity of en-dogenous antioxidant defences and modulate the cellu-lar redox state.Changes in the cellular redox state may have wide-ranging consequences for cellular growth and differentiation.The majority of in vitro and in vivo studies conducted so far have attributed the protective effect of bioactive polyphenols to their chemical reac-tivity toward free radicals and their capacity to prevent the oxidation of important intracellular components.However,in recent years a possible novel aspect in the mode of action of these compounds has been sug-gested; that is,the ultimate stimulation of the heme oxygenase-1 (HO-1) pathway is likely to account for the established and powerful antioxidant/anti-inflam-matory properties of these polyphenols.The products of the HO-catalyzed reaction,particularly carbon mon-oxide (CO) and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli.In this context,it is interesting to note that induction of HO-1 expression by means of natural compounds contributes to protec-tion against liver damage in various experimental mod-els.The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against various stressors in several pathological conditions.