Investigation into the antioxidant capacity of L-arginine and L-citrulline in relation to their vascular protective properties

Oxidative stress plays a prominent role in the development of endothelial dysfunction. L-arginine and L-citrulline have been demonstrated to have beneficial effects in vascular disease and this thesis aimed to determine whether this protective effect is mediated via an antioxidant mechanism. With evidence to suggest L-citrulline may have antioxidant properties in plants, and the current contradictions that exist concerning the antioxidant properties of L-arginine in cells and in humans, a study aimed at fully characterising the antioxidant properties of both molecules was needed. The ability of L-arginine and L-citrulline to scavenge both superoxide and hydroxyl radicals were investigated with an antioxidant effect only demonstrated against hydroxyl radicals. The mechanism of antioxidant action was shown to be two fold: 1) through inhibition of hydroxyl radical production and 2) through direct scavenging of the hydroxyl radical. Three model systems were developed to test the effect of endogenous and exogenous ROS on biological function. This allowed investigation into whether the antioxidant properties demonstrated in vitro were transferable to physiological and pathophysiological systems. Both amino acids were able to regulate endogenous ROS in platelets but this was shown to have little effect on overall platelet function. In terms of exogenous radicals, L-citrulline but not L-arginine, was able to protect against superoxide mediated endothelial dysfunction in vessels however this was deemed to be through a ROS independent effect Both amino acids inhibited hydroxyl radical mediated lipid peroxidation at concentrations of amino acid found in the plasma. Taken together, these studies suggest that the improvement in vascular function seen upon administration of L-arginine and L-citrulline is in part mediated through an ability to scavenge hydroxyl radicals. However, their inability to directly affect superoxide levels draws into question whether significant antioxidant effects occurs in vivo and would suggest that a certain proportion of their protective effect on the vascular system is mediated via an antioxidant independent mechanism.EThOS - Electronic Theses Online ServiceGBUnited Kingdo