Different behavior of agmatine in liver mitochondria: Inducer of oxidative stress or scavenger of reactive oxygen species?

Agmatine, at concentrations of 10 mu M or 100 mu M, is able to induce oxidative stress in rat liver mitochondria (RLM), as evidenced by increased oxygen uptake, H2O2 generation, and oxidation of sulthydryl groups and glutathione. One proposal for the production of H2O2 and, most probably, other reactive oxygen species (ROS), is that they are the reaction products of agmatine oxidation by an unknown mitochondrial amine oxidase. Alternatively, by interacting with an iron-sulfur center of the respiratory chain, agmatine can produce an imino radical and subsequently the superoxide anion and other ROS. The observed oxidative stress causes a drop in ATP synthesis and amplification of the mitochondrial permeability transition (MPT) induced by Ca2+. Instead, 1 mM agmatine generates larger amounts of H2O2 than the lower concentrations, but does not affect RLM respiration or redox levels of thiols and glutathione. Indeed, it maintains the normal level of ATP synthesis and prevents Ca2+-induced MPT in the presence of phosphate. The self-scavenging effect against ROS production by agmatine at higher concentrations is also proposed. (c) 2007 Elsevier B.V. All rights reserved.