The role of radical reactions in organomercurials impact on lipid peroxidation.
The organomercury compounds RHgX and R(2)Hg are broad-spectrum biocidal agents acting via diverse mechanisms in biological systems. Despite the enormous amount of studies carried out in last decades to elucidate the detailed mechanisms of organomercurials toxicity their biomolecular mode of action is still under debate. Among various toxicity mechanisms the action of RHgX and R(2)Hg at the membrane level due to the lipophilic properties of their molecules is discussed. Organomercurials are supposed to induce membrane associated oxidative stress in living organism through different mechanisms including the enhancement of the lipid peroxidation and intracellular generation of reactive oxygen species (ROS), H(2)O(2), O(2)(-), HO(). The perturbation of antioxidative defense system and the peroxidation of unsaturated fatty acids in membrane lipid bilayer are consequences of this impact. On the other hand, the involvement of organomercurials in radical and redox biochemical processes is manifested in carbon to metal bond cleavage that leads to the generation of reactive organic radicals R(). This pathway is discussed as one of the multiple mechanisms of organomercurials toxicity. The goal of this review is to present recent results in the studies oriented towards the role of organomercurials in the xenobiotic-mediated enhancement of radical production and hence in the promotion of lipids peroxidation. The application of natural and synthetic antioxidants as detoxification agents is presented.
Milaeva
E R
ER
Organic Chemistry Department, Moscow State Lomonosov University, Lenin Hill, 119992 Moscow, Russian Federation. milaeva@org.chem.msu.ru
D000975:Antioxidants / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D007700:Kinetics; D008051:Lipid Bilayers; D015227:Lipid Peroxidation / Q000187:drug effects*; D009941:Organomercury Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species
D000975:Antioxidants; D002614:Chelating Agents; D005231:Fatty Acids, Unsaturated; D008051:Lipid Bilayers; D009941:Organomercury Compounds; D017382:Reactive Oxygen Species