Toxicity of oxygen from naturally occurring redox‐active pro‐oxidants

Abstract

The survival of all aerobic life forms requires the ground-state of molecular oxygen, O2. However, the activation of O2 to reactive oxygen species (ROS) is responsible for universal toxicity. ROS are responsible in deleterious intracellular reactions associated with oxidative stress including membrane lipid peroxidation, and the oxidation of proteins and DNA. Redox-active allelochemicals such as quinones and phenolic compounds are involved in activating O2 to its deleterious forms including superoxide anion free radical, O2.-, hydrogen peroxide, H2O2, and hydroxyl radical, OH. Molecular oxygen is also activated in biologically relevant photosensitizing reactions to the singlet form, 1O2. The insect lifestyle exposes them to a broad diversity of pro-oxidant allelochemicals and, like mammalian species, they have developed an elaborate antioxidant system comprised of chemical antioxidants and a bank of anti-oxidant enzymes. We have found that an insect's antioxidant adaptation to a particular food correlates well with its risk of exposure to potential pro-oxidants.

trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways

“…As previously reported, trans-resveratrol can produce ROS, directly by reacting as phenoxyl radical with O 2 [17,18], or indirectly by impairing mitochondrial integrity [19,26,48]. In order to investigate whether ROS could be produced under our experimental conditions, we performed cytofluorimetric analyses of MCF-7 cells pre-loaded with the ROS-sensitive fluorophore DHCF-DA.…”

“…In fact, the generation of phenoxyl radicals of polyphenols by the peroxidase-H 2 O 2 system, which co-oxidizes cellular glutathione or NADH, accompanied by O 2 uptake to form ROS has been demonstrated [17,18]. In addition, polyphenols have been proposed to induce oxidative stress indirectly by targeting mitochondrial electron transport chain, thereby generating a downstream flux of ROS [26,48]. In agreement with previous works, which identified a role for oxyradicals in cytotoxicity of polyphenols [6,46,19], we observed an early increase of ROS levels after treatment with high doses of trans-resveratrol in human breast cancer cells MCF-7.…”

“…It has been also demonstrated that, under the phenoxyl radical form, polyphenols can cause mitochondrial toxicity by collapsing the mitochondrial transmembrane potential, thereby allowing ROS being generated at high extent [19]. Moreover it has been reported that several natural-occurring flavonoids, and trans-resveratrol itself, are able to affect mitochondrial respiration [24] by inhibiting NADH oxidase, succinoxidase and ATP synthesis [3], thus inducing the generation of partially reduced oxygen species [26,48]. Particularly, a direct relationship between flavonoids redox potential and the above mentioned mitochondrial phenomena, has been proposed [25].…”

Total antioxidant capacity of honeybee haemolymph in relation to age and exposure to pesticide, and comparison to antioxidant capacity of seminal plasma

“…ROS generated in the process of oxidative metabolism can cause oxidation of proteins, RNAs, DNAs and peroxidation of membrane lipids (Michiels et al 1994;Felton 1995;Felton and Summers 1995;Pardini 1995). The destructive reaction contributes to the processes of ageing, carcinogenesis and cell death.…”

Effects of Trolox on the activity and gene expression of cytochrome P450 in hepatic ischemia/reperfusion

“…During the acute phase of reperfusion, ROS can cause direct cellular damage through protein oxidation and degradation, lipid peroxidation, and DNA damage (Pardini, 1995). During the subacute phase of injury, cytokines produced by the initial acute phase activation of pro-inflammatory signal transduction cascades lead to the recruitment of neutrophils which amplify the redox burden in damaged tissue (Kurokawa et al, 1996).…”