Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble antioxidants as suppressing agents

Abstract

The oxidation of guanosine to 8-oxo-2'-deoxyguanosine (8-oxo-dG) in DNA is closely associated with induction of various diseases, but the endogenous oxidant species involved remains unclear. Hydrogen peroxides (H2O2) have been considered to be the oxidant, while lipid peroxides are another possible oxidant because generated easily in bio-membranes surrounding DNA. The oxidant potency was compared between lipid peroxides and H2O2. Linoleic acid hydroperoxides (LOOH) formed 8-oxo-dG at a higher level than H2O2 in guanosine or double-stranded DNA. In the presence of a physiological concentration of Fe2+ to produce hydroxyl radicals, LOOH was also a stronger oxidant. In a lipid micelle, LOOH markedly produced 8-oxo-dG at a concentration one-tenth of that of H2O2. Upon adding to rat hepatic mitochondria, phosphatidylcholine hydroperoxides produced 8-oxo-dG abundantly. Employing HepG2 cells after pretreated with glutathione peroxidase inhibitor, LOOH formed 8-oxo-dG more abundantly than H2O2. Then, antioxidants to suppress the 8-oxo-dG formation were examined, when the nuclei of pre-incubated HepG2 with antioxidants were exposed to LOOH. Water-soluble ascorbic acid, trolox, and N-acetyl cysteine showed no or weak antioxidant potency, while lipid-soluble 2,6-dipalmitoyl ascorbic acid, α-tocopherol, and lipid-soluble phytochemicals exhibited stronger potency. The present study shows preferential formation of 8-oxo-dG upon LOOH and the inhibition by lipid-soluble antioxidants.

Oxidative Stress and Inflammation in Early Onset First Episode Psychosis: A Systematic Review and Meta-Analysis

“…Six separate meta-analyses were performed for inflammatory and/or oxidative markers with data available in at least 2 nonoverlapping studies (CAT, glutathione [GSH], glutathione peroxidase [GPx], SOD, TAS, and cell/DNA oxidative damage [as linoleic acid hydroperoxides or 8-oxo-2’-deoxyguanosine, whose data were analyzed as equivalent ( Kanazawa et al, 2016 ]). Four studies contributed to the 6 independent meta-analyses ( Mico et al, 2011 ; Parellada et al, 2012 ; Martinez-Cengotitabengoa et al, 2014 ; Simsek et al, 2016b ).…”

Oxidative guanine base damage plays a dual role in regulating productive ALT-associated homology-directed repair

“… 24 Lipid peroxides are an endogenous source of 8oxoG. 76 Thus, factors that suppress oxidative damage and alleviate oxidative lesion-induced replication stress at telomeres may act as potential negative regulators of 8oxoG-driven ALT. Our findings provide direct evidence that a common oxidative base lesion can modulate ALT by impairing replication.…”

The snapshot of metabolic health in evaluating micronutrient status, the risk of infection and clinical outcome of COVID-19

“…Apart from the anti-inflammatory properties of vitamin A, it also provides the cells with antioxidant protection. Lipid peroxidation is a sign of cell damage due to oxidative stress and leads to 8-oxo-2 0deoxyguanosine (8-oxo-dG) formation [106]. Vitamin A insufficiencies cannot compensate for the toxic load of ROS, leading to increments in 8-oxo-dG levels.…”