Role of Quinones in Toxicology

Abstract

Quinones represent a class of toxicological intermediates which can create a variety of hazardous effects in vivo, including acute cytotoxicity, immunotoxicity, and carcinogenesis. The mechanisms by which quinones cause these effects can be quite complex. Quinones are Michael acceptors, and cellular damage can occur through alkylation of crucial cellular proteins and/or DNA. Alternatively, quinones are highly redox active molecules which can redox cycle with their semiquinone radicals, leading to formation of reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and ultimately the hydroxyl radical. Production of ROS can cause severe oxidative stress within cells through the formation of oxidized cellular macromolecules, including lipids, proteins, and DNA. Formation of oxidatively damaged bases such as 8-oxodeoxyguanosine has been associated with aging and carcinogenesis. Furthermore, ROS can activate a number of signaling pathways, including protein kinase C and RAS. This review explores the varied cytotoxic effects of quinones using specific examples, including quinones produced from benzene, polycyclic aromatic hydrocarbons, estrogens, and catecholamines. The evidence strongly suggests that the numerous mechanisms of quinone toxicity (i.e., alkylation vs oxidative stress) can be correlated with the known pathology of the parent compound(s).

Catechol estrogens induce oxidative DNA damage and estradiol enhances cell proliferation

“…We have previously reported that benzoquinone 35 and its derivatives 36,37 induce DNA damage via the NADH-dependent redox cycle. Thus, catechol estrogens appear to cause DNA damage by a similar mechanism, as suggested by Bolton et al 11,38 Comparison of the abilities of 2-OHE 2 and 4-OHE 2 to cause DNA damage revealed that in the presence of Cu(II), 4-OHE 2 causes more extensive strand breaks in plasmid DNA than 2-OHE 2 . 25 2-OHE 2 and 4-OHE 2 induced Cu(II)-dependent oxidative DNA damage to a similar extent at low nanomolar concentrations, suggesting that they have comparable abilities to generate reactive oxygen species.…”

Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox4

“…Quinone derivative compounds induce a broad spectrum of effects in humans and represent a class of toxicological intermediates, which may induce acute cytotoxicity, immunotoxicity, and carcinogenesis, and lead to cellular damage [1]. They can be formed from benzene or polycyclic aromatic hydrocarbons and are toxicologically important components of air pollution [2] and cigarette smoke [3].…”

Assessment of effect of hydroalcoholic and decoction methods on extraction of antioxidants from selected Indian medicinal plants

“…In fact, oxidative stress results from an imbalance between the generation of ROS and endogenous antioxidant systems. ROS are major sources of primary catalysts that initiate oxidation in vivo and in vitro and create oxidative stress which results in numerous diseases and disorders [1] such as cancer [2] , cardiovascular disease [3] , neural disorders [4] , Alzheimer's disease [5] , mild congnitive impairment [6] , Parkinson's disease [7] , alcohol induced liver disease [8] , ulcerative colitis [9] , ageing [10] , and atherosclerosis [11] .…”