Copper toxicity, oxidative stress, and antioxidant nutrients

Author: Gaetke, L.M.; Chow, C.K.

Description: Copper (Cu) is an integral part of many important enzymes involved in a number of vital biological processes. Although normally bound to proteins, Cu may be released and become free to catalyze the formation of highly reactive hydroxyl radicals. Data obtained from in vitro and cell culture studies are largely supportive of Cu’s capacity to initiate oxidative damage and interfere with important cellular events. Oxidative damage has been linked to chronic Cu-overload and/or exposure to excess Cu caused by accidents, occupational hazards, and environmental contamination. Additionally, Cu-induced oxidative damage has been implicated in disorders associated with abnormal Cu metabolism and neurodegenerative changes. Interestingly, a deficiency in dietary Cu also increases cellular susceptibility to oxidative damage. A number of nutrients have been shown to interact with Cu and alter its cellular effects. Vitamin E is generally protective against Cu-induced oxidative damage. While most in vitro or cell culture studies show that ascorbic acid aggravates Cu-induced oxidative damage, results obtained from available animal studies suggest that the compound is protective. High intakes of ascorbic acid and zinc may provide protection against Cu toxicity by preventing excess Cu uptake. Zinc also removes Cu from its binding site, where it may cause free radical formation. Beta-carotene, alpha-lipoic acid and polyphenols have also been shown to attenuate Cu-induced oxidative damage. Further studies are needed to better understand the cellular effects of this essential, but potentially toxic, trace mineral and its functional interaction with other nutrients.

Subject headings: Animals; Antioxidants/metabolism/pharmacology; Ascorbic Acid/metabolism/therapeutic use; Copper/metabolism/toxicity; Flavonoids; Humans; Hydroxyl Radical/metabolism; Oxidative Stress/drug effects/physiology; Phenols/metabolism/therapeutic use; Polymers/metabolism/therapeutic use; Polyphenols; Thioctic Acid/metabolism/therapeutic use; Vitamin E/metabolism/therapeutic use; Zinc/metabolism/therapeutic use; beta Carotene/metabolism/therapeutic use

Publication year: 2003

Journal or book title: Toxicology

Volume: 189

Issue: 1-2

Pages: 147-163

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Type: Journal Article

Serial number: 1049