Role of oxidative stress in cadmium toxicity and carcinogenesis
By Jie Liu, W. Qu, M. Kadiiska. Toxicology and Applied Pharmacology, 2009
829 citations recorded by the source corpus.
Cadmium (Cd) is a toxic metal, targeting the lung, liver, kidney, and testes following acute intoxication, and causing nephrotoxicity, immunotoxicity, osteotoxicity and tumors after prolonged exposures. Reactive oxygen species (ROS) are often implicated in Cd toxicology. This minireview focused on direct evidence for the generation of free radicals in intact animals following acute Cd overload and discussed the association of ROS in chronic Cd toxicity and carcinogenesis. Cd-generated superoxide anion, hydrogen peroxide, and hydroxyl radicals in vivo have been detected by the electron spin resonance spectra, which are often accompanied by activation of redox sensitive transcription factors (e.g., NF-κB, AP-1 and Nrf2) and alteration of ROS-related gene expression. It is generally agreed upon that oxidative stress plays important roles in acute Cd poisoning. However, following long-term Cd exposure at environmentally-relevant low levels, direct evidence for oxidative stress is often obscure. Alterations in ROS-related gene expression during chronic exposures are also less significant compared to acute Cd poisoning. This is probably due to induced adaption mechanisms (e.g, metallothionein and glutathione) following chronic Cd exposures, which in turn diminish Cd-induced oxidative stress. In chronic Cd-transformed cells, less ROS signals are detected with fluorescence probes. Acquired apoptotic tolerance renders damaged cells to proliferate with inherent oxidative DNA lesions, potentially leading to tumorigenesis. Thus, ROS are generated following acute Cd overload and plays important roles in tissue damage. Adaptation to chronic Cd exposure reduces ROS production, but acquired Cd tolerance with aberrant gene expression plays important roles in chronic Cd toxicity and carcinogenesis.
Subfields: Health, Toxicology and Mutagenesis, Nutrition and Dietetics, Pollution
View Paper: https://www.semanticscholar.org/paper/4420588302014fad42ac020607f1a139f4a39ba1
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In Health, Toxicology and Mutagenesis
Citations in the corpus
- Oxidative Stress, Mitochondrial Dysfunction, and Aging (2011, neutral): “hyperoxia, toxins, and transition metals [16–26].”
- Cellular mechanisms of cadmium-induced toxicity: a review (2014, background): “Depletion of hepatic GSH by diethyl maleate also dramatically enhances Cd-generated POBN radical adduct signals in the bile suggesting that disruption of the cellular GSH system is a key element for cadmium-induced oxidative stress in the liver (Liu et al. 2009).”
- Cadmium stress: an oxidative challenge (2010, neutral): “Differences in intracellular GSH level regulation between acute and chronic Cd exposure are a possible underlying cause for the distinct redox signatures observed in both situations (Liu et al. 2009).”
- Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic (2021, background): “Alternatively, Cd could disrupt the antioxidant glutathione which will eventually lead to oxidative stress (Liu et al., 2009; Wu et al., 2016).”
- Pulmonary Oxidative Stress, Inflammation and Cancer: Respirable Particulate Matter, Fibrous Dusts and Ozone as Major Causes of Lung Carcinogenesis through Reactive Oxygen Species Mechanisms (2013, background): “In addition to oxidative DNA damage, metals cause changes in DNA methylation and histone modifications, leading to epigenetic silencing or reactivation of gene expression [107–109].”
- Cadmium toxicity and treatment: An update (2017, neutral): “It scavenges hydroxyl and superoxide radicals (19).”