Abstract Heavy metals are naturally occurring components of the Earth’s crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO · ), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O 2 ·− ), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO − ). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer’s and Parkinson’s diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid ( EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.

Klaudia Jomova

Suliman Y. Alomar

Eugenie Nepovimova

Kamil Kuca

Marian Valko

Archives of Toxicology

毒理学档案提供有关毒理学最新进展的最新信息。该杂志特别强调与化学物质的明确影响和毒性机制相关的研究，包括分子水平的毒性活动，在人类和实验动物中。覆盖范围包括对分析和毒代动力学以及法医毒理学的新见解。毒理学家普遍感兴趣的评论文章是该杂志的另一个重要特征。

The Archives of Toxicology is a journal that provides the latest information on advancements in toxicology. It particularly emphasizes research related to the effects of chemicals and their toxic mechanisms, including toxic activities at the molecular level in humans and experimental animals. The scope includes new insights into analytical toxicology, toxicokinetics, and forensic toxicology. Additionally, review articles that are of general interest to toxicologists are another significant feature of the journal.

《Archives of Toxicology》是一本提供毒理学最新进展的期刊。该杂志特别强调与化学物质的影响及其毒性机制相关的研究，包括分子水平的毒性活动，涉及人类和实验动物。内容涵盖对分析毒理学、毒代动力学以及法医毒理学的新见解。此外，毒理学家普遍感兴趣的评论文章也是该杂志的重要特色之一。

Category	Quartile
医学	2
医学, 毒理学	1

Heavy metals: toxicity and human health effects

ivySCI AI Smartly Parses PDF, Answers Researchers' Questions, and Helps You Understand Papers in Seconds

Journal Info