INDUCTION OF OXIDATIVE STRESS AS AN ELEMENT OF CADMIUM TOXICITY

Ostrovska S. S., Pisarevska I. А., Deev V. V., Baklunov V. V., Strizak О. V., Kravchenko M. K., Velikodna О. V.

LITERATURE REVIEWS

Scentific article

Abstract. Cadmium (Cd) is a heavy metal, xenobiotic and a major public health concern due to its cumulative toxicity. Agricultural land and foodstuffs contaminated with Cd are the main sources of its entering into the food chain. Tobacco smoking is also a source of chronic exposure to Cd. Cd affects the lungs, liver, kidneys, gonads, and other organs. Its action in acute intoxication is manifested as nephrotoxicity, immunotoxicity, cardiotoxicity, as well as osteotoxicity in chronic exposure. Cd is associated with the development of cancer and is classified as a human carcinogen category I by the International Agency for Research on Cancer (IARC). Modern technology has proven that the main molecular mechanism underlying polytropic toxicity of Cd is the induction of oxidative stress (OS), which plays a decisive role in the pathogenesis of toxicity not only in humans, but also in animals, fish and plants. The review summarizes modern views on the role of Cd in the induction of OS and modification of a number of biomolecules, including in some diseases. OS leads to serious oxidative damage to macromolecules, primarily mitochondria (MT), in which Cd disrupts the transfer of electrons along the electron transport chain. The toxicity of Cd is associated with an increase in the production of reactive oxygen species (ROS) precisely at the level of the MT electron transport chain, which are key intracellular targets of its toxicity. Another important mechanism by which Cd induces OS is the depletion of intracellular glutathione (GLT), the first line of defense of cells against OS. GLT is present in all subcellular compartments, and is also involved in chelation of xenobiotics, reducing their toxicity. Depletion of GLT enhances Cd-induced organ toxicity, resulting in ROS-mediated cell death. Lipid peroxidation (LPO) is a consequence of Cd-induced OS and correlates with levels of its effect, causing tissue necrosis, which is associated with LPO in many organs. Cd plays a destructive role in the central nervous system, increasing the permeability of the blood-brain barrier, affects glial cells, triggering a pro-inflammatory cascade that destroys synaptic connections, while OS plays a major role in Cd-mediated toxicity, including ROS production, inhibition of the MT electron transport chain, and depletion of GLT. The role of Cd-induced OS in various compartments and cells of the central nervous system is being reviewed. Various epigenetic changes in mammalian cells under the action of Cd have been revealed, which increases the pathogenic risks of cancer development. It has been shown that changes in the expression of genes associated with ROS production during chronic exposure are less significant compared with acute Cd poisoning, which is associated with induced adaptation mechanisms, such as overexpression of metallothionein and GLT, which, in turn, reduces Cd-induced OS. In cells under the chronic action of Cd, resistance to apoptosis is acquired, which leads to the proliferation of damaged cells with oxidative DNA damage, while the acquired tolerance to Cd with aberrant gene expression contributes to the development of cancer. Сhronic exposure to low Cd content, mainly in food, which increases the risk of an increase in Cd-induced cancers.

cadmium, toxic effect, oxidative stress.

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«Bulletin of problems biology and medicine» Issue 2 (160), 2021 year, 44-48 pages, index UDK 546.48:612.014.46:66.094.1:616-092(048.8)

10.29254/2077-4214-2021-2-160-44-48