Current understanding of hexavalent chromium [Cr(VI)] neurotoxicity and new perspectives. 2022

John P Wise, and Jamie L Young, and Jun Cai, and Lu Cai
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA; Pediatric Research Institute, The Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY 40292, USA. Electronic address: john.wise.1@louisville.edu.

Hexavalent chromium [Cr(VI)] is a global environmental pollutant that increases risk for several types of cancers and is increasingly being recognized as a neurotoxicant. Traditionally, the brain has been viewed as a largely post-mitotic organ due to its specialized composition of neurons, and consequently, clastogenic effects were not considered in neurotoxicology. Today, we understand the brain is composed of at least eight distinct cell types - most of which continue mitotic activity throughout lifespan. We have learned these dividing cells play essential roles in brain and body health. This review focuses on Cr(VI), a potent clastogen and known human carcinogen, as a potentially neurotoxic agent targeting mitotic cells of the brain. Despite its well-established role as a human carcinogen, Cr(VI) neurotoxicity studies have failed to find a significant link to brain cancers. In the few studies that did find a link, Cr(VI) was identified as a risk for gliomas. Instead, in the human brain, Cr(VI) appears to have more subtle deleterious effects that can impair childhood learning and attention development, olfactory function, social memory, and may contribute to motor neuron diseases. Studies of Cr(VI) neurotoxicity with animal and cell culture models have demonstrated elevated markers of oxidative damage and redox stress, with widespread neurodegeneration. One study showed mice exposed to Cr(VI)-laden tannery effluent exhibited longer periods of aggressive behavior toward an "intruder" mouse and took longer to recognize mice previously encountered, recapitulating the social memory deficits observed in humans. Here we conducted a critical review of the available literature on Cr(VI) neurotoxicity and synthesize the collective observations to thoroughly evaluate Cr(VI) neurotoxicity - much remains to be understood and recognized.

UI MeSH Term Description Entries
D002857 Chromium A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens.
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004785 Environmental Pollutants Substances or energies, for example heat or light, which when introduced into the air, water, or land threaten life or health of individuals or ECOSYSTEMS. Environmental Pollutant,Pollutant,Pollutants,Pollutants, Environmental,Pollutant, Environmental
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

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