Employing a Toxic Aging Coin approach to assess hexavalent chromium (Cr[VI])-induced neurotoxic effects on behavior: Heads for age differences

Vielee, Samuel T.; Isibor, Jessica; Buchanan, William J.; Roof, Spencer H.; Patel, Maitri; Meaza, Idoia; Williams, Aggie; Toyoda, Jennifer H.; Lu, Haiyan; Wise, Sandra S.; Kouokam, J. Calvin; Young Wise, Jamie; Abouiessa, AbouEl-Makarim; Cai, Jun; Cai, Lu; Wise, John P.

doi:10.1016/j.taap.2024.117007

Toxicology and Applied Pharmacology

2024

DOI: 10.1016/j.taap.2024.117007

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Employing a Toxic Aging Coin approach to assess hexavalent chromium (Cr[VI])-induced neurotoxic effects on behavior: Heads for age differences

Samuel T. Vielee,

Jessica Isibor,

William J. Buchanan

et al.

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Cited by 2 publications

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Female Rat Behavior Effects from Low Levels of Hexavalent Chromium (Cr[VI]) in Drinking Water Evaluated with a Toxic Aging Coin Approach

Vielee,

Isibor,

Buchanan

et al. 2024

Applied Sciences

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We are facing a critical aging crisis, with geriatric populations (65+) growing to unprecedented proportions and ~4 million people (a 6.5-fold increase) expected to become centenarians by 2050. This is compounded by environmental pollution, which affects individuals of all ages and contributes to age-related diseases. As we have a limited understanding of how environmental pollutants affect older populations distinctly from younger populations, these longer-lived geriatric populations present a key knowledge gap. To address this knowledge gap, we employ a “Toxic Aging Coin” approach: heads consider how age impacts chemical toxicity, and tails consider how chemicals act as gerontogens—or how they accelerate biological aging. We employed this approach to investigate hexavalent chromium (Cr[VI]) impacts on female rats exposed to 0.05 or 0.1 mg Cr(VI)/L in drinking water for 90 days; these are the maximum contaminant levels (i.e., the highest levels permitted) from the World Health Organization and U.S. Environmental Protection Agency, respectively. During exposure, rats performed a battery of behavior assays to assess grip strength, locomotor coordination, anxiety, spatial memory, sociability, and social novelty preference. We observed age differences in Cr(VI) neurotoxicity, with grip strength, locomotor function, and spatial memory in middle-aged females being particularly affected. We further compared these results in females to results in males, noting many sex differences, especially in middle-aged rats. These data emphasize the need to consider age and sex as variables in toxicology and to revisit drinking water regulations for Cr(VI).

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Female Rat Behavior Effects from Low Levels of Hexavalent Chromium (Cr[VI]) in Drinking Water Evaluated with a Toxic Aging Coin Approach

Vielee,

Isibor,

Buchanan

et al. 2024

Applied Sciences

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Chromium Selectively Accumulates in the Rat Hippocampus after 90 Days of Exposure to Cr(VI) in Drinking Water and Induces Age- and Sex-Dependent Metal Dyshomeostasis

Vielee,

Buchanan,

Roof

et al. 2024

Toxics

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Hexavalent chromium (Cr[VI]) is a widespread environmental pollutant in air and water that is primarily attributed to industrial pollution. The current maximum contaminant levels (MCLs) for drinking water from the World Health Organization and the U.S. Environmental Protection Agency (0.05 and 0.1 mg/L, respectively) were set based on contact dermatitis and warrant further toxicological investigation. While Cr(VI) is neurotoxic and accumulates in the brain, most animal studies only report whole-brain Cr, leaving large knowledge gaps. Few studies consider differences between ages or sexes, and fewer consider essential metal dyshomeostasis. We sought to investigate where Cr accumulates in the brain, considering sex and age differences, following a 90-day drinking water exposure to current MCLs. Here, we report Cr levels in six brain regions of rats exposed to drinking water Cr(VI). We observed Cr only accumulated in the hippocampus, and only in older females. We further assessed changes to essential metals in the hippocampus, observing opposite effects across sexes and between young rats compared to older rats. In sum, our data indicate drinking water Cr(VI) selectively targeted the hippocampus, with geriatric females accumulating the most Cr, and induced significant essential metal dyshomeostasis even in tissues lacking evident Cr accumulation.

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Employing a Toxic Aging Coin approach to assess hexavalent chromium (Cr[VI])-induced neurotoxic effects on behavior: Heads for age differences

Cited by 2 publications

References 41 publications

Female Rat Behavior Effects from Low Levels of Hexavalent Chromium (Cr[VI]) in Drinking Water Evaluated with a Toxic Aging Coin Approach

Female Rat Behavior Effects from Low Levels of Hexavalent Chromium (Cr[VI]) in Drinking Water Evaluated with a Toxic Aging Coin Approach

Chromium Selectively Accumulates in the Rat Hippocampus after 90 Days of Exposure to Cr(VI) in Drinking Water and Induces Age- and Sex-Dependent Metal Dyshomeostasis

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