Chemicals formed in well-done cooked meats may be risk factors for Parkinson’s

Exposure to compounds formed in red meat cooked at high temperatures may be a risk factor for Parkinson’s disease, NIEHS-funded scientists found. Research suggests that red meat may contribute to development of the disease; this study uncovered the potential mechanisms driving that relationship.

The compounds, called heterocyclic aromatic amines (HAAs), are transformed in the body to form toxic metabolic byproducts. Some of these byproducts can damage the nervous system by causing mitochondrial dysfunction, a known driver of Parkinson’s disease.

For this study, the researchers used a neuronal cell line widely employed in Parkinson’s disease research because of its similarities to nerve cells in the body. They first exposed the cells to three HAAs formed in well-done cooked meats. They also exposed the cells to HAA metabolic byproducts called N-hydroxylated metabolites. Next, they assessed cell death, DNA damage, and mitochondrial dysfunction.

Among all chemicals, only one — the N-hydroxylated PhIP metabolite — caused significant cell death. This compound was a thousandfold more toxic than the other chemicals. Although all three HAAs formed DNA adducts — meaning they attached to DNA in a way that might induce mutations — levels were 300-fold higher for PhIP. In addition, PhIP adduct levels were higher and more persistent in mitochondrial DNA compared with nuclear DNA. Exposure to PhIP metabolites also resulted in mitochondrial dysfunction, which was indicated by a decrease in mitochondrial enzyme activity.

According to the authors, these findings suggest that PhIP and its N-hydroxylated metabolite cause mitochondrial dysfunction, and that consuming well-done cooked red meat containing PhIP is a potential risk factor for Parkinson’s disease. (MA)

Citation: Bellamri M, Brandt K, Cammerrer K, Syeda T, Turesky RJ, Cannon JR. 2023. Nuclear DNA and mitochondrial damage of the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in human neuroblastoma cells. Chem Res Toxicol; doi: 10.1021/acs.chemrestox.3c00109. [Online 8 July 2023]

Algal toxin may harm women’s reproductive health

Toxins produced by cyanobacteria, an aquatic bacterium also known as blue-green algae, may harm women’s reproductive health, according to NIEHS-funded researchers. Cyanobacteria can produce toxins called microcystins (MCs) that people may encounter in contaminated food or water, or during water sports. A type of MC called MC-LR has been linked to a range of adverse health outcomes, but much remains unknown about how it may affect women’s reproductive health.

To address this gap, researchers examined how MC-LR affects follicles, which are small sacs within the ovaries, and ovulation. During the menstrual cycle, hormones prompt follicles to mature and release an egg in a process called ovulation.

The researchers exposed mice, a cell-based 3D model of a follicle, and hormone-producing human ovarian cells to MC-LR at a range of doses. They then assessed changes in gene and protein expression to determine the effects of MC-LR on follicle maturation, hormone secretion, and ovulation.

Compared with controls, mice exposed to long-term, low-dose MC-LR had 50% fewer corpora lutea — hormone-secreting structures that form after ovulation — suggesting that the algal toxin disrupted the ovulation process. When stimulated to produce more than one egg within a cycle, exposed mice had significantly fewer ovulated eggs compared with unexposed mice. Exposed mice accumulated MC-LR in the ovaries and had significantly lower expression of genes important in follicle maturation. Findings from the 3D model and human cell experiments showed that MC-LR reduced activity of a protein required for follicle maturation.

The study demonstrates how MC-LR disrupts follicle maturation and ovulation, and it suggests that exposure to the toxin, particularly during cyanobacterial bloom seasons, may heighten women’s risk of ovarian disorders, according to the authors. (MA)

Citation: Wang Y, Pattarawat P, Zhang J, Kim E, Zhang D, Fang M, Jannaman EA, Yuan Y, Chatterjee S, Kim JJ, Scott GI, Zhang Q, Xiao S. 2023. Effects of cyanobacterial harmful algal bloom toxin microcystin-LR on gonadotropin-dependent ovarian follicle maturation and ovulation in mice. Environ Health Perspect 131(6):67010.

Everyday air pollution can harm brain development in adolescents

NIEHS-funded researchers found that young adolescents’ brains developed differently when they were exposed to air pollution during childhood, even when pollutant levels were well below national air quality standards. This study is the first to assess how air pollution may affect the growth of children’s functional networks, which pass information between different regions of the brain and are essential for cognitive and emotional development.

The study included approximately 9,500 children from ages 9 to 13 who were enrolled in the Adolescent Brain Cognitive Development Study, a long-term pediatric health study. At the beginning of the study and two years later, the team used magnetic resonance imaging to examine networks between different brain regions in each participant. Using each child’s home address and environmental data sets, they also estimated annual exposure levels to fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2).

The researchers found that greater exposure to PM2.5 was linked to increased connectivity among brain regions, whereas more exposure to NO2 predicted decreased connectivity across development. Exposure to higher O3 levels was associated with more connections over time within the cortex, specifically in regions typically engaged during passive rest and mind-wandering. However, higher O3 exposure was linked to fewer connections between the cortex and brain regions that regulate emotions and memory as children aged. These changes in network connectivity may lead to dysregulation of various brain processes, making children more susceptible to neurological problems.

These findings demonstrate that low-level air pollution exposure in childhood altered brain network patterns over time. According to the authors, the results can help inform the development of stricter air quality standards to protect health. (LS)

Citation: Cotter DL, Campbell CE, Sukumaran K, McConnell R, Berhane K, Schwartz J, Hackman DA, Ahmadi H, Chen JC, Herting MM. 2023. Effects of ambient fine particulates, nitrogen dioxide, and ozone on maturation of functional brain networks across early adolescence. Environ Int 177:108001.

Stricter drinking water standards for arsenic benefit highly exposed populations

A federal regulation lowering the amount of arsenic allowed in public water systems reduced arsenic exposure among communities across the U.S., NIEHS-funded scientists found. Reductions were greatest in places with the highest levels of arsenic in water.

In 2006, the U.S. Environmental Protection Agency reduced the maximum amount of arsenic allowed in public water systems from 50 to 10 micrograms per liter. In this study, the researchers used data from roughly 8,500 participants in the National Health and Nutrition Examination Survey — an annual health assessment of people in the U.S. — to track whether the new standard lowered participants’ arsenic exposures. To determine arsenic exposure, they tracked urine levels of a metabolite, or byproduct, of arsenic processing in the body. The researchers then compared changes in metabolite levels before and after the regulation was implemented. They organized the data by region, race and ethnicity, education, and county-level water arsenic concentration.

Among one third of the participants classified as most exposed to arsenic at baseline, the team observed an average 9% decrease in urinary metabolite levels from 2003-2014. Within that group, they saw even greater reductions among Mexican American participants, people living in the South and West, and those with the least education.

According to the authors, these findings suggest that federal water regulations for contaminants can most benefit the highest exposed groups and can help reduce disparities in drinking water quality. (LS)

Citation: Spaur M, Bostick BC, Chillrud SN, Factor-Litvak P, Navas-Acien A, Nigra AE. 2023. Impact of lowering the US maximum contaminant level on arsenic exposure: differences by race, region, and water arsenic in NHANES 2003-2014. Environ Pollut 333:122047.