30
Jun
Zebrafish Study Links Glyphosate Exposure to Heart Damage Through Aging and Reduced Creation of Cardiac Muscle Cells
(Beyond Pesticides, June 30, 2023) Exposure to environmentally relevant concentrations of the herbicide glyphosate (GLY) has the potential to induce heart damage (cardiotoxicity) through the aging (senescence) of cells and a reduction of the number of rapidly increasing (proliferating) cells, according to a study published in Ecotoxicology and Environmental Safety. Specifically, glyphosate induces toxic effects on cardiomyocytes (cardiac muscles) responsible for contractions that pump the blood. Cardiovascular (heart) disease (CVD) is one of the leading causes of death in the U.S., with approximately 700,000 people dying annually of heart disease, equating to 25% of all U.S. deaths. Additionally, heart conditions are one leading cause of disability in the U.S.
Research has shown that environmental pollutant exposure can increase the risk of developing cardiovascular disease, including stroke, heart attack, heart failure, atrial fibrillation, and cardiac arrest. Considering chemical exposure exacerbates adverse disease effects, reviews like these highlight the significance of evaluating synergism between diseases and toxic chemicals to safeguard human health. The study warns, “Our findings offer important information regarding the potential mechanisms of GLY cardiotoxicity toxicity. Notably, our study provides new insights into the relationship between GLY and senescence. Cardiac dysfunction of GLY to non-target organisms need to be noted in future study. Our study raises concerns about the cardiovascular health of populations chronically exposed to GLY.”
Glyphosate-based herbicides (GBHs) are the most commonly used pesticides globally, readily contaminating soil, water, and food resources. Although GBHs’ ubiquitous nature has links to various chronic diseases, including cancers (e.g., non-Hodgkin lymphoma), and reproductive and developmental dysfunctions, much less research considers exposure effects on cardiovascular (heart) health.
For the experiment, researchers obtained AC16 human cardiomyocytes from American Type Culture Collection (Rockville, Maryland) and the Tg(myl7:nDsRed) and Tg(myl7:eGFP) transgenic line in a male and female zebrafish from the Chinese Zebrafish Resource Center. The researchers exposed the AC16 and zebrafish cardiomyocyte cells to various concentrations of glyphosate. The results find low concentrations (30 μg/L) of glyphosate structurally enlarged AC16 cardiac muscle cells, indicating a senescent (aging) state. Additionally, the increased expression of P16, P21, and P53 proteins following glyphosate exposure further highlights glyphosate’s role in the senescence of AC16 cells (senescence induction). However, the mechanical mechanism involved in glyphosate-induced senescence of AC16 cardiomyocytes was through reactive oxygen species (ROS)-mediated DNA damage. In zebrafish, cardiomyocyte reduction occurs from the notch signaling pathway (intracellular signaling mechanism that plays a role in vascular development) stimulated by glyphosate, which decreases the proliferation capacity of these cardiac muscle cells. Like AC16 cardiomyocytes, the cardiotoxicity of glyphosate in zebrafish has links to DNA damage and mitochondrial damage. In both human and zebrafish cardiomyocytes, glyphosate causes endoplasmic reticulum (ER) stress by hampering ER protein processing signals, thus activating the PERK-eIF2α-ATF4 pathway responsible for autophagy (cellular breakdown of old, damaged, dysfunctional components) gene transcription. Thus, the results suggest the underlying mechanism involved in cardiotoxicity is ER stress from glyphosate exposure.
Overall, symptoms of cardiotoxicity include weakened heart muscles (myocarditis), elevated levels of proteins (troponins) in heart muscles, abnormal electrical activity in the heart (ECG), heart attack (myocardial infarction), heart failure (systolic dysfunction), blood clotting impairment (coagulopathy), inflamed blood vessels (endotheliitis), heart cell death (necroptosis), vascular damage, hypertrophy, fluid leakage around heart sac (myocardial edema) and tissue scarring of the heart (myocardial fibrosis). Although epidemiological studies highlight ambient pollutants, like air pollution at the primary residence, as a major constituent of heart diseases, many individuals continuously experience exposure to contaminants in the workplace. Risks linked to heart diseases and occupational chemical exposure are less studied and lack adequate policies and practices that mitigate exposure, especially for those disproportionately affected by toxic pesticides.
Because of the disproportionate risk in people of color communities, the contamination and poisoning associated with glyphosate is an environmental justice issue. However, pesticide exposure affects a large portion of the population, and the intermediate relationship between heart illnesses and pesticides needs more research. With the range of ever-present environmental hazards, advocates argue that regulators act quickly and embrace a precautionary approach.
Almost five decades of extensive glyphosate-based herbicide use (e.g., Roundup) has put human, animal, and environmental health at risk. Glyphosate has been the subject of extensive controversy about its safety for humans, non-human organisms, and ecosystems. Science and environmental advocates have noted the multiple risks that glyphosate use represents, with Beyond Pesticides listing glyphosate as having endocrine, reproductive, neurotoxic, hepatic, renal, developmental, and carcinogenic effects on human health. The chemical’s ubiquity threatens 93 percent of all U.S. endangered species, resulting in biodiversity loss and ecosystem disruption (e.g., soil erosion and loss of services). Exposure to GBHs has implications for specific alterations in microbial gut composition and trophic cascades. Past studies find a strong association between glyphosate exposure and the development of various health anomalies, including cancer, Parkinson’s disease, and autism. Although the U.S. Environmental Protection Agency (EPA) classifies glyphosate herbicides as “not likely to be carcinogenic to humans,” stark evidence, like from the World Health Organization (WHO), demonstrates links to cancers, such as non-Hodgkin lymphoma. Thus, EPA’s classification can perpetuate adverse impacts among vulnerable individuals like pregnant women and infants.
This study provides one of the first understandings of the mechanism involved in glyphosate-mediated cardiotoxicity. Cellular aging and restricted cardiomyocyte proliferation are significant risk factors for heart failure. During the progression of heart failure, the damaged cardiac cells are incapable of regenerating themselves, and thus fibrotic tissue replaces new cardiomyocytes. The notch signaling pathway is essential for the increasing growth and development of cardiomyocytes, playing an important role in cardiac development. However, glyphosate reduces cardiomyocytes’ growth and development capacity through this notch pathway, decreasing the number of cardiomyocytes.
Glyphosate is far from the only pesticide with cardiotoxic effects. Organophosphate (OP) insecticides can disrupt redox reactions (oxidative state changes), Renin-Angiotensin System (RAS) responsible for water and sodium (liquid) homeostasis, blood pressure, cardiac physiology, and proteins for signaling cells (cytokine) to produce the cardiotoxic symptoms. Exposure to specific OPs like malathion, paraoxon, and chlorpyrifos stimulates ROS, cardiac-lipid peroxidation (oxidative degradation of lipids leading to lipoxidation, which plays a role in the onset of heart diseases), and protein damage in heart tissues. Like glyphosate-mediated cardiovascular effects, the subcellular alterations in cardiologic function from OP exposure led to various aforementioned heart diseases.
Cardiovascular disease is becoming increasingly prevalent, and understanding the risks pesticide exposure plays in disease development is essential to consider. With too many illnesses in the U.S. associated with pesticide exposure, eliminating pesticide use is critical for safeguarding public health and addressing cost burdens for local communities. Policies should enforce stricter pesticide regulations and increase research on the long-term impacts of pesticide exposure, while advancing practices and products that are compatible with organic systems and regenerative. Beyond Pesticides tracks the most recent studies on pesticide exposure through our Pesticide-Induced Diseases Database (PIDD). This database supports the clear need for strategic action to shift from pesticide dependency. For more information on pesticide-related illnesses, see PIDD pages on cardiovascular disease, cancer, and other diseases. Learn more about how pesticides can adversely affect human and environmental health by reading Beyond Pesticides’ journal, Pesticides and You article “Highly Destructive Pesticide Effects Unregulated.”
One way to reduce human and environmental contamination from pesticides is to buy, grow, and support organic. Considering 90 percent of Americans have at least one pesticide compound in their body, primarily from dietary exposure, including food and drinking water, advocates maintain that current restrictions on their use must adequately detect and assess total chemical contaminants. Thus, Beyond Pesticides advocates a precautionary approach to pest management in land management and agriculture by transiting to organic. Furthermore, given the wide availability of non-pesticidal alternative strategies, families, chemical occupational workers, and the agricultural sector can apply these methods to promote a safe and healthy environment. For more information on the benefits of organic, see the Beyond Pesticides webpage, Health Benefits of Organic Agriculture.
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
