Abstract
The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera) leaf extract on methoxyacetic acid (MAA) induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.
Highlights
Methoxyacetic acid (MAA, CH3OCH2COOH) is a primary metabolite of ester phthalates, a class of industrial chemicals used in a large variety of consumer products including household products, food and personal care products including agricultural adjuvant, pesticides, cosmetics and perfumes, electronics and pharmaceuticals
The most widely-used phthalates are the di-2-ethyl hexyl phthalate (DEHP)- a low cost plasticizer used in PVC, benzylbutylphthalate (BBzP)- used in the manufacture of foamed PVC used as a flooring material, the diisodecyl phthalate (DIDP)-viscosity controlling reagent, the diisononyl phthalate (DINP) and small phthalates-used as solvents in perfumes and pesticides
Monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono(2ethylhexyl) phthalate (MEHP) have been detected in urine specimens, and their diester parent compounds in house dust samples, from pregnant and lactating women living in New York City [1]
Summary
Methoxyacetic acid (MAA, CH3OCH2COOH) is a primary metabolite of ester phthalates, a class of industrial chemicals used in a large variety of consumer products including household products (building materials, plastic objects, textiles, adhesives, paints and deodorants), food and personal care products including agricultural adjuvant, pesticides, cosmetics and perfumes, electronics (coatings, stabilizers and surfactants) and pharmaceuticals (enteric coating of oral pills, viscosity control agents, surfactants and stabilizers). Whereas MAA caused significant increase in senescence-associated b-galactosidase staining, the number of cells showing senescence like growth arrest (Figures 1C and 1D) declined in the presence of withanone suggesting that the MAA-induced cellular damage caused premature senescence in normal fibroblasts, and withanone protected the cells from such deteriorative phenotype.
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