Effects of a Complex Mixture of Therapeutic Drugs at Environmental Levels on Human Embryonic Cells

Abstract

The potential risk associated with the presence of low levels of pharmaceuticals in aquatic environments is currently under debate. In this study we investigated the effects of 13 drugs merged to mimic both the association and low concentration (ng/L) profiles detected in the environment. The mixture comprised atenolol, bezafibrate, carbamazepine, cyclophosphamide, ciprofloxacin, furosemide, hydrochlorothiazide, ibuprofen, lincomycin, ofloxacin, ranitidine, salbutamol, and sulfamethoxazole. At environmental exposure levels, the drug mix inhibited the growth of human embryonic cells HEK293, with the highest effect observed as a 30% decrease in cell proliferation compared to controls. Pharmaceuticals activated stress-response signaling protein kinases (ERK1/2), and induced overexpression of glutathione-S-transferase P1 gene. No evidence was found for apoptosis or necrosis in HEK293 cells, although morphological changes were observed. The drug mixture effectively stimulated the expression of cell-cycle progression-mediating genes p16 and p21, with a slight accumulation of cells in the G2/M phase of the cell-cycle. Our results suggest that a mixture of drugs at ng/L levels can inhibit cells proliferation by affecting their physiology and morphology. This also suggests that water-borne pharmaceuticals can be potential effectors on aquatic life.

Review of risk from potential emerging contaminants in UK groundwater

“…They used this for a mixture of dioxin and dioxin analogues. Pomati et al (2006; investigated the effects and interactions of a mixture of commonly used pharmaceuticals, including carbamazepine, ibuprofen and sulfamethoxazole at low concentrations, designed to mimic those found in the environment using in vitro tests on human and zebrafish cells. They concluded that a mixture of drugs at ng/L levels can inhibit cell proliferation by affecting their physiology and morphology and that waterborne pharmaceuticals may have an effect on aquatic life.…”

Estimation of Residual Antibiotics in Pharmaceutical Effluents and their Fate in Affected Areas

“…Frequent contact of the bacteria with even minor concentrations of antibiotics can cause the occurrence or persistence of resilient bacteria strains [17][18][19][20][21]. Earlier research showed that the maximum of the antibiotics in the environment showed straight hazardous properties [22,23] and bad effects [24][25][26].…”

Efficient degradation of sulfamethoxazole by the Fe(II)/HSO5− process enhanced by hydroxylamine: Efficiency and mechanism

“…An increasing number of antibiotics are environmentally widespread and routinely found in aquatic environment including effluent of wastewater treatment plant, surface water, even drinking water (Kümmerer, 2009;Rivera-Utrilla et al, 2013), and they are of great concern for their toxicity and potential to induce resistance of drug acting on aquatic ecosystems and human health (Marx et al, 2015;Pomati et al, 2006). Industrial pharmaceutical wastewater treatment plants without effective treatment of antibiotics have become a significant threat for aquatic environment (Larsson, 2007).…”