A toxicological study on photo-degradation products of environmental ibuprofen: Ecological and human health implications

Abstract

Increasing quantities of pharmaceutical waste in the environment have disrupted the balance of ecosystems, and may have subsequent effects on human health. Although a handful of previous studies have shown the impacts of pharmaceutically active compounds on the environment, the toxicological effects of their degradation products remain largely unknown. In the current study, the photo-degradation products of environmental ibuprofen were assessed for both ecotoxicological and human health effects using a series of in vitro assays. Here, six of the major degradation products are synthesized with high purity (>98 %) and characterized with 1 HNMR, 13 CNMR, FT-IR and HRMS. To evaluate human health effects, three gut microbiota species, Lactobacillus acidophilus, Enterococcus faecalis and Escherichia coli, and two human cell lines, HEK293T and HepG2, are exposed to various concentrations of ibuprofen and its degradation products. On L. acidophilus, the ibuprofen degradation product (±)-(2R,3R)-2-(4isobutylphenyl)-5-methylhexan-3-ol shows a greater toxic effect while ibuprofen enhances its growth at lower concentrations. At higher concentrations, ibuprofen shows at least a 2-fold higher toxicity compared to that of its degradation products. However, E. faecalis shows little or no effect upon exposure to these compounds. An induction of the SOS response in E. coli is observed but limited to only ibuprofen and 4-acetylbenzoic acid. In human cell line studies, survival of both HEK293T and HepG2 cell lines is profoundly impaired by the photo-degradation products of (±)-(2R,3R)-2-(4-isobutylphenyl)-5-methylhexan-3-ol, (±)-(2R,3S)-2-(4-isobutylphenyl)-5methylhexan-3-ol, and (±)-1-(4-(1-hydroxy-2methylpropyl)phenyl)ethan-1-one. In this work, the bioluminescence bacterium, Aliivibrio fischeri, is used as a model to assess environmental impact.Both ibuprofen and its degradation products inhibit the growth of this gram-negative bacteria with the primary compound showing the most significant impact. Overall, our results highlight that *

Response of Rhodococcus cerastii IEGM 1278 to toxic effects of ibuprofen

“…The toxicity of IBP to lower and higher plants is described in a few studies [48,50]. At the same time, the majority of ecotoxicological studies are devoted only to IBP itself, while information on detection and toxicity of its partial oxidation products is quite scarce [51][52][53]. There are only a few data indicating negative effects of IBP and its metabolites, other NSAIDs included, on nitrogen fixation, induction of oxidative stress in microorganisms, and destabilization of cell membranes [21,54,55].…”

Enhanced catalytic ozonation of ibuprofen using a 3D structured catalyst with MnO2 nanosheets on carbon microfibers

“…The presence of Ibuprofen in environmental matrices has been attributed to municipal sewage, hospital sewage, pharmaceutical wastewater, and even reclaimed wastewater, and as such Ibuprofen is recognized as a refractory organic pollutant that is recalcitrant to biodegradation process 1 , 2 . The continuous discharge of ibuprofen into the water environment leads to an irreversible accumulation in the environment, which poses severe risks to human health and the environment 3 , 4 . It is urgent to develop technologies that can efficiently degrade ibuprofen in the water environment to minimize its risk.…”

Potential roles of gut microbiota and microbial metabolites in chronic inflammatory pain and the mechanisms of therapy drugs

“…88 At the same time, ibuprofen and its degradation products were found to be toxic to Lactobacillus acidophilus, E. coli, and Clostridium fischeri by in vitro bacterial culture experiments, and inhibited their growth. 89 Aspirin. Aspirin has a good antiinflammatory effect, but its specificity is not strong.…”