Metabolism of diclofenac in plants – Hydroxylation is followed by glucose conjugation

Evaluation of biological endpoints in crop plants after exposure to non‐steroidal anti‐inflammatory drugs (NSAIDs): Implications for phytotoxicological assessment of novel contaminants

“…Using an in vitro culture was advantageous as it eliminated effects due to inherent heterogenetic variation, however the authors also acknowledge this as a limitation (Hillis et al, 2008). In another in vitro study, horseradish (Armoracia rusticana) root cells were able to uptake DCF and its human metabolites, but this did not cause any visually detectable effects or tissue damage (Huber et al, 2012); which is in contrast to the findings of the growth study reported herein. This discrepancy may be explained by use of cell cultures as opposed to whole plants, or the use of different test species (A. rusticana vs. R. sativus), although both derive from the same plant family (Brassicaceae).…”

“…A number of studies have demonstrated that large molecules such as pharmaceuticals are able to bioaccumulate in plant cells (Eggen et al, 2011;Herklotz et al, 2010;Karnjanapiboonwong et al, 2011), and that concentrations can change over time, including declining due to metabolism (Boonsaner and Hawker, 2010). This has been demonstrated for a number of the compounds used in this study, namely DCF, NAP and IBU (Calderón-Preciado et al, 2011Huber et al, 2012;Sabourin et al, 2012;Tanoue et al, 2012;Wu et al, 2013). Undertaking co-current uptake and phytotoxicity studies would allow researchers to tease out further details regarding the temporal influence on accumulation, and it may be possible to identify threshold tissue concentrations at which phytotoxicological impacts are large enough to be observed via the use of phytomorphological endpoint measurements.…”

“…Furthermore, and perhaps most importantly, they neglect to account for the influence of the soil system upon bioavailability of the target compound. Several studies that have investigated pharmaceutical uptake by plants, have found different and sometimes opposing effects (Boonsaner and Hawker, 2010;Calderón-Preciado et al, 2011;Cortes et al, 2013;Eggen et al, 2011;Huber et al, 2012), which is likely due to differences in experimental design and therefore compound behaviour and bioavailability (Wu et al, 2013). Therefore the design of an experiment must be chosen to reflect the research question being posed.…”

Plant uptake of pharmaceutical and personal care products from recycled water and biosolids: a review

“…Huber et al (Bartha et al, 2010;Huber et al, 2009Huber et al, , 2012 were among the first to study the metabolism of pharmaceuticals in plant tissues. They proposed that mechanisms for the detoxification of xenobiotics in plants were closely related to those in the mammalian system.…”

“…The conjugated molecules may then undergo phase III, during which storage in the plant vacuole, cleavage/degradation, and formation of bound residues in cell walls or transport within plants may take place. Huber and coworkers exposed barley and a hairy root cell culture of horseradish to diclofenac and acetaminophen, and identified two metabolites of diclofenac in plants (Huber et al, 2012): 4-OHdiclofenac (phase I metabolite) and 4-OH-diclofenac glucopyranoside (phase II metabolite); and three phase II metabolites of acetaminophen (Huber et al, 2009): acetaminophen glucoside, acetaminophen glutathione, and the corresponding cysteine conjugate. In Indian mustard, the same authors observed that concentrations of acetaminophen in plant tissues significantly decreased after a 24-h exposure, which was concurrent to an increase in the glutathione S-transferase (GST) activity in leaves and the appearance of the acetaminophen-glutathione conjugate (Bartha et al, 2010).…”