nutrients for the plants can be easily screened for root exudates and metabolites
produced in the rhizoplane. A wide array of studies identifying uptake of pharmaceuticals in plants using both approaches can be found in the literature [79]. These
approaches can be used to study the transfer of pharmaceuticals and their metabolites
to edible plants and transformed products when using reclaimed wastewater in
agriculture. Additionally, they may provide useful information about translocation
and distribution of metabolites in plant tissues [38, 43, 48].
4.2 In Vitro Models
Researchers have made use of models to avoid the complexity of soil-grown plant
systems and to simplify their studies. Even though mechanisms like transpirationdriven uptake and translocation or interactions with the soil and plant microbiota are
absent or disturbed in these model systems, they are a viable approach when it comes
to identifying new metabolites and describe metabolic pathways exclusive of plant
cells. Most known models involve the use of cell suspensions of different plant
species [41, 58, 80–83].
In vitro studies can be rapidly set up in order to identify metabolites in plant
tissues by incubating cut stems devoid of their root system or excised leaves or roots
in a solution containing pharmaceuticals and/or metabolites. Pioneering studies who
served to establish the general model of xenobiotic detoxification in plants were
conducted using excised leaves and roots exposed to different herbicides
[84, 85]. Furthermore, by using cut stems or detached leaves, it is possible to
quantify phytotoxicity and plant short-term response towards pharmaceuticals [86].
Pharmaceutical metabolism can be studied also in enzymatic extracts obtained
from plant tissues. Some in vitro studies using enzyme extracts incubated with
pharmaceuticals have found similar metabolic patterns both in radish tissue enzyme
extracts and in the intact plants [27]. Plant enzyme extracts have been used to
investigate metabolism of MFM in specific plant compartments [49] and synthetic
estrogens at specific plant development stages [87].
4.3 Examples of Method Applications
The particularities and complementarities of these different approaches can be
illustrated using CBZ as an example of a recalcitrant pharmaceutical that can be
taken up and metabolized in plants. Wu and coworkers studied CBZ metabolism
using carrot cell suspensions [80]. They could determine that only about 5% of the
initial CBZ amount was metabolized in plant cells and transformed into
CBZ-epoxide and CBZ-10,11-diol (Fig. 12). Both metabolites were also identified
as main metabolites of CBZ in leaves of tomato, cucumber, sweet potato, and carrot
and fruits of cucumber and tomato [31].
Metabolism of Pharmaceuticals in Plants and Their Associated Microbiota
245
produced in the rhizoplane. A wide array of studies identifying uptake of pharmaceuticals in plants using both approaches can be found in the literature [79]. These
approaches can be used to study the transfer of pharmaceuticals and their metabolites
to edible plants and transformed products when using reclaimed wastewater in
agriculture. Additionally, they may provide useful information about translocation
and distribution of metabolites in plant tissues [38, 43, 48].
4.2 In Vitro Models
Researchers have made use of models to avoid the complexity of soil-grown plant
systems and to simplify their studies. Even though mechanisms like transpirationdriven uptake and translocation or interactions with the soil and plant microbiota are
absent or disturbed in these model systems, they are a viable approach when it comes
to identifying new metabolites and describe metabolic pathways exclusive of plant
cells. Most known models involve the use of cell suspensions of different plant
species [41, 58, 80–83].
In vitro studies can be rapidly set up in order to identify metabolites in plant
tissues by incubating cut stems devoid of their root system or excised leaves or roots
in a solution containing pharmaceuticals and/or metabolites. Pioneering studies who
served to establish the general model of xenobiotic detoxification in plants were
conducted using excised leaves and roots exposed to different herbicides
[84, 85]. Furthermore, by using cut stems or detached leaves, it is possible to
quantify phytotoxicity and plant short-term response towards pharmaceuticals [86].
Pharmaceutical metabolism can be studied also in enzymatic extracts obtained
from plant tissues. Some in vitro studies using enzyme extracts incubated with
pharmaceuticals have found similar metabolic patterns both in radish tissue enzyme
extracts and in the intact plants [27]. Plant enzyme extracts have been used to
investigate metabolism of MFM in specific plant compartments [49] and synthetic
estrogens at specific plant development stages [87].
4.3 Examples of Method Applications
The particularities and complementarities of these different approaches can be
illustrated using CBZ as an example of a recalcitrant pharmaceutical that can be
taken up and metabolized in plants. Wu and coworkers studied CBZ metabolism
using carrot cell suspensions [80]. They could determine that only about 5% of the
initial CBZ amount was metabolized in plant cells and transformed into
CBZ-epoxide and CBZ-10,11-diol (Fig. 12). Both metabolites were also identified
as main metabolites of CBZ in leaves of tomato, cucumber, sweet potato, and carrot
and fruits of cucumber and tomato [31].
Metabolism of Pharmaceuticals in Plants and Their Associated Microbiota
245