References
-
Carter, L. J., Chefetz, B., Abdeen, Z. & Boxall, A. Emerging investigator series: towards a framework for establishing the impacts of pharmaceuticals in wastewater irrigation systems on agro-ecosystems and human health. Environ. Sci. Process Impacts. 21, 605–622 (2019).
-
Patel, M. et al. Pharmaceuticals of Emerging Concern in Aquatic Systems: Chemistry, Occurrence, Effects, and Removal Methods. Chem. Rev. 119, 3510–3673 (2019).
-
Poudel, S., Shrestha, A., Kandel, N., Adhikari, S. & Paudel, S. R. A Review of Reclaimed Water Reuse for Irrigation in South Asian Countries. ACS ES&T Wat. 3, 3790–3806 (2023).
-
Wang, Y. et al. Antiepileptic drug carbamazepine promotes horizontal transfer of plasmid-borne multi-antibiotic resistance genes within and across bacterial genera. ISME J. 13, 509–522 (2019).
-
Nguyen, M. K. et al. Occurrence, fate, and potential risk of pharmaceutical pollutants in agriculture: Challenges and environmentally friendly solutions. Sci. Total Environ. 899, 165323 (2023).
-
Garduño-Jiménez, A. L. & Carter, L. J. Insights into mode of action mediated responses following pharmaceutical uptake and accumulation in plants. Front. Agron. 5, 1293555 (2024).
-
Machado, T. M., Töpfer, N. & Soltani, F. Metabolic modelling: Insights into the machine room of plant metabolism. J Plant. Physiol. 154584 (2025).
-
Cordes, H., Thiel, C., Baier, V., Blank, L. M. & Kuepfer, L. Integration of genome-scale metabolic networks into whole-body PBPK models shows phenotype-specific cases of drug-induced metabolic perturbation. npj Syst. Biol. Appl. 4, 10 (2018).
-
Sahoo, S., Haraldsdóttir, H. S., Fleming, R. M. T. & Thiele, I. Modeling the effects of commonly used drugs on human metabolism. FEBS J. 282, 297–317 (2015).
-
Sandermann, H., Diesperger, H. & Scheel, D. Metabolism of Xenobiotics by Plant Cell Cultures. in Plant Tissue Culture and Its Bio-technological Application (eds Barz, W., Reinhard, E. & Zenk, M. H.) Proceedings in Life Sciences 178–196 Springer, Berlin, Heidelberg, (1977).
-
Malchi, T., Eyal, S., Czosnek, H., Shenker, M. & Chefetz, B. Plant pharmacology: Insights into in-planta kinetic and dynamic processes of xenobiotics. Crit. Rev. Environ. Sci. Technol. 52, 3525–3546 (2022).
-
Coleman, J., Blake-Kalff, M. & Davies, E. Detoxification of xenobiotics by plants: chemical modification and vacuolar compartmentation. Trends Plant Sci. 2, 144–151 (1997).
-
Kaushik, G. et al. Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers. Biochem. Biophys. Res. Commun. 474 (2), 291–295 (2016).
-
Gorovits, R., Sobol, I., Akama, K., Chefetz, B. & Czosnek, H. Pharmaceuticals in treated wastewater induce a stress response in tomato plants. Sci. Rep. 10, 1856 (2020).
-
Riemenschneider, C., Seiwert, B., Moeder, M., Schwarz, D. & Reemtsma, T. Extensive Transformation of the Pharmaceutical Carbamazepine Following Uptake into Intact Tomato Plants. Environ. Sci. Technol. 51, 6100–6109 (2017).
-
Gerlin, L., Cottret, L., Escourrou, A., Genin, S. & Baroukh, C. A multi-organ metabolic model of tomato predicts plant responses to nutritional and genetic perturbations. Plant. Physiol. 188, 1709–1723 (2022).
-
Shiade, S. R. G. et al. Plant metabolites and signaling pathways in response to biotic and abiotic stresses: Exploring bio stimulant applications. Plant. Stress. 12, 100454 (2024).
-
Dordio, A. V. et al. Evaluation of carbamazepine uptake and metabolization by Typha spp., a plant with potential use in phytotreatment. Bioresour. Technol. 102, 7827–7834 (2011).
-
Schröder, P. Exploiting Plant Metabolism for the Phytoremediation of Organic Xenobiotics. in Phytoremediation: Methods and Reviews (ed. Willey, N.) Methods in Biotechnology 23, 251–263 (Humana Press, Totowa, NJ, 2007).
-
Lu, Z. Y. et al. Unmasking Spatial Heterogeneity in Phytotoxicology Mechanisms Induced by Carbamazepine by Mass Spectrometry Imaging and Multiomics Analyses. Environ. Sci. Technol. 58, 13986–13994 (2024).
-
Sauvêtre, A., May, R., Harpaintner, R., Poschenrieder, C. & Schröder, P. Metabolism of carbamazepine in plant roots and endophytic rhizobacteria isolated from Phragmites australis. J. Hazard. Mater. 342, 85–95 (2018).
-
Lieven, C. et al. MEMOTE for standardized genome-scale metabolic model testing. Nat. Biotechnol. 38, 272–276 (2020).
-
Raman, K. et al. FROG analysis Ensures the Reproducibility of Genome Scale Metabolic Models. Preprint bioRxiv. https://doi.org/10.1101/2024.09.24.614797 (2024).
-
Heirendt, L. et al. Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v.3.0. Nat. Protoc. 14, 639–702 (2019).
-
Nanda, P., Patra, P., Das, M. & Ghosh, A. Reconstruction and analysis of genome-scale metabolic model of weak Crabtree positive yeast Lachancea kluyveri. Sci. Rep. 10, 16314 (2020).
-
García-García, A. L. et al. Pure Organic Active Compounds Against Abiotic Stress: A Biostimulant Overview. Front. Plant Sci. 11, 575829 (2020).
-
Jiménez-Arias, D. et al. A Beginner’s Guide to Osmoprotection by Biostimulants. Plants. 10, 363 (2021).
-
Thorn, C. F. et al. PharmGKB summary: carbamazepine pathway. Pharmacogenet. Genomics. 21, 906 (2011).
-
Whirl-Carrillo, M. et al. An Evidence-Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine. Clin. Pharmacol. Ther. 110, 563–572 (2021).
-
Meech, R., Miners, J. O., Lewis, B. C. & Mackenzie, P. I. The glycosidation of xenobiotics and endogenous compounds: Versatility and redundancy in the UDP glycosyltransferase superfamily. Pharmacol. Ther. 134, 200–218 (2012).
-
Leitão, I. et al. Stress response of lettuce (Lactuca sativa) to environmental contamination with selected pharmaceuticals: A proteomic study. J. Proteomics. 245, 104291 (2021).
-
Landa, P., Prerostova, S., Langhansova, L., Marsik, P. & Vanek, T. Transcriptomic response of Arabidopsis thaliana (L.) Heynh. Roots to ibuprofen. Int. J. Phytoremediation. 19, 695–700 (2017).
-
Landa, P. et al. Transcriptomic response of Arabidopsis thaliana roots to naproxen and praziquantel. Ecotox. Environ. Safe. 166, 301–310 (2018).
-
Righetti, L. et al. Thinking Out of the Box: On the Ability of Zea mays L. to Biotrasform Aflatoxin B1 Into Its Modified Forms. Front. Plant Sci. 11, 599158 (2021).
-
Zhang, Y. et al. Enhanced phytoremediation of mixed heavy metal (mercury)–organic pollutants (trichloroethylene) with transgenic alfalfa co-expressing glutathione S-transferase and human P450 2E1. J. Hazard. Mater. 260, 1100–1107 (2013).
-
Groot, C. C. de, Marcelis, L. F. M., Boogaard, R. van den & Lambers, H. Interactive effects of nitrogen and irradiance on growth and partitioning of dry mass and nitrogen in young tomato plants. Funct. Plant Biol. 29, 1319–1328 (2002).
-
Carter, L. J., Williams, M., Böttcher, C. & Kookana, R. S. Uptake of Pharmaceuticals Influences Plant Development and Affects Nutrient and Hormone Homeostases. Environ. Sci. Technol. 49, 12509–12518 (2015).
-
Leitão, I. et al. Antioxidative response of lettuce (Lactuca sativa) to carbamazepine-induced stress. Environ. Sci. Pollut. Res. 28, 45920–45932 (2021).
-
Knudsen, C., Gallage, N. J., Hansen, C. C., Møller, B. L. & Laursen, T. Dynamic metabolic solutions to the sessile life style of plants. Nat. Prod. Rep. 35, 1140–1155 (2018).
-
Shameer, S., Ratcliffe, R. G. & Sweetlove, L. J. Leaf Energy Balance Requires Mitochondrial Respiration and Export of Chloroplast NADPH in the Light. Plant Physiol. 180, 1947–1961 (2019).
-
Varma, A. & Palsson, B. O. Metabolic Flux Balancing: Basic Concepts, Scientific and Practical Use. Nat. Biotechnol. 12, 994–998 (1994).
-
Kauffman, K. J., Prakash, P. & Edwards, J. S. Advances in flux balance analysis. Curr. Opin. Biotechnol. 14, 491–496 (2003).
-
Raman, K. & Chandra, N. Flux balance analysis of biological systems: applications and challenges. Brief. Bioinform. 10, 435–449 (2009).
-
Wahman, R., Sauvêtre, A., Schröder, P., Moser, S. & Letzel, T. Untargeted Metabolomics Studies on Drug-Incubated Phragmites australis Profiles. Metabolites. 11, 2 (2020).
-
Chowdhury, N. B. et al. Dissecting the metabolic reprogramming of maize root under nitrogen-deficient stress conditions. J. Exp. Bot. 73, 275–291 (2022).
-
Knight, E. R., Carter, L. J. & McLaughlin, M. J. Bioaccumulation, uptake, and toxicity of carbamazepine in soil–plant systems. Environ. Toxicol. Chem. 37, 1122–1130 (2018).
-
Voss, I., Sunil, B., Scheibe, R. & Raghavendra, A. S. Emerging concept for the role of photorespiration as an important part of abiotic stress response. Plant Biol. 15, 713–722 (2013).
-
Akram, N. A., Shafiq, F. & Ashraf, M. Ascorbic Acid-A Potential Oxidant Scavenger and Its Role in Plant Development and Abiotic Stress Tolerance. Front. Plant Sci. 8, 613 (2017).
-
Ofaim, S. et al. Genome-scale reconstruction of Paenarthrobacter aurescens TC1 metabolic model towards the study of atrazine bioremediation. Sci. Rep. 10, 13019 (2020).
-
Dhakar, K. et al. Strategies for Enhancing in vitro Degradation of Linuron by Variovorax sp. Strain SRS 16 Under the Guidance of Metabolic Modeling. Front. Bioeng. Biotechnol. 9, 602464 (2021).
-
Kahlaoui, B. et al. Response of two tomato cultivars to field-applied proline under irrigation with saline water: Growth, chlorophyll fluorescence and nutritional aspects. Photosynthetica. 52, 421–429 (2014).
-
Pascual, L. S., López-Climent, M. F., Segarra-Medina, C., Gómez-Cadenas, A. & Zandalinas, S. I. Exogenous spermine alleviates the negative effects of combined salinity and paraquat in tomato plants by decreasing stress-induced oxidative damage. Front. Plant Sci. 14, 1193207 (2023).
-
Todaka, D. et al. Application of ethanol alleviates heat damage to leaf growth and yield in tomato. Front. Plant Sci. 15, 1325365 (2024).
-
M. Ali, R., Elfeky, S. S. & Abbas, H. Response of Salt Stressed Ricinus communis L. To Exogenous Application of Glycerol and/or Aspartic acid. J. Biol. Sci. 8, 171–175 (2008).
-
Kaya, C., Aydemir, S., Sonmez, O., Ashraf, M. & Dikilitas, M. Regulation of growth and some key physiological processes in salt-stressed maize (Zea mays L.) plants by exogenous application of asparagine and glycerol. Acta Bot. Croat. 72, 157–168 (2013).
-
Raoufi, A., Rahemi, M. & Akbari, M. Glycerol foliar application improves salt tolerance in three pistachio rootstocks. J. Saudi Soc. Agri Sci. 19 (6), 426–437 (2020).
-
Hosseinifard, M. et al. Contribution of Exogenous Proline to Abiotic Stresses Tolerance in Plants: A Review. Int. J. Mol. Sci. 23, 5186 (2022).
-
Li, Z. et al. Global Metabolites Reprogramming Induced by Spermine Contributing to Salt Tolerance in Creeping Bentgrass. Int. J. Mol. Sci. 23, 4472 (2022).
-
Bashir, K. et al. Ethanol-Mediated Novel Survival Strategy against Drought Stress in Plants. Plant Cell Physiol. 63, 1181–1192 (2022).
-
Nguyen, H. M. et al. Ethanol Enhances High-Salinity Stress Tolerance by Detoxifying Reactive Oxygen Species in Arabidopsis thaliana and Rice. Front. Plant Sci. 8, 1001 (2017).
-
Das, A. K. et al. Ethanol Treatment Enhances Physiological and Biochemical Responses to Mitigate Saline Toxicity in Soybean. Plants. 11, 272 (2022).
-
Rahman, M. M. et al. Ethanol Positively Modulates Photosynthetic Traits, Antioxidant Defense and Osmoprotectant Levels to Enhance Drought Acclimatization in Soybean. Antioxidants. 11, 516 (2022).
-
Bai, J., Jin, K., Qin, W., Wang, Y. & Yin, Q. Proteomic Responses to Alkali Stress in Oats and the Alleviatory Effects of Exogenous Spermine Application. Front. Plant Sci. 12, 627129 (2021).
-
Nahar, K. et al. Physiological and biochemical mechanisms of spermine-induced cadmium stress tolerance in mung bean (Vigna radiata L.) seedlings. Environ. Sci. Pollut. Res. 23, 21206–21218 (2016).
-
Li, Y. et al. Glycerol-Induced Powdery Mildew Resistance in Wheat by Regulating Plant Fatty Acid Metabolism, Plant Hormones Cross-Talk, and Pathogenesis-Related Genes. Int. J. Mol. Sci. 21, 673 (2020).
-
Raza, A. et al. Assessment of proline function in higher plants under extreme temperatures. Plant. Biol. 25, 379–395 (2023).
-
Heberle, H., Meirelles, G. V., da Silva, F. R., Telles, G. P. & Minghim, R. InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams. BMC Bioinformatics. 16, 169 (2015).
-
Guan, C. et al. Proline Biosynthesis Enzyme Genes Confer Salt Tolerance to Switchgrass (Panicum virgatum L.) in Cooperation With Polyamines Metabolism. Front. Plant Sci. 11, 46 (2020).
-
Hasan, M. M. et al. Spermine: Its Emerging Role in Regulating Drought Stress Responses in Plants. Cells. 10, 261 (2021).
-
Chowdhury, N. B. et al. A multi-organ maize metabolic model connects temperature stress with energy production and reducing power generation. iScience. 26, 108400 (2023).
-
Gorovits, R. et al. Interplay of stress responses to carbamazepine treatment, whitefly infestation and virus infection in tomato plants. Plant Stress. 1, 100009 (2021).
-
Mascellani, A. et al. Biochemical and physiological changes in Zea mays L. after exposure to the environmental pharmaceutical pollutant carbamazepine. Chemosphere. 329, 138689 (2023).
