Paracetamol ecotoxicological bioassay using the bioindicators Lens culinaris Med. and Pisum sativum L
Paracetamol is one of the most widely used drugs worldwide, yet its environmental presence and hazardous impact on nontarget organisms could rapidly increase. In this study, the possible cytotoxic efects of paracetamol were evaluated using two bioindicator plants Lens culinaris and Pisum sativum. Co...
- Autores:
-
SALAZAR MERCADO, SEIR ANTONIO
VEGA GALVIS, DIANA GABRIELA
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2023
- Institución:
- Universidad Francisco de Paula Santander
- Repositorio:
- Repositorio Digital UFPS
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.ufps.edu.co:ufps/6823
- Acceso en línea:
- https://repositorio.ufps.edu.co/handle/ufps/6823
- Palabra clave:
- Binucleate cell
Cell abnormalities
Pharmacological compounds
Mitotic inhibition
Micronuclei
- Rights
- openAccess
- License
- Esta bajo una licencia CC BY (licencia Creative Commons Attribution 4.0 International)
id |
RUFPS2_8bb3dc50c7bd66e355098878bde32798 |
---|---|
oai_identifier_str |
oai:repositorio.ufps.edu.co:ufps/6823 |
network_acronym_str |
RUFPS2 |
network_name_str |
Repositorio Digital UFPS |
repository_id_str |
|
dc.title.eng.fl_str_mv |
Paracetamol ecotoxicological bioassay using the bioindicators Lens culinaris Med. and Pisum sativum L |
title |
Paracetamol ecotoxicological bioassay using the bioindicators Lens culinaris Med. and Pisum sativum L |
spellingShingle |
Paracetamol ecotoxicological bioassay using the bioindicators Lens culinaris Med. and Pisum sativum L Binucleate cell Cell abnormalities Pharmacological compounds Mitotic inhibition Micronuclei |
title_short |
Paracetamol ecotoxicological bioassay using the bioindicators Lens culinaris Med. and Pisum sativum L |
title_full |
Paracetamol ecotoxicological bioassay using the bioindicators Lens culinaris Med. and Pisum sativum L |
title_fullStr |
Paracetamol ecotoxicological bioassay using the bioindicators Lens culinaris Med. and Pisum sativum L |
title_full_unstemmed |
Paracetamol ecotoxicological bioassay using the bioindicators Lens culinaris Med. and Pisum sativum L |
title_sort |
Paracetamol ecotoxicological bioassay using the bioindicators Lens culinaris Med. and Pisum sativum L |
dc.creator.fl_str_mv |
SALAZAR MERCADO, SEIR ANTONIO VEGA GALVIS, DIANA GABRIELA |
dc.contributor.author.none.fl_str_mv |
SALAZAR MERCADO, SEIR ANTONIO VEGA GALVIS, DIANA GABRIELA |
dc.subject.proposal.eng.fl_str_mv |
Binucleate cell Cell abnormalities Pharmacological compounds Mitotic inhibition Micronuclei |
topic |
Binucleate cell Cell abnormalities Pharmacological compounds Mitotic inhibition Micronuclei |
description |
Paracetamol is one of the most widely used drugs worldwide, yet its environmental presence and hazardous impact on nontarget organisms could rapidly increase. In this study, the possible cytotoxic efects of paracetamol were evaluated using two bioindicator plants Lens culinaris and Pisum sativum. Concentrations of 500, 400, 300, 200, 100, 50, 25, 5, 1 mg L−1, and a control (distilled water) were used for a total of 10 treatments, which were subsequently applied on seeds of Lens culinaris Med. and Pisum sativum L.; after 72 h of exposure, root growth, mitotic index, percentage of chromosomal abnormalities, and the presence of micronucleus were evaluated. The cytotoxic efect of paracetamol on L. culinaris and P. sativum was demonstrated, reporting the inhibition of root growth, the presence of abnormalities, and a signifcant micronucleus index at all concentrations used, which shows that this drug has a high degree of toxicity. |
publishDate |
2023 |
dc.date.issued.none.fl_str_mv |
2023-03-18 |
dc.date.accessioned.none.fl_str_mv |
2024-04-05T13:39:58Z |
dc.date.available.none.fl_str_mv |
2024-04-05T13:39:58Z |
dc.type.spa.fl_str_mv |
Artículo de revista |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.content.spa.fl_str_mv |
Text |
dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/ART |
dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
http://purl.org/coar/resource_type/c_6501 |
status_str |
publishedVersion |
dc.identifier.uri.none.fl_str_mv |
https://repositorio.ufps.edu.co/handle/ufps/6823 |
dc.identifier.doi.none.fl_str_mv |
10.1007/s11356-023-26475-7 |
url |
https://repositorio.ufps.edu.co/handle/ufps/6823 |
identifier_str_mv |
10.1007/s11356-023-26475-7 |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Mercado, SAS, Galvis, DGV Bioensayo ecotoxicológico de paracetamol utilizando los bioindicadores Lens culinaris Med. y Pisum sativum L. Environ Sci Pollut Res 30 , 61965–61976 (2023). https://doi.org/10.1007/s11356-023-26475-7 |
dc.relation.citationedition.spa.fl_str_mv |
Vol.30 (2023) |
dc.relation.citationendpage.spa.fl_str_mv |
61976 |
dc.relation.citationissue.spa.fl_str_mv |
(2023) |
dc.relation.citationstartpage.spa.fl_str_mv |
61965 |
dc.relation.citationvolume.spa.fl_str_mv |
30 |
dc.rights.eng.fl_str_mv |
Esta bajo una licencia CC BY (licencia Creative Commons Attribution 4.0 International) |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.uri.spa.fl_str_mv |
https://creativecommons.org/licenses/by/4.0/ |
dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
dc.rights.creativecommons.spa.fl_str_mv |
Atribución 4.0 Internacional (CC BY 4.0) |
rights_invalid_str_mv |
Esta bajo una licencia CC BY (licencia Creative Commons Attribution 4.0 International) https://creativecommons.org/licenses/by/4.0/ Atribución 4.0 Internacional (CC BY 4.0) http://purl.org/coar/access_right/c_abf2 |
eu_rights_str_mv |
openAccess |
dc.format.extent.spa.fl_str_mv |
12 Páginas |
dc.format.mimetype.spa.fl_str_mv |
application/pdf |
dc.publisher.spa.fl_str_mv |
Environmental Science and Pollution Research |
dc.source.spa.fl_str_mv |
https://link.springer.com/article/10.1007/s11356-023-26475-7#article-info |
institution |
Universidad Francisco de Paula Santander |
bitstream.url.fl_str_mv |
https://repositorio.ufps.edu.co/bitstream/ufps/6823/1/Paracetamol%20ecotoxicological%20bioassay%20using%20the%20bioindicators%20Lens.pdf https://repositorio.ufps.edu.co/bitstream/ufps/6823/2/license.txt https://repositorio.ufps.edu.co/bitstream/ufps/6823/3/Paracetamol%20ecotoxicological%20bioassay%20using%20the%20bioindicators%20Lens.pdf.txt https://repositorio.ufps.edu.co/bitstream/ufps/6823/4/Paracetamol%20ecotoxicological%20bioassay%20using%20the%20bioindicators%20Lens.pdf.jpg |
bitstream.checksum.fl_str_mv |
1ebbd6967474ab498f6b4e5f5ac282bf 2f9959eaf5b71fae44bbf9ec84150c7a ec13e09790f6e95691443fbbc45fda9b 7162263958e1140117373711a70e8627 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio Universidad Francisco de Paula Santander |
repository.mail.fl_str_mv |
bdigital@metabiblioteca.com |
_version_ |
1814095070166515712 |
spelling |
SALAZAR MERCADO, SEIR ANTONIOd3fe7e1ec57f59c892212006893d7af1600VEGA GALVIS, DIANA GABRIELAd6f6fe60a121b73b20298e7de571a2246002024-04-05T13:39:58Z2024-04-05T13:39:58Z2023-03-18https://repositorio.ufps.edu.co/handle/ufps/682310.1007/s11356-023-26475-7Paracetamol is one of the most widely used drugs worldwide, yet its environmental presence and hazardous impact on nontarget organisms could rapidly increase. In this study, the possible cytotoxic efects of paracetamol were evaluated using two bioindicator plants Lens culinaris and Pisum sativum. Concentrations of 500, 400, 300, 200, 100, 50, 25, 5, 1 mg L−1, and a control (distilled water) were used for a total of 10 treatments, which were subsequently applied on seeds of Lens culinaris Med. and Pisum sativum L.; after 72 h of exposure, root growth, mitotic index, percentage of chromosomal abnormalities, and the presence of micronucleus were evaluated. The cytotoxic efect of paracetamol on L. culinaris and P. sativum was demonstrated, reporting the inhibition of root growth, the presence of abnormalities, and a signifcant micronucleus index at all concentrations used, which shows that this drug has a high degree of toxicity.12 Páginasapplication/pdfengEnvironmental Science and Pollution ResearchMercado, SAS, Galvis, DGV Bioensayo ecotoxicológico de paracetamol utilizando los bioindicadores Lens culinaris Med. y Pisum sativum L. Environ Sci Pollut Res 30 , 61965–61976 (2023). https://doi.org/10.1007/s11356-023-26475-7Vol.30 (2023)61976(2023)6196530Esta bajo una licencia CC BY (licencia Creative Commons Attribution 4.0 International)https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessAtribución 4.0 Internacional (CC BY 4.0)http://purl.org/coar/access_right/c_abf2https://link.springer.com/article/10.1007/s11356-023-26475-7#article-infoParacetamol ecotoxicological bioassay using the bioindicators Lens culinaris Med. and Pisum sativum LArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85Binucleate cellCell abnormalitiesPharmacological compoundsMitotic inhibitionMicronucleiAguiar LL, Andrade-Vieira LF, de Oliveira David JA (2016) Evaluation of the toxic potential of cofee wastewater on seeds, roots and meristematic cells of Lactuca sativa L. Ecotoxicol Environ Saf 133:366–372. https://doi.org/10.1016/j.ecoenv.2016.07.019Almeida F, Nunes B (2019) Efects of acetaminophen in oxidative stress and neurotoxicity biomarkers of the gastropod Phorcus lineatus. Environ Sci Pollut Res Int 26(10):9823–9831. https://doi. org/10.1007/s11356-019-04349-1An J, Zhou Q, Sun F, Zhang L (2009) Ecotoxicological efects of paracetamol on seed germination and seedling development of wheat (Triticum aestivum L.). J Hazard Mater 169(1–3):751–757. https:// doi.org/10.1016/j.jhazmat.2009.04.011Aswani V, Rajsheel P, Bapatla RB, Sunil B, Raghavendra AS (2019) Oxidative stress induced in chloroplasts or mitochondria promotes proline accumulation in leaves of pea (Pisum sativum): another example of chloroplast-mitochondria interactions. Protoplasma 256(2):449–457. https://doi.org/10.1007/s00709-018-1306-1Azzazy MF (2020) Plant bioindicators of pollution in Sadat City, Western Nile Delta. Egypt PloS one 15(3):e0226315. https://doi.org/ 10.1371/journal.pone.0226315Badar Z, Shanableh A, El-Keblawy A, Mosa KA, Semerjian L, Mutery AA, Hussain MI, Bhattacharjee S, Tsombou FM, Ayyaril SS, Ahmady IM, Elnaggar A, Mousa M, Semreen MH (2022) Assessment of uptake, accumulation and degradation of paracetamol in spinach (Spinacia oleracea L.) under controlled laboratory conditions. Plants (Basel, Switzerland) 11(13):1626. https://doi.org/10. 3390/plants11131626Bagheri M, He X, Oustriere N, Liu W, Shi H, Limmer MA, Burken JG (2021) Investigating plant uptake of organic contaminants through transpiration stream concentration factor and neural network models. The Sci Total Environment 751:141418. https://doi.org/10. 1016/j.scitotenv.2020.141418Bartha B, Huber C, Harpaintner R, Schröder P (2010) Efects of acetaminophen in Brassica juncea L. Czern.: investigation of uptake, translocation, detoxifcation, and the induced defense pathways. Environmental Sci Poll Res Int 17(9):1553–1562. https://doi.org/ 10.1007/s11356-010-0342-yBebianno MJ, Mello ACP, Serrano MAS, Flores-nunes F, Mattos JJ, Zacchi FL (2017) Ecotoxicology and environmental safety transcriptional and cellular efects of paracetamol in the oyster Crassostrea gigas. Ecotoxicol Environ Saf 144(June):258–267. https:// doi.org/10.1016/j.ecoenv.2017.06.034Blackford AN, Stucki M (2020) How cells respond to DNA breaks in mitosis. Trends Biochem Sci 45(4):321–331. https://doi.org/10. 1016/j.tibs.2019.12.010Bosker T, Bouwman LJ, Brun NR, Behrens P, Vijver MG (2019) Microplastics accumulate on pores in seed capsule and delay germination and root growth of the terrestrial vascular plant Lepidium sativum. Chemosphere 226:774–781. https://doi.org/ 10.1016/j.chemosphere.2019.03.163Cameron EE, Moss SA, Keitaanpaa SJ, Bushell MA (2021) Pharmacists’ experiences of consumer stockpiling: insights from COVID19. J Pharm Pract Res 51(6):464–471. https://doi.org/10.1002/ jppr.1758Çanl M (2018) A new perspective to aberrations caused by barium and vanadium ions on Lens culinaris Medik. Ecotoxicol Environ Saf 160:19–23. https://doi.org/10.1016/j.ecoenv.2018.05.020Causil L, Coronado J, Verbel L, Vega M, Donado K, y Pacheco C (2017) Efecto citotóxico del hipoclorito de sodio (NaClO), en células apicales de raíces de cebolla (Allium cepa L.). Revista Colombiana De Ciencias Hortícolas 11(1):97–104. https://doi.org/ 10.17584/rcch.2017v11i1.5662Chen L, Liu JR, Hu WF, Gao J, Yang JY (2021) Vanadium in soil-plant system: source, fate, toxicity, and bioremediation. J Hazardous Materials 405:124200. https://doi.org/10.1016/j.jhazmat.2020.124200Chuang YH, Zhang Y, Zhang W, Boyd SA, Li H (2015) Comparison of accelerated solvent extraction and quick, easy, cheap, efective, rugged and safe method for extraction and determination of pharmaceuticals in vegetables. J Chromatogr A 1404:1–9. https:// doi.org/10.1016/j.chroma.2015.05.022Chuang YH, Liu CH, Sallach JB, Hammerschmidt R, Zhang W, Boyd SA, Li H (2019) Mechanistic study on uptake and transport of pharmaceuticals in lettuce from water. Environment Int 131:104976. https://doi.org/10.1016/j.envint.2019.104976Correia B, Freitas R, Figueira E, Soares AM, Nunes B (2016) Oxidative efects of the pharmaceutical drug paracetamol on the edible clam Ruditapes philippinarum under diferent salinities. Comparative biochemistry and physiology. Toxicology & Pharmacology : CBP 179:116–124. https://doi.org/10.1016/j.cbpc.2015.09.006Daniel D, Dionísio R, de Alkimin GD, Nunes B (2019) Acute and chronic effects of paracetamol exposure on Daphnia magna: how oxidative efects may modulate responses at distinct levels of organization in a model species. Environ Sci Pollut Res Int 26(4):3320–3329. https://doi.org/10.1007/s11356-018-3788-yDatta S, Singh J, Singh J, Singh S, Singh S (2018) Assessment of genotoxic efects of pesticide and vermicompost treated soil with Allium cepa test. Sustainable Environment Res 28(4):171–178. https://doi.org/10.1016/j.serj.2018.01.005Di Salvatore M, Carafa AM, Carratù G (2008) Assessment of heavy metals phytotoxicity using seed germination and root elongation tests: a comparison of two growth substrates. Chemosphere 73(9):1461–1464Dodueva IE, Lebedeva MA, Kuznetsova KA, Gancheva MS, Paponova SS, Lutova LL (2020) Plant tumors: a hundred years of study. Planta 251(4):82. https://doi.org/10.1007/s00425-020-03375-5El-Amier Y, Elhindi K, El-Hendawy S, Al-Rashed S, Abd-ElGawad A (2019) Antioxidant system and biomolecules alteration in Pisum sativum under heavy metal stress and possible alleviation by 5-Aminolevulinic acid. Molecules (basel, Switzerland) 24(22):4194. https://doi.org/10.3390/molecules24224194Faqihi A, Sayed SF (2021) Self-medication practice with analgesics (NSAIDs and acetaminophen), and antibiotics among nursing undergraduates in University College Farasan Campus, Jazan University, KSA. Annales pharmaceutiques francaises, 79(3), 275– 285. DOI: 10.1016/j.pharma.2020.10.012Fiskesjo, G. (1985). The Allium Test as Standard Environmental Monitoring 12:99–112Freo U, Ruocco C, Valerio A, Scagnol I, Nisoli E (2021) Paracetamol: a review of guideline recommendations. J Clin Med 10(15):3420. https://doi.org/10.3390/jcm10153420García-Medina S, Galar-Martínez M, Gómez-Oliván LM, TorresBezaury R, Islas-Flores H, Gasca-Pérez E (2020) The relationship between cyto-genotoxic damage and oxidative stress produced by emerging pollutants on a bioindicator organism (Allium cepa): the carbamazepine case. Chemosphere 253:126675. https://doi.org/ 10.1016/j.chemosphere.2020.126675Giménez V, Nunes B (2019) Efects of commonly used therapeutic drugs, paracetamol, and acetylsalicylic acid, on key physiological traits of the sea snail Gibbula umbilicalis. Environ Sci Pollut Res Int 26(21):21858–21870. https://doi.org/10.1007/ s11356-019-04653-wGomaa M, Zien-Elabdeen A, Hifney AF, Adam MS (2021) Phycotoxicity of antibiotics and non-steroidal anti-infammatory drugs to green algae Chlorella sp. and Desmodesmus spinosus: assessment of combined toxicity by Box-Behnken experimental design. Environmental Technol Innov 23(101586):101586. https://doi.org/10. 1016/j.eti.2021.101586Gómez-Oliván LM, Neri-Cruz N, Galar-Martínez M, Vieyra-Reyes P, García- Medina S, Razo-Estrada C, Dublán-García O, Corral-Avitia AY (2012) Assessing the oxidative stress induced by paracetamol spiked in artifcial sediment on Hyalella azteca. Water Air Soil Pollut 223(8):5097–5104. https://doi.org/10.1007/ s11270-012-1261-yGómez-Oliván LM, Neri-Cruz N, Galar-Martínez M et al (2014) Binary mixtures of diclofenac with paracetamol, ibuprofen, naproxen, and acetylsalicylic acid and these pharmaceuticals in isolated form induce oxidative stress on Hyalella azteca. Environ Monit Assess 186:7259– 7271. https://doi.org/10.1007/s10661-014-3925-0Gutiérrez-Noya VM, Gómez-Oliván LM, Ramírez-Montero M, Islas-Flores H, Galar-Martínez M, Dublán-García O, Romero R (2020) Ibuprofen at environmentally relevant concentrations alters embryonic development, induces teratogenesis and oxidative stress in Cyprinus carpio. The Sci Total environment 710:136327. https://doi.org/10.1016/j.scitotenv.2019.136327Hillis DG, Fletcher J, Solomon KR, Sibley PK (2011) Efects of ten antibiotics on seed germination and root elongation in three plant species. Arch Environ Contam Toxicol 60(2):220–232. https://doi.org/10.1007/s00244-010-9624-0Jaeschke H, Murray FJ, Monnot AD, Jacobson-Kram D, Cohen SM, Hardisty JF, Atillasoy E, Hermanowski-Vosatka A, Kufner E, Wikof D, Chappell GA, Bandara SB, Deore M, Pitchaiyan SK, Eichenbaum G (2021) Assessment of the biochemical pathways for acetaminophen toxicity: implications for its carcinogenic hazard potential. Regul Toxicol Pharmacol: RTP 120:104859. https://doi.org/10.1016/j.yrtph.2020.104859Kalinec GM, Thein P, Parsa A, Yorgason J, Luxford W, Urrutia R, Kalinec F (2014) Acetaminophen and NAPQI are toxic to auditory cells via oxidative and endoplasmic reticulum stress-dependent pathways. Hear Res 313:26–37. https://doi. org/10.1016/j.heares.2014.04.007Kalsbeek D, Golsteyn RM (2017) G2/M-phase checkpoint adaptation and micronuclei formation as mechanisms that contribute to genomic instability in human cells. Int J Mol Sci 18(11):2344. https://doi.org/10.3390/ijms18112344Kato TA, Haskins JS (2023) Mitotic index analysis. In: Gotoh E (ed) Chromosome Analysis. Methods in Molecular Biology, vol 2519. Humana, New York, NY. https://doi.org/10.1007/ 978-1-0716-2433-3_3Khan Z, Shahwar D, Yunus Ansari MK, Chandel R (2019) Toxicity assessment of anatase (TiO2) nanoparticles: a pilot study on stress response alterations and DNA damage studies in Lens culinaris Medik. Heliyon 5(7):e02069. https://doi.org/10.1016/j. heliyon.2019.e02069Kirkland D, Kovochich M, More SL, Murray FJ, Monnot AD, Miller JV, Jaeschke H, Jacobson-Kram D, Deore M, Pitchaiyan SK, Unice K, Eichenbaum G (2021) A comprehensive weight of evidence assessment of published acetaminophen genotoxicity data: implications for its carcinogenic hazard potential. Regul Toxicol Pharmacol: RTP 122:104892. https://doi.org/10.1016/j. yrtph.2021.104892Kudrna J, Hnilicka F, Kubes J, Vachova P, Hnilickova H, Kuklova M (2020) Efect of acetaminophen (APAP) on physiological indicators in Lactuca sativa. Life (basel, Switzerland) 10(11):303. https://doi.org/10.3390/life10110303Kummerová M, Zezulka Š, Babula P, Váňová L (2013) Root response in Pisum sativum and Zea mays under fuoranthene stress: morphological and anatomical traits. Chemosphere 90(2):665–673. https://doi.org/10.1016/j.chemosphere.2012.09.047Kwon M, Leibowitz ML, Lee JH (2020) Small but mighty: the causes and consequences of micronucleus rupture. Exp Mol Med 52(11):1777–1786. https://doi.org/10.1038/s12276-020-00529-zLandrigan PJ, Stegeman JJ, Fleming LE, Allemand D, Anderson DM, Backer LC, Brucker-Davis F, Chevalier N, Corra L, Czerucka D, Bottein MD, Demeneix B, Depledge M, Deheyn DD, Dorman CJ, Fénichel P, Fisher S, Gaill F, Galgani F, Gaze WH et al (2020) Human health and ocean pollution. Ann Glob Health 86(1):151. https://doi.org/10.5334/aogh.2831Lapi F, Marconi E, Grattagliano I et al (2022) To clarify the safety profle of paracetamol for home-care patients with COVID-19: a real-world cohort study, with nested case–control analysis, in primary care. Intern Emerg Med 17:2237–2244. https://doi.org/ 10.1007/s11739-022-03054-1Lee WM (2017) Acetaminophen (APAP) hepatotoxicity-isn’t it time for APAP to go away? J Hepatol 67(6):1324–1331. https://doi. org/10.1016/j.jhep.2017.07.005Leitão I, Leclercq CC, Ribeiro DM, Renaut J, Almeida AM, Martins LL, Mourato MP (2021) Stress response of lettuce (Lactuca sativa) to environmental contamination with selected pharmaceuticals: a proteomic study. J Proteomics 245:104291. https:// doi.org/10.1016/j.jprot.2021.104291Leston S, Nunes M, Viegas I, Ramos F, Pardal MÂ (2013) The efects of chloramphenicol on Ulva lactuca. Chemosphere 91(4):552– 557. https://doi.org/10.1016/j.chemosphere.2012.12.061Li Y, Chuang YH, Sallach JB, Zhang W, Boyd SA, Li H (2018) Potential metabolism of pharmaceuticals in radish: comparison of in vivo and in vitro exposure. Environ Pollut 242(Pt A):962–969. https://doi.org/10.1016/j.envpol.2018.07.060Liang C, Lan Z, Zhang X, Liu Y (2016) Mechanism for the primary transformation of acetaminophen in a soil/water system. Water Res 98:215–224Liu X, Liu X, Wang H, Dou Z, Ruan K, Hill DL, Li L, Shi Y, Yao X (2020) Phase separation drives decision making in cell division. J Biol Chem 295(39):13419–13431. https://doi.org/10.1074/jbc. REV120.011746Luzhna L, Kathiria P, Kovalchuk O (2013) Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond. Front Genet 4:131. https://doi.org/10.3389/fgene.2013.00131Lyu J, Park J, Kumar Pandey L, Choi S, Lee H, De Saeger J, Depuydt S, Han T (2018) Testing the toxicity of metals, phenol, efuents, and receiving waters by root elongation in Lactuca sativa L. Ecotoxicol Environ Saf 149:225–232. https://doi.org/10.1016/j.ecoenv. 2017.11.006Maciejowski J, Hatch EM (2020) Nuclear membrane rupture and its consequences. Annu Rev Cell Dev Biol 36:85–114. https://doi. org/10.1146/annurev-cellbio-020520-120627Mefe R, de Santiago-Martín A, Teijón G, Martínez Hernández V, López-Heras I, Nozal L, de Bustamante I (2021) Pharmaceutical and transformation products during unplanned water reuse: insights into natural attenuation, plant uptake and human health impact under field conditions. Environment Int 157:106835. https://doi.org/10.1016/j.envint.2021.106835Mendoza N Salazar S. (2022). Cytogenotoxicity of ffth-generation quaternary ammonium using three plant bioindicators. Environ Toxicol Pharmacol 95:103972. https://doi.org/10.1016/j.etap. 2022.103972Mercado S, Caleño J (2021) Use of Lens culinaris Med test as environmental bioindicator to identify the cytogenotoxic efect of paraquat pesticide. Environ Sci Pollut Res Int 28(37):51321–51328. https://doi.org/10.1007/s11356-021-14352-0Mostafa E, Tawfk AM, Abd-Elrahman KM (2022) Egyptian perspectives on potential risk of paracetamol/acetaminophen-induced toxicities: lessons learnt during COVID-19 pandemic. Toxicol Rep 9:541–548. https://doi.org/10.1016/j.toxrep.2022.03.035Nikitaki Z, Holá M, Donà M, Pavlopoulou A, Michalopoulos I, Angelis KJ, Georgakilas AG, Macovei A, Balestrazzi A (2018) Integrating plant and animal biology for the search of novel DNA damage biomarkers. Mutat Res, Rev Mutat Res 775:21–38. https://doi. org/10.1016/j.mrrev.2018.01.001Nogueira AF, Nunes B (2021) Efects of paracetamol on the polychaete Hediste diversicolor: occurrence of oxidative stress, cyclooxygenase inhibition and behavioural alterations. Environ Sci Pollut Res Int 28(21):26772–26783. https://doi.org/10.1007/ s11356-020-12046-7Nunes B, Antunes SC, Santos J, Martins L, Castro BB (2014) Toxic potential of paracetamol to freshwater organisms: a headache to environmental regulators? Ecotoxicol Environ Saf 107:178–185. https://doi.org/10.1016/j.ecoenv.2014.05.027O’Keefe JB, Newsom LC, Taylor TH Jr (2021) A survey of providerreported use and perceived efectiveness of medications for symptom management in telemedicine and outpatient visits for mild COVID-19. Infectious Diseases and Therapy 10(2):839–851. https://doi.org/10.1007/s40121-021-00432-8Pandolf S, Valdenassi L, Bjørklund G, Chirumbolo S, Lysiuk R, Lenchyk L, Doşa MD, Fazio S (2022) COVID-19 medical and pharmacological management in the European countries compared to Italy: an overview. Int J Environ Res Public Health 19(7):4262. https://doi.org/10.3390/ijerph19074262Park JC, Yoon D-S, Byeon E, Seo JS, Hwang U-K, Han J, Lee J-S (2018) Adverse efects of two pharmaceuticals acetaminophen and oxytetracycline on life cycle parameters, oxidative stress, and defensome system in the marine rotifer Brachionus rotundiformis. Aquatic Toxicol (amsterdam, Netherlands) 204:70–79. https://doi. org/10.1016/j.aquatox.2018.08.018Parolini M (2020) Toxicity of the non-steroidal anti-infammatory drugs (NSAIDs) acetylsalicylic acid, paracetamol, diclofenac, ibuprofen and naproxen towards freshwater invertebrates: a review. The Sci Total Environment 740:140043. https://doi.org/10.1016/j.scitotenv. 2020.140043Parolini M, Binelli A, Cogni D, Provini A (2010) Multi-biomarker approach for the evaluation of the cyto-genotoxicity of paracetamol on the zebra mussel (Dreissena polymorpha). Chemosphere 79(5):489–498. https://doi.org/10.1016/j.chemosphere.2010.02. 053Perussolo MC, Guiloski IC, Lirola JR, Fockink DH, Corso CR, Bozza DC, Prodocimo V, Mela M, Ramos LP, Cestari MM, Acco A, Silva de Assis HC (2019) Integrated biomarker response index to assess toxic efects of environmentally relevant concentrations of paracetamol in a neotropical catfsh (Rhamdia quelen). Ecotoxicol Environmental Safety 182:109438. https://doi.org/10.1016/j. ecoenv.2019.109438Phong HNP, Le GK, Nguyen TMH, Bui XT, Nguyen KH, Rene ER et al (2019) Acetaminophen micropollutant: Historical and current occurrences, toxicity, removal strategies and transformation pathways in diferent environments. Chemosphere 236:124391Piedade F, Bio S, y Nunes B (2020) Efectos de la exposición a corto plazo de fármacos comunes (paracetamol y ácido acetilsalicílico) sobre biomarcadores del mejillón Mytilus spp. Toxicología y Farmacología Ambiental 73(103276):103276. https://doi.org/10. 1016/j.etap.2019.103276Priac A, Badot PM, Crini G (2017) Treated wastewater phytotoxicity assessment using Lactuca sativa: focus on germination and root elongation test parameters. CR Biol 340(3):188–194. https://doi. org/10.1016/j.crvi.2017.01.002Qi F, Zhang F (2020) Cell cycle regulation in the plant response to stress. Front Plant Sci 10:1765. https://doi.org/10.3389/fpls.2019. 01765Quispe-Cañari JF, Fidel-Rosales E, Manrique D, Mascaró-Zan J, Huamán-Castillón KM, Chamorro-Espinoza SE, Garayar-Peceros H, Ponce-López VL, Sifuentes-Rosales J, Alvarez-Risco A, Yáñez JA, Mejia CR (2021) Self-medication practices during the COVID-19 pandemic among the adult population in Peru: a crosssectional survey. Saudi Pharmaceut J: SPJ : The Ofcial Public Saudi Pharmaceut Soc 29(1):1–11. https://doi.org/10.1016/j.jsps. 2020.12.001Rede D, Santos L, Ramos S, Oliva-Teles F, Antão C, Sousa SR, Delerue-Matos C (2019) Individual and mixture toxicity evaluation of three pharmaceuticals to the germination and growth of Lactuca sativa seeds. The Sci Total Environment 673:102–109. https://doi.org/10.1016/j.scitotenv.2019.03.432Reinstadler V, Ausweger V, Grabher AL, Kreidl M, Huber S, Grander J, Haslacher S, Singer K, Schlapp-Hackl M, Sorg M, Erber H, Oberacher H (2021) Monitoring drug consumption in Innsbruck during coronavirus disease 2019 (COVID-19) lockdown by wastewater analysis. The Sci Total Environment 757:144006. https://doi.org/10. 1016/j.scitotenv.2020.144006Restrepo R, Reyes D, Ortiz MC, Rojas Ruiz, Fernando A, Kouznetsov VV (2012) Aberraciones cromosomales en bulbos de cebolla Allium cepa inducidas por moléculas híbridas 4-aminoquinolínicas. Univ Sci 17(3):253–261. http://www.scielo.org.co/scielo. php?script=sci_arttext&pid=S0122-74832012000300001&lng= en&tlng=es. Accessed 5 Sep 2022Romano S, Galante H, Figueira D, Mendes Z, Rodrigues AT (2021) Time-trend analysis of medicine sales and shortages during COVID-19 outbreak: Data from community pharmacies. Res Social Adm Pharm 17(1):1876–1881Saeedi BJ, Hunter-Chang S, Luo L, Li K, Liu KH, Robinson BS (2022) Oxidative stress mediates end-organ damage in a novel model of acetaminophen-toxicity in Drosophila. Sci Rep 12(1):19309Salazar SA, Maldonado Bayona HA (2020) Evaluation of the cytotoxic potential of sodium hypochlorite using meristematic root cells of Lens culinaris Med. Sci Total Environ 701:134992Salazar SA, Quintero Caleño JD (2020) Determination of malathion’s toxic efect on Lens culinaris Medik cell cycle. Heliyon 6(9):e04846. https://doi.org/10.1016/j.heliyon.2020.e04846Salazar SA, Torres-León CA, Rojas-Suárez JP (2019) Cytotoxic evaluation of sodium hypochlorite, using Pisum sativum L as efective bioindicator. Ecotoxicol Environ Saf 173:71–76. https://doi.org/ 10.1016/j.ecoenv.2019.02.027Salazar SA, Quintero Caleño JD, Rojas Suárez JP (2020) Cytogenotoxic efect of propanil using the Lens culinaris Med and Allium cepa L test. Chemosphere 249:126193. https://doi.org/10.1016/j. chemosphere.2020.126193Scherer MD, Sposito J, Falco WF, Grisolia AB, Andrade L, Lima SM, Machado G, Nascimento VA, Gonçalves DA, Wender H, Oliveira SL, Caires A (2019) Cytotoxic and genotoxic efects of silver nanoparticles on meristematic cells of Allium cepa roots: a close analysis of particle size dependence. The Sci Total Environment 660:459–467. https://doi.org/10.1016/j.scitotenv.2018.12.444Sharp DJ (2002) Cell division: MAST sails through mitosis. Current Biology : CB 12(17):R585–R587. https://doi.org/10.1016/s0960- 9822(02)01098-9Sommer S, Buraczewska I, Kruszewski M (2020) Micronucleus assay: the state of art, and future directions. Int J Mol Sci 21(4):1534. https://doi.org/10.3390/ijms21041534Spyres MB, Aldy K, Farrugia LA, Kang AM, Love JS, Campleman SL et al (2021) The toxicology investigators consortium 2020 annual report. J Med Toxicol 17:333–362Sun C, Dudley S, McGinnis M, Trumble J, Gan J (2019) Acetaminophen detoxification in cucumber plants via induction of glutathione S-transferases. The Sci Total Environment 649:431–439. https://doi.org/10.1016/j.scitotenv.2018.08.346Svobodníková L, Kummerová M, Zezulka Š, Babula P, Sendecká K (2020) Root response in Pisum sativum under naproxen stress: Morpho-anatomical, cytological, and biochemical traits. Chemosphere 258:127411. https://doi.org/10.1016/j.chemosphere.2020. 127411Talukdar D, Talukdar T (2014) Coordinated response of sulfate transport, cysteine biosynthesis, and glutathione-mediated antioxidant defense in lentil (Lens culinaris Medik.) genotypes exposed to arsenic. Protoplasma 251(4):839–855. https://doi.org/10.1007/ s00709-013-0586-8Wolny E, Betekhtin A, Rojek M, Braszewska-Zalewska A, Lusinska J, Hasterok R (2018) Germination and the early stages of seedling development in Brachypodium distachyon. Int J Mol Sci 19(10):2916. https://doi.org/10.3390/ijms19102916Xia L, Zheng L, Zhou JL (2017) Efects of ibuprofen, diclofenac and paracetamol on hatch and motor behavior in developing zebrafsh (Danio rerio). Chemosphere 182:416–425. https://doi.org/10. 1016/j.chemosphere.2017.05.054Zhu J (2016) Review abiotic stress signaling and responses in plants. Cell 167(2):313–324. https://doi.org/10.1016/j.cell.2016.08.029ORIGINALParacetamol ecotoxicological bioassay using the bioindicators Lens.pdfParacetamol ecotoxicological bioassay using the bioindicators Lens.pdfapplication/pdf8128122https://repositorio.ufps.edu.co/bitstream/ufps/6823/1/Paracetamol%20ecotoxicological%20bioassay%20using%20the%20bioindicators%20Lens.pdf1ebbd6967474ab498f6b4e5f5ac282bfMD51open accessLICENSElicense.txtlicense.txttext/plain; charset=utf-814828https://repositorio.ufps.edu.co/bitstream/ufps/6823/2/license.txt2f9959eaf5b71fae44bbf9ec84150c7aMD52open accessTEXTParacetamol ecotoxicological bioassay using the bioindicators Lens.pdf.txtParacetamol ecotoxicological bioassay using the bioindicators Lens.pdf.txtExtracted texttext/plain60723https://repositorio.ufps.edu.co/bitstream/ufps/6823/3/Paracetamol%20ecotoxicological%20bioassay%20using%20the%20bioindicators%20Lens.pdf.txtec13e09790f6e95691443fbbc45fda9bMD53open accessTHUMBNAILParacetamol ecotoxicological bioassay using the bioindicators Lens.pdf.jpgParacetamol ecotoxicological bioassay using the bioindicators Lens.pdf.jpgGenerated Thumbnailimage/jpeg15413https://repositorio.ufps.edu.co/bitstream/ufps/6823/4/Paracetamol%20ecotoxicological%20bioassay%20using%20the%20bioindicators%20Lens.pdf.jpg7162263958e1140117373711a70e8627MD54open accessufps/6823oai:repositorio.ufps.edu.co:ufps/68232024-04-06 03:03:24.807An error occurred on the license name.|||https://creativecommons.org/licenses/by/4.0/open accessRepositorio Universidad Francisco de Paula Santanderbdigital@metabiblioteca.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0000-0002-3287-703Xd3fe7e1ec57f59c892212006893d7af16000000-0002-7038-4471d6f6fe60a121b73b20298e7de571a224600 |