Permetrin’in HepG2 Hücrelerine Doza ve Zamana Bağlı Etkileri: Hücre Sağkalımı, Lipid Peroksidasyonu ve Antioksidan Savunma Sistemi

Permetrinin tüm dünyada yoğun kullanımıyla insanlar ve diğer hedef dışı canlılar maruz kalmasına ragmen doz ve zamana bağlı in vitro hepatotoksisitesi ile ilgili sınırlı bilgi bulunmaktadır. Bu çalışmada, HepG2 hücrelerine permetrinin üç farklı dozu (1 uM, 10 uM, 100 uM) üç farklı zaman aralığında (24, 48, 72 saat) uygulanarak hücre canlılığı (WST-1 ve Tripan Mavisi testi ile), lipid peroksidasyon (yüksek performanslı sıvı kromatografisi ile), ve antioksidan (SOD-1, SOD-2 ve GPx-1) gen ekspresyon düzeylerinin (gerçek zamanlı PCR ile) değerlendirilmesi amaçlanmıştır. Permetrinin LC50 dozu 1111 µM olarak hesaplandı. Tüm zamanlarda en düşük doz hariç hücre canlılığında önemli azalma belirlendi (P

Dose- and Time-dependent Effects of Permethrin on HepG2 Cells: Cell Survival, Lipid Peroxidation and Antioxidant Defence System

There is very limited knowledge about in vitro hepatotoxicity of permethrin concerning dose and duration even though humans and nontargeted beings are exposed. In this study, three different doses of permethrin (1 uM, 10 uM, 100 uM) were administered in three different time periods (24, 48, 72 h) and cell viability (WST-1 and Trypan blue test), lipid peroxidation (high performance lipid chromatography), and antioxidant (SOD-1, SOD-2 and GPx-1) gene expression levels (real time PCR) were evaluated. The LC50 dose of permethrin was calculated as 1111 µM. Significant decrease in cell viability was detected in every time period except at the lowest dose (P

___

  • 1. Zhang SY, Ueyama J, Ito Y, Yanagiba Y, Okamura A, Kamijima M, Nakajima T: Permethrin may induce adult male mouse reproductive toxicity due to cis isomer not trans isomer. Toxicology, 248 (2-3): 136-141, 2008. DOI: 10.1016/j.tox.2008.03.018
  • 2. Wang X, Martínez MA, Dai M, Chen D, Ares I, Romero A, Castellano V, Martínez M, Rodríguez JL, Martínez-Larrañaga MR, Anadon A, Yuan Z: Permethrin-induced oxidative stress and toxicity and metabolism. A review. Environ Res, 149, 86-104, 2016. DOI: 10.1016/j.envres.2016.05.003
  • 3. U.S.EPA: Environmental Protection Agency. Reregistration eligibility decision (RED) on permethrin. EPA 738-R-09-306; US EPA: Washington, DC: 1-93, 2009.
  • 4. Price RJ, Walters DG, Finch JM, Gabriel KL, Capen CC, Osimitz TG, Lake BG: A mode of action for induction of liver tumors by pyrethrins in the rat. Toxicol Appl Pharmacol, 218 (2): 186-195, 2007. DOI: 10.1016/j. taap.2006.11.004
  • 5. Hakoi K, Cabral R, Hoshiya T, Hasegawa R, Shirai T, Ito N: Analysis of carcinogenic activity of some pesticides in a medium‐term liver bioassay in the rat. Teratog Carcinog Mutagen, 12 (6): 269-276, 1992. DOI: 10.1002/ tcm.1770120605
  • 6. Imamura L, Hasegawa H, Kurashina K, Hamanishi A, Tabuchi A, Tsuda M: Repression of activity-dependent c-fos and brain-derived neurotrophic factor mRNA expression by pyrethroid insecticides accompanying a decrease in Ca2+ influx into neurons. J Pharmacol Exp Ther, 295 (3): 1175-1182, 2000.
  • 7. Ishmael J, Litchfield MH: Chronic toxicity and carcinogenic evaluation of permethrin in rats and mice. Fundam Appl Toxicol, 11 (2): 308-322, 1988. DOI: 10.1016/0272-0590(88)90156-X
  • 8. Gabbianelli R, Palan M, Flis DJ, Fedeli D, Nasuti C, Skarydova L, Ziolkowski W: Imbalance in redox system of rat liver following permethrin treatment in adolescence and neonatal age. Xenobiotica, 43 (12): 1103-1110, 2013. DOI: 10.3109/00498254.2013.796427
  • 9. Abdou R, Sasaki K, Khalil W, Shah S, Murasawa Y, Shimoda M: Effects of several pyrethroids on hepatic cytochrome P450 activities in rats. J Vet Med Sci, 72 (4): 425-433, 2010. DOI:
  • 10.1292/jvms.09-0347 10. Roma GC, Oliveira PRD, Bechara GH, Mathias MIC: Cytotoxic effects of permethrin on mouse liver and spleen cells. Microsc Res Tech, 75 (2): 229-238, 2012. DOI: 10.1002/jemt.21047
  • 11. Nasuti C, Fattoretti P, Carloni M, Fedeli D, Ubaldi M, Ciccocioppo R, Gabbianelli R: Neonatal exposure to permethrin pesticide causes lifelong fear and spatial learning deficits and alters hippocampal morphology of synapses. J Neurodev Disord, 6:7, 2014. DOI: 10.1186/1866-1955-6-7
  • 12. Jin Y, Chen R, Liu W, Fu Z: Effect of endocrine disrupting chemicals on the transcription of genes related to the innate immune system in the early developmental stage of zebrafish (Danio rerio). Fish Shellfish Immunol, 28 (5-6): 854-861, 2010. DOI: 10.1016/j.fsi.2010.02.009
  • 13. Vadhana MSD, Nasuti C, Gabbianelli R: Purine bases oxidation and repair following permethrin insecticide treatment in rat heart cells. Cardiovasc Toxicol, 10 (3): 199-207, 2010. DOI: 10.1007/s12012-010-9079-6
  • 14. Wang P, Xu MY, Liang YJ, Wang HP, Sun YJ, Long DX, Wu YJ: Subchronic toxicity of low dose propoxur, permethrin, and their combination on the redox status of rat liver. Chem Biol Interact, 272, 21-27, 2017. DOI: 10.1016/j.cbi.2017.04.023
  • 15. Mozhdeganloo Z, Jafari AM, Koohi MK, Heidarpour M: Permethrininduced oxidative damage in liver of rainbow trout (Oncorhynchus mykiss) and its attenuation by vitamin C. Iran J Vet Res, 17 (1): 31-35, 2016.
  • 16. Roma GC, De Oliveira PR, Araujo AM, Bechara GH, Mathias MIC: Genotoxic and mutagenic effects of permethrin in mice: micronuclei analysis in peripheral blood erythrocytes. Microsc Res Tech, 75 (12): 17321736, 2012. DOI: 10.1002/jemt.22124
  • 17. Hu F, Li L, Wang C, Zhang Q, Zhang X, Zhao M: Enantioselective induction of oxidative stress by permethrin in rat adrenal pheochromocytoma (PC12) cells. Environ Toxicol Chem, 29 (3): 683-690, 2010. DOI: 10.1002/ etc.73
  • 18. Donato MT, Tolosa L, Gómez-Lechón MJ: Culture and functional characterization of human hepatoma HepG2 cells. Methods Mol Biol, 1250, 77-93, 2015. DOI: 10.1007/978-1-4939-2074-7_5
  • 19. Ramirez T, Strigun A, Verlohner A, Huener HA, Peter E, Herold M, Bordag N, Mellert W, Walk T, Spitzer M, Jiang X, Sperber S, Hofmann T, Hartung T, Kamp H, van Ravenzwaay B: Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells. Arch Toxicol, 92 (2): 893-906, 2018. DOI: 10.1007/s00204-017-2079-6
  • 20. Romero A, Ares I, Ramos E, Castellano V, Martínez M, MartínezLarrañaga M, Anadón A, Martínez MA: Evidence for dose-additive effects of a type II pyrethroid mixture. In vitro assessment. Environ Res, 138, 58-66, 2015. DOI: 10.1016/j.envres.2015.02.008
  • 21. Želježić D, Mladinić M, Žunec S, Vrdoljak AL, Kašuba V, Tariba B, Živković T, Marjanović AM, Pavičić I, Milić M, Rozgaj R, Kopjar N: Cytotoxic, genotoxic and biochemical markers of insecticide toxicity evaluated in human peripheral blood lymphocytes and an HepG2 cell line. Food Chem Toxicol, 96, 90-106, 2016. DOI: 10.1016/j.fct.2016.07.036
  • 22. Mateos R, Goya L, Bravo L: Determination of malondialdehyde by liquid chromatography as the 2, 4-dinitrophenylhydrazone derivative: A marker for oxidative stress in cell cultures of human hepatoma HepG2. J Chromatogr B Analyt Technol Biomed Life Sci, 805 (1): 33-39, 2004. DOI: 10.1016/j.jchromb.2004.02.004
  • 23. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248-254, 1976. DOI: 10.1006/abio.1976.9999
  • 24. Rudzok S, Krejči S, Graebsch C, Herbarth O, Mueller A, Bauer M: Toxicity profiles of four metals and 17 xenobiotics in the human hepatoma cell line HepG2 and the protozoa Tetrahymena pyriformis-A comparison. Environ Toxicol, 26 (2): 171-186, 2011. DOI: 10.1002/tox.20541
  • 25. Ayala A, Muñoz MF, Argüelles S: Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy2-nonenal. Oxid Med Cell Longev, 2014:360438, 2014. DOI: 10.1155/ 2014/360438
  • 26. Zarkovic N, Cipak A, Jaganjac M, Borovic S, Zarkovic K: Pathophysiological relevance of aldehydic protein modifications. J Proteomics, 92, 239-247, 2013. DOI: 10.1016/j.jprot.2013.02.004
  • 27. Abd El-Aal HAHM: Lipid peroxidation end-products as a key of oxidative stress: Effect of antioxidant on their production and transfer of free radicals. In, Catala A (Ed): Lipid Peroxidationed, InTech, 2012. DOI: 10.5772/45944
  • 28. Ho E, Galougahi KK, Liu CC, Bhindi R, Figtree GA: Biological markers of oxidative stress: Applications to cardiovascular research and practice. Redox Biol, 1 (1): 483-491, 2013. DOI: 10.1016/j.redox.2013.07.006
  • 29. Issam C, Zohra H, Monia Z, Hassen BC: Effects of dermal subchronic exposure of pubescent male rats to permethrin (PRMT) on the histological structures of genital tract, testosterone and lipoperoxidation. Exp Toxicol Pathol, 63 (4): 393-400, 2011. DOI: 10.1016/j.etp.2010.02.016
  • 30. Grotto D, Maria LS, Valentini J, Paniz C, Schmitt G, Garcia SC, Pomblum VJ, Rocha JBT, Farina M: Importance of the lipid peroxidation biomarkers and methodological aspects for malondialdehyde quantification. Quim Nova, 32 (1): 169-174, 2009. DOI: 10.1590/S010040422009000100032
  • 31. Lee YY, Kim HG, Jung HI, Shin YH, Hong SM, Park EH, Sa JH, Lim CJ: Activities of antioxidant and redox enzymes in human normal hepatic and hepatoma cell lines. Mol Cells, 14 (2): 305-311, 2002.
Kafkas Üniversitesi Veteriner Fakültesi Dergisi-Cover
  • ISSN: 1300-6045
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 1995
  • Yayıncı: Kafkas Üniv. Veteriner Fak.
Sayıdaki Diğer Makaleler

Asidik Koşullar Altında Listeria monocytogenes’in Glutamat Dekarboksilazlarının Asit Direnç Sistemlerine Katkılarının Değerlendirilmesi ve Farklı Rollerinin Araştırılması

Yufang GU, Xiaowei FANG, Chen WANG, Xiongyan LIANG, Chun FANG, Yuying YANG, Xueyang CHEN, Weihuan FANG

Buzağılarda Atresia Coli’de Kolonoskopik Tanı: 19 Olgu (2016-2018)

Kamil Serdar İNAL, Taylan ÖNYAY, Birsen Deniz ÖZBAKIR, Hatice Özlem NİSBET, Cenk YARDIMCI, Kamil SAĞLAM, Ahmet ÖZAK

Teke ve Koçların Prepusyal Svap Örneklerinden Genital Mikoplazma Türlerinin Karakterizasyonu

Hüban GÖÇMEN, Selim ALÇAY, Ruben S. ROSALES, Anne RIDLEY

Assessment of Regulations on Occupational Health and Safety in Agriculture in Turkey from the Point of Livestock Raising and Veterinary Medicine

AYŞE MENTEŞ GÜRLER, Şule SANAL, Gökhan ASLIM

Propolis Ekstrelerinin Gıda Kaynaklı Patojenlerin Biyojen Amin Üretimi Üzerindeki Etkileri

Aykut BURGUT

Treatment of a Full-Thickness Skin Wound in Gluteal Region of the Vervet Monkey with Topical Insulin

Çağrı GÜLTEKİN, Gökhan ULUKAN, Gökay YEŞİLOVALI, Süleyman ÖZDEMİR, Mehmet Ege İNCE, F. Eser ÖZGENCİL

Comparison of Tenderness and Calpains Activity of Yak Meat in Different Ages During Postmortem Aging

Pengcheng WEN, Qiaoneng YANG, Weibing ZHANG, Min YANG, Qi LIANG, Yaoyao JIAO, Yanli ZHU

Broyler Dişi Damızlık Rasyonlarında Kullanılan İz Mineral Premiksi Formunun Üreme Performansı, Kuluçka Özellikleri ve Kuluçka Sonrası Civcivlerde Büyüme Performansı ve Karkas Parametreleri Üzerine Etkileri

Hasan Rustu KUTLU, Seyyednaeim SABER, Yusuf UZUN, Ladine CELIK, Ozcan YUCELT, Mikail BAYLAN

Köpeklerde Birbirine Bağlı Gastroözefageal Çoklu Balık Kancalarının Endoskopik ve Cerrahi Girişimlerle Uzaklaştırılması: 13 Olgu (2010-2017)

Kamil Serdar İNAL, Taylan ÖNYAY, Cenk YARDIMCI, Ahmet ÖZAK

Effect of β-glucanase on Performance, Carcass Characteristics, Microflora, Plasma Constitutes and Immunity in Local Broiler Hybrid “Golpayegani-Ross”

Mohammadebrahim TASIRNAFAS, Kazem KARIMI, Ghobad ASGARI JAFARABADI, Fatemeh NOORBAKHSH, Alireza SEIDAVI