Determination of the impacts of titanium dioxide nanoparticles on a number of xenobiotic-metabolizing enzymes in rat liver

Ayça Taş; Neşe Keklikcioğlu Çakmak; Tuğba Agbektaş; Cemile Zontul; Esma Özmen; Yavuz Siliğ

Research Article

Determination of the impacts of titanium dioxide nanoparticles on a number of xenobiotic-metabolizing enzymes in rat liver

Year 2020, Volume: 3 Issue: 3, 77 - 83, 31.12.2020

Ayça Taş Neşe Keklikcioğlu Çakmak Tuğba Agbektaş Cemile Zontul Esma Özmen Yavuz Siliğ

Abstract

Nanotechnology techniques are used in many applications, such as cancer treatment, radiological imaging methods, and pharmaceutical industry, as well as in the microbiology field, tissue regeneration, injury healing, treatment of some chronic diseases, and production of vaccines. Whereas products of nanotechnology have a lot of benefits mentioned in our life, they also have some systemic, genetic, and toxic effects in organisms. This study’s goal was to reveal the impacts of titanium dioxide (TiO2) nanoparticles on a number of xenobiotic-metabolizing enzymes in the rat liver fraction. In the current research, adult Wistar albino rats having a weight of approximately 150-200 g and fed under normal conditions were utilized. The incubation of four various concentrations of TiO2 nanoparticles (0.5, 1, 5, and 10 ppm) was performed in the liver fractions. We studied the effects of TiO2 nanoparticles on some enzymes identified in the microsomal fraction, such as N-nitrosodimethylamine demethylase (cytochrome P4502E1), NADPH cytochrome c reductase, NADH cytochrome b5 reductase, and other enzymes found in the cytosolic fraction, e.g. glutathione-S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PDH), and glutathione level (GSH). GST, G6PDH, NADH-cytochrome b5 reductase, and NADPH cytochrome c reductase levels decreased statistically significantly, whereas the GSH level increased significantly in comparison with controls (p <0.05). Cytochrome P4502E1 induction did not change in comparison with controls (p> 0.05). Accordingly, in this study, we have shown that TiO2 nanoparticles are capable of inhibiting xenobiotic-metabolizing enzymes. Therefore, this inhibition can affect the detoxification system negatively.

Keywords

Xenobiotic-Metabolizing Enzymes,, Titanium Dioxide, Nanoparticles

References

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12. Khosravi-Katuli K, Prato E, Lofrano G, Guida M, Vale G, Libralato G: Effects of nanoparticles in species of aquaculture interest. Environ Sci Pollut Res Int, 24 (21): 17326-17346, 2017. DOI: 10.1007/s11356-017-9360-3
13. Minetto D, Volpi Ghirardini A, Libralato G: Saltwater ecotoxicology of Ag, Au, CuO, TiO2, ZnO and C60 engineered nanoparticles: An overview. Environ Int, 92-93: 189-201, 2016. DOI: 10.1016/j.envint.2016.03.041
14. Heinlaan M, Ivask A, Blinova I, Dubourguier HC, Kahru A: Toxicity of nanosized and bulk ZnO, CuO and TiO2 to bacteria Vibrio fischeri and crustaceans Daphnia magna and Thamnocephalus platyurus. Chemosp, 71(7): 1308-1316, 2008. DOI: 10.1016/j.chemosphere.2007.11.047
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19. Fabian E, Landsiedel R, Ma-Hock L, Wiench K, Wohlleben W, Van Ravenzwaay B: Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats. Arch of Toxicol, 82 (3): 151-157, 2008. DOI: 10.1016/0378-5173(94)90461-8
20. Li S, Zhu H, Zhu R, Sun X, Yao S, Wang S: Impact and mechanism of TiO2 nanoparticles on DNA synthesis in vitro. Sci in Chi Ser B: Chem, 51 (4): 367-372, 2008. DOI: 10.1007/s11426-008-0049-9
21. Zhu RR, Wang SL, Zhang R, Sun XY, Yao SD: A novel toxicological evaluation of TiO2 nanoparticles on DNA structure. Chi J of Chem, 25 (7): 958-961, 2007. DOI:10.1002/cjoc.200790186
22. Tas A, Cakmak NK, Gumus E, Atabey M, Silig Y: Chemotherapeutic effects of doxorubicin loaded PEG coated TiO2 nanocarriers on breast cancer cell lines. Ann of Med Res, 26 (5): 821-826, 2019. DOI: 10.5455/annalsmedres.2019.02.078
23. Tas A, Cakmak NK, Silig Y: Cytotoxicity Studies of TiO2/ZnO Nanocomposites on Cervical Cancer Cells. Int J Mod Res Eng Technol, 3 (12), 2018.
24. Bolukbasi Sahin S, Keklikcioglu Cakmak N, Tas A, Ozmen E, Cevik E, Gumus E, Silig Y: The Cytotoxic Effects of Titanium Oxide Nanoparticle on MDA-MB–231 and MCF–7 Cells. Int J of Sci and Techno Res, 4 (8), 2018.
25. Mahbubul I, Elcioglu EB, Saidur R, Amalina M: Optimization of ultrasonication period for better dispersion and stability of TiO2–water nanofluid. Ultra Sonochem, 37: 360-367, 2017. DOI: 10.1016/j.ultsonch.2017.01.024
26. Sugibayashi K, Todo H, Kimura E: Safety evaluation of titanium dioxide nanoparticles by their absorption and elimination profiles. The J of Toxicol Sci, 33 (3): 293-298, 2008. DOI: 10.2131/jts.33.293
27. Eraslan G, Kanbur M, Karabacak M, Arslan K, Siliğ Y, Soyer Sarica Z, Tekeli M, Taş A: Effect on oxidative stress, hepatic chemical metabolizing parameters, and genotoxic damage of mad honey intake in rats. Hum & Exper Toxicol, 37 (9): 991-1004, 2018. DOI: 10.1177/0960327117745691
28. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analyti Biochem, 72 (1-2): 248-254, 1976. DOI: 10.1016/0003-2697(76)90527-3
29. Warholm M, Guthenberg C, von Bahr C, Mannervik B: [62] Glutathione transferases from human liver. Methods in enzymologyed. Met in Enzymol, 499-504, 1985. DOI.org/10.1016/S0076-6879(85)13065-X
30. Beutler E: Red cell metabolism: a manual of biochemical methods. 1984.
31. Beutler E: Red cell metabolism-A manual of biochemical methods. Lon: Aca Pre, 16, 1971.
32. Yoo J-SH, Ishizaki H, Yang CS: Roles of cytochrome P450IIE1 in the dealkylation and denitrosation of N-nitrosodimethylamine and N-nitrosodiethylamine in rat liver microsomes. Carcino, 11 (12): 2239-2243, 1990. DOI:10.1093/carcin/11.12.2239
33. Dignam JD, Strobel HW: Preparation of homogeneous NADPH-cytochrome P-450 reductase from rat liver. Biochem and Biophy Res Com, 63 (4): 845-852, 1975. DOI:10.1016/0006-291X(75)90644-0
34. Strittmatter P: The nature of the flavin binding in microsomal cytochrome b5 reductase. J of Biologi Chem, 236 (8): 2329-2335, 1961.
35. Choudhary R, Khurana D, Kumar A, Subudhi S: Stability analysis of Al2O3/water nanofluids. Journal of Experimental Nanoscience, 12 (1): 140-151, 2017. DOI:10.1080/17458080.2017.1285445
36. Langford JI, Wilson A: Scherrer after sixty years: a survey and some new results in the determination of crystallite size. J of App Crystallo, 11 (2): 102-113, 1978. DOI: 10.1107/S0021889878012844
37. Aware DV, Jadhav SS: Synthesis, characterization and photocatalytic applications of Zn-doped TiO 2 nanoparticles by sol–gel method. App Nanoscience, 6 (7): 965-972, 2016. DOI: 10.1007/s13204-015-0513-8
38. Mohajerani A, Burnett L, Smith J. V, Kurmus H, Milas J, Arulrajah A, ... & Abdul Kadir A: Nanoparticles in Construction Materials and Other Applications, and Implications of Nanoparticle Use. Materials, 12(19), 3052, 2019. DOI: 10.3390/ma12193052
39. Aitken RJ, Chaudhry M, Boxall A, Hull M: Manufacture and use of nanomaterials: current status in the UK and global trends. Occup Med, 56 (5): 300-306, 2006. DOI: 10.1093/occmed/kql051
40. Beck-Speier I, Dayal N, Karg E, Maier KL, Schumann G, Schulz H, Semmler M, Takenaka S, Stettmaier K, Bors W: Oxidative stress and lipid mediators induced in alveolar macrophages by ultrafine particles. Free Rad Bio and Med, 38 (8): 1080-1092, 2005. DOI: 10.1016/j.freeradbiomed.2005.01.004
41. Gurr J-R, Wang AS, Chen C-H, Jan K-Y: Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicol, 213 (1-2): 66-73, 2005. DOI: 10.1016/j.tox.2005.05.007
42. Sayes CM, Wahi R, Kurian PA, Liu Y, West JL, Ausman KD, Warheit DB, Colvin VL: Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci, 92 (1): 174-185, 2006. DOI: 10.1093/toxsci/kfj17
43. Bickley L, Lange A, Winter M, Tyler C: Fish hepatocyte cultures as an alternative to in vivo tests for screening oestrogen receptor active chemicals. Compa Biochem and Physiol, Part A, 4 (146): S72, 2007. DOI:10.1016/j.cbpa.2007.01.078
44. Franke WW, Deumling B, Ermen B, Jarasch E-D, Kleinig H: NUCLEAR MEMBRANES FROM MAMMALIAN LIVER: I. Isolation Procedure and General Characterization. The Journal of cell biology, 46 (2): 379-395, 1970. DOI:10.1083/jcb.46.2.379
45. Kasper CB: Isolation and properties of the nuclear envelope. Met Enzymol, 31: 279-292, 1974. DOI: 10.1016/0076-6879(74)31029-4
46. Raza H: Dual localization of glutathione S‐transferase in the cytosol and mitochondria: implications in oxidative stress, toxicity and disease. The FEBS J, 278 (22): 4243-4251, 2011. DOI: 10.1111/j.1742-4658.2011.08358.x
47. Haase A, Rott S, Mantion A, Graf P, Plendl J, Thünemann AF, Meier WP, Taubert A, Luch A, Reiser G: Effects of silver nanoparticles on primary mixed neural cell cultures: uptake, oxidative stress and acute calcium responses. Toxicol Sci, 126 (2): 457-468, 2012. DOI: 10.1093/toxsci/kfs003
48. Sereemaspun A, Hongpiticharoen P, Rojanathanes R, Maneewattanapinyo P, Ekgasit S, Warisnoicharoen W: Inhibition of human cytochrome P450 enzymes by metallic nanoparticles: a preliminary to nanogenomics. Int J Pharmacol, 4 (6): 492-495, 2008. DOI: 10.3923/ijp.2008.492.495
49. Cakmak NK, Tas A, Silig Y: Evaluation of Synergistic Effect of TiO 2 and Al2O3 Nanoparticles on Hela Cell Line. Int J of Sci and Technol Res. 4 (10), 2018.

Year 2020, Volume: 3 Issue: 3, 77 - 83, 31.12.2020

Ayça Taş Neşe Keklikcioğlu Çakmak Tuğba Agbektaş Cemile Zontul Esma Özmen Yavuz Siliğ

Abstract

References

1. Fadeel B: The Right Stuff: On the Future of Nanotoxicology. Front in Toxicol, 1: 1-4, 2019. DOI: 10.3389/ftox.2019.00001
2. Mobasser S, & Firoozi A. A. Review of nanotechnology applications in science and engineering. J Civil Eng Urban, 6(4): 84-93, 2016 .
3. Ferin J, Oberdorster G, Penney D: Pulmonary retention of ultrafine and fine particles in rats. Am J Respir Cell Mol Biol, 6 (5): 535-542, 1992. DOI: 10.1165/ajrcmb/6.5.535
4. Khan I, Saeed K, & Khan I. Nanoparticles: Properties, applications and toxicities. Arabian J of Chem, 12(7): 908-931, 2019. DOI:10.1016/j.arabjc.2017.05.011
5. Jeevanandam J, Barhoum A, Chan Y. S, Dufresne A, & Danquah M. K. Review on nanoparticles and nanostructured materials: history, sources, toxicity and regulations. Beilstein J of Nanotech, 9(1): 1050-1074, 2018. DOI:10.3762/bjnano.9.98
6. Singh AV, Laux P, Luch A, Sudrik C, Wiehr S, Wild A-M, Santomauro G, Bill J, Sitti M: Review of emerging concepts in nanotoxicology: opportunities and challenges for safer nanomaterial design. Toxicol mecha and met, 29 (5): 378-387, 2019. DOI: 10.1080/15376516.2019.1566425
7. Hagens WI, Oomen AG, de Jong WH, Cassee FR, Sips AJ: What do we (need to) know about the kinetic properties of nanoparticles in the body? Regul Toxicol Pharmacol, 49 (3): 217-229, 2007. DOI: 10.1016/j.yrtph.2007.07.006
8. Oberdorster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H, Group Irfrsıntsw: Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol, 2: 8, 2005. DOI: 10.1186/1743-8977-2-8
9. Hou J, Wang L, Wang C, Zhang S, Liu H, Li S, Wang X: Toxicity and mechanisms of action of titanium dioxide nanoparticles in living organisms. J Environ Sci (China), 75: 40-53, 2019. DOI: 10.1016/j.jes.2018.06.010
10. Szymańska R, Kołodziej K, Ślesak I, Zimak-Piekarczyk P, Orzechowska A, Gabruk M, Żądło A, Habina I, Knap W, Burda K: Titanium dioxide nanoparticles (100–1000 mg/l) can affect vitamin E response in Arabidopsis thaliana. Environ Pollut, 213: 957-965, 2016. DOI: 10.1016/j.envpol.2016.03.026
11. Trouiller B, Reliene R, Westbrook A, Solaimani P, Schiestl RH: Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res, 69 (22): 8784-8789, 2009. DOI: 10.1158/0008-5472.CAN-09-2496
12. Khosravi-Katuli K, Prato E, Lofrano G, Guida M, Vale G, Libralato G: Effects of nanoparticles in species of aquaculture interest. Environ Sci Pollut Res Int, 24 (21): 17326-17346, 2017. DOI: 10.1007/s11356-017-9360-3
13. Minetto D, Volpi Ghirardini A, Libralato G: Saltwater ecotoxicology of Ag, Au, CuO, TiO2, ZnO and C60 engineered nanoparticles: An overview. Environ Int, 92-93: 189-201, 2016. DOI: 10.1016/j.envint.2016.03.041
14. Heinlaan M, Ivask A, Blinova I, Dubourguier HC, Kahru A: Toxicity of nanosized and bulk ZnO, CuO and TiO2 to bacteria Vibrio fischeri and crustaceans Daphnia magna and Thamnocephalus platyurus. Chemosp, 71(7): 1308-1316, 2008. DOI: 10.1016/j.chemosphere.2007.11.047
15. Sadiq IM, Dalai S, Chandrasekaran N, Mukherjee A: Ecotoxicity study of titania (TiO(2)) NPs on two microalgae species: Scenedesmus sp. and Chlorella sp. Ecotoxicol Environ Saf, 74 (5): 1180-1187, 2011. DOI: 10.1016/j.ecoenv.2011.03.006
16. Atha DH, Wang H, Petersen EJ, Cleveland D, Holbrook RD, Jaruga P, Dizdaroglu M, Xing B, Nelson BC: Copper oxide nanoparticle mediated DNA damage in terrestrial plant models. Environ Sci Technol, 46 (3): 1819-1827, 2012. DOI: 10.1021/es202660k
17. Lahann J: Environmental nanotechnology: Nanomaterials clean up. Nat Nanotech, 3 (6): 320, 2008.
18. Jani PU, McCarthy DE, Florence AT: Titanium dioxide (rutile) particle uptake from the rat GI tract and translocation to systemic organs after oral administration. Int J of Pharma, 105 (2): 157-168, 1994. DOI: 10.1016/0378-5173(94)90461-8
19. Fabian E, Landsiedel R, Ma-Hock L, Wiench K, Wohlleben W, Van Ravenzwaay B: Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats. Arch of Toxicol, 82 (3): 151-157, 2008. DOI: 10.1016/0378-5173(94)90461-8
20. Li S, Zhu H, Zhu R, Sun X, Yao S, Wang S: Impact and mechanism of TiO2 nanoparticles on DNA synthesis in vitro. Sci in Chi Ser B: Chem, 51 (4): 367-372, 2008. DOI: 10.1007/s11426-008-0049-9
21. Zhu RR, Wang SL, Zhang R, Sun XY, Yao SD: A novel toxicological evaluation of TiO2 nanoparticles on DNA structure. Chi J of Chem, 25 (7): 958-961, 2007. DOI:10.1002/cjoc.200790186
22. Tas A, Cakmak NK, Gumus E, Atabey M, Silig Y: Chemotherapeutic effects of doxorubicin loaded PEG coated TiO2 nanocarriers on breast cancer cell lines. Ann of Med Res, 26 (5): 821-826, 2019. DOI: 10.5455/annalsmedres.2019.02.078
23. Tas A, Cakmak NK, Silig Y: Cytotoxicity Studies of TiO2/ZnO Nanocomposites on Cervical Cancer Cells. Int J Mod Res Eng Technol, 3 (12), 2018.
24. Bolukbasi Sahin S, Keklikcioglu Cakmak N, Tas A, Ozmen E, Cevik E, Gumus E, Silig Y: The Cytotoxic Effects of Titanium Oxide Nanoparticle on MDA-MB–231 and MCF–7 Cells. Int J of Sci and Techno Res, 4 (8), 2018.
25. Mahbubul I, Elcioglu EB, Saidur R, Amalina M: Optimization of ultrasonication period for better dispersion and stability of TiO2–water nanofluid. Ultra Sonochem, 37: 360-367, 2017. DOI: 10.1016/j.ultsonch.2017.01.024
26. Sugibayashi K, Todo H, Kimura E: Safety evaluation of titanium dioxide nanoparticles by their absorption and elimination profiles. The J of Toxicol Sci, 33 (3): 293-298, 2008. DOI: 10.2131/jts.33.293
27. Eraslan G, Kanbur M, Karabacak M, Arslan K, Siliğ Y, Soyer Sarica Z, Tekeli M, Taş A: Effect on oxidative stress, hepatic chemical metabolizing parameters, and genotoxic damage of mad honey intake in rats. Hum & Exper Toxicol, 37 (9): 991-1004, 2018. DOI: 10.1177/0960327117745691
28. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analyti Biochem, 72 (1-2): 248-254, 1976. DOI: 10.1016/0003-2697(76)90527-3
29. Warholm M, Guthenberg C, von Bahr C, Mannervik B: [62] Glutathione transferases from human liver. Methods in enzymologyed. Met in Enzymol, 499-504, 1985. DOI.org/10.1016/S0076-6879(85)13065-X
30. Beutler E: Red cell metabolism: a manual of biochemical methods. 1984.
31. Beutler E: Red cell metabolism-A manual of biochemical methods. Lon: Aca Pre, 16, 1971.
32. Yoo J-SH, Ishizaki H, Yang CS: Roles of cytochrome P450IIE1 in the dealkylation and denitrosation of N-nitrosodimethylamine and N-nitrosodiethylamine in rat liver microsomes. Carcino, 11 (12): 2239-2243, 1990. DOI:10.1093/carcin/11.12.2239
33. Dignam JD, Strobel HW: Preparation of homogeneous NADPH-cytochrome P-450 reductase from rat liver. Biochem and Biophy Res Com, 63 (4): 845-852, 1975. DOI:10.1016/0006-291X(75)90644-0
34. Strittmatter P: The nature of the flavin binding in microsomal cytochrome b5 reductase. J of Biologi Chem, 236 (8): 2329-2335, 1961.
35. Choudhary R, Khurana D, Kumar A, Subudhi S: Stability analysis of Al2O3/water nanofluids. Journal of Experimental Nanoscience, 12 (1): 140-151, 2017. DOI:10.1080/17458080.2017.1285445
36. Langford JI, Wilson A: Scherrer after sixty years: a survey and some new results in the determination of crystallite size. J of App Crystallo, 11 (2): 102-113, 1978. DOI: 10.1107/S0021889878012844
37. Aware DV, Jadhav SS: Synthesis, characterization and photocatalytic applications of Zn-doped TiO 2 nanoparticles by sol–gel method. App Nanoscience, 6 (7): 965-972, 2016. DOI: 10.1007/s13204-015-0513-8
38. Mohajerani A, Burnett L, Smith J. V, Kurmus H, Milas J, Arulrajah A, ... & Abdul Kadir A: Nanoparticles in Construction Materials and Other Applications, and Implications of Nanoparticle Use. Materials, 12(19), 3052, 2019. DOI: 10.3390/ma12193052
39. Aitken RJ, Chaudhry M, Boxall A, Hull M: Manufacture and use of nanomaterials: current status in the UK and global trends. Occup Med, 56 (5): 300-306, 2006. DOI: 10.1093/occmed/kql051
40. Beck-Speier I, Dayal N, Karg E, Maier KL, Schumann G, Schulz H, Semmler M, Takenaka S, Stettmaier K, Bors W: Oxidative stress and lipid mediators induced in alveolar macrophages by ultrafine particles. Free Rad Bio and Med, 38 (8): 1080-1092, 2005. DOI: 10.1016/j.freeradbiomed.2005.01.004
41. Gurr J-R, Wang AS, Chen C-H, Jan K-Y: Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicol, 213 (1-2): 66-73, 2005. DOI: 10.1016/j.tox.2005.05.007
42. Sayes CM, Wahi R, Kurian PA, Liu Y, West JL, Ausman KD, Warheit DB, Colvin VL: Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci, 92 (1): 174-185, 2006. DOI: 10.1093/toxsci/kfj17
43. Bickley L, Lange A, Winter M, Tyler C: Fish hepatocyte cultures as an alternative to in vivo tests for screening oestrogen receptor active chemicals. Compa Biochem and Physiol, Part A, 4 (146): S72, 2007. DOI:10.1016/j.cbpa.2007.01.078
44. Franke WW, Deumling B, Ermen B, Jarasch E-D, Kleinig H: NUCLEAR MEMBRANES FROM MAMMALIAN LIVER: I. Isolation Procedure and General Characterization. The Journal of cell biology, 46 (2): 379-395, 1970. DOI:10.1083/jcb.46.2.379
45. Kasper CB: Isolation and properties of the nuclear envelope. Met Enzymol, 31: 279-292, 1974. DOI: 10.1016/0076-6879(74)31029-4
46. Raza H: Dual localization of glutathione S‐transferase in the cytosol and mitochondria: implications in oxidative stress, toxicity and disease. The FEBS J, 278 (22): 4243-4251, 2011. DOI: 10.1111/j.1742-4658.2011.08358.x
47. Haase A, Rott S, Mantion A, Graf P, Plendl J, Thünemann AF, Meier WP, Taubert A, Luch A, Reiser G: Effects of silver nanoparticles on primary mixed neural cell cultures: uptake, oxidative stress and acute calcium responses. Toxicol Sci, 126 (2): 457-468, 2012. DOI: 10.1093/toxsci/kfs003
48. Sereemaspun A, Hongpiticharoen P, Rojanathanes R, Maneewattanapinyo P, Ekgasit S, Warisnoicharoen W: Inhibition of human cytochrome P450 enzymes by metallic nanoparticles: a preliminary to nanogenomics. Int J Pharmacol, 4 (6): 492-495, 2008. DOI: 10.3923/ijp.2008.492.495
49. Cakmak NK, Tas A, Silig Y: Evaluation of Synergistic Effect of TiO 2 and Al2O3 Nanoparticles on Hela Cell Line. Int J of Sci and Technol Res. 4 (10), 2018.

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Details

Primary Language	English
Subjects	Engineering
Journal Section	Original Research Articles
Authors	Ayça Taş 0000-0002-7132-1325 Neşe Keklikcioğlu Çakmak 0000-0002-8634-9232 Tuğba Agbektaş This is me 0000-0003-3433-8870 Cemile Zontul This is me 0000-0002-1436-5145 Esma Özmen 0000-0003-3223-6854 Yavuz Siliğ 0000-0002-0562-7457
Publication Date	December 31, 2020
Acceptance Date	December 31, 2020
Published in Issue	Year 2020 Volume: 3 Issue: 3

Cite

APA	Taş, A., Keklikcioğlu Çakmak, N., Agbektaş, T., Zontul, C., et al. (2020). Determination of the impacts of titanium dioxide nanoparticles on a number of xenobiotic-metabolizing enzymes in rat liver. Scientific Journal of Mehmet Akif Ersoy University, 3(3), 77-83.

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