Antihistamin Levosetirizin Dihidroklorürün Sitogenetik Belirteçler Üzerindeki Etkisi
Year 2020,
Volume: 1 Issue: 1, 29 - 35, 29.06.2020
Hüsniye Kutlu
,
İbrahim Halil Kenger
,
Rima Çelik
,
Lale Dönbak
,
Ahmet Kayraldız
Abstract
Levosetirizin dihidroklorür, alerjik hastalıkların tedavisinde kullanılan ikinci nesil bir antihistaminik olan Alerinit'in aktif bileşenidir. Bu çalışma, insan periferal lenfositlerinde kromozomal anomali (CA) ve mikronükleus (MN) testleri kullanılarak levosetirizinin olası genotoksik ve sitotoksik etkilerini belirlemek için yapılmıştır. Bu çalışmada, hücre kültürleri 24 ve 48 saat boyunca Levocetirizine ön çalışması ile belirlenen 2, 4, 8 ve 16 μg / ml konsantrasyonları ile muamele edilmiştir. Çalışmamız sonucunda Levosetirizin'in bütün konsantrasyonlarında, CA / hücre hızı, anormal hücre yüzdesi ve mitotik indeks değerleri, MN frekansı, binükleer mikronükleus hücre hızı ve nükleer bölünme indeksi değerlerinde kontrol ile karşılaştırıldığında anlamlı bir değişikliğe neden olmadığını gözlemledik. Bu araştırmaya göre; levosetirizin dihidroklorürün genotoksik ve sitotoksik etkisi yoktur.
Supporting Institution
Kahramanmaraş Sütçü İmam Üniversitesi Bilimsel Araştırma Projeleri Yönetim Birimi tarafından desteklenmiştir.
Project Number
2018/2-14 YLS
References
- Von-Hertzen L.C. The Hygiene Hypothesis in the Development of Atopy and Asthma-still a Matter of Controversy? Oxford Journals Medicine. 1998;91(11):767-771.
- Zeyrek F, Zeyrek D.C. Alerjik Hastalıklar ve Parazitoz. Türkiye Parazitoloji Dergisi. 2006;30(2):135-140.
- Kaufman D.W, Kelly J.P, Rosenberg L, Anderson T.E, Mitchell A.A. Recent Patterns of Medication Use in the Ambulatory Adult Population of the United States: the Slone Survey. Jama. 2002;287(3):337-344.
- O’Donoghue M, Tharp M.D. Antihistamines and Their Role as Antipruritics. Dermatol. Ther. 2005;18(4):333–340.
- Lagraow B, Montvale NJ, Editor. Physicians Desk Reference. 59th ed. New Jersey:Thomson PDR; 2004.
- Snyder R.D. A Review and Investigation into the Mechanistic Basis of the Genotoxicity of Antihistamines. Mutat. Res. 1998;411(3):235–248.
- Iwase Y, Uno Y, Ohkouchi A, Molinier B, Simonnard A, Lebrun C, et al. Mutagenicity and Clastogenicity Studies with Mizolastine. Japanese Pharmacology and Therapeutics 1998;26(4):107-116.
- Tucker JD, Auletta A, Cimino MC, Dearfield KL, Jacobson-Kram D, Tice RR, et al. Sister Chromatid Exchange: Second Report of the Gene-Tox Program. Mutat. Res.1993;297(2):101–180.
- Benze J, Gypen L, Vanderberghe J, Lampo A, De Coster R, Bowden C, et al. Carcinogenicity Studies of Astemizole in Mice and Rats. Cancer Res. 1995;55(23):5589–5594.
- Roshdy HM. Cytogenetic and Mutagenic Effects of Levocetirizine and Montelukast Alone or in Combination on Pregnant Mice and Embryos. Res. J. Pharm., Biol. Chem. 2015;6(9):979-988.
- Evans HJ. Handbook of Mutagenicity Test Procedures. In: Kilbey, BJ, Legator M, Nichols W and Ramel C. Human peripheral blood 63 lymphocytes for the analysis of chromosome aberrations in mutagen tests. Amsterdam: Elsevier Science Publishers;1984.p.405-427.
- Perry PE, Thomson J. The methodology of sister chromatid exchanges. In: Kilbey, B.J., Legator, M., Nichols, W., Ramel, C. Handbook of mutagenicity test procedures. Amsterdam: Elsevier Science Publishers; 1984.p.495-529.
- Albertini R J, Anderson D, Douglas G R, Hagmar L, Hemminki K, Merlo F, Natarajan A T, Norppa H, Shuker D E G, Tice R, Waters M D, Aitio A. IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. Mutat. Res. 2000;463,111–172.
- Rothfuss A, Schutz P, Bochum S, Volm T, Eberhardt E, Kreienberg R, et al. Induced Micronucleus Frequencies in Peripheral Lymphocytes as a Screening Test for Carriers of a BRCA1 Mutation in Breast Cancer Families. Cancer Research. 2000;60(2):390-394.
- Eastmond DA, Tucker JD. Identification of Aneuploidy-Inducing Agents Using Cytokinesis-Blocked Human Lymphocytes and an Anti-Kinetochore Antibody. Environmental and Molecular Mutagenesis. 1989;13(1):34-43.
- Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K, Speck W. Salmonella Mutagenicity Tests: III. Results from the Testing of 255 Chemicals. Environ. Mol. Mutagen. 1987;9:100-109.
- Hite M, Algon J, Peck HM. The Effect of Cyproheptadine on the Chromosomes of Human Lymphocytes in Vitro. Arzneimforschung 1977;27(6):1203–1206.
- Müller L, Korte A, Madle S. Mutagenicity testing of doxylamine succinate, an antinauseant drug. Toxicol Lett. 1989;49(1):79–86.
- Mortelmans K, Haworth S, Lawlor T, Speck K, Tainer B, Zeiger E. Salmonella Mutagenicity Tests: II. Results from the Testing of 270 Chemicals. Environ. Mutagen. 1986;8(7):1–119.
- Galloway SM, Armstrong MJ, Reuben C, Colman S, Brown B, Cannon C, et al. Chromosome Aberrations and Sister Chromatid Exchanges in Chinese Hamster Ovary Cells: Evaluations of 108 Chemicals. Environ. Mol. Mutagen. 1987;1–175.
- Hansen EB, Jr Heflich RH, Korfmacher WA, Miller DW, Cerniglia CE. Microbial Transformation of the Antihistaminic Drug Triprolidine Hydrochloride. J. Pharm. Sci. 1988;10:259–264.
- Greenman DL, Sheldon W, Schieferstein G, Allen R, Allaben WT. Triprolidine: 104-week Feeding Study in Rats. Fundam. Appl. Toxicol. 1995;27(2):223–231.
- McGregor DB, Brown AG, Howgate S, McBride D, Riach C, Caspary WJ. Responses of the L5178Y Mouse Lymphoma Cell Forward Mutation Assay. V: 27 Coded Chemicals. Environ. Mol. Mutagen. 1991;17(3):196–219.
- Lijinsky W. Induction of Tumours in Rats by Feeding Nitrosatable Amines Together with Sodium Nitrite. Food Chem. Toxicol. 1984;22(9):715–720.
- Gocke E. Review of the Genotoxic Properties of Chlorpromazine and Related Phenothiazines. Mutat. Res. 1996;366(1):9–21.
- Oberly TJ, Bewsey BJ, Probst G.S. An Evaluation of the L5178Y TK ± Mouse Lymphoma Forward Mutation Assay Using 42 Chemicals. Mutat. Res. 1984;125(2):291–306.
- Gibson JP, Huffmann KW, Newberne JW. Preclinical Safety Studies with Terfenadine. Arzneimforschung. 1982;32(9):1179–1184.
Effect of Antihistamine Levocetirizine Dihydrochloride on Cytogenetic Markers
Year 2020,
Volume: 1 Issue: 1, 29 - 35, 29.06.2020
Hüsniye Kutlu
,
İbrahim Halil Kenger
,
Rima Çelik
,
Lale Dönbak
,
Ahmet Kayraldız
Abstract
Levocetirizine dihydrochloride is the active ingredient of Alerinit, a second-generation antihistamine, used in the treatment of allergic diseases. This study was carried out to determine the probable genotoxic and cytotoxic effects of levocetirizine using chromosomal abnormality (CA) and micronucleus (MN) tests in human peripheral lymphocytes. In this study, cell cultures were treated with 2, 4, 8 and 16 μg / ml concentrations determined by preliminary study of Levocetirizine during 24 and 48 hours. As a result of our study, we observed that Levocetirizine does not cause any significant change compared to control in CA / Cell rate, abnormal cell percentage and mitotic index values, MN frequency, binuclear micronucleus cell rate and nuclear division index values at within the all studied concentrations and treatment periods. According to this research; levocetirizine dihydrochloride has no genotoxic and cytotoxic effects.
Project Number
2018/2-14 YLS
References
- Von-Hertzen L.C. The Hygiene Hypothesis in the Development of Atopy and Asthma-still a Matter of Controversy? Oxford Journals Medicine. 1998;91(11):767-771.
- Zeyrek F, Zeyrek D.C. Alerjik Hastalıklar ve Parazitoz. Türkiye Parazitoloji Dergisi. 2006;30(2):135-140.
- Kaufman D.W, Kelly J.P, Rosenberg L, Anderson T.E, Mitchell A.A. Recent Patterns of Medication Use in the Ambulatory Adult Population of the United States: the Slone Survey. Jama. 2002;287(3):337-344.
- O’Donoghue M, Tharp M.D. Antihistamines and Their Role as Antipruritics. Dermatol. Ther. 2005;18(4):333–340.
- Lagraow B, Montvale NJ, Editor. Physicians Desk Reference. 59th ed. New Jersey:Thomson PDR; 2004.
- Snyder R.D. A Review and Investigation into the Mechanistic Basis of the Genotoxicity of Antihistamines. Mutat. Res. 1998;411(3):235–248.
- Iwase Y, Uno Y, Ohkouchi A, Molinier B, Simonnard A, Lebrun C, et al. Mutagenicity and Clastogenicity Studies with Mizolastine. Japanese Pharmacology and Therapeutics 1998;26(4):107-116.
- Tucker JD, Auletta A, Cimino MC, Dearfield KL, Jacobson-Kram D, Tice RR, et al. Sister Chromatid Exchange: Second Report of the Gene-Tox Program. Mutat. Res.1993;297(2):101–180.
- Benze J, Gypen L, Vanderberghe J, Lampo A, De Coster R, Bowden C, et al. Carcinogenicity Studies of Astemizole in Mice and Rats. Cancer Res. 1995;55(23):5589–5594.
- Roshdy HM. Cytogenetic and Mutagenic Effects of Levocetirizine and Montelukast Alone or in Combination on Pregnant Mice and Embryos. Res. J. Pharm., Biol. Chem. 2015;6(9):979-988.
- Evans HJ. Handbook of Mutagenicity Test Procedures. In: Kilbey, BJ, Legator M, Nichols W and Ramel C. Human peripheral blood 63 lymphocytes for the analysis of chromosome aberrations in mutagen tests. Amsterdam: Elsevier Science Publishers;1984.p.405-427.
- Perry PE, Thomson J. The methodology of sister chromatid exchanges. In: Kilbey, B.J., Legator, M., Nichols, W., Ramel, C. Handbook of mutagenicity test procedures. Amsterdam: Elsevier Science Publishers; 1984.p.495-529.
- Albertini R J, Anderson D, Douglas G R, Hagmar L, Hemminki K, Merlo F, Natarajan A T, Norppa H, Shuker D E G, Tice R, Waters M D, Aitio A. IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. Mutat. Res. 2000;463,111–172.
- Rothfuss A, Schutz P, Bochum S, Volm T, Eberhardt E, Kreienberg R, et al. Induced Micronucleus Frequencies in Peripheral Lymphocytes as a Screening Test for Carriers of a BRCA1 Mutation in Breast Cancer Families. Cancer Research. 2000;60(2):390-394.
- Eastmond DA, Tucker JD. Identification of Aneuploidy-Inducing Agents Using Cytokinesis-Blocked Human Lymphocytes and an Anti-Kinetochore Antibody. Environmental and Molecular Mutagenesis. 1989;13(1):34-43.
- Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K, Speck W. Salmonella Mutagenicity Tests: III. Results from the Testing of 255 Chemicals. Environ. Mol. Mutagen. 1987;9:100-109.
- Hite M, Algon J, Peck HM. The Effect of Cyproheptadine on the Chromosomes of Human Lymphocytes in Vitro. Arzneimforschung 1977;27(6):1203–1206.
- Müller L, Korte A, Madle S. Mutagenicity testing of doxylamine succinate, an antinauseant drug. Toxicol Lett. 1989;49(1):79–86.
- Mortelmans K, Haworth S, Lawlor T, Speck K, Tainer B, Zeiger E. Salmonella Mutagenicity Tests: II. Results from the Testing of 270 Chemicals. Environ. Mutagen. 1986;8(7):1–119.
- Galloway SM, Armstrong MJ, Reuben C, Colman S, Brown B, Cannon C, et al. Chromosome Aberrations and Sister Chromatid Exchanges in Chinese Hamster Ovary Cells: Evaluations of 108 Chemicals. Environ. Mol. Mutagen. 1987;1–175.
- Hansen EB, Jr Heflich RH, Korfmacher WA, Miller DW, Cerniglia CE. Microbial Transformation of the Antihistaminic Drug Triprolidine Hydrochloride. J. Pharm. Sci. 1988;10:259–264.
- Greenman DL, Sheldon W, Schieferstein G, Allen R, Allaben WT. Triprolidine: 104-week Feeding Study in Rats. Fundam. Appl. Toxicol. 1995;27(2):223–231.
- McGregor DB, Brown AG, Howgate S, McBride D, Riach C, Caspary WJ. Responses of the L5178Y Mouse Lymphoma Cell Forward Mutation Assay. V: 27 Coded Chemicals. Environ. Mol. Mutagen. 1991;17(3):196–219.
- Lijinsky W. Induction of Tumours in Rats by Feeding Nitrosatable Amines Together with Sodium Nitrite. Food Chem. Toxicol. 1984;22(9):715–720.
- Gocke E. Review of the Genotoxic Properties of Chlorpromazine and Related Phenothiazines. Mutat. Res. 1996;366(1):9–21.
- Oberly TJ, Bewsey BJ, Probst G.S. An Evaluation of the L5178Y TK ± Mouse Lymphoma Forward Mutation Assay Using 42 Chemicals. Mutat. Res. 1984;125(2):291–306.
- Gibson JP, Huffmann KW, Newberne JW. Preclinical Safety Studies with Terfenadine. Arzneimforschung. 1982;32(9):1179–1184.