Determination of the embryotoxic effect of Metronidazole using an in ovo model
Abstract
Metronidazole is an imidazole group bactericidal antibiotic used against anaerobic bacteria and some protozoa. There is no detailed information about the embryotoxic effect of Metronidazole. This study aims to determine the embryotoxic activity of Metronidazole using an in ovo method. A total of 210 fertile chicken eggs were placed in an incubator, divided into seven equal groups of 30. The first group was considered as the control group. On the seventh day of the study, Metronidazole was administered to the other six groups within 50 µL saline solution at doses of 250, 125, 62.5, 31.25, and 15.62 µg·egg-1 (5; 2.5; 1.25; 0.625; 0.312 mg·kg-1). At the end of the incubation period, the eggs hatched, and the number of live and dead embryos was determined. There were no significant differences in deaths between the groups (P>0.05 in all cases). No anomaly was detected in the macroscopic morphology of the embryos. As a result, it can be stated that Metronidazole may be safe for use during pregnancy. However, it is necessary to conduct molecular and histopathological studies to investigate the effects of this drug on organogenesis, especially in mammalian embryos.
Downloads
References
Freeman CD, Klutman NE, Lamp KC. Metronidazole : a therapeutic review and update. Drugs. [Internet]. 1997; 54:679–708. doi: https://doi.org/c55f26
Ceruelos AH, Romero–Quezada L, Ledezma JR, Contreras LL. Therapeutic uses of Metronidazole and its side effects: an update. Eur. Rev. Med. Pharmacol. Sci. [Internet]. 2019; 23(1):397–401. doi: https://doi.org/gsbcbt
Yazar E. Chemotherapeutics. In: Yazar E, editor. Veterinary Medicines Guide and Treatment Manual. Ankara, Türkiye: Atlas Yayınevi; 2023; p 79–236.
Yazar E. Veterinary Drug and Vaccine From A to Z. Istanbul, Türkiye: Nobel Tıp Press; 2018; p 56–156.
Dingsdag SA, Hunter N. Metronidazole : an update on metabolism, structure–cytotoxicity and resistance mechanisms. J. Antimicrob. Chemother. [Internet]. 2018; 73(2):265–79. doi: https://doi.org/gcg9fr
Eren F, Aldan MA, Dogan VB, Gül G, Selcuk HH, Soysal A. A case with reversible neurotoxicity induced by Metronidazole. Ideggyogy. Sz. [Internet]. 2017; 70(11–12):429–432. doi: https://doi.org/k5s4
Quickfall D, Daneman N, Dmytriw AA, Juurlink DN. Metronidazole –induced neurotoxicity. Can. Med. Assoc. J. [Internet]. 2021; 193(42):E1630. doi: https://doi.org/k5s5
Dobiáš L, Černá M, Rössner P, Šrám R. Genotoxicity and carcinogenicity of Metronidazole . Mutat. Res. – Genet. Toxicol. [Internet]. 1994; 317(3):177–94. doi: https://doi.org/fxbksk
Jelinek R, Peterka M, Rychter Z. Chick Embryotoxicity Screening Test–130 Substances Tested. Indian J. Exp. Biol. 1985; 23(10):588–595.
Canbar R, Uslu M, Arslan MS, Kızılay H. Determination of Embryotoxic effects of Atipamezole using in ovo model. Rev. Cientif. FCV–LUZ. [Internet]. 2023; 33(1):1–4. doi: https://doi.org/k5xh
Uslu M, Canbar R, Akcakavak G, Yazar E. Determination of the embryotoxic effect of maropitant using an in ovo model. Pol. J. Vet. Sci. [Internet]. 2022; 25(2):357–9. doi: https://doi.org/j2p7
Canbar R, Akcakavak G, Uslu M, Bas AL. Determination of embryotoxic effects of Tarantula cubensis alcoholic extract with in ovo model. Magy. Allatorvosok Lapja. 2021; 143(8):497–504.
Canbar R, Uslu M, Tufan Ö, Yazar E. Determination of embryotoxic dose limit of detomidine with in–ovo model. Eurasian J. Vet. Sci. [Internet]. 2021; 37(2):71–75. doi: https://doi.org/gkjqqc
Ozparlak H. [The use of chick embryos in embryotoxicity and teratogenicity tests]. Selcuk Univ. Fen Fak. Fen Derg. [Internet]. 2015 [cited 25 Jun 2023]; 40:13–22. Turkish. Available in: https://bit.ly/3R9D9mh.
Jelinek R. Use of chick embryo in screening for embryotoxicity. Teratog. Carcinog. Mutagen. [Internet]. 1982; 2(3‐4):255–261. doi: https://doi.org/ch6ffn
Hill E, Hoffman D. Avian models for toxicity testing. J. Am. Coll. Toxicol. [Internet]. 1984; 3(6):357–376. doi: https://doi.org/bc244f
Nwosu OC, Bloom K. The safety of metronidazole in pregnancy. Health Care Women Int. [Internet]. 2021; 42(4–6):726–738. doi: https://doi.org/k5xk
Rebuelto M, Loza ME. Antibiotic treatment of dogs and cats during pregnancy. Vet. Med. Int. [Internet]. 2010; 2010:1–8. doi: https://doi.org/dz75sd
Hamilton JW, Denison MS, Bloom SE. Development of basal and induced aryl hydrocarbon (benzo [a] pyrene) hydroxylase activity in the chicken embryo in ovo. Proc. the National Academy Sci. [Internet]. 1983; 80(11):3372–6. doi: https://doi.org/d2jk7m
Chacko M, Bhide S. Carcinogenicity, perinatal carcinogenicity and teratogenicity of low dose Metronidazole (MNZ) in Swiss mice. J. Cancer Res. Clin. Oncol. [Internet]. 1986; 112:135–140. doi: https://doi.org/dvzcw8
Struthers BJ. Metronidazole appears not to be a human teratogen: review of literature. Infect. Dis. Obstet. Gynecol. [Internet]. 1997; 5(5):326–335. doi: https://doi.org/cwkq56
Sobel R, Sobel JD. Metronidazole for the treatment of vaginal infections. Expert Opin. Pharmacother. [Internet]. 2015; 16(7):1109–1115. doi: https://doi.org/gq94jd
Morgan I. Metronidazole treatment in pregnancy. Int. J. Gynaecol. Obstet. [Internet]. 1978; 15(6):501–512. doi: https://doi.org/k5xn
Rodin P, Hass G. Metronidazole and pregnancy. Br. J. Vener. Dis. [Internet]. 1966; 42(3):210. doi: https://doi.org/bnsp3m
Caro‐Patón T, Carvajal A, Martín de Diego I, Martín‐Arias LH, Alvarez–Requejo A, Pinilla ER. Is Metronidazole teratogenic? A meta‐analysis. Br. J. Clin. Pharmacol. [Internet]. 1997; 44(2):179–182. doi: https://doi.org/dhqdk9
Burtin P, Taddio A, Ariburnu O, Einarson TR, Koren G. Safety of Metronidazole in pregnancy: a meta–analysis. Am. J. Obstet. Gynecol. [Internet]. 1995; 172(2):525–529. doi: https://doi.org/fdnnzb
Roe JFC. A critical appraisal of the toxicology of Metronidazole. In: Phillips I, Collier J, editors. Metronidazole. Proceedings of the 2nd International Symposium on Anaerobic Infection. Geneva, April 1979. New York: Grune and Stratton, 1979: 215–222.
Tiboni GM, Marotta F, Castigliego AP. Teratogenic effects in mouse fetuses subjected to the concurrent in utero exposure to miconazole and metronidazole. Reprod. Toxicol. [Internet]. 2008; 26(3–4):254–261. doi: https://doi.org/fft2jk
Damjanov I. Metronidazole and alcohol in pregnancy. J. Am. Med. Assoc. [Internet]. 1986; 256(4):472. doi: https://doi.org/cm5s9s
Copyright (c) 2024 Muhittin Uslu, Rahmi Canbar, Mustafa Sedat Arslan, Harun Kızılay
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.