EMBRYOTOXICITY OF FLUOROQUINOLONES IN RATS

Authors

  • AL-Musawy A. A. H Department of Physiology, College of Vet. Medicine, Basrah University
  • AL-Myahi A. J Department of Physiology, College of Vet. Medicine, Basrah University
  • Al-Snafi Ali Esmail Department of Pharmacology, College of Medicine, Thi-Qar University

Abstract

This study was designed to investigate the possible developmental fetotoxicity and teratogenicity of Norfloxacin (NFX), Ciprofloxacin (CPX) and Enrofloxacin (ENX) in rats. Eighty pregnant female rats were divided into four equal groups, the first three groups were given daily single  oral doses of NFX,700mg/kg/day, CPX 550mg/kg/day, and ENX 750mg/kg/ day respectively and the last group was given dimethyl sulphoxide ( DMS) 0.5 ml/animal/day. All animals administered the drugs and the vehicle  from the day 1 to the day 15 of gestation period . Ten animals from each group were sacrificed at day 15 of gestation  by cervical dislocation, the other ten animal from each group were left till labor. Embryos and pups  were evaluated for litter size ,weight, resorption ratio, fetal lost and external features . The effect of drugs on the length of gestation period  was also  evaluated . The results revealed that  fluroquinolones were significantly decrease  litter size, and fetal weight, and increase fetal resorption ratio and fetal lost as compared to control either fetuses evaluated at day 15 of pregnancy or those  evaluated  after  birth . Gross examination showed some teratogenic abnormalities in fetuses and  pups of mothers treated with fluoroquinolones during the first 15 days  of  pregnancy .

References

-Agrawala, I.P., Achar, M.V.S., Boradkar, R.V., and Roy, N. (1968). Galactogogne action of Cuminum cyminum and Nigell sativa. Ind . J. Med. Res. 56,841-844.

-Al-Snafi, A. E. and Shafik, N.A. (1997). Embryotoxicity of Norfloxacin in mice. The Medical Journal of Tikrit University3:200-203.

-Amwayi, P. J. A. and Otiang, G. E. (1997). Use of biometric embryonic growth parameters as indicator of exposure to a teratogen. East African medical journal. 74(1), 6-11.

-Arora, N.K., (1994). Are Fluoroquinolones safe in children?. India J Pediatr. 61(6): 601-603.

-Arriaga-Alba, M., Rivera-Sánchez, R., Parra-Cervantes, G., Barron Moreno, F., Flores-Paz, R. and Elbia García-Jiménez, E. (2000). Antimutagenesis of b-carotene to mutations induced by quinolone on Salmonella typhimurium. Arch Med Res.31:156–161.

-Bader, F.M. and Badre, R.S. (1975). Induction of dominant lethal mutation in male mice by ethyl alcohol. Nature. 253,134-136.

-Friedman, J.M. and Polifka, J.E. (2000). Teratogenic effects of drugs: a resource for clinicians (TERIS). 2nd ed. Baltimore: Johns Hopkins University Press.

-Greenfield, M. (2004). Commonly used antibiotics in pregnancy. Available : http://drspock.com/.

-Gürbay, A., Gonthier, B., Signorini-Allibe, N., Barret , L., Favier, A. and Hincal, F. (2006). Ciprofloxacin-induced DNA damage in primary culture of rat astrocytes and protection by vitamin E. Neurotoxicol. 27: 6-10.

-Jeffry, C. W., Soo, S. K., James, D. R., Lisa, A. G., Nicholas, A. M., Lee, T. B. and Sharon, D. R. (2000). Inhibition of Clinically Relevarnt mutant variants of HIV-I by quinazolinone Non-Nucleoside reverse transcriptase inhibitors. J. Med. Chem., 43(10), 2019-2030.

-Jinang, J. B., Hesson, D. P., Dusak, B. A., Dexter, D. L., Kang, G. Y. and Hamel, E.(1990). Synthesis and biological evaluation of 2-styryl quinazolinone 4(3H)- ones, a new class of antimiotic anticancer agents which inhibit tubulin polymerization. J. Med. Chem. 33, 1721-1228.

-Katzung, B.G. and Trevor (1998). AJ. Examination and board review pharmacology. 5 ed. Stamford: Appleton and Lange,.

Kim, J.G., Yun, H.I., Shin, H.C., Han, S.S. and Chung, M.K. ( 2000). Embryo lethality and teratogenicity of a new fluoroquinolones antibacterial DW-116 in rats. Arch. Toxical. 74: 120-124.

-Kim, J.G., D.H. Shin, S.H. Kim T.H. Ahn , S.S. Kung, etal., (2003). Developmental toxicity evaluation of the new fluoroquinolones antibacterial DW-116 in rats. Teratogenesis Carcinogenesis Mutagenesis. 1: 123-136.

-Kim, J.G., Shin, D.H., Kim, S.H., Oh, K.S., Jung Y.H., et al., (2004). Peri- and postnatal developmental toxicity of the fluoroquinolone antibacterial DW-116 in rats. Food Chem. Toxicol. 42: 389-395.

-Kim, J.G., Shin, D.H., Kim, S.H., Oh, K.S. , Bae, C. S. et al., (2005). Developmental toxicity assessment of the new flouruquinolone antibacterial DW-116 in rabbits. J.Appl. Toxicol.25: 52-59.

-Lemus, J.A., Blanco, G., Arroyo, B.,Martinez, F. and Grande, J. (2009). Fatal embryo chondral damage associated with fluoroquinolones in eggs of threatened avian scavengers. Environ. Pollut. 157: 2421-2427

-Marcondes, F.K., Bianchi, F.J. and Tanno, A.P. (2002). Determination of the estrus cycle phases of the rats: Some helpful considerations. Brazilizn J. Biol. 62: 609-614.

-McKellar, Q.A., Gibson, I.F., Monteiro, A. and Bregante, M. (1999). Pharmacokinetics of enrofloxacin and danofloxacin in plasma, inflammatory exudates and bronchial secretions of calves following subcutaneous administration. Antimicrob Agents Chemotherap. 43: 1988-1992.

-Nahum, G.G., Uhl, K. and Kennedy, D.L. (2006). Antibiotic use in pregnancy and lactation: what is and is not known about teratogenic and toxic risks. Obstet Gynecol. May.107(5):1120-38.

-Sanjib, I., Chandana, C.B., Pritam, M. and Mohan, B. (2005). Neutropenic mice with E. coli and Staphylococcal. Pharmacokinetics studies of enrofloxacin in infections. Am. J. Vet. Res., 38: 732-749.

ciprofloxacin in albino rat. J. Morphol. Sci., vol. 27, no.1,p. 14-18.

-Schaefer, C., Amoura –Elefant, E., Vial, T., Ornoy, A., Garbis, H., Robert, E., Rodriguez –Pinilla, E., Pexieder, T., Prapas, N., Merlob, P. and Eur, J. (1996). Obstet Gynecol. Reprod Biol. 69 83.

-Siddiqui, M.A. And Naqvi, S.N.H. (2010). Evaluation of the teratogenic potentias of ciprofloxacin in albino rat. J. Morphol. Sci., vol. 27, no.1,p. 14-18.

-Stahlmann, R., (2003). Children as Special Population on Risk – Quinolones as example for xenobiotics exhibiting skeletal toxicity. Arch toxicol. 77(1): 7 – 11.

-Surenda, S. P., Kishor, K., Seth, K. and Arora, R. C. (1968). Role of alkyl substitution in 2, 3 –Disubstitute and 3-substituted 4-quinazolinones on inhibition of pyretic acid oxidation. Pharmacology.12, 138-141.

-Vancutsem, P.M., Babish, J.G. and Schwark, W.S. (1990). The fluoroquinolone antimicrobials: structure,antimicrobial activity, pharmacokinetics, clinical use in domestic animals and toxicity. Cornell Vet. 80(2): 173-86.

-Wolfson, J.S. and Hooper, D.C, (1985). The Fluoroquinolones : Structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrobial Agent and chemotherapy. 28,581-586.

-Wolfson, J.S. and Hooper, D.C, (1989). Fluoroquinolone antimicrobial agents. Clin. Microbiol Rev. 2:378-424.

Downloads

Published

2021-06-23

Issue

Vol. 5 No. 3 (2011)

Section

ARTICLE