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An Experimental Study of the Systemic Alteration of Nitroimidazoles in the Middle Stage of Embryonic Development
Document Type : Original Article
Authors
1 Graduate student, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
2 Department of Avian Medicine, School of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
3 Center of Comparative&experimental medicine, Basic sciences in infection diseases research center, School of medicine, Shiraz University of Medical Sciences, Shiraz, Iran
4 School of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
Abstract
Nitroimidazole compounds have been traditionally used in the veterinary and human medicine, but their uses are sometimes associated with some side effects. Toxicopathological effects of nitroimidazoles have always been a major concern. There is scant information available about the pathological alterations of nitroimidazole compounds in the embryo. The objective of this study was to determine the macroscopic and microscopic lesions of metronidazole in the chicken embryo. Fertile broiler eggs were divided into two equal treatment groups as follows: group 1: saline-injected group, the eggs were injected with sterile physiological saline solution into the chorioallantoic sac. Group 2, individuals were injected with metronidazole at a dosage of 25 mg/Kg egg-weight three times into the chorioallantoic sac. Macroscopically, the embryos were stunted. The feet and wings were small and the feather formation was seriously affected. In this group, the embryos were affected by schistosomus reflexus. Microscopically, all organs were hyperemic. Based on macroscopic and microscopic findings, it is concluded that metronidazole at the above-mentioned concentration is toxic to the chicken embryo. The current study also advises caution in the extended use of nitroimidazole compounds.
Keywords
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Bottenberg MM, Hegge KA, Eastman DK, Kumar R (2011). Metronidazole‐Induced encephalopathy: a Case Report and Review of the Literature. J. Clin. Pharmacol. 51(1): 112-116.
Burtin P, Taddio A, Ariburnu O, Einarson TR, Koren G (1995). Safety of metronidazole in pregnancy: a meta-analysis. Am. J. Obstet. Gynecol. 172(2): 525-529.
Carroll MW, Jeon D, Mountz JM, Lee JD, Jeong YJ, Zia N, Lee M, Lee J, Via LE, Lee S (2013). Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis. Antimicrob. Agents Chemother. 57(8): 3903-3909.
Coskun Y, Erarslan E, Dogan M, Koç H, Yigit SN, Yüksel I (2012). Severe Hepatotoxicity as a Result of Extended Use of Ornidazole. J. Clin. Gastroenterol. 46(6): 529-530.
Dowling PM (2013). Miscellaneous Antimicrobials: lonophores, Nitrofurans, Nitroimidazoles, Rifamycins. Antimicrobial Therapy in Veterinary Medicine 315.
Frasca D, Dahyot-Fizelier C, Adier C, Mimoz O, Debaene B, Couet W, Marchand S (2014).
Metronidazole and hydroxymetronidazole central nervous system distribution: 2. cerebrospinal fluid concentration measurements in patients with external ventricular drain. Antimicrob. Agents Chemother. 58(2): 1024-1027.
Giguère S, Prescott JF, Dowling PM (2013). Antimicrobial therapy in veterinary medicine, John Wiley & Sons.
Hamburger V (1942). A manual of experimental embryology, University of Chicago Press Chicago.
Han J, Zhang L, Yang S, Wang J, Tan D (2014). Detrimental Effects of Metronidazole on Selected Innate Immunological Indicators in Common Carp (Cyprinus carpio L.). Bull. Environ. Contam. Toxicol. 92(2): 196-201.
Hari A, Srikanth BA, Lakshmi GS (2013). Metronidazole induced cerebellar ataxia. Indian J Pharmacol 45(3): 295.
Heisterberg L (1984). Placental transfer of metronidazole in the first trimester of pregnancy. J. Perinatal Med. 12(1): 43-45.
Hoogenboom L, Oorsprong M, Van Vliet T, Kuiper H (1991). The use of pig hepatocytes for cytotoxicity studies of veterinary drugs: a comparative study with furazolidone and other nitrofurans. Toxicol. In Vitro 5(1): 31-38.
Jacobsen ID, Große K, Hube B (2012). Embryonated Chicken Eggs as Alternative Infection Model for Pathogenic Fungi. Host-Fungus Interactions, Springer: 487-496.
Kuriyama A, Jackson JL, Doi A, Kamiya T (2011). Metronidazole-induced central nervous system toxicity: a systematic review. Clin. Neuropharmacol. 34(6): 241-247.
Lamp KC, Freeman CD, Klutman NE, Lacy MK (1999). Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials. Clin. Pharmacokinet. 36(5): 353-373.
Leitsch D, Janssen BD, Kolarich D, Johnson PJ, Duchêne M (2014). Trichomonas vaginalis flavin reductase 1 and its role in metronidazole resistance. Mol. Microbiol. 91(1): 198-208.
Lucasti C, Popescu I, Ramesh MK, Lipka J, Sable C (2013). Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial.
J. Antimicrob. Chemother. 68(5): 1183-1192.
Manousaridis I, Mavridou S, Goerdt S, Leverkus M, Utikal J (2013). Cutaneous side effects of inhibitors of the RAS/RAF/MEK/ERK signalling pathway and their management. J. Eur. Acad. Dermatol. Venereol. 27(1): 11-18.
McDonald HM, O'LOUGHLIN JA, Vigneswaran R, Jolley PT, McDONALD PJ (1994). Bacterial vaginosis in pregnancy and efficacy of short-course oral metronidazole treatment: a randomized controlled trial. Obstet. Gynecol. 84(3): 343-348.
Mukherjee T, Boshoff H (2011). Nitroimidazoles for the treatment of TB: past, present and future. Future Med. Chemis. 3(11): 1427-1454.
Oda SS (2012). Histopathological and biochemical alterations of metronidazole-induced toxicity in male rats. GV 9(3): 303-310.
Ohta Y, Kidd M (2001). Optimum site for in ovo amino acid injection in broiler breeder eggs. Poult. Sci. 80(10): 1425-1429.
Pasupuleti V, Escobedo AA, Deshpande A, Thota P, Roman Y, Hernandez AV (2014). Efficacy of 5- Nitroimidazoles for the Treatment of Giardiasis: A Systematic Review of Randomized Controlled Trials. PLoS Negl. Trop. Dis. 8(3): e2733.
Patterson S, Wyllie S (2014). Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects. Trends Parasitol.
Pinches M (2006). Getting results in clinical pathology 4. Influence of medications on biochemical parameters. In Practice (0263841X) 28(5):
Radko L, Minta M (2012). Cytotoxicity of Some Nitroimidazole Derivatives-Comparative Studies on Human and Rat Hepatoma Cell Lines. Bull Vet Inst Pulawy 56(4): 579-584.
Sarna JR, Furtado S, Brownell AKW (2013). Neurologic Complications of Metronidazole. The Canadian J. Neur. Sci. 40(6): 768-776.
Senousy BE, Belal SI, Draganov PV (2010). Hepatotoxic effects of therapies for tuberculosis. Nature Reviews Gastroenterology and Hepatology 7(10): 543-556.
Sweetman SC, Pharm B, PharmS F, Eds. (2009). Martindale: The Complete Drug Reference. London, Pharmaceutical Press.
Tavakkoli H, Derakhshanfar A, Noori Gooshki S (2013). A short preliminary experimental study on teratogenic effect of methenamine in embryonic model. Int. J. Adv. Biol. Biom. Res. 1(12): 1523-1528.
Tavakkoli H, Derakhshanfar A, Noori Gooshki S (2014). The effect of florfenicol egg-injection on embryonated chicken egg. Int. J. Adv. Biol. Biom. Res. 2(2): 496-503.
Tavakkoli H, Derakhshanfar A, Noori Gooshki S (2014). Toxicopathological lesions of fosfomycin in embryonic model. Euro. J. Exp. Bio. 4(2): 63-71.
Turnbull A, Lin Z, Matthews B (2013). Severe bilateral anterior uveitis secondary to giardiasis, initially misdiagnosed as a side effect of metronidazole. Eye 27(10): 1225-1226.
Bergan T (1984). Antibacterial activity and pharmacokinetics of nitroimidazoles. A review. Scand. J. Infect. Dis. Suppl. 46(64-71.
Bottenberg MM, Hegge KA, Eastman DK, Kumar R (2011). Metronidazole‐Induced encephalopathy: a Case Report and Review of the Literature. J. Clin. Pharmacol. 51(1): 112-116.
Burtin P, Taddio A, Ariburnu O, Einarson TR, Koren G (1995). Safety of metronidazole in pregnancy: a meta-analysis. Am. J. Obstet. Gynecol. 172(2): 525-529.
Carroll MW, Jeon D, Mountz JM, Lee JD, Jeong YJ, Zia N, Lee M, Lee J, Via LE, Lee S (2013). Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis. Antimicrob. Agents Chemother. 57(8): 3903-3909.
Coskun Y, Erarslan E, Dogan M, Koç H, Yigit SN, Yüksel I (2012). Severe Hepatotoxicity as a Result of Extended Use of Ornidazole. J. Clin. Gastroenterol. 46(6): 529-530.
Dowling PM (2013). Miscellaneous Antimicrobials: lonophores, Nitrofurans, Nitroimidazoles, Rifamycins. Antimicrobial Therapy in Veterinary Medicine 315.
Frasca D, Dahyot-Fizelier C, Adier C, Mimoz O, Debaene B, Couet W, Marchand S (2014).
Metronidazole and hydroxymetronidazole central nervous system distribution: 2. cerebrospinal fluid concentration measurements in patients with external ventricular drain. Antimicrob. Agents Chemother. 58(2): 1024-1027.
Giguère S, Prescott JF, Dowling PM (2013). Antimicrobial therapy in veterinary medicine, John Wiley & Sons.
Hamburger V (1942). A manual of experimental embryology, University of Chicago Press Chicago.
Han J, Zhang L, Yang S, Wang J, Tan D (2014). Detrimental Effects of Metronidazole on Selected Innate Immunological Indicators in Common Carp (Cyprinus carpio L.). Bull. Environ. Contam. Toxicol. 92(2): 196-201.
Hari A, Srikanth BA, Lakshmi GS (2013). Metronidazole induced cerebellar ataxia. Indian J Pharmacol 45(3): 295.
Heisterberg L (1984). Placental transfer of metronidazole in the first trimester of pregnancy. J. Perinatal Med. 12(1): 43-45.
Hoogenboom L, Oorsprong M, Van Vliet T, Kuiper H (1991). The use of pig hepatocytes for cytotoxicity studies of veterinary drugs: a comparative study with furazolidone and other nitrofurans. Toxicol. In Vitro 5(1): 31-38.
Jacobsen ID, Große K, Hube B (2012). Embryonated Chicken Eggs as Alternative Infection Model for Pathogenic Fungi. Host-Fungus Interactions, Springer: 487-496.
Kuriyama A, Jackson JL, Doi A, Kamiya T (2011). Metronidazole-induced central nervous system toxicity: a systematic review. Clin. Neuropharmacol. 34(6): 241-247.
Lamp KC, Freeman CD, Klutman NE, Lacy MK (1999). Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials. Clin. Pharmacokinet. 36(5): 353-373.
Leitsch D, Janssen BD, Kolarich D, Johnson PJ, Duchêne M (2014). Trichomonas vaginalis flavin reductase 1 and its role in metronidazole resistance. Mol. Microbiol. 91(1): 198-208.
Lucasti C, Popescu I, Ramesh MK, Lipka J, Sable C (2013). Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial.
J. Antimicrob. Chemother. 68(5): 1183-1192.
Manousaridis I, Mavridou S, Goerdt S, Leverkus M, Utikal J (2013). Cutaneous side effects of inhibitors of the RAS/RAF/MEK/ERK signalling pathway and their management. J. Eur. Acad. Dermatol. Venereol. 27(1): 11-18.
McDonald HM, O'LOUGHLIN JA, Vigneswaran R, Jolley PT, McDONALD PJ (1994). Bacterial vaginosis in pregnancy and efficacy of short-course oral metronidazole treatment: a randomized controlled trial. Obstet. Gynecol. 84(3): 343-348.
Mukherjee T, Boshoff H (2011). Nitroimidazoles for the treatment of TB: past, present and future. Future Med. Chemis. 3(11): 1427-1454.
Oda SS (2012). Histopathological and biochemical alterations of metronidazole-induced toxicity in male rats. GV 9(3): 303-310.
Ohta Y, Kidd M (2001). Optimum site for in ovo amino acid injection in broiler breeder eggs. Poult. Sci. 80(10): 1425-1429.
Pasupuleti V, Escobedo AA, Deshpande A, Thota P, Roman Y, Hernandez AV (2014). Efficacy of 5- Nitroimidazoles for the Treatment of Giardiasis: A Systematic Review of Randomized Controlled Trials. PLoS Negl. Trop. Dis. 8(3): e2733.
Patterson S, Wyllie S (2014). Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects. Trends Parasitol.
Pinches M (2006). Getting results in clinical pathology 4. Influence of medications on biochemical parameters. In Practice (0263841X) 28(5):
Radko L, Minta M (2012). Cytotoxicity of Some Nitroimidazole Derivatives-Comparative Studies on Human and Rat Hepatoma Cell Lines. Bull Vet Inst Pulawy 56(4): 579-584.
Sarna JR, Furtado S, Brownell AKW (2013). Neurologic Complications of Metronidazole. The Canadian J. Neur. Sci. 40(6): 768-776.
Senousy BE, Belal SI, Draganov PV (2010). Hepatotoxic effects of therapies for tuberculosis. Nature Reviews Gastroenterology and Hepatology 7(10): 543-556.
Sweetman SC, Pharm B, PharmS F, Eds. (2009). Martindale: The Complete Drug Reference. London, Pharmaceutical Press.
Tavakkoli H, Derakhshanfar A, Noori Gooshki S (2013). A short preliminary experimental study on teratogenic effect of methenamine in embryonic model. Int. J. Adv. Biol. Biom. Res. 1(12): 1523-1528.
Tavakkoli H, Derakhshanfar A, Noori Gooshki S (2014). The effect of florfenicol egg-injection on embryonated chicken egg. Int. J. Adv. Biol. Biom. Res. 2(2): 496-503.
Tavakkoli H, Derakhshanfar A, Noori Gooshki S (2014). Toxicopathological lesions of fosfomycin in embryonic model. Euro. J. Exp. Bio. 4(2): 63-71.
Turnbull A, Lin Z, Matthews B (2013). Severe bilateral anterior uveitis secondary to giardiasis, initially misdiagnosed as a side effect of metronidazole. Eye 27(10): 1225-1226.
Volume 2, Issue 5 - Serial Number 5
May and June 2014Pages 1468-1474
- Receive Date 31 July 2014
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