Document Type : Original Article
Authors
Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
Abstract
Aminoglycoside antibiotics (AGs) can cause neuromuscular blockade and paralysis of skeletal muscles. To compare the paralytic effects of selected AGs on some motor behaviors in mice, 24 male mice weighing 20.00 to 25.00 g were divided into four treatment groups. Each group was given one of four AGs (gentamicin, dihydrostreptomycin, apramycin and amikacin) at incremental doses that increased half-logarithmically compared to the therapeutic dose (16.00 mg kg-1). Motor behavioral tests included open field test, inclined plane, horizontal bars, static rods, parallel bars and rotarod. Finally, the data were analyzed using descriptive and analytical statistics. Gentamicin and dihydrostreptomycin at 32.00 times of the therapeutic dose produced complete paralysis of the limbs, respiratory arrest, and even death in some animals. However, apramycin and amikacin did not show significant effects on skeletal muscle and motor behaviors at 32.00 times of the therapeutic dose. After administration of apramycin at 100 times of the therapeutic dose, four out of six mice (66.67%) died from respiratory depression. Amikacin at this dose did not cause animal death, although it caused some changes in motor behaviors with a significant difference in comparison with control values. Gentamicin demonstrated significantly more potent effects on motor behaviors compared to the other AGs. Overall, the order of potency was gentamicin > dihydrostreptomycin > apramycin > amikacin. High doses of AGs could impair the skeletal muscle function and disrupt motor behaviors in mice. Furthermore, the paralytic potency of selected AGs on skeletal muscle was significantly different.
Keywords
- Aminoglycoside antibiotics
- Behavioral tests
- Motor behaviors
- Neuromuscular blockade
- Skeletal muscle paralysis
Main Subjects
- Dowling PM. Aminoglycosides and aminocyclitols. In: Giguère S, Prescott JF, Dowling PM (Eds). Antimicrobial therapy in veterinary medicine. 5th New Jersey, USA: Wiley Blackwell 2013; 233 - 255.
- Maddison JE, Watson ADJ, Elliot J. Antibacterial drugs. In: Maddison JE, Page SW, Church DB (Eds). Small animal clinical pharmacology. 2nd London, England: Saunders 2008; 148 - 185.
- Riviere JE, Papich MG. Veterinary pharmacology and therapeutics. 10th New Jersey, USA: Wiley Blackwell 2018; 877-902.
- Amici M, Eusebi F, Miledi R. Effects of the antibiotic gentamicin on nicotinic acetylcholine receptors. Neuro-pharmacology 2005; 49(5): 627-637.
- Krause KM, Serio AW, Kane TR, et al. Aminoglycosides: an overview. Cold Spring Harb Perspect Med 2016; 6(6): a027029. doi: 10.1101/cshperspect.a027029.
- Forge A, Schacht J. Aminoglycoside antibiotics. Audiol Neurootol 2000; 5(1): 3-22.
- Mahi-Birjand M, Yaghoubi S, Abdollahpour-Alitappeh M, et al. Protective effects of pharmacological agents against aminoglycoside-induced nephrotoxicity: a systematic Expert Opin Drug Saf 2020; 19(2): 167-186.
- Wanamaker BP, Massey K. Applied pharmacology for veterinary 5th ed. Amsterdam, The Netherlands: Elsevier 2014; 229-267.
- Jospe-Kaufman M, Siomin L, Fridman M. The relationship between the structure and toxicity of aminoglycoside antibiotics. Bioorg Med Chem Lett 2020; 30(13): 127218. doi: 10.1016/j.bmcl. 2020.127218.
- Hilal-Dandan R, Brunton L. Goodman and Gilman manual of pharmacology and therapeutics. 2nd New York City, USA: McGraw Hill Education 2013; 1848-1869.
- Begg EJ, Barclay ML. Aminoglycosides--50 years on. Br J Clin Pharmacol 1995; 39(6): 597-603.
- Halouzková BA, Hartinger JM, Krátký V, et al. Dosing of aminoglycosides in chronic kidney disease and end-stage renal disease patients treated with intermittent hemodialysis. Kidney Blood Press Res 2022; 47(7): 448-458.
- Ogier JM, Lockhart PJ, Burt RA. Intravenously delivered aminoglycoside antibiotics, tobramycin and amikacin, are not ototoxic in mice. Hear Res 2020; 386: 107870. doi: 10.1016/j.heares.2019.107870.
- Singh YN, Marshall IG, Harvey AL. Pre- and postjunctional blocking effects of aminoglycoside, polymyxin, tetracycline and lincosamide antibiotics. Br J Anaesth 1982; 54(12): 1295-1306.
- Wong J, Brown G. Does once-daily dosing of aminoglycosides affect neuromuscular function? J Clin Pharm Ther 1996; 21(6): 407-411.
- Albiero L, Bamonte F, Ongini E, et al. Comparison of neuromuscular effects and acute toxicity of some aminoglycoside Arch Int Pharmacodyn Ther 1978; 233(2): 343-350.
- Chinyanga HM, Stoyka WW. The effect of colymycin M, gentamicin and kanamycin on depression of neuromuscular transmission induced by pancuronium bromide. Can Anaesth Soc J 1974; 21(6): 569-579.
- Paradelis AG, Triantaphyllidis C, Markomichelakis JM, et al. The neuromuscular blocking activity of amino-deoxykanamycin as compared with that of other aminoglycoside antibiotics. Arzneimittelforschung 1977; 27(1): 141-143.
- Singh YN, Harvey AL, Marshall IG. Antibiotic-induced paralysis of the mouse phrenic nerve-hemidiaphragm preparation, and reversibility by calcium and by neostigmine. Anesthesiology 1978; 48(6): 418-424.
- Wright JM, Collier B. The effects of neomycin upon transmitter release and action. J Pharmacol Exp Ther 1977; 200(3): 576-587.
- Hedley J. BSAVA small animal formulary. Part B: exotic pets. 10th Hoboken, USA: Wiley Blackwell 2020; 148.
- Mayer J, Mans C. Rodents. In: Carpenter JW, Marion C (Eds). Exotic animal formulary. 5th Amsterdam, Netherlands: Elsevier 2017; 459-493.
- Deacon RMJ. Measuring motor coordination in mice. J Vis Exp 2013; 75: e2609. doi: 10.3791/2609.
- Liu M, Kato M, Hashimoto Y. Neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin, astromicin, isepamicin and netilmicin on the diaphragm and limb muscles in the rabbit. Pharmacology 2001; 63(3): 142-146.
- Walsh RN, Cummins RA. The open-field test: a critical review. Psychol Bull 1976; 83(3): 482-504.
- Contet C, Rawlins JN, Deacon RM. A comparison of 129S2/SvHsd and C57BL/6JOlaHsd mice on a test battery assessing sensorimotor, affective and cognitive behaviors: implications for the study of genetically modified mice. Behav Brain Res 2001; 124(1): 33-46.
- Nagy ZM, Forrest EJ. Open-field behavior of C3H mice: effect of size and illumination of field. Psychon Sci 1970; 20(1): 19-21.
- Nagy ZM, Glaser HD. Open-field behavior of C57BL/6J mice: effect of illumination, age, and number of test days. Psychon Sci 1970; 19(3): 143-145.
- Bakre AG, Olayemi JO, Olowoparija SF, et al. Neurobehavioural and muscle-relaxant activities of nifedipine in mice. J Int Res Med Pharm Sci 2020; 15(2): 1-11.
- Deacon RMJ, Brook RC, Meyer D, et al. Behavioral phenotyping of mice lacking the KATP channel subunit Kir6. 2. Physiol Behav 2006; 87(4): 723-733.
- Taylor SM. Lesion localization and the neurologic examination. In: Nelson RW, Couto CG (Eds). Small animal internal medicine. 6th Amsterdam, Netherlands: Elsevier 2019; 1037-1062.
- Jacquez B, Choi H, Bird CW, et al. Characterization of motor function in mice developmentally exposed to ethanol using the Catwalk system: Comparison with the triple horizontal bar and rotarod tests. Behav Brain Res 2021; 396: 112885. doi: 10.1016/j.bbr. 2020.112885.
- Kuribara H, Higuchi Y, Tadokoro S. Effects of central depressants on rota-rod and traction performances in mice. Jpn J Pharmacol 1977; 27(1): 117-126.
- Guenther K, Deacon RM, Perry VH, et al. Early behavioural changes in scrapie-affected mice and the influence of dapsone. Eur J Neurosci 2001; 14(2): 401-409.
- Ahmad SS, Priyambada S, Vijayalakshmi P. Comparative study of muscle relaxant activity of midazolam with diazepam in male albino mice. Int J Pharm Sci Rev Res 2019; 58(2): 39-44.
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