Acute Toxic Effects of levamisole and Ivermectin in Mice | ||||
| Journal of Applied Veterinary Sciences | ||||
| Article 10, Volume 8, Issue 3, July 2023, Page 75-81 PDF (516.83 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/javs.2023.213855.1236 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
Farah F. Almawla1; Banan Kh. Al-baggou  2
| ||||
| 1Department of Physiology, Biochemistry, and Pharmacology at the College of Veterinary Medicine, University of Mosul, Iraq | ||||
| 2Veterinary Toxicology and pharmacology, college of Veterinary Medicine ,University of Mosul,Iraq | ||||
| Abstract | ||||
| The study's objectives were to investigate the acute toxicity and related biochemical effects of levamisole and ivermectin in mice. The 24 h oral median lethal dose (LD50) of levamisole was determined by the up-and-down method and was 155.5 mg/ kg of body weight. The treated mice showed signs of acute poisoning represented by excessive grooming, lacrimation, piloerection, straub tail, tachycardia, bulged eyes, tremor, convulsion and finally death within 24 h of treatment. The approximate lethal dose (ALD) of levamisole was 368 mg/kg, and the mice showed signs of poisoning similar to the previous signs of poisoning within 24 h of treatment. The 24 h oral LD50 of ivermectin was 115.2 mg/kg and the mice showed acute signs of poisoning, represented by excessive grooming, lacrimation, closed eyelids, piloerection, tachycardia, rapid respiration, depression, flat body appearance, paralysis and finally death within 24 h of treatment, while the approximate lethal dose of ivermectin was 121 mg/kg and also with the presence of severe poisoning signs as mentioned before. Non-lethal toxic doses of levamisole at 100 and 150 mg/kg and ivermectin at 75 and 100 mg/kg led to significant blood biochemical changes after 24 h of treatment, represented by a significant increase in the activity of the enzymes alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH), and a significantly increased total bilirubin concentration in the blood plasma of mice. These results proved the presence of acute toxicity and biochemical effects of both anthelmintics levamisole and ivermectin even though they have wide safety margins. | ||||
| Keywords | ||||
| Biochemical changes; Ivermectin; Levamisole; Mice; Toxic effects | ||||
| References | ||||
|
REFERENCES ABDOU, K. A., and SHARKAWY, A. A., 2004. Some toxicological studies on ivermectin in goats. In Proceeding of the 20 Annual meeting of the Egyptian Society of toxicology. Bibliotheca Alexandria, Alexandria University, Alexandria, Egypt, 18-19.
ABONGWA, M., MARTIN, R. J., and ROBERTSON, A. P., 2017. A brief review on the mode of action of antinematodal drugs. Acta veterinaria, 67(2), 137-152.https://doi.org/10.1515/acve-2017-0013.
AL-NAJMAWI, T. K., and AL-ZUBAIDY, M. H., 2022. Acute toxicity events of ivermectin in chicks’ model. Iraqi Journal of Veterinary Sciences, 36(4), 1119-1124. https://doi.org/10.33899/ijvs.2022.133188.2188
ARISE, R. O., and MALOMO, S. O., 2009. Effects of ivermectin and albendazole on some liver and kidney function indices in rats. Afr J Biochem Res, 3(5), 190-197.
BHARDWAJ, K., ABRAHAM, J., and KAUR, S., 2020. Natural product as avermectins and milbemycins for agriculture perspectives. Natural Bioactive Products in Sustainable Agriculture, 259-271. https://doi.org/10.1007/978-981-15-3024-1_12
CAMPBELL, C. W. 2012. History of avermectin and ivermectin, with notes on the history of other macrocyclic lactone antiparasitic agents. Current pharmaceutical biotechnology, 13(6), 853-865. https://doi.org/10.2174/138920112800399095.
CAMPILLO, J. T., EIDEN, C., BOUSSINESQ, M., PION, S. D., FAILLIE, J. L., and CHESNAIS, C. B., 2022. Adverse reactions with levamisole vary according to its indications and misuse: A systematic pharmacovigilance study. British Journal of Clinical Pharmacology, 88(3), 1094-1106. https://doi.org/10.1111/bcp.15037.
CHARLIER, J., HOSTE, H., and SOTIRAKI, S., 2023. COMBAR–Combatting anthelmintic resistance in ruminants. Parasite, 30. https://doi.org/10.1051%2Fparasite%2F2023006
DEPASS, L. R. 1989. Alternative approaches in median lethality (LD50) and acute toxicity testing. Toxicology letters, 49(2-3), 159-170. https://doi.org/10.1016/0378-4274(89)90030-1
DIXON, W. J. 1980. Efficient analysis of experimental observations. Annual review of pharmacology and toxicology, 20(1), 441-462. https://doi.org/10.1146/annurev.pa.20.040180.002301
DONG, Z., XING, S. Y., ZHANG, J. Y., and ZHOU, X. Z., 2020. 14-Day repeated intraperitoneal toxicity test of ivermectin microemulsion injection in wistar rats. Frontiers in Veterinary Science, 7, 1091. https://doi.org/10.3389/fvets.2020.598313.
EL-SABER BATIHA, G., ALQAHTANI, A., ILESANMI, O. B., SAATI, A. A., EL-MLEEH, A., HETTA, H. F., and MAGDY BESHBISHY, A., 2020. Avermectin derivatives, pharmacokinetics, therapeutic and toxic dosages, mechanism of action, and their biological effects. Pharmaceuticals, 13(8), 196. https://doi.org/10.3390/ph13080196.
GUPTA, R. C., MUKHERJEE, I. R. M., MALIK, J. K., DOSS, R. B., DETTBARN, W. D., and MILATOVIC, D., 2019. Insecticides. In Biomarkers in toxicology, 455-475. Academic Press. https://doi.org/10.1016/B978-0-12-814655-2.00026-8
HASSAN, F. S., and Al-BAGGOU, B. K., 2022. Some Biochemical changes induced by Toxic Effects of Sulfur in Mice. Journal of Applied Veterinary Sciences 7(4), 97–103. https://dx.doi.org/10.21608/javs2022.155557.1173.
KAMGNO, J., GARDON, J., GARDON-WENDEL, N., DUKE, B. O., and BOUSSINESQ, M., 2004. Adverse systemic reactions to treatment of onchocerciasis with ivermectin at normal and high doses given annually or three-monthly. Transactions of the Royal Society of Tropical Medicine and Hygiene, 98(8), 496-504. https://doi.org/10.1016/j.trstmh.2003.10.018.
KAPLAN, R. M., and VIDYASHANKAR, A. N., 2012. An inconvenient truth: global worming and anthelmintic resistance. Veterinary parasitology, 186(1-2). 70-78. https://doi.org/10.1016/j.vetpar.2011.11.048.
KHALAF, W. K. 2022. Detection of Internal Parasites in Turkeys in Erbil city. Journal of Applied Veterinary Sciences, 7(4), 1-5. https://dx.doi.org/10.21608/javs.2022.143017.1155.
LYNN, R. C. 2008. Antiparasitic drugs. Georgis’ parasitology for veterinarians, 9, 254-294.
MANSOOR, A. S. 2004. Neurobehavioral toxicity of levamisole in chicks. M.Sc. Thesis, College of Veterinary Medicine, University of mosul, Iraq.
MIDTHUN, K. M., NELSON, L. S., and LOGAN, B. K., 2021. Levamisole a toxic adulterant in illicit drug preparations: a review. Therapeutic Drug Monitoring, 43(2), 221. https://doi.org/10.1097/ftd.0000000000000851
ODO, U. U., CHRISTIAN EZEOYILI, I., AGUZIE, I. O., OLUAH, S. N., MADU, J., and NWANI, C. D., 2020. Effect of ivermectin® on biometric characteristics and organ biomarkers of African catfish Clarias gariepinus. Marine and Freshwater Behaviour and Physiology, 53(1), 17-33. https://doi.org/10.1080/10236244.2020.1734000.
OSAMA, A., FATMA, A., MOHAMED, E., HAMED, M. F., and HAMZAH, O., 2015. Studying the effect of Echinacea purpurea root on hematological, biochemical and histopathological alterations in cyclophosphamide treated Rats. Ann Vet Anim Sci, 3(2), 63-72. http://naturepub.org/navas.
OTHMAN, H. M., OTHMAN, F. M., and ALJALI, A. A., 2022. The effect of different dosages on hematological and some biochemical parameters of ivermectin after administration in goats. Libyan Journal of Basic Sciences, 17(1), 35-43. https://ljbs.omu.edu.ly/ eISSN 2707-6261.
POODA, H. S., RAYAISSE, J. B., HIEN, D. F. D. S., LEFÈVRE, T., YERBANGA, S. R., BENGALY, Z., and MOULINE, K., 2015. Administration of ivermectin to peridomestic cattle: a promising approach to target the residual transmission of human malaria. Malaria journal, 14, 1-12. https://doi.org/10.1186/s12936-015-1001-z.
QIAN, K., ZHONG, S., XIE, K., YU, D., YANG, R., and GONG, D. W., 2015. Hepatic ALT isoenzymes are elevated in gluconeogenic conditions including diabetes and suppressed by insulin at the protein level. Diabetes/metabolism research and reviews, 31(6), 562-571. https://doi.org/10.1002/dmrr.2655.
REHNI, A. K., and SINGH, T. G., 2010. Levamisole-induced reduction in seizure threshold: a possible role of nicotinic acetylcholine receptor-mediated pathway. Naunyn-Schmiedeberg's archives of pharmacology, 382, 279-285. https://doi.org/10.1007/s00210-010-0543-4.
ROMINE, N. M., MARTIN, R. J., and BEETHAM, J. K., 2014. Transcriptomic evaluation of the nicotinic acetylcholine receptor pathway in levamisole-resistant and-sensitive Oesophagostomum dentatum. Molecular and biochemical parasitology, 193(1), 66-70. https://doi.org/10.1016/j.molbiopara.2014.02.002.
SADATI, N. Y., YOUSSEFI, M. R., HOSSEINIFARD, S. M., TABARI, M. A., and GIORGI, M., 2021. Pharmacokinetics and pharmacodynamics of single and multiple-dose levamisole in belugas (Huso huso): Main focus on immunity responses. Fish and Shellfish Immunology, 114, 152-160. https://doi.org/10.1016/j.fsi.2021.04.016.
SHARMA, N., RAHAL, A., MISHRA, A., CHATURVEDI, V., GANGWAR, C., and DASS, G., 2020. Successful Management of Levamisole Toxicity in Sheep: A Case Report. http://jakraya.com/journal/pdf/27-vcsArticle_4.pdf.
SHOOP, W., and SOLL, M., 2002. Chemistry, pharmacology and safety of the macrocyclic lactones: ivermectin, abamectin and eprinomectin. In Macrocyclic lactones in antiparasitic therapy (pp. 1-29). Wallingford UK: CAB International. https://doi.org/10.1079/9780851996172.0001.
Swor, T. M., Whittenburg, J. L., and Chaffin, M. K., 2009. Ivermectin toxicosis in three adult horses. Journal of the American Veterinary Medical Association, 235(5), 558-562. https://doi.org/10.2460/javma.235.5.558.
TAWFEEK, S. E., DOMOUKY, A. M., and ABDEL-KAREEM, R. H., 2021. Protective effect of vitamin C against ivermectin induced nephrotoxicity in different age groups of male wistar rats: bio-histopathological study. Anatomy and Cell Biology, 54(4), 501-517. https://doi.org/10.5115/acb.21.124.
TRAILOVIC, S. M., and NEDELJKOVIC, J. T., 2011. Central and peripheral neurotoxic effects of ivermectin in rats. Journal of Veterinary Medical Science, 73(5), 591-599. https://doi.org/10.1292/jvms.10-0424.
VAN GENDEREN, P.J.J. 2008. Antihelminthic drugs. In Side Effects of Drugs Annual (Vol. 30, pp. 364-368). Elsevier. https://doi.org/10.1016/S0378-6080(08)00031-7.
ZOGHROBAN, H. S., ELMANSORY, B. M., ISSA, Y. A., ELTOKHY, A. K., SAFIA, H. S. A., EL MAGHRABY, G. M., and SALAMA, A.M. 2023. Novel insights on the therapeutic effect of levamisole on the chronic toxoplasmosis in mice model. Experimental Parasitology, 248, 108515. https://doi.org/10.1016/j.exppara.2023.108515
| ||||
|
Statistics Article View: 501 PDF Download: 494 |
||||
