: Investigating the effects of oral administration of metronidazole on the biochemical factors of pigeon blood
Subject Areas : Pultry Diseases
masoud soltani alvar
1
*
,
mohamad reza sorush
2
,
mohamad hossein naserbakht
3
,
hamidreza shabani
4
1 - Department of Veterinary Medicine, Faculty of Agriculture and Veterinary Medicine, Shushtar Branch, Islamic Azad University, Shushtar, Iran
2 - Doctor of Veterinary Medicine Student, Faculty of Veterinary Medicine, Shushtar Azad University, Shushtar, Iran
3 - Doctor of Veterinary Medicine Student, Faculty of Veterinary Medicine, Shushtar Azad University, Shushtar, Iran
4 - Doctor of Veterinary Medicine Student, Faculty of Veterinary Medicine, Shushtar Azad University, Shushtar, Iran
Keywords: antibiotic, metronidazole, pigeon,
Abstract :
Metronidazole is a commonly used antibiotic for pigeons, but improper usage can lead to adverse effects. This study aimed to evaluate the impact of oral metronidazole on the biochemical parameters of pigeon blood. Thirty adult pigeons (regardless of sex) were purchased from local bird shops in Shushtar and randomly assigned to three groups: a control group a group receiving 25 mg/kg body weight of metronidazole, and a group receiving 50 mg/kg. Blood samples were collected to measure oxidative stress markers (malondialdehyde, superoxide dismutase, catalase), liver enzymes (AST ALT ALP), and kidney function indicators (uric acid, creatinine, BUN). In addition, liver and kidney tissues were sampled for histopathological evaluation.Results showed that oral metronidazole significantly increased levels of malondialdehyde, superoxide dismutase, and catalase (P<0.05), indicating elevated oxidative stress. At 50 mg/kg, there was a significant increase in liver enzymes AST and ALT (P<0.05), while the 25 mg/kg group showed no significant difference from the control. Similarly, uric acid, BUN, and creatinine levels were significantly elevated at 50 mg/kg, but not at 25 mg/kg. Histological analysis revealed dose-dependent damage, including liver necrosis, hyperemia, hepatic artery enlargement, and renal glomerulonephritis at the higher dose.In conclusion, while metronidazole is effective, the 50 mg/kg dose leads to significant oxidative stress an organ damage in pigeons. A lower dose of 25 mg/kg appears safer and may be preferable. Further studies are recommended to comprehensively understand the drug’s risks and therapeutic potential in avian species.
1. اصول زاده ر، سلطانی الوار م، پدرام ب. 1398. بررسی هیستوپاتولوژیک کبد به دنبال تجویز داروهای آسپرومازین و زایلازین به عنوان پیش داروی بیهوشی در کبوتر، دوفصلنامه علمی پژوهشی هیستوبیولوژی دامپزشکی، 7 (3): 61-70.
2. برکی تبار ص، پیغان ر، راضی جلالی م. 1398. بررسی تاثیر داروهای مترونیدازول و لوامیزول به صورت خوراکی و حمام بر برخی آنزیم ها و پروتئین های پلاسمای خون ماهی کپور معمولی، نشریه دامپزشکی ایران، 15 (1): 5-14.
3. بهزادی منش ش. 1399. شناسایی فون پرندگان و بررسی الگوی پراكنش آنها در پارك جنگلی شهید باهنر اراك،پنجمین همایش ملی پژوهشی توسعه و ترویج در کشاورزی، منابع طبیعی پایدار و محیط زیست،جیرفت، 1-1.
4. توکلی، هادی و چاکری بیرجندی، حسین و سالارپور، رضوان،1396،گزارش وقوع همزمان کاندیدیازیس و تریکوموناس در کبوتر: علایم درمانگاهی، کالبدگشایی و آثار بیماری بر کارایی پرنده،یازدهمین کنگره دانشجویان دامپزشکی ایران،بابل، 1-1.
5. دهقان م.ح، مجیدپور ع. 1384. اثر مترونیدازول در کاهش سطح لیپیدهای خون، مجله دانشگاه علوم پزشکی و خدمات بهداشتی درمانی اردبیل، 5 (3): 235-240.
6. حیدرپور م. 1398. خون شناسی دامپزشکی، انتشارات دانشگاه فردوسی مشهد، چاپ اول، 1-20.
7. روث د، دیوید ام، جاناتان ب. 1391. ایمونولوژی رایت، انتشارات ارجمند، مترجمین: فتح الله (ی): ع، خدایی م، ناظر م، ولایی ه. 1-2-12.
8. مقربیان ن، خاکساری م، بلادی نژاد س، گرمایی ب، اسدپور ا. 1400. بهبود سمیت کلیوی و کبدی ناتشی از سیس پلاتین توسط پالماتین در موش های صحرایی نر، 1-1.
9. موسوی م، عابدی غ، جهاندیده ع، حصارکی س. 1398. تغییرات هیستوپاتولوژی و آنزیمهای سرم بهوسیله پروپوفول در ترکیب با داروهای پیشبیهوشی در کبوتر اهلی، مجله جراحی دامپزشکی ایران 14 (2): 1-1.
10. مهبد امیر س.ع. 1387. هماتولوژی عملی، چاپ چهارم، تهران، نشر اشراقیه، ص ۱۶۶-۱۵۳.
11. لطفی ف، اصغری ا، عابدی غ. 1394. مقایسه بالینی و هیستوپاتولوژی متامیزول و میدازولام به عنوان داروی پیش بیهوشی در کبوتر، آسیب شناسی درمانگاهی دامپزشکی (دامپزشکی تبریز)، 317-326.
12. AbdRabou MA, Alrashdi BM, Alruwaili HK, Elmazoudy RH, Alwaili MA, Othman SI, Alghamdi FA, Fahmy GH. Exploration of Maternal and Fetal Toxicity Risks for Metronidazole-Related Teratogenicity and Hepatotoxicity through an Assessment in Albino Rats. Toxics. 2023 Mar 25;11(4):303. doi: 10.3390/toxics11040303. PMID: 37112529; PMCID: PMC10141390.
13. Adiss DG,Shaffer N,fowler BS,Tauxe Rv.The epidemiology of Appendicitis and appendectomy in the united states. Am J Epidemiol 1990; 132: 910.
14. Ajiji P., Uzunali A., Ripoche E., Vittaz E., Vial T., Maison P. Investigating the efficacy and safety of metronidazole during pregnancy; A systematic review and meta-analysis. Eur. J. Obstet. Gynecol. Reprod. Biol. X. 2021;11:100128.
15. Ambrose PG, Bhavnani SM, Rubino CM, Louie A, Gumbo T, Forrest A, Drusano GL. Pharmacokinetics-pharmacodynamics of antimicrobial therapy: it's not just for mice anymore. Clin Infect Dis. 2007 Jan 01;44(1):79-86.
16. Andersson RE,Meta analysis of the clinical and laboratory diagnosis of appendicitis, Br J surg 2004; 91: 28-37.
17. Annaheim D, Vogler BR, Sigrist B, Vögtlin A, Hüssy D, Breitler C, Hartnack S, Grund C, King J, Wolfrum N, Albini S. Screening of Healthy Feral Pigeons (Columba livia domestica) in the City of Zurich Reveals Continuous Circulation of Pigeon Paramyxovirus-1 and a Serious Threat of Transmission to Domestic Poultry. Microorganisms. 2022 Aug 17;10(8):1656. doi: 10.3390/microorganisms10081656. PMID: 36014074; PMCID: PMC9412584.
18. Armet AM, Deehan EC, O’Sullivan AF, Mota JF, Field CJ, Prado CM, et al.. Rethinking healthy eating in light of the gut microbiome. Cell Host Microbe 2022; 30(6): 764–85.
19. Boronat A, Rodriguez-Morato J, Serreli G, Fito M, Tyndale RF, Deiana M, et al.. Contribution of biotransformations carried out by the microbiota, drug-metabolizing enzymes, and transport proteins to the biological activities of phytochemicals found in the diet. Adv Nutr 2021; 12(6): 2172–89
20. Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, Fish DN, Napolitano LM, Sawyer RG, Slain D, Steinberg JP, Weinstein RA., American Society of Health-System Pharmacists. Infectious Disease Society of America. Surgical Infection Society. Society for Healthcare Epidemiology of America. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013 Feb 01;70(3):195-283.
21. Brauner A, Fridman O, Gefen O, Balaban NQ. Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nat Rev Microbiol. 2016 Apr;14(5):320-30.
22. Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter (2002). "Leukocyte functions and percentage breakdown". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 0-8153-4072-9.
23. Chong C.Y.L., Orr D., Plank L.D., Vatanen T., O’Sullivan J.M., Murphy R. Randomised Double-Blind Placebo-Controlled Trial of Inulin with Metronidazole in Non-Alcoholic Fatty Liver Disease (NAFLD) Nutrients. 2020;12:937.
24. Christensen JJ, Arnesen EK, Andersen R, Eneroth H, Erkkola M, Hoyer A, et al.. The Nordic Nutrition Recommendations 2022 – principles and methodologies. Food Nutr Res 2020; 64: 4402. doi: 10.29219/fnr.v64.4402
25. Daniels, V. G. , Wheater, P. R. , & Burkitt, H.G. (1979). Functional histology: A text and colour atlas. Edinburgh: Churchill Livingstone. ISBN 0-443-01657-7.
26. D'iakova AM, Stefani NV, Andreev VG, Pavlov VV. Funktsiia pochek pri radiosensibilizatsii metronidazolom [Kidney function during radiosensitization with metronidazole]. Med Radiol (Mosk). 1984 Aug;29(8):16-20. Russian. PMID: 6472068.
27. Eguchi A., Mizukami S., Nakamura M., Masuda S., Murayama H., Kawashima M., Inohana M., Nagahara R., Kobayashi M., Yamashita R., et al. Metronidazole enhances steatosis-related early-stage hepatocarcinogenesis in high fat diet-fed rats through DNA double-strand breaks and modulation of autophagy. Environ. Sci. Pollut. Res. Int. 2022;29:779–789.
28. Fridkin S, Baggs J, Fagan R, Magill S, Pollack LA, Malpiedi P, Slayton R, Khader K, Rubin MA, Jones M, Samore MH, Dumyati G, Dodds-Ashley E, Meek J, Yousey-Hindes K, Jernigan J, Shehab N, Herrera R, McDonald CL, Schneider A, Srinivasan A., Centers for Disease Control and Prevention (CDC). Vital signs: improving antibiotic use among hospitalized patients. MMWR Morb Mortal Wkly Rep. 2014 Mar 07;63(9):194-200.
29. Garcia-Martinez R, Noiret L, Sen S, Mookerjee R, Jalan R. Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury. Liver Int. 2015 Feb;35(2):335-43.
30. Garcia-Martinez R, Caraceni P, Bernardi M, Gines P, Arroyo V, Jalan R. Albumin: pathophysiologic basis of its role in the treatment of cirrhosis and its complications. Hepatology. 2013 Nov;58(5):1836-46. [
31. Goodman D.A; Goodman C.B; MONK J.S. Use of the newtrophil: lymphocyte ratio in the diagnosis of appendicitis: Am surg. 1995, 257-259.
32. Gosselin R, Hawes E, Moll S, Adcock D. Performance of various laboratory assays in the measurement of dabigatran in patients receiving therapeutic doses: a prospective study based on peak and trough plasma levels. Am J Clin Pathol. 2014 Feb;141(2):262-7.
33. Hall MP, Band PA, Meislin RJ, Jazrawi LM, Cardone DA. Platelet-rich plasma: current concepts and application in sports medicine. J Am Acad Orthop Surg. 2009 Oct;17(10):602-8.
34. Handin, Robert I.; Samuel E. Lux; Thomas P. Stossel (2003). Blood: Principles and Practice of Hematology (2nd ed.). Philadelphia: Lippincott Williams and Wilkins. p. 471. ISBN 978-0-7817-1993-3. Retrieved 2013-06-18.
35. Hashemnia M, Javedani M, Nikoosafat Z, Abdoli Jamoor S. Study of Hematological, Biochemical and Histopathological Changes Due to Long-Term Administration of Ketamine in Rat. JRUMS 2018; 17 (7) :639-656.
36. Hernández Ceruelos A, Romero-Quezada LC, Ruvalcaba Ledezma JC, López Contreras L. Therapeutic uses of metronidazole and its side effects: an update. Eur Rev Med Pharmacol Sci. 2019 Jan;23(1):397-401.
37. Huang Y, Liu X, Xu X, Liu J. Intra-articular injections of platelet-rich plasma, hyaluronic acid or corticosteroids for knee osteoarthritis : A prospective randomized controlled study. Orthopade. 2019 Mar;48(3):239-247.
38. Jafarinia B, Delpisheh A, Soleimany A, Sayehmiri K. The effect of Metronidazole on reducing blood lipids: a systematic review and meta-analysis. Tehran Univ Med J 2016; 74 (1) :58-62.
39. Khalil WK, Mahmoud MA, Zahran MM, Mahrous KF. A sub-acute study of metronidazole toxicity assessed in Egyptian Tilapia zillii. J Appl Toxicol. 2007 Jul-Aug;27(4):380-90. doi: 10.1002/jat.1217. PMID: 17265432.
40. Ko YY, Jeong YH, Lim DY. Influence of Ketamine on Catecholamine Secretion in the Perfused Rat Adrenal Medulla. Korean J Physiol Pharmacol 2008; 12 (3): 101-9.
41. Kubota T, Anzawa N, Hirota K, Yoshida H, Kushikata T, Matsuki A. Effects of ketamine and pentobarbital on noradrenaline release from the medial prefrontal cortex in rats. Can J Anaesth 1999; 46 (4): 388-92.
42. Löfmark S, Edlund C, Nord CE. Metronidazole is still the drug of choice for treatment of anaerobic infections. Clin Infect Dis. 2010 Jan 01;50 Suppl 1:S16-23.
43. Loomans JI, Lock J, Peters M, Leebeek FW, Cnossen MH, Fijnvandraat K. [Haemophilia]. Ned Tijdschr Geneeskd. 2014;158:A7357.
44. Lynch TJ. Choosing optimal antimicrobial therapies. Med Clin North Am. 2012 Nov;96(6):1079-94.
45. Mahajan A., Taliun D., Thurner M., Robertson N.R., Torres J.M., Rayner N.W., Payne A.J., Steinthorsdottir V., Scott R.A., Grarup N., et al. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat. Genet. 2018;50:1505–1513. doi: 10.1038/s41588-018-0241-6.
46. Mathew J, Sankar P, Varacallo M. Physiology, Blood Plasma. [Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK531504/
47. Mazuski JE, Tessier JM, May AK, Sawyer RG, Nadler EP, Rosengart MR, Chang PK, O'Neill PJ, Mollen KP, Huston JM, Diaz JJ, Prince JM. The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection. Surg Infect (Larchmt). 2017 Jan;18(1):1-76.
48. McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.
49. Meng L, Mui E, Holubar MK, Deresinski SC. Comprehensive Guidance for Antibiotic Dosing in Obese Adults. Pharmacotherapy. 2017 Nov;37(11):1415-1431.
50. Myhrstad MCW, Wolk A. Antioxidants and phytochemicals - a scoping review for Nordic Nutrition Recommendations 2023. Food Nutr Res. 2023 Dec 1;67. doi: 10.29219/fnr.v67.10324. PMID: 38084155; PMCID: PMC10710867.
51. Nemeth J, Oesch G, Kuster SP. Bacteriostatic versus bactericidal antibiotics for patients with serious bacterial infections: systematic review and meta-analysis. J Antimicrob Chemother. 2015 Feb;70(2):382-95.
52. Pankuch GA, Jacobs MR, Appelbaum PC. Susceptibilities of 428 gram-positive and -negative anaerobic bacteria to Bay y3118 compared with their susceptibilities to ciprofloxacin, clindamycin, metronidazole, piperacillin, piperacillin-tazobactam, and cefoxitin. Antimicrob Agents Chemother. 1993 Aug;37(8):1649-54.
53. Patel P, Wermuth HR, Calhoun C, et al. Antibiotics. [Updated 2023 May 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535443.
54. Onufrak NJ, Forrest A, Gonzalez D. Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing. Clin Ther. 2016 Sep;38(9):1930-47.
55. Pankey GA, Sabath LD. Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections. Clin Infect Dis. 2004 Mar 15;38(6):864-70.
56. Salerno F, Navickis RJ, Wilkes MM. Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: a meta-analysis of randomized trials. Clin Gastroenterol Hepatol. 2013 Feb;11(2):123-30.e1.
57. Sarmadian H, Zarinfar N, Fani A, Mousavi F M, Didgar F, Khaki M, et al . Effect of metronidazole on amount of blood’s lipids of hyperlipidemia people. J Arak Uni Med Sci 2008; 11 (3) :63-69.
58. Sarmast shoshtari MH, Askarpour SH, Alamshah M, Elahi A. Diagnostic value of Quantitative crp measurement in patient with acute Appendicitis, Pak J Med Sci July-September 2006; 22: 300-303.
59. Shehab N, Patel PR, Srinivasan A, Budnitz DS. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis. 2008 Sep 15;47(6):735-43.
60. Singla RK, Dubey AK, Garg A, Sharma RK, Fiorino M, Ameen SM, et al.. Natural polyphenols: chemical classification, definition of classes, subcategories, and structures. J AOAC Int 2019; 102(5): 1397–400.
61. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan SL, Montoya JG, Wade JC. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014 Jul 15;59(2):147-59.
62. Sun H., Saeedi P., Karuranga S., Pinkepank M., Ogurtsova K., Duncan B.B., Stein C., Basit A., Chan J.C.N., Mbanya J.C., et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res. Clin. Pract. 2022;183:109119. doi: 10.1016/j.diabres.2021.109119.
63. Sy SK, Zhuang L, Derendorf H. Pharmacokinetics and pharmacodynamics in antibiotic dose optimization. Expert Opin Drug Metab Toxicol. 2016;12(1):93-114.
64. Tamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of Adverse Events With Antibiotic Use in Hospitalized Patients. JAMA Intern Med. 2017 Sep 01;177(9):1308-1315.
65. van Duijkeren E, Schink AK, Roberts MC, Wang Y, Schwarz S. Mechanisms of Bacterial Resistance to Antimicrobial Agents. Microbiol Spectr. 2018 Jan;6(1): 1-1.
66. van Schalkwyk J, Yudin MH., INFECTIOUS DISEASE COMMITTEE. Vulvovaginitis: screening for and management of trichomoniasis, vulvovaginal candidiasis, and bacterial vaginosis. J Obstet Gynaecol Can. 2015 Mar;37(3):266-274.
67. Varacallo M, Chakravarty R, Denehy K, Star A. Joint perception and patient perceived satisfaction after total hip and knee arthroplasty in the American population. J Orthop. 2018 Jun;15(2):495-499.
68. Varacallo MA, Herzog L, Toossi N, Johanson NA. Ten-Year Trends and Independent Risk Factors for Unplanned Readmission Following Elective Total Joint Arthroplasty at a Large Urban Academic Hospital. J Arthroplasty. 2017 Jun;32(6):1739-1746.
69. Varacallo M, Luo TD, Johanson NA. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Aug 4, 2023. Total Knee Arthroplasty Techniques. 1: 1-1.
70. Vujkovic M., Keaton J.M., Lynch J.A., Miller D.R., Zhou J., Tcheandjieu C., Huffman J.E., Assimes T.L., Lorenz K., Zhu X., et al. Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis. Nat. Genet. 2020;52:680–691. doi: 10.1038/s41588-020-0637-y.
71. Yuan S, Xu F, Li X, Chen J, Zheng J, Mantzoros CS, Larsson SC. Plasma proteins and onset of type 2 diabetes and diabetic complications: Proteome-wide Mendelian randomization and colocalization analyses. Cell Rep Med. 2023 Sep 19;4(9):101174. doi: 10.1016/j.xcrm.2023.101174. Epub 2023 Aug 30. PMID: 37652020; PMCID: PMC10518626.
72. Weir CB, Le JK. Metronidazole. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539728/
73. Williams CS, Woodcock KR. Do ethanol and metronidazole interact to produce a disulfiram-like reaction? Ann Pharmacother. 2000 Feb;34(2):255-
74. Zemanova N., Lněničkova K., Vavrečkova M., Anzenbacherova E., Anzenbacher P., Zapletalova I., Hermanova P., Hudcovic T., Kozakova H., Jourova L. Gut microbiome affects the metabolism of metronidazole in mice through regulation of hepatic cytochromes P450 expression. PLoS ONE. 2021;16:e0259643.
75. Zheng J., Haberland V., Baird D., Walker V., Haycock P.C., Hurle M.R., Gutteridge A., Erola P., Liu Y., Luo S., et al. Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases. Nat. Genet. 2020;52:1122–1131.
76-Zheng Y., Ley S.H., Hu F.B. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat. Rev. Endocrinol. 2018;14:88–98. doi: 10.1038/nrendo.2017.151