The pathophysiological effects of ciprofloxacin on biochemical and histological changes in liver, kidney, and hippocampus pyramidal cells in male Wistar rats

Document Type : Research Paper

Authors

Department of Biology, Faculty of Science, Arak University, Arak, Iran

Abstract

Background and Objective: Ciprofloxacin is effective against a wide range of bacterial illnesses. This investigation evaluated the pathophysiological effect of ciprofloxacin on liver, kidney, and hippocampus pyramidal cells in male Wistar rats.
Materials and Methods: Forty adult Wistar rats were randomly assigned to four groups: control (Saline 0.5 ml, orally, 30 days) and ciprofloxacin (25, 50, 100 mg/kg, orally, 30 days). Rats were euthanized when the treatment was completed. Blood samples were collected for chemical analysis, while liver, kidney, and brain samples were excised for histological examination.
Results: Compared to the control group, ciprofloxacin-treated groups exhibited significant increases in MDA, liver enzymes, urea, and creatinine levels, whereas SOD, GSH, and CAT enzyme levels were significantly reduced. Ciprofloxacin treatment induced severe vacuolation, marked hepatocyte degeneration, dilated sinusoids, congested central veins, severe hepatic hemorrhage, glomerular atrophy, as well as several changes, including dilation of renal convoluted tubules, degenerated epithelial cells, and luminal dilation. In the ciprofloxacin-treated groups, the number of healthy neurons in CA1, CA2, and CA3 hippocampus areas decreased dose-dependently as opposed to the control group.
Conclusion: By increasing oxidative stress, ciprofloxacin was found to elevate serum levels of liver enzymes, urea, and creatinine. Moreover, it induced histopathological changes in the liver and kidney and decreased the number of healthy neurons in hippocampal pyramidal cells compared with the control group.

Keywords

References

  1. Asensio M, Ortiz-Rivero S, Ana Marin, Jose JG. Etiopathogenesis and pathophysiology of cholestasis. Exploration of Digestive Diseases 2022; 1 (2):97-117.
  2. Shojaie L, Iorga A, Dara L. Cell death in liver diseases: a review. International journal of molecular sciences 2020; 21 (24):9682.
  3. Nagami GT, Kraut JA. The role of the endocrine system in the regulation of acid–base balance by the kidney and the progression of chronic kidney disease. International Journal of Molecular Sciences 2024; 25 (4):2420.
  4. Temido-Ferreira M, Coelho JE, Pousinha PA, Lopes LV. Novel players in the aging synapse: impact on cognition. Journal of Caffeine and Adenosine Research 2019; 9 (3):104-127.
  5. Darbandi N, Komijani M, Tajiani Z. New findings about comparing the effects of antibiotic therapy and phage therapy on memory and hippocampal pyramidal cells in rats. Journal of Clinical Laboratory Analysis 2023; 37 (11-12):e24942.
  6. Jourdan A, Sangha B, Kim E, Nawaz S, Malik V, Vij R, et al. Antibiotic hypersensitivity and adverse reactions: management and implications in clinical practice. Allergy, Asthma & Clinical Immunology 2020; 16:1-7.
  7. Allameh A, Niayesh-Mehr R, Aliarab A, Sebastiani G, Pantopoulos K. Oxidative stress in liver pathophysiology and disease. Antioxidants 2023; 12 (9):1653.
  8. Shariati A, Arshadi M, Khosrojerdi MA, Abedinzadeh M, Ganjalishahi M, Maleki A, et al. The resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing the efficacy of this antibiotic. Frontiers in Public Health 2022; 10:1025633.
  9. World Health Organization model list of essential medicines: 21st list 2019. World Health Organization; 2019.
  10. Samar I, RA, BDEWI SY, HASAN MS. Effects of ciprofloxacin on liver and kidney functions and histopathological features in rats. International Journal of Pharmaceutical Research 2019; 11 (1):907-911.
  11. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods in Enzymology: Elsevier; 1978; 302-310.
  12. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry 1974; 47 (3):469-474.
  13. Aebi H. Catalase in vitro. Methods in enzymology. 105: Elsevier; 1984. p. 121-126.
  14. Colak E, Ustuner MC, Tekin N, Colak E, Burukoglu D, Degirmenci I, et al. The hepatocurative effects of Cynara scolymus L. leaf extract on carbon tetrachloride-induced oxidative stress and hepatic injury in rats. Springer Plus 2016; 5:1-9.
  15. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 2006, hard cover edition,Elsevier.
  16. Darbandi N, Ramezani M, Noori M. Mespilus germanica Flavonoids Attenuate Cognitive Dysfunction in the Streptozotocin-induced Rat Model of Alzheimer's Disease. Indian Journal of Pharmaceutical Sciences 2018; 80 (4).
  17. Elizalde-Velázquez GA, Rosas-Ramírez JR, Raldua D, García-Medina S, Orozco-Hernández JM, Rosales-Pérez K, et al. Low concentrations of ciprofloxacin alone and in combination with paracetamol induce oxidative stress, upregulation of apoptotic-related genes, histological alterations in the liver, and genotoxicity in Danio rerio. Chemosphere 2022; 294:133667.
  18. Liu X, Chen Q, Ali N, Zhang J, Wang M, Wang Z. Single and joint oxidative stress–related toxicity of sediment-associated cadmium and lead on Bellamya aeruginosa. Environmental Science and Pollution Research 2019; 26:24695-24706.
  19. Yang Q, Yuan, Ke J, Show PL, Ge Y, Liu Y, Guo R, et al. Antibiotics: An overview on theenvironmental occurrence, toxicity, degradation, and removal methods. Bioengineered 2021; 12 (1):7376-7416.
  20. Shen R, Yu Y, Lan R, Yu R, Yuan Z, Xia Z. Thecardiovascular toxicity induced by high doses of gatifloxacin andciprofloxacin in zebrafish. Environmental Pollution 2019; 254:112861.
  21. Rosas-Ramírez JR, Orozco-Hernández JM, Elizalde-Velázquez GA, Raldúa D, Islas-Flores H, Gómez-Oliván LM. Teratogenic effects induced by paracetamol, ciprofloxacin, and their mixture on Danio rerio embryos: Oxidative stress implications. Science of the Total Environment 2022; 806:150541.
  22. Vahidi-Eyrisofla N, Ahmadifar M, Eini A, Kalami A. The study of levofloxacin effects on liver tissue in wistar rat. J Liver 2015; 4 (173):2167-0889.
  23. Mojoyinola AO, Ishaya HB, Makena W, Jacob CB, Jonga UM, Anochie VC, et al. Protective effect of ciprofloxacin-induced oxidative stress, testicular and hepatorenal injury by Citrullus lanatus L.(Watermelon) seeds in adult Wistar rats. South African Journal of Botany 2023; 156:365-375.
  24. Radovanovic M, Dushenkovska T, Cvorovic I, Radovanovic N, Ramasamy V, Milosavljevic K, et al. Idiosyncratic drug-induced liver injury due to ciprofloxacin: a report of two cases and review of the literature. The American Journal of Case Reports 2018; 19:1152.
  25. Zoratti C, Rita M, Lisa R, Valeria AI, Giuliana D, Saveria CL, et al. Antibiotics and Liver Cirrhosis: What the Physicians Need to Know. Antibiotics-Basel 2022; 11 (1).
  26. Anu A, Koit, Kekäläinen NJ, Paloheinä M, Pohjoismäki JL, Gerhold JM, Goffart S. Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerae 2. Nucleic Acids Research 2018; 46 (18):9625-9636.
  27. Ali, Rikaby AA, Ghadhban RF, Majeed SK. The effects of ciprofloxacin on male rabbits: Biochemical and histopathological study. Al-Qadisiyah Journal of Veterinary Medicine Sciences 2016; 15 (1).
  28. Igbayilola Y, Saka W, Aina S, Mofolorunso A, Oyabambi A, Morakinyo A. Adverse effect of graded Ciprofloxacin oral intake in male Sprague-Dawley rats. Journal of African Association of Physiological Sciences 2020; 8 (1):62-70.
  29. Rakshit S, Shukla P, Verma A, Kumar Nirala S, Bhadauria M. Protective role of rutin against combined exposure to lipopolysaccharide and D‐galactosamine‐induced dysfunctions in liver, kidney, and brain: Hematological, biochemical, and histological evidences. Journal of Food Biochemistry 2021; 45 (2):e13605.
  30. Mathew, U., Charles II, Kingsly, A., Trevor, B. H. O., & Ernest, A. Histological effect of ciprofloxacin on the kidney histology of adult rats. International Journal of Healthcare Sciences 2020; 7 (2):360-369.
  31. AbdEl-Aziz AA, Naguib Y, Zahran WA, Mahrous H, Khalil H, El-Nahas SA. Detection of oxidative stress induced by ciprofloxacin in imatuer rat. Research Journal of Applied Biotechnology 2018; 4 (1):77-81.
  32. Hamdi H, El-Ghareeb AE-W, Sharawy E. Fetal exposure to the antibiotic drug (Ciprofloxacin) in Albino rats. J Pharm Chem Pharmacol 2018; 2 (1):39-42.
  33. Hajji M, Jebali H, Mrad A, Blel Y, Brahmi N, Kheder R, et al. Nephrotoxicity of ciprofloxacin: five cases and a review of the literature. Drug Safety-Case Reports 2018; 5:1-5.
  34. Hao W-Z, Li X-J, Zhang P-W, Chen J-X. A review of antibiotics, depression, and the gut microbiome. Psychiatry Research 2020; 284:112691.
  35. Megur A, Baltriukienė D, Bukelskienė V, Burokas A. The microbiota–gut–brain axis and Alzheimer’s disease: neuroinflammation is to blame? Nutrients 2020; 13 (1):37.
  36. Hurkacz M, Dobrek L, Wiela-Hojeńska A. Antibiotics and the nervous system—which Face of antibiotic therapy is real, dr. Jekyll (neurotoxicity) or mr. Hyde (neuroprotection)? Molecules 2021; 26 (24):7456.
Journal of Basic and Clinical Pathophysiology
Volume 13, Issue 1 - Serial Number 1
February 2025
Pages 21-29

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