Metronidazole-induced neurotoxicity: Possible central serotonergic and noradrenergic system involvement

Moses W Bariweni; Iyele Kamenebali; Denyefa, Johnson Bedford

doi:10.55940/medphar202474

Authors

Moses W Bariweni Niger Delta University, Wilberforce Island
Iyele Kamenebali Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University
Denyefa, Johnson Bedford Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University

DOI:

https://doi.org/10.55940/medphar202474

Keywords:

Neurotoxicity, Neurotransmission, Metronidazole, Antibiomania, Antidepressants, Depression

Abstract

Background: Metronidazole is a synthetic 5-nitroimidazole antibiotic. It remains a first-line therapy for anaerobic, parasitic, and bacterial infections in human and veterinary medicine. However, Metronidazole-induced neurotoxicity is a rising challenge. The mechanism of neurotoxicity induction is still unknown.
Objective: To investigate a possible interference of metronidazole with central monoaminergic mechanisms using the Forced Swim Test.
Methods: sixty adult rats were divided into 10 groups (n=10 for metronidazole and saline, n=5 for other groups). Group 1 = 5 ml/kg normal saline; Group 2 = 50 mg/kg metronidazole; group 3= 15 mg/kg imipramine; Group 4 =15 mg/kg imipramine + 50 mg/kg metronidazole. Group 5 = 5 mg/kg fluoxetine; Group 6 received 5 mg/kg fluoxetine + 50 mg/kg metronidazole; Group 7 = labetalol 10 mg/kg; Groups 8, 9 and 10 received labetalol 10 mg/kg + 50 mg/kg metronidazole, PCPA (p-chlorophenylalanine) 100 mg/kg and PCPA 100 mg/kg + 50 mg/kg metronidazole daily X 28 days. On day 28, FST was done 1h after the respective treatments. On day 29, blood samples were collected under halothane anesthesia for hematological assessment.
Results: Immobility time increased (P<0.01) in the groups treated with metronidazole, labetalol, PCPA, labetalol + metronidazole, and PCPA+ metronidazole. Swimming was reduced by metronidazole, PCPA, metronidazole + PCPA and metronidazole + labetalol. Metronidazole + labetalol reduced climbing. These effects were not reduced by co-treatment with imipramine or fluoxetine. White blood cell count increased (p<0.01) in all treatment groups. Lymphocyte percent increased in the metronidazole-treated groups.
Conclusion: Interference with postsynaptic central monoaminergic neurotransmission and immunomodulation may contribute to metronidazole-induced neurotoxicity.

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