Fluconazole Toxicity in a Rat Model: Histopathological and Neurobehavioral Effects

Background: The harmful effects of medications on cells can be either direct or indirect. These effects are due to increased free radicals or changes in the gene expression of specific proteins in the cells. Objectives: This study examined the effects of fluconazole at high dosages on the brain and liver of rats and their neurological behavior and motor activity. It also investigated the mechanisms that caused these changes by testing key enzymes and proteins. Methods: We used two LD50 percentages: 10% and 20%. Three groups of animals were formed. Group I was the control group. Fluconazole was given to groups II and III as a daily oral dose for 14 days at 583 mg/kg and 292 mg/kg, respectively. Results: Neurobehavioral testing revealed that rats with fluconazole 583 mg/kg experienced hyperactivity, increased movement, and poor cognition. The findings showed a substantial dose-related rise in malondialdehyde and caspase-3 and an increase in liver function enzymes but no significant change in cholinesterase activity. A fluconazole dose of 538 mg/kg also caused severe histological alterations in the brain and liver. Furthermore, enhanced glial fibrillary acidic protein (GFAP) expression has been observed in brain tissue. Conclusion: These findings led us to conclude that fluconazole is toxic at higher doses because it alters rat neuromotor behavior and negatively affects liver and brain tissues. It results in altered levels of some enzymes, elevated oxidative stress markers and increased apoptosis with a higher expression of GFAP in brain tissues.