Fluconazole Toxicity in Rat Model: Histopathological and Neurobehavioral Effects

Document Type : Original Articles


1 Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq

2 Department of veterinary pathology and poultry Diseases، College of Veterinary Medicine، University of Mosul، Mosul، Iraq

3 Department of Pathology and Poultry Diseases, College of Veterinary Medicine, University of Mosul, Mosul, Iraq



BACKROUND: The harmful effect of medications on cells can be either direct or indirect, due to an increase in free radicals or changes in the gene expression of certain proteins in the cells. OBJECTIVE: This study examined the effects of fluconazole at high dosages on the brain and liver, as well as how it affected rats' neurological behavior and motor activity, and then investigated into the mechanisms that caused these changes by testing certain key enzymes and proteins. METHODS: There were two LD50 percentages used, 10% and 20%, respectively. Three groupings of animals were formed. Group I was the control group. Fluconazole was given to groups II and III as a single oral dose every day for 14 days at levels of 583 mg/kg and 292 mg/kg, respectively. RESULTS: Neurobehavioral testing revealed that rats given 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, as well as an increase in liver function enzymes, but no significant variation in cholinesterase activity. A dose of 538 mg/kg also caused severe histological alterations in the brain and liver. Furthermore, enhanced GFAP expression has been observed in brain tissue. CONCLUSIONS: These findings led us to the conclusion that fluconazole is toxic at higher doses because it alters rat neuromotor behavior and has a negative effect on liver and brain tissues, resulting in altered levels of some enzymes, elevated oxidative stress markers, and increased apoptosis with increased expression of GFAP in brain tissues.