Subacute Exposure to the Fungicide Imazalil Decreased Hippocampal Cholinesterase Activity and Caused Learning and Memory Impairments in Rats

Abstract

The fungicide Imazalil (IMZ) is widely used to maintain the freshness of fruits and vegetables after harvest. Despite its widespread use, the neurotoxic effects of IMZ remain poorly studied. Thus, in this work, we aimed to investigate the effects of subacute IMZ exposure on memory and learning, as well as on cholinesterase (ChE) activity, in orally exposed rats. To do so, Wistar rats were exposed to doses corresponding to 1/8, 1/4, and 1/2 of the LD50 of IMZ. Each dose was divided into four equal parts and administered once daily for four consecutive days, while behavioral performance was assessed using the Barnes Maze. On day 5, we measured ChE activity in the hippocampus and serum. The enzymatic activity assays demonstrated a dose-dependent decrease in both cholinesterase activities at 1/4 LD50 of IMZ. In addition, rats in the control group exhibited a typical learning curve in the Barnes maze, characterized by reduced latency and fewer attempts to locate the escape box from the first session (S1) to the final session (S4). The typical learning curve was prevented by a 1/4 LD50 treatment. Additionally, this dose prevented an increase in spatial navigation strategy use, observed in the control group (S1 vs. S4). To our knowledge, these results proved that IMZ inhibits in vivo the activity of both brain and serum ChEs, and exhibits evidence of learning and memory impairments, suggesting that IMZ has neurotoxic effects in rats, probably mediated by alterations in the cholinergic system.