Toxicopathological Effects of Brodifacoum in Rats Following Secondary Exposure

Background: Brodifacoum is a highly lethal ۴-hydroxycoumarin anticoagulant rodenticide that acts as a vitamin K antagonist. Its lipophilic nature enables long-term retention in tissues allowing predators and scavengers to become exposed through contaminated prey. Despite its widespread use its toxicopathological effects remain insufficiently defined.Objectives: This study aimed to investigate the toxicopathological effects of brodifacoum using male rats following secondary exposure through contaminated liver homogenate.Methods: Ninety rats were randomly divided into four groups: group G۱ received brodifacoum bait for ۲۴ to ۴۸ hours (primary toxicity), group G۲ served as an untreated control, group G۳ received an untreated liver homogenate from G۲ to be used as a secondary control and group G۴ received a liver homogenate contaminated with brodifacoum from G۱ (secondary toxicity). Hepatic residues were determined using high-performance liquid chromatography (HPLC), and cytochrome P۴۵۰ (CYP۴۵۰) levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Gross examination, hemorrhagic scoring, and histopathological examinations were conducted on major organs.Results: HPLC analysis confirmed that brodifacoum significantly accumulated in the liver. G۴ showed around a fivefold higher residue level (۱۷.۸۷±۰.۱۱ µg/g) compared with G۱ (۳.۵۳±۰.۴۹ µg/g). Hepatic CYP۴۵۰ content showed a ۱.۸-fold increase in G۴ relative to G۳ (P<۰.۰۰۰۱). Gross and microscopic examinations revealed marked hemorrhagic and degenerative changes, most prominent in the lungs, liver, and kidneys in G۴. Conclusion: The results of the current study support the use of male rats as a model to evaluate the toxicopathological effects of brodifacoum following secondary exposure.

کلیدواژه ها:

Anticoagulant rodenticide (ARs) ، Secondary toxicity ، Cytochrome P۴۵۰ (CYP۴۵۰) ، Hepatic bioaccumulation ، Hemorrhagic score