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Updated: Sep 6, 2025
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Evaluation of hepatotoxicity and nephrotoxicity induced by fenpyroximate in subchronic-orally exposed Wistar rats
Imen Ayed-Boussema1,2, Karima Rjiba1,2, Hiba Hamdi1
1Laboratory of Research on Biologically Compatible Compounds, LR01SE17, University of Monastir, Faculty of Dental Medicine, Monastir, Tunisia.
Backgrounds:
Fenpyroximate (FEN) is an acaricide that inhibits the complex I of the mitochondrial respiratory chain. The aim of this work was to explore the hepatotoxic and nephrotoxic effects of FEN on Wistar rats.
Methods:
The study involved five groups: a control group and four groups treated with FEN at 1, 2, 4, and 8 mg/Kg bw for 28 consecutive days. Histological examination and biochemical analysis of hepatic and renal biomarkers were performed. The malondialdehyde (MDA), protein carbonyl levels, and antioxidant enzymes activities were measured. Comet assay was conducted to explore FEN genotoxicity.
Results:
FEN induced a disturbance of the hepatic and renal functions as evidenced by an increase in AST, ALT, ALP, creatinine, and uric acid levels and histopathological modifications in the two examined tissues. FEN increased hepatic and renal lipid peroxidation and protein oxidation. The activities of liver and kidney SOD, CAT, , and GST are increased significantly in FEN-treated rats at doses of 2 and 4 mg/kg bw. However, with the dose of 8 mg/kg bw of FEN, these activities are decreased. Moreover, FEN increased DNA damage in a dose-dependent manner.
Conclusion:
FEN was hepatotoxic and nephrotoxic very likely through induction of oxidative stress.
Insights
Fenpyroximate (FEN) causes liver and kidney damage in rats by increasing oxidative stress. This acaricide also led to DNA damage, indicating potential genotoxicity.
Area of Science:
- Toxicology
- Environmental Health
- Biochemistry
Background:
- Fenpyroximate (FEN) is an acaricide targeting mitochondrial complex I.
- Understanding its toxicological profile is crucial for risk assessment.
Purpose of the Study:
- To investigate the hepatotoxic and nephrotoxic effects of Fenpyroximate in Wistar rats.
- To explore the role of oxidative stress and genotoxicity in FEN-induced toxicity.
Main Methods:
- Wistar rats were treated with FEN (1-8 mg/kg) for 28 days.
- Assessed liver and kidney function via biochemical markers and histopathology.
- Measured oxidative stress markers (MDA, protein carbonyls) and antioxidant enzyme activities (SOD, CAT, GST).
- Evaluated genotoxicity using the Comet assay.
Main Results:
- FEN significantly elevated liver and kidney damage markers (AST, ALT, ALP, creatinine, uric acid) and caused histopathological changes.
- Increased lipid peroxidation and protein oxidation in liver and kidneys.
- FEN induced DNA damage in a dose-dependent manner.
- Antioxidant enzyme activities initially increased but decreased at the highest FEN dose.
Conclusions:
- Fenpyroximate exhibits significant hepatotoxic and nephrotoxic potential in rats.
- Oxidative stress is a likely mechanism underlying FEN-induced organ damage.
- FEN demonstrated dose-dependent genotoxicity, highlighting potential risks.
