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Microsomal enzyme induction by permethrin in rats
1Departamento de Toxicologia, Facultad de Veterinaria, Universidad de Leon, Spain.
Abstract:
The synthetic pyrethroid, permethrin, was evaluated for its ability to alter hepatic microsomal drug-metabolizing function. The influence of permethrin (25:75 cis-trans) on plasma antipyrine kinetics and gamma-glutamyl transpeptidase (gamma-GTP) activity were studied in rats. After 3 days of administration of 90 mg permethrin/kg/day, there was no significant change in the antipyrine half-life and the area under the curve, while the apparent volume of distribution and clearance were significantly increased. Treatment with 190 mg permethrin/kg/day for 3 days decreased antipyrine half-life and the area under the curve, and increased the apparent volume of distribution and the clearance significantly. The gamma-GTP activity was significantly increased within 21 days and 14 days after the start of permethrin administration, at doses of 90 and 190 mg permethrin/kg/day, respectively. The antipyrine kinetics results indicate that permethrin is capable of producing a dose-dependent marked enzyme-inducing effect.
Insights
The synthetic pyrethroid, permethrin, alters liver drug metabolism in rats. Higher doses of permethrin significantly impact antipyrine kinetics and increase gamma-glutamyl transpeptidase (gamma-GTP) activity, indicating enzyme induction.
Area of Science:
- Toxicology
- Pharmacology
- Biochemistry
Background:
- Hepatic microsomal drug-metabolizing enzymes are crucial for xenobiotic detoxification.
- Synthetic pyrethroids, like permethrin, are widely used insecticides with potential toxicological implications.
- Understanding permethrin's effects on liver function is vital for assessing its safety.
Purpose of the Study:
- To investigate the impact of permethrin on hepatic microsomal drug-metabolizing function in rats.
- To evaluate the dose-dependent effects of permethrin on plasma antipyrine pharmacokinetics.
- To assess the influence of permethrin on gamma-glutamyl transpeptidase (gamma-GTP) activity.
Main Methods:
- Rats were administered varying doses of permethrin (90 mg/kg/day and 190 mg/kg/day) for 3 days.
- Plasma antipyrine kinetics, including half-life, area under the curve, volume of distribution, and clearance, were analyzed.
- Gamma-glutamyl transpeptidase (gamma-GTP) activity in liver microsomes was measured.
Main Results:
- Low-dose permethrin (90 mg/kg/day) did not significantly alter antipyrine half-life or area under the curve but increased clearance and volume of distribution.
- High-dose permethrin (190 mg/kg/day) significantly decreased antipyrine half-life and area under the curve, while increasing clearance and volume of distribution.
- Permethrin administration led to a significant increase in gamma-GTP activity within 14-21 days, dose-dependently.
Conclusions:
- Permethrin exhibits a dose-dependent enzyme-inducing effect on hepatic drug metabolism in rats.
- The observed alterations in antipyrine kinetics suggest accelerated drug metabolism following permethrin exposure.
- Increased gamma-GTP activity further supports permethrin's role as an inducer of hepatic microsomal enzymes.