Liver tumor promoting effect of etofenprox in rats and its possible mechanism of action

Abstract

-To investigate the liver tumor-promoting effects of etofenprox (ETF), a pyrethroid-like insecticide, 6 week-old male F344 rats were given an intraperitoneal injection of N-diethylnitrosamine (DEN). After 2 weeks from the DEN treatment, 12 rats per group received a powdered diet containing 0, 0.25, 0.50, or 1.0% ETF for 8 weeks. At the time of 2nd week of ETF administration, all animals were subjected to two-thirds partial hepatectomy (PH). One rat per group except for the 0.25% ETF group died due to surgical operation of PH. The number and area of glutathione S-transferase placental form (GST-P) positive foci significantly increased in the livers of DEN-initiated rats given 0.50% and 1.0% ETF compared with the DEN-alone group. Quantitative real-time RT-PCR analysis revealed that the mRNA expression of phase I enzymes Cyp2b1/2, phase II enzymes such as Akr7a3, Gsta5, Ugt1a6, Nqo1 significantly increased in the DEN+ETF groups. The immunohistochemistry showed the translocation of CAR from the cytoplasm to the nuclei of hepatocytes in the ETF-treated groups. Reactive oxygen species (ROS) production increased in microsomes isolated from the livers of ETF-treated rats, and thiobarbituric acid-reactive substances (TBARS) levels and 8-hydroxy-2-deoxyguanosine (8-OHdG) content significantly increased in all of the ETF-treated groups and DEN+1.0% ETF group, respectively. The results of the present study indicate that ETF has a liver tumor-promoting activity in rats, and suggest that ETF activates the constitutive active/androstane receptor (CAR) and enhances microsomal ROS production, resulting in the upregulation of Nrf2 gene batteries; such an oxidative stress subsequently induces liver tumor-promoting effects by increased cellular proliferation.

Çevresel Kirletici Etofenproks un Zebra Balıklarında (Danio rerio) Subletal Genotoksik Etkileri

“…Hojo et al found etofenprox had a stimulating effect on liver tumor in rats and increased reactive oxygen species production in microsomes isolated from the livers of etofenprox treated rats. Besides the thiobarbituric acid-reactive substances levels and 8-OHdG content also significantly increased in all of the etofenprox treated groups (22).…”

A simple HPLC-UVD method for detection of etofenprox in green tea using sample hydration

“…ETF induces liver tumor-promoting effects via increased cellular proliferation. (4). Hayashi et al (5) reported that contamination of rice-based chow with etofenprox, diethyl phthalate, and alkylphenols significantly impaired first delivery and sperm counts in mice.…”