Effects of Several Pyrethroids on Hepatic Cytochrome P450 Activities in Rats

Abdou, Rania; Sasaki, Kenji; Khalil, Waleed F.; Shah, Syed Sher; Murasawa, Youhei; Shimoda, Minoru

doi:10.1292/jvms.09-0347

Cited by 22 publications

(18 citation statements)

References 28 publications

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“…However, the underlying mechanism by which pyrethroids induced oxidative stress is still unknown. It was reported that decreased activity of mitochondria complex I and cytochrome P450 [32], and mitochondrial dysfunction was involved in pyrethroid-induced oxidative stress [33]. …”

Section: Discussionmentioning

confidence: 99%

Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration

et al. 2015

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Fenpropathrin is one of the widely used pyrethroids in agriculture and household and also reported to have neurotoxic effects in rodent models. In our Parkinson’s disease (PD) clinic, there was a unique patient with a history of daily exposure to fenpropathrin for 6 months prior to developing Parkinsonian symptoms progressively. Since whether fenpropathrin is related to any dopaminergic degeneration was unknown, we aimed in this study to evaluate the neurotoxic effects of fenpropathrin on the dopaminergic system and associated mechanisms in vitro and in vivo. In cultured SH-SY5Y cells, fenpropathrin caused cell death, reactive oxygen species generation, Lewy body-associated proteins aggregation, and Lewy body-like intracytoplasmic inclusions formation. In rodent animals, two different injections of fenpropathrin were used for administrations, intraperitoneal (i.p), or stereotaxical (ST). The rats exhibited lower number of pokes 60 days after first i.p injection, while the rats in ST group showed a significant upregulation of apomorphine-evoked rotations 60 days after first injection. Dcreased tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT2) immunoreactivity, while increased dopamine transporter (DAT) immunoreactivity were observed in rats of either i.p or ST group 60 days after the last exposure to fenpropathrin. However, the number of TH-positive cells in the substantia nigra was more reduced 120 days after the first i.p injection than those of 60 days. Our data demonstrated that exposure to fenpropathrin could mimic the pathologic and pathogenetic features of PD especially in late onset cases. These results imply fenpropathrin as a DA neurotoxin and a possible environmental risk factor for PD.

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Section: Discussionmentioning

confidence: 99%

Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration

et al. 2015

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“…Inhibition of cytochrome P450 activity caused by pyrethroids has not been extensively studied. However, cis-permethrin and fenpropathrin were reported to be inhibitors of CYP1A measured on rat liver microsomes in vitro [47]. Moreover, deltamethrin was found to inhibit several hepatic cytochrome P450 activities in a fish (Cyprinus carpio L.) at a concentration equal to 0.2 mg/L during 72-h exposure and fish-liver microsome (ECOD) activity [48].…”

Section: Sublethal Effects Of A-cypermethrinmentioning

confidence: 98%

The effects of epoxiconazole and α‐cypermethrin on Daphnia magna growth, reproduction, and offspring size

Gottardi¹,

Birch²,

Dalhoff³

et al. 2017

Enviro Toxic and Chemistry

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Two of the main classes of pesticides commonly used in agriculture are azole fungicides and pyrethroid insecticides. Because azoles have been shown to synergize the effect of pyrethroids, the effect of their mixture is of concern. The aim of the present study was to investigate the effect of sublethal concentrations of epoxiconazole and α-cypermethrin and their mixture on growth, reproduction, and in vivo cytochrome P450 activity of the aquatic crustacean Daphnia magna over 42 d. Continuous exposure to nonlethal concentrations of α-cypermethrin at 20 ng/L negatively affected adult growth and number and size of neonates within the first 14 d of exposure. Exposure to epoxiconazole at 25 μg/L increased protein content of adults within 1 to 3 d after initiating exposure and increased cumulative number of offspring at exposure times >31 d. Epoxiconazole enhanced the negative effect of α-cypermethrin up to 3-fold leading to decreased growth, cytochrome P450 activity, and reproduction of D. magna within the first 14 d of exposure. After 14 d, the synergistic interactions disappeared. The reported effects, although lacking direct negative consequence in the long term, might have cumulative toxicity with other stressors such as food scarcity, predation, and pathogens, posing an additional hazard for the organisms at the beginning of their life cycle. Environ Toxicol Chem 2017;36:2155-2166. © 2017 SETAC.

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“…Abdou et al (2010) reported that ETF induced CYP1A in rats subjected to oral administration of ETF for 5 days. On the contrary, in the present study, CYP2B was induced in all of the DEN+ETF groups, while CYP1A was not induced.…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, in the present study, CYP2B was induced in all of the DEN+ETF groups, while CYP1A was not induced. The reason why CYP2B was not induced in the study of Abdou et al (2010) is unclear, but it is suspected that ETF has the potential to induce CYP1A in a shortterm administration, while it will have the potential to induce CYP2B and inhibit CYP1A in a long-term administration. PB induces a large spectrum of drug-metabolizing enzymes, and is a typical CYP2B inducer in rats (Waxman and Azaroff, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, metofluthrin has been shown to induce CYP2B in rat and human hepatocytes and to have a hepatocarcinogenic potential in rats . Etofenprox (2-[4-etoxyphenyl]-2-methylpropyl-3-phenoxy benzyl ether: ETF) has been shown to induce CYP1A in rats (Abdou et al, 2010). It has been evaluated by the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) that ETF is not genotoxic but tumorigenic to the thyroid glands in rats (1993).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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-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.

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Effects of Several Pyrethroids on Hepatic Cytochrome P450 Activities in Rats

Cited by 22 publications

References 28 publications

Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration

Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration

The effects of epoxiconazole and α‐cypermethrin on Daphnia magna growth, reproduction, and offspring size

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

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