Hydrolytic metabolism of pyrethroids by human and other mammalian carboxylesterases

Ross, Matthew K.; Borazjani, Ali; Edwards, Carol C.; Potter, Philip M.

doi:10.1016/j.bcp.2005.11.020

Cited by 152 publications

(145 citation statements)

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“…Whereas there are numerous studies that have examined laboratory animal metabolism of pyrethroids, there are relatively few examples of human metabolism of pyrethroids (Choi et al, 2002;Nishi et al, 2006;Ross et al, 2006). In these studies, the extensive hydrolysis of trans-permethrin in rat and mouse liver microsomes (Soderlund and Casida, 1977;Shono et al, 1979) and by mouse carboxylesterases (Stok et al, 2004) was also evident in human liver microsomes (Choi et al, 2002;Ross et al, 2006). For cis-permethrin, however, Choi et al (2002) reported that there was no detectable oxidative or hydrolytic metabolism in human liver fractions.…”

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confidence: 95%

“…For cis-permethrin, however, Choi et al (2002) reported that there was no detectable oxidative or hydrolytic metabolism in human liver fractions. Ross et al (2006) observed limited hydrolysis of cis-permethrin in human liver microsomes compared with rat liver microsomes. Ross et al (2006) and Nishi et al (2006) also reported limited hydrolysis of cis-permethrin by purified human carboxylesterases.…”

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confidence: 95%

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Species Differences in the in Vitro Metabolism of Deltamethrin and Esfenvalerate: Differential Oxidative and Hydrolytic Metabolism by Humans and Rats

Godin¹,

Scollon²,

Hughes³

et al. 2006

Drug Metab Dispos

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ABSTRACT:Pyrethroids are neurotoxic pesticides whose pharmacokinetic behavior plays a role in their potency. This study examined the elimination of esfenvalerate and deltamethrin from rat and human liver microsomes. A parent depletion approach in the presence and absence of NADPH was used to assess species differences in biotransformation pathways, rates of elimination, and intrinsic hepatic clearance. Esfenvalerate was eliminated primarily via NADPH-dependent oxidative metabolism in both rat and human liver microsomes. The intrinsic hepatic clearance (CL INT ) of esfenvalerate was estimated to be 3-fold greater in rodents than in humans on a per kilogram body weight basis. Deltamethrin was also eliminated primarily via NADPH-dependent oxidative metabolism in rat liver microsomes; however, in human liver microsomes, deltamethrin was eliminated almost entirely via NADPHindependent hydrolytic metabolism. The CL INT for deltamethrin was estimated to be 2-fold more rapid in humans than in rats on a per kilogram body weight basis. Metabolism by purified rat and human carboxylesterases (CEs) were used to further examine the species differences in hydrolysis of deltamethrin and esfenvalerate. Results of CE metabolism revealed that human carboxylesterase 1 (hCE-1) was markedly more active toward deltamethrin than the class 1 rat CEs hydrolase A and B and the class 2 human CE (hCE-2); however, hydrolase A metabolized esfenvalerate 2-fold faster than hCE-1, whereas hydrolase B and hCE-1 hydrolyzed esfenvalerate at equal rates. These studies demonstrate a significant species difference in the in vitro pathways of biotransformation of deltamethrin in rat and human liver microsomes, which is due in part to differences in the intrinsic activities of rat and human carboxylestersases.Pyrethroids are synthetic analogs of the natural pyrethrins, the insecticidal components of extracts from the pyrethrum flower (Chrysanthemum cinerariaefolium). The pyrethroids modulate nerve axon sodium channels, resulting in neurotoxic effects (Narahashi, 1985;Smith et al., 1997). The adverse effects produced by pyrethroids are due to the parent compounds in that no evidence currently exists that pyrethroid metabolites alter sodium channels and are neurotoxic. For the limited number of pyrethroids evaluated, the brain concentrations of pesticide appear to correlate with acute neurotoxicity (White et al., 1976;Rickard and Brodie, 1985). Pharmacokinetic parameters, particularly clearance of the parent chemical from the blood, will influence the effective concentration in the brain and therefore can have a significant influence on their toxic potency.The metabolic pathway and rate of phase I biotransformation of pyrethroids are dependent upon their chemical structure and stereochemistry (Ueda et al., 1975;Soderlund and Casida, 1977;Shono et al, 1979). In laboratory animals, different metabolic pathways preferentially transform cis-and trans-isomers of pyrethroids; transisomers are typically transformed by the more rapid hydrolytic pathways, whereas ...

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mentioning

confidence: 95%

mentioning

confidence: 95%

Species Differences in the in Vitro Metabolism of Deltamethrin and Esfenvalerate: Differential Oxidative and Hydrolytic Metabolism by Humans and Rats

Godin¹,

Scollon²,

Hughes³

et al. 2006

Drug Metab Dispos

Self Cite

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“…These hepatic enzymes are expressed abundantly in the mammalian liver and utilized by insects to gain resistance against insecticides (Ross et al, 2006;Zhou et al, 2007). Individual susceptibility plays a major role in pyrethroid induced adverse effects like skin paresthesia.…”

Section: Carboxylesterasesmentioning

confidence: 99%

“…The determination of the carboxylesterase activity in human isolated lymphocytes was a first step in the search of a marker of pyrethroid susceptibility in man . The study of Ross et al, (2006) has demonstrated that hCbE-1 and hCbE-2 are human pyrethroid-hydrolyzing CbE and that these enzymes will be useful biomarkers of susceptibility in populations that are occupationally and environmentally exposed to these xenobiotics.…”

Section: Carboxylesterasesmentioning

confidence: 99%

Biological Markers of Human Exposure to Pesticides

Araoud¹

2011

Pesticides in the Modern World - Pests Control and Pesticides Exposure and Toxicity Assessment

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“…Many pyrethroids, which are widely used as insecticides due to their selective toxicity against pests rather than mammals (Ross et al, 2006), have been shown to be CYP inducers: permethrin and deltamethrin induce CYP1A, 2B and 3A in human hepatocytes (Das et al, 2008), and pyrethrin induces CYP2B and 3A in rat and Liver tumor promoting effect of etofenprox in rats and its possible mechanism of action human hepatocytes (Price et al, 2008). Furthermore, metofluthrin has been shown to induce CYP2B in rat and human hepatocytes and to have a hepatocarcinogenic potential in rats .…”

Section: Introductionmentioning

confidence: 99%

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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Hydrolytic metabolism of pyrethroids by human and other mammalian carboxylesterases

Cited by 152 publications

References 31 publications

Species Differences in the in Vitro Metabolism of Deltamethrin and Esfenvalerate: Differential Oxidative and Hydrolytic Metabolism by Humans and Rats

Species Differences in the in Vitro Metabolism of Deltamethrin and Esfenvalerate: Differential Oxidative and Hydrolytic Metabolism by Humans and Rats

Biological Markers of Human Exposure to Pesticides

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

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