The in vitro metabolism of a pyrethroid insecticide, permethrin, and its hydrolysis products in rats

Nakamura, Y.; Sugihara, Kazumi; Sone, Tomomichi; Isobe, Masakazu; Ohta, Shigeru; Kawa, Shigeyuki

doi:10.1016/j.tox.2007.03.016

Cited by 69 publications

(51 citation statements)

References 45 publications

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“…Our data revealed higher CCE copy number in mosquitoes surviving deltamethrin exposure (R+ phenotype), supporting their role in pyrethroid resistance. Although the association between pyrethroid resistance and these CCE genes in Thailand might be due to multiresistant individuals carrying both pyrethroid-and organophosphate-resistance genes, the role of CCEs in pyrethroid metabolism has been demonstrated in mammals (Hodgson 2003;Nakamura et al 2007) and mosquitoes Chandor-Proust et al 2013). However, no individual mosquito CCE has yet been validated as a pyrethroid metabolizer, and insecticide sequestration may also confer resistance.…”

Section: Gene Amplifications Associated With Pyrethroid Resistancementioning

confidence: 99%

Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing

et al. 2015

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The capacity of mosquitoes to resist insecticides threatens the control of diseases such as dengue and malaria. Until alternative control tools are implemented, characterizing resistance mechanisms is crucial for managing resistance in natural populations. Insecticide biodegradation by detoxification enzymes is a common resistance mechanism; however, the genomic changes underlying this mechanism have rarely been identified, precluding individual resistance genotyping. In particular, the role of copy number variations (CNVs) and polymorphisms of detoxification enzymes have never been investigated at the genome level, although they can represent robust markers of metabolic resistance. In this context, we combined target enrichment with high-throughput sequencing for conducting the first comprehensive screening of gene amplifications and polymorphisms associated with insecticide resistance in mosquitoes. More than 760 candidate genes were captured and deep sequenced in several populations of the dengue mosquito Ae. aegypti displaying distinct genetic backgrounds and contrasted resistance levels to the insecticide deltamethrin. CNV analysis identified 41 gene amplifications associated with resistance, most affecting cytochrome P450s overtranscribed in resistant populations. Polymorphism analysis detected more than 30,000 variants and strong selection footprints in specific genomic regions. Combining Bayesian and allele frequency filtering approaches identified 55 nonsynonymous variants strongly associated with resistance. Both CNVs and polymorphisms were conserved within regions but differed across continents, confirming that genomic changes underlying metabolic resistance to insecticides are not universal. By identifying novel DNA markers of insecticide resistance, this study opens the way for tracking down metabolic changes developed by mosquitoes to resist insecticides within and among populations.

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Section: Gene Amplifications Associated With Pyrethroid Resistancementioning

confidence: 99%

Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing

et al. 2015

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“…Its concentration in the urine is the most representative marker for pyrethroid exposure in rodents (Nakamura et al, 2007) and humans (Leng et al, 1997).…”

Section: Urine 3-phenoxybenzoic Acid Levelsmentioning

confidence: 99%

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

et al. 2013

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a b s t r a c tPesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41.50 g/L and it was completely eliminated after 96 h.

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“…20 Oxidative stress and reactive oxygen species so produced in response to stress, as well as endocrine disturbance are among the most significant effects of pesticide toxicology. [21][22][23][24][25] CYP may also induce oxidative stress and endocrine disturbance in organisms. Giray et al 14 also reported that oral administration of CYP to rats induce significant oxidative stress in cerebral and hepatic tissues.…”

Section: Introductionmentioning

confidence: 99%

Dose-Dependent Hematological, Hepatic and Gonadal Toxicity of Cypermethrin in Wistar Rats

Das¹,

Ghosh²,

Paramanik³

et al. 2017

Toxicol Forensic Med Open J

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CitationPesticides are used frequently and may have various adverse effects on human health in different ways. Cypermethrin (CYP) is a synthetic type II pyrethroid pesticide that has been used extensively to control a wide variety of pests in agriculture, forestry, horticulture, and public health. Objectives: This study aimed to investigate the dose-dependent hematological, hepatic and gonadal toxicity of CYP in mature male and female Wistar rats. Methods: Rats were randomly divided into nine groups, different doses of CYP were administered for 14 consecutive days and different hematological, hepatic and gonadal parameters were assayed. Results: Erythrocyte count, hemoglobin percentage, hepatic reduced glutathione (GSH) content and sperm count were significantly diminished. Serum aspartic and alanine transaminase, hepatic malondialdehyde (MDA), testicular cholesterol content were increased following CYP treatment in male rats at 40 and 80 mg/kg body weight (1/9 and 1/4.5 LD 50 ). Elevated ovarian cholesterol content and decreased 17β hydroxy steroid dehydrogenase (HSD) levels were also observed in CYP-exposed female rats at a dose level of 34.33 and 51.5 mg/kg body wt. (1/9 and 1/6 LD 50 ). Conclusion: Taken together, CYP initiated hematological, hepatic and gonadal toxicity in mature male rats with a body weight of 40 mg/kg (1/9 LD 50 ) and gonadal toxicity in mature female rats with a body weight of 34.33 mg/kg (1/9 LD 50 ) and above.

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The in vitro metabolism of a pyrethroid insecticide, permethrin, and its hydrolysis products in rats

Cited by 69 publications

References 45 publications

Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing

Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

Dose-Dependent Hematological, Hepatic and Gonadal Toxicity of Cypermethrin in Wistar Rats

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