Evidence for dose-additive effects of a type II pyrethroid mixture. In vitro assessment

Romero, Alejandro; Arés, Irma; Ramos, Eva; Castellano, V.; Martínez-Larrañaga, María Rosa; Anadón, Arturo; Martínez, Marta

doi:10.1016/j.envres.2015.02.008

Cited by 40 publications

(21 citation statements)

References 47 publications

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“…Effect of β-cyfluthrin, omega-3 and their combination on the oxidative stress markers: MDA, NO, TAC, total thiol content and total protein (TP) levels in brain and testis of male rats: β-cyf administration exihibeted significant (P<0.05) increase in MDA and NO levels in brain and testis tissues ( Table 3). Similar results were obtained by 43,44 who reported elevation in the levels of MDA and NO after exposure to mixture of type II pyrethroid. The increase in MDA induced by the pyrethroid could be as a result of the generation of ROS that attacked the unsaturated lipids, thereby causing the generation of lipid peroxides leading to alteration of membrane permeability and cell function.…”

Section: Resultssupporting

confidence: 79%

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2017

IJPSR

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ABSTRACT:The present study was designed to evaluate the protective effect of omega-3 against β-cyfluthrin (β-cyf)-induced neurotransmitters' impairment, oxidative damage, testicular toxicity and genotoxicity. Adult male Wistar rats were divided equally into four groups: Group (I): Control, Group (II): β-cyf (5 mg/kg body weight/day), Group (III): omega-3 (400 mg/kg body weight/da y) + β-cyf (5 mg/kg body weight/day), Group (IV): omega-3 (400 mg/kg body weight/day). β-cyf's treatment for 8 weeks inhibited the activities of AChE, DA, LDH, total ATPase and Na + /K + ATPase. Also, β-cyf resulted in an increase in oxidative stress as indicated by elevations in the levels of MDA and NO while, the levels of TAC, thiol content and TP were decreased in brain and testis. Sperm count, sperm motility and testosterone levels were reduced while, sperm abnormalities, FSH and LH levels were increased in β-cyf-treated group. Also, β-cyf administration led to a significant increase in TNFα, IL-6 and APP mRNA expressions. In addition, β-cyf caused histopathological alterations in brain and testis. The present results showed that omega-3 could improve all the measured parameters. In conclusion, omega-3 could exhibit protective effects against β-cyf induced neurological and testicular damage.

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Section: Resultssupporting

confidence: 79%

Untitled

2017

IJPSR

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“…These insecticides correspond to type I pyrethroids (seven compounds: allethrin (also known as allethrin 1), bifenthrin, cis -permethrin, trans -permethrin, resmethrin, tefluthrin and tetramethrin) or type II pyrethroids (seven compounds: β-cyfluthrin, λ-cyhalothrin, β-cypermethrin, deltamethrin, esfenvalerate, fenpropathrin and τ-fluvalinate) and can be considered as adequately reflecting the structural and historical diversity of these pesticides. Moreover, at least some of them are insecticides used in large-scale commercial agricultural and domestic applications and have already been tested in in vitro toxicity assays [30–33]. Our data demonstrate that the pyrethroids allethrin and tetramethrin are inhibitors of various drug transporters, but only when used at relative high concentrations likely not reached in humans environmentally exposed to these insecticides.…”

Section: Introductionmentioning

confidence: 79%

Inhibition of Human Drug Transporter Activities by the Pyrethroid Pesticides Allethrin and Tetramethrin

et al. 2017

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Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulatory effects of these pesticides towards activities of main ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, using transporter-overexpressing cells. The pyrethroids allethrin and tetramethrin were found to inhibit various ABC and SLC drug transporters, including multidrug resistance-associated protein (MRP) 2, breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP) 1B1, organic anion transporter (OAT) 3, multidrug and toxin extrusion transporter (MATE) 1, organic cation transporter (OCT) 1 and OCT2, with IC50 values however ranging from 2.6 μM (OCT1 inhibition by allethrin) to 77.6 μM (OAT3 inhibition by tetramethrin) and thus much higher than pyrethroid concentrations (in the nM range) reached in environmentally pyrethroid-exposed humans. By contrast, allethrin and tetramethrin cis-stimulated OATP2B1 activity and failed to alter activities of OATP1B3, OAT1 and MATE2-K, whereas P-glycoprotein activity was additionally moderately inhibited. Twelve other pyrethoids used at 100 μM did not block activities of the various investigated transporters, or only moderately inhibited some of them (inhibition by less than 50%). In silico analysis of structure-activity relationships next revealed that molecular parameters, including molecular weight and lipophilicity, are associated with transporter inhibition by allethrin/tetramethrin and successfully predicted transporter inhibition by the pyrethroids imiprothrin and prallethrin. Taken together, these data fully demonstrated that two pyrethoids, i.e., allethrin and tetramethrin, can act as regulators of the activity of various ABC and SLC drug transporters, but only when used at high and non-relevant concentrations, making unlikely any contribution of these transporter activity alterations to pyrethroid toxicity in environmentally exposed humans.

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“…Pyrethroids have been demonstrated to cause oxidative damage in several animal species (El-Demerdash et al, 2003;Giray et al, 2000;Prasamthi et al, 2005), being the lipid peroxidation one of the main toxicity mechanisms of these compounds (Kovacic, 2003;Tiwari et al, 2010;Romero et al, 2012) as well as decreased activities of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase (Liu and Shi, 2006). Romero et al (2015) demonstrated in SH-SY5Y neuronal cells that six Type II pyrethoids (α-cypermethrin, cyfluthrin, λ-cyhalothrin, deltamethrin, cyphenothrin and esfenvalerate) evoke induction of both nitric oxide and lipid peroxide levels measured as malondialdehyde. Oxidative stress has been a matter of concern in the pathogenesis of neurodegenerative diseases (Patel et al, 2006;Gupta et al, 2010).…”

Section: Discussionmentioning

confidence: 98%