The Role of P-glycoprotein in Preventing Developmental and Neurotoxicity

Stevens, Jim; Breckenridge, Charles B.; Wright, Jayne

doi:10.1016/b978-0-12-374367-1.00097-5

Cited by 4 publications

(4 citation statements)

References 77 publications

(108 reference statements)

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“…This conclusion is in quite agreement with available toxicological data (Stevens et al, 1991;Kontchou and Gschwind, 1998;Extoxnet) showing that this herbicide is slightly toxic for humans and non-toxic or moderately toxic for other organisms. The good parallelism observed between metolachlor data provided by these two experimental models and those reported in the literature are in accordance with the results of previous studies performed with other compounds (Donato et al, 1997;Monteiro et al, 2003Monteiro et al, , 2008.…”

Section: Discussionsupporting

confidence: 80%

“…This widespread use of pesticides (65% being herbicides, Stevens et al, 1991) for agricultural and non-agricultural purposes has resulted in the presence of their residues in various environmental matrices. The presence of pesticides in soil and water systems has been well documented worldwide (Huber et al, 2000;Cerejeira et al, 2003) and can cause serious problems both to the environment and to human health (Koeman, 1984).…”

Section: Introductionmentioning

confidence: 99%

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Toxicity assessment of the herbicide metolachlor comparative effects on bacterial and mitochondrial model systems

Pereira

Férnandes

Martins

et al. 2009

Toxicology in Vitro

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a b s t r a c tMetolachlor is one of the most intensively used chloroacetamide herbicides. However, its effects on the environment and on non-target animals and humans as well as its interference at a cell/molecular level have not yet been fully elucidated. The aim of this study was: firstly, to evaluate the potential toxicity of metolachlor at a cell/subcellular level by using two in vitro biological model systems (a strain of Bacillus stearothermophilus and rat liver mitochondria); secondly, to evaluate the relative sensibility of these models to xenobiotics to reinforce their suitability for pollutant toxicity assessment. Our results show that metolachlor inhibits growth and impairs the respiratory activity of B. stearothermophilus at concentrations two to three orders of magnitude higher than those at which bacterial cells are affected by other pesticides. Also at concentrations significantly higher than those of other pesticides, metolachlor depressed the respiratory control ratio, membrane potential and respiration of rat liver mitochondria when malate/glutamate or succinate were used as respiratory substrates. Moreover, metolachlor impaired the respiratory activity of rat liver mitochondria in the same concentration range at which it inhibited bacterial respiratory system (0.4-5.0 lmol/mg of protein). In conclusion, the high concentration range at which metolachlor induces toxicity in vitro suggests that this compound is safer than other pesticides previously studied in our laboratory, using the same model systems. The good parallelism between metolachlor effects on both models and the toxicity data described in the literature, together with results obtained in our laboratory with other compounds, indicate the suitability of these systems to assess toxicity in vitro.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Toxicity assessment of the herbicide metolachlor comparative effects on bacterial and mitochondrial model systems

Pereira

Férnandes

Martins

et al. 2009

Toxicology in Vitro

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“…However, overdose or uncontrolled administration can lead to the development of severe toxicity. To illustrate the role of species differences in the expression of efflux transporter, Stevens et al [ 204 ] investigated the effect of the placenta-fetal barrier on the toxic effect of AVM using rodents. They concluded that the use of animal models in toxicological research and extrapolation to humans is necessary to note the variation in genetic makeup between organisms and between animals and humans.…”

Section: Toxicity and Side Effectsmentioning

confidence: 99%

Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects

et al. 2020

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Avermectins are a group of drugs that occurs naturally as a product of fermenting Streptomyces avermitilis, an actinomycetes, isolated from the soil. Eight different structures, including ivermectin, abamectin, doramectin, eprinomectin, moxidectin, and selamectin, were isolated and divided into four major components (A1a, A2a, B1a and B2a) and four minor components (A1b, A2b, B1b, and B2b). Avermectins are generally used as a pesticide for the treatment of pests and parasitic worms as a result of their anthelmintic and insecticidal properties. Additionally, they possess anticancer, anti-diabetic, antiviral, antifungal, and are used for treatment of several metabolic disorders. Avermectin generally works by preventing the transmission of electrical impulse in the muscle and nerves of invertebrates, by amplifying the glutamate effects on the invertebrates-specific gated chloride channel. Avermectin has unwanted effects or reactions, especially when administered indiscriminately, which include respiratory failure, hypotension, and coma. The current review examines the mechanism of actions, biosynthesis, safety, pharmacokinetics, biological toxicity and activities of avermectins.

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“…69,70 Avermectin B1 (abamectin), comprising avermectin B 1a ( 9 ) and avermectin B 1b ( 10 ), is an important commercial product for mite control. 71 Avermectins target insect glutamate-gated chloride channels (GluCls) and γ-aminobutyric acid type A receptors (GABAARs), forcing channels to remain open, leading to increased chloride anion flow through the cell membrane. This results in hyperpolarization of the neuronal membrane and decreased neural transmission, leading to paralysis and death.…”

Section: Microbial Polyketides and Polyketide–nonribosomal Peptide Hy...mentioning

confidence: 99%

Microbial polyketides and their roles in insect virulence: from genomics to biological functions

et al. 2022

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The Role of P-glycoprotein in Preventing Developmental and Neurotoxicity

Cited by 4 publications

References 77 publications

Toxicity assessment of the herbicide metolachlor comparative effects on bacterial and mitochondrial model systems

Toxicity assessment of the herbicide metolachlor comparative effects on bacterial and mitochondrial model systems

Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects

Microbial polyketides and their roles in insect virulence: from genomics to biological functions

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