Effects of methylparathion on membrane fluidity and its implications for the mechanisms of toxicity

Lopes, Vanessa; Antunes-Madeira, M.C.; Madeira, Vı́tor M.C.

doi:10.1016/s0887-2333(97)00024-6

Cited by 10 publications

(4 citation statements)

References 33 publications

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“…However, there is insufficient information to assess the carcinogenic potential of MCs applying Environmental Protection Administration Guidelines for Carcinogen Risk Assessment. Several studies have demonstrated that the mechanism underlying an agent's toxicity is related to its membrane interactions (Donato et al, 1997a;Lopes et al, 1997;Sikkema et al, 1995). The present study confirms that the toxic mechanism of an agent is related to membrane interactions but also concludes that it is related to the type of membrane transport it undergoes (Fei et al, 2010;Song et al, 2010).…”

supporting

confidence: 85%

Transmembrane Transport of Microcystin to Danio rerio Zygotes: Insights into the Developmental Toxicity of Environmental Contaminants

Song

Gao

2011

Toxicological Sciences

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Microcystins (MCs) produced by cyanobacteria and their continuing "blooms" are a worldwide problem owing to the toxicity of microcystin-LR (MC-LR) to plants and animals. In the present study, we investigated membrane transport of MC-LR and its toxic effects on zebrafish embryos using fragmentation of embryos, scanning electron microscope (SEM), fluorescence microscopy, and toxic exposure tests. At a concentration < 0.04 mmol/l, MC-LR was predominantly adsorbed on outer membrane surface of embryos according to Langmuir isotherm. The absorption characteristics of MC-LR within the range from 0.05 to 0.4 mmol/l conformed to Freundlich isotherm model. At concentrations > 0.50 mmol/l MC-LR directly entered the cytoplasm via partition. Thinning and disruption of membranes was confirmed using SEM and fluorescence morphological observations. Exposure to different concentrations of MC-LR resulted in differences in membrane transport and toxicity characteristics. At low concentrations, more than 75% of the adsorbed MC-LR accumulated on the outer membrane surface and resulted in axial malformation, tail curving, and tail twisting. Increasing the concentration of MC-LR to between 0.05 and 0.4 mmol/l improved membrane transport and it was evident in cytoplasm of embryos, resulting in serious pericardial edema, hatching gland edema, hemagglutination, hemorrhage, and vacuolization. At > 0.50 mmol/l, more than 70% of the adsorbed MC-LR entered the cytoplasm and this was lethal to the embryos. The current research outlines a new method and mechanism for the transmembrane transport of large molecular weight organic compounds and could be important for studies concerning molecular toxicology.

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confidence: 85%

Transmembrane Transport of Microcystin to Danio rerio Zygotes: Insights into the Developmental Toxicity of Environmental Contaminants

Song

Gao

2011

Toxicological Sciences

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Section: Academic Pressmentioning

confidence: 99%

“…Examples of the above compounds include anesthetics, calcium channel blocking drugs, alcohols, and insecticides (Makriyannis et al, 1986;Bae et al, 1989;Barry and Gawrisch, 1994;Mavromoustakos et al, 1995;Antunes-Madeira et al, 1996). In particular, the influence of organochlorine and organophosphorus insecticides on the physical properties of lipid bilayers and implications at the level of membrane cell function have been studied in our laboratory (Antunes-Madeira and Madeira, 1993; AntunesMadeira et al, 1994 AntunesMadeira et al, , 1996Videira et al, 1996Videira et al, , 1999aLopes et al, 1997;Donato et al, 1997).It is largely accepted that the basic mechanism of acute toxicity of organophosphorus compounds is associated with the specific inhibition of acetylcholinesterase (Ohkawa, 1982). However, the current understanding of how these compounds interact with the acetylcholinesterase is incomplete (Kardos and Sultatos, 2000), since the capacity to phosphorylate the enzyme appears to decrease as the organophosphorus concentration increases.…”

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confidence: 99%

Ethylazinphos Interaction with Membrane Lipid Organization Induces Increase of Proton Permeability and Impairment of Mitochondrial Bioenergetic Functions

Videira

Antunes-Madeira

Madeira

2001

Toxicology and Applied Pharmacology

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Ethylazinphos increases the passive proton permeability of lipid bilayers reconstituted with dipalmitoylphosphatidylcholine (DPPC) and mitochondrial lipids. A sharp increase of proton permeability is detected at insecticide/lipid molar ratios identical to those inducing phase separation in the plane of DPPC bilayers, as revealed by differential scanning calorimetry (DSC). Ethylazinphos progressively depresses the transmembrane potential (⌬⌿) of mitochondria supported by piruvate/malate, succinate, or ascorbate/TMPD. Additionally, a decreased depolarization induced by ADP depends on ethylazinphos concentration, reflecting a phosphorylation depression. This loss of phosphorylation is a consequence of a decreased ⌬⌿. A decreased respiratory control ratio is also observed, since ethylazinphos stimulates state 4 respiration and inhibits ADPstimulated respiration (state 3). Ethylazinphos concentrations up to 100 nmol/mg mitochondrial protein increase the rate of state 4 together with a decrease in ⌬⌿, without significant perturbation of state 3 and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled respiration. For increased insecticide concentrations, the state 3 and FCCP-uncoupled respiration are inhibited to approximately the same extent. The perturbations are more pronounced when the energization is supported by pyruvate/ malate and less effective when succinate is used as substrate. The present data, in association with previous DSC studies, indicate that ethylazinphos, at concentrations up to 100 nmol/mg mitochondrial protein, interacts with the lipid bilayer of mitochondrial membrane, changing the lipid organization and increasing the proton permeability of the inner membrane. The increased proton permeability explains the decreased oxidative phosphorylation coupling. Resulting disturbed ATP synthesis may significantly underlie the mechanisms of ethylazinphos toxicity, since most of cell energy in eukaryotes is provided by mitochondria. © 2001 Academic PressKey Words: ethylazinphos; membrane organization; proton permeability; mitochondrial respiration; transmembrane potential; oxidative phosphorylation.The two major components of the biological membranes are lipids and proteins. Together they determine the organization and function of membranes. These dynamic and versatile barriers are, in turn, involved in most cellular functions (Kinnunen, 1991). A large number of drugs with different chemical structures and pharmacological effects are able to accumulate in membrane lipid domains, changing their organization and physical properties and, consequently, their function (Sikkema et al., 1995;Mouritsen and Jørgensen, 1998), since the preservation of an exact degree of organization is essential for most membrane activities (Eze, 1990;Mouritsen and Jørgensen, 1998;Williams, 1998). Examples of the above compounds include anesthetics, calcium channel blocking drugs, alcohols, and insecticides (Makriyannis et al., 1986;Bae et al., 1989;Barry and Gawrisch, 1994;Mavromoustakos et al., 1995;Antunes-Madeira...

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“…On the other hand, the least toxic affects the membrane structure to a lesser extent. The insecticides possessing intermediate toxicity have shown to have also intermediate effects ( − ).…”

Section: Introductionmentioning

confidence: 99%

Structure Effect on the Interaction of Phenylurea Herbicides with Model Biomembrane as an Environmental Mobility Parameter

Librando

Forte

Sarpietro

2003

Environ. Sci. Technol.

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During recent years, intensive use of herbicides has raised increasing concern mainly due to their massive pollution of the environment. As these herbicides are directly or indirectly toxic to a wide range of organisms, their potential for contaminating soil, surface water, and groundwater makes these xenobiotics of special interest from a health and environmental point of view. Knowledge of the mechanisms by which they exert their toxic effects is becoming a need. Because of the herbicides' lipophilicity, a possible site of interaction in the cell is represented by biomembranes. The interaction of four herbicides, difenoxuron, diuron, linuron, and metoxuron, with model membranes constituted of dimyristoylphosphatidylcholine multilamellar vesicles was investigated by the differential scanning calorimetry technique. The aim was to study the effects exerted by an increasing amount of the examined compounds on thermotropic behavior of the model phospholipid membranes and to correlate the obtained results with structural features of the herbicides due to their environmental mobility. Among the herbicides studied, linuron is the most effective in perturbing the ordinate structure of vesicles forming phospholipids, whereas metoxuron is the least effective and the others exert an intermediate effect. Linuron exerts its effect both on the transition temperature of the gel to the liquid crystalline phase and on the enthalpy change. Difenoxuron, diuron, and metoxuron cause a change in the transition temperature but have an insignificant effect on the enthalpy change. The calorimetric results, correlated with the structural features of the herbicides, are consistent with their partition coefficient, log K(ow), suggesting that the more hydrophobic compound character causes a greater liposolubility and consequential cellular absorption with more effectiveness on the membrane order.

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Effects of methylparathion on membrane fluidity and its implications for the mechanisms of toxicity

Cited by 10 publications

References 33 publications

Transmembrane Transport of Microcystin to Danio rerio Zygotes: Insights into the Developmental Toxicity of Environmental Contaminants

Transmembrane Transport of Microcystin to Danio rerio Zygotes: Insights into the Developmental Toxicity of Environmental Contaminants

Ethylazinphos Interaction with Membrane Lipid Organization Induces Increase of Proton Permeability and Impairment of Mitochondrial Bioenergetic Functions

Structure Effect on the Interaction of Phenylurea Herbicides with Model Biomembrane as an Environmental Mobility Parameter

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