Kinetic parameters of OPT pesticide desulfuration by c-DNA expressed human CYPs

Buratti, Franca M.; Volpe, Maria Teresa; Fabrizi, Laura; Meneguz, Annarita; Vittozzi, Luciano; Testai, Emanuela

doi:10.1016/s1382-6689(02)00010-8

Cited by 60 publications

(41 citation statements)

References 29 publications

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“…Preliminary Studies. The absence of nonspecific esterases in Supersome preparations that could interfere with AChE activity determination has been previously shown (Buratti et al, 2002). The direct inhibition of AChE activity, due to unmetabolized malathion or impurities, was measured in standard incubations of control Supersomes in the absence of NADP.…”

Section: Resultsmentioning

confidence: 96%

“…It has been suggested that in vitro concentrations of OPTs Յ10 M are the most appropriate to mimic in vivo conditions (Buratti et al, 2002, based on chlorpyrifos plasma concentrations (90 nM) measured in human volunteers (Nolan et al, 1984) and on the estimation of environmental exposure in U.S. adults and children (about 1.4 -1.61 g/kg/day) (Schurdut et al, 1998;Rigas et al, 2001), obtained by applying pharmacokinetic models to biomonitoring data. On the same line, starting from urinary alkylphosphate levels, a body burden of 208 g/kg azinphos-methyl (corresponding to 6.5 M in plasma) was estimated in orchard workers at the steady state (Carrier and Brunet, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…In recent years a number of papers have been published on the activity of human P450s involved in the biotransformation of some members of the OPT class (Butler and Murray, 1997;Mutch et al, 1999;Kappers et al, 2001;Tang et al, 2001;Vittozzi et al, 2001;Buratti et al, 2002. It has been demonstrated with human liver microsomes and recombinant human P450s that at low pesticide concentrations (Ͻ10 M), azinphos-methyl, chlorpyrifos, diazinon, and parathion are mainly desulfurated by CYP1A2 (Buratti et al, 2002.…”

mentioning

confidence: 99%

“…It has been demonstrated with human liver microsomes and recombinant human P450s that at low pesticide concentrations (Ͻ10 M), azinphos-methyl, chlorpyrifos, diazinon, and parathion are mainly desulfurated by CYP1A2 (Buratti et al, 2002. The role of CYP2B6 to total hepatic oxon formation seemed to be relevant in a wide range of pesticide concentrations (Tang et al, 2001;, whereas the contribution of CYP3A4 was significant only at high OPT levels (Mutch et al, 1999;Kappers et al, 2001;Buratti et al, 2002.…”

mentioning

confidence: 99%

“…To study low pesticide concentrations representative of actual human exposure, we took advantage of a method based on AChE inhibition that is able to detect nanomolar levels of oxon (Ma and Chambers, 1994;Buratti et al, 2002).…”

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confidence: 99%

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Malathion Bioactivation in the Human Liver: The Contribution of Different Cytochrome P450 Isoforms

Buratti

D'Aniello²,

Volpe³

et al. 2004

Drug Metab Dispos

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101

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ABSTRACT:Among organophosphorothioate (OPT) pesticides, malathion is considered relatively safe for use in mammals. Its rapid degradation by carboxylesterases competes with the cytochrome P450 (P450)-catalyzed formation of malaoxon, the toxic metabolite. However, impurities in commercial formulations are potent inhibitors of carboxylesterase, allowing a dramatic increase in malaoxon formation. Malathion desulfuration has been characterized in human liver microsomes (HLMs) with a method based on acetylcholinesterase inhibition that is able to detect nanomolar levels of oxon. The active P450 isoforms have been identified by means of a multifaceted strategy, including the use of cDNA-expressed human P450s and correlation, immunoinhibition, and chemical inhibition studies in a panel of phenotyped HLMs. HLMs catalyzed malaoxon formation with a high level of variability (>200-fold). One or two components (K mapp1 ‫؍‬ 53-67 M; K mapp2 ‫؍‬ 427-1721 M) were evidenced, depending on the relative specific P450 content. Results from different approaches indicated that, at low malathion concentration, malaoxon formation is catalyzed by CYP1A2 and, to a lesser extent, 2B6, whereas the role of 3A4 is relevant only at high malathion levels. These results are in line with those found with chlorpyrifos, diazinon, azynphos-methyl, and parathion, characterized by the presence of an aromatic ring in the molecule. Since malathion has linear chains as substituents at the thioether sulfur, it can be hypothesized that, independently from the chemical structure, OPTs are bioactivated by the same P450s. These results also suggest that CYP1A2 and 2B6 can be considered as possible metabolic biomarkers of susceptibility to OPT-induced toxic effects at actual human exposure levels.

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Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Malathion Bioactivation in the Human Liver: The Contribution of Different Cytochrome P450 Isoforms

Buratti

D'Aniello²,

Volpe³

et al. 2004

Drug Metab Dispos

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101

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Voltammetry and Spectroscopy Study of In Vitro Interaction of Fenitrothion with DNA

Ahmadi

Jafari

2010

Electroanalysis

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The interaction of Fenitrothion with DNA has been studied using the voltammetric and spectroscopic methods. An irreversible reduction was concluded from the CV data of Fenitrothion. The values of (an) , respectively. Also the voltammetric, spectroscopic, thermodynamic and activation energy of DNA-Fenitrothion complex revealed that the mode of interaction might be partial-intercalative and complex formation is entropy favored.

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Reversible cholinesterase inhibitors as pre‐treatment for exposure to organophosphates: assessment using azinphos‐methyl

Petroianu

Nurulain

Al‐Hasan

et al. 2014

J of Applied Toxicology

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Pre-treatment with reversible acetylcholinesterase (AChE) inhibitors before organophosphorous compound (OPC) exposure can reduce OPC-induced mortality. However, pyridostigmine, the only substance employed for such prophylaxis, is merely efficacious against a limited number of OPCs. In search of more efficacious and broad-range alternatives, we have compared in vivo the ability of five reversible AChE inhibitors (pyridostigmine, physostigmine, ranitidine, tacrine and K-27) to reduce mortality induced by the OPC azinphos-methyl. Protection was quantified using Cox analysis by determining the relative risk (RR) of death in rats that were administered these AChE inhibitors in equitoxic dosage (25% of LD01) 30 min before azinphos-methyl exposure. Azinphos-methyl-induced mortality was significantly reduced by all five tested compounds as compared with the reference group that was only exposed to azinphos-methyl without prior pre-treatment (RR = 1). The most efficacious prophylactic agents were K-27 (RR = 0.15) and physostigmine (RR = 0.21), being significantly more efficacious than ranitidine (RR = 0.62) and pyridostigmine (RR = 0.37). Pre-treatment with tacrine (RR = 0.29) was significantly more efficacious than pre-treatment with ranitidine, but the difference between tacrine and pyridostigmine was not significant. Our results indicate that prophylactic administration of the oxime K-27 may be a promising alternative in cases of imminent OPC exposure.

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Kinetic parameters of OPT pesticide desulfuration by c-DNA expressed human CYPs

Cited by 60 publications

References 29 publications

Malathion Bioactivation in the Human Liver: The Contribution of Different Cytochrome P450 Isoforms

Malathion Bioactivation in the Human Liver: The Contribution of Different Cytochrome P450 Isoforms

Voltammetry and Spectroscopy Study of In Vitro Interaction of Fenitrothion with DNA

Reversible cholinesterase inhibitors as pre‐treatment for exposure to organophosphates: assessment using azinphos‐methyl

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