Vasic VM

References (6)

Title : UV-C light irradiation enhances toxic effects of chlorpyrifos and its formulations - Savic_2019_Food.Chem_271_469
Author(s) : Savic JZ , Petrovic SZ , Leskovac AR , Lazarevic Pasti TD , Nastasijevic BJ , Tanovic BB , Gasic SM , Vasic VM
Ref : Food Chem , 271 :469 , 2019
Abstract : UV-C irradiation is widely used in the food industry. However, the health effects from dietary exposure to the irradiated pesticide residues retained in foodstuffs are underestimated. In this study, technical chlorpyrifos (TCPF) and its oil in water (EW) and emulsifiable concentrate (EC) formulations were irradiated by UV-C, and their photodegradation products were subjected to toxicity assessment, including determination of acetylcholinesterase (AChE) activity, genotoxicity and oxidative stress using human blood cells as a model system. Toxicity studies were performed using the chlorpyrifos concentrations in the range of those proposed as the maximum residue levels in plant commodities. TCPF, EW and EC photodegradation products induced DNA damage and oxidative stress, and their genotoxicity did not decrease as a function of irradiation time. Irradiated TCPF and EC are more potent AChE inhibitors than irradiated EW. Accordingly, the application of UV-C irradiation must be considered when processing the plants previously treated with chlorpyrifos formulations.
ESTHER : Savic_2019_Food.Chem_271_469
PubMedSearch : Savic_2019_Food.Chem_271_469
PubMedID: 30236704

Title : In vitro evaluation of neurotoxicity potential and oxidative stress responses of diazinon and its degradation products in rat brain synaptosomes - Colovic_2015_Toxicol.Lett_233_29
Author(s) : Colovic MB , Vasic VM , Avramovic NS , Gajic MM , Djuric DM , Krstic DZ
Ref : Toxicol Lett , 233 :29 , 2015
Abstract : Although primary toxic action of organophosphorous insecticides is associated with acetylcholinesterase inhibition, later studies suggest that oxidative stress may be responsible for induced organophosphates toxicity. These studies mostly include thio forms, while the effects of their metabolites/degradation products have been less investigated. Therefore, this paper studies the toxic effects of diazinon degradation products, diazoxon and 2-isopropyl-6-methyl-4-pyrimidinol, and compares them with the toxic potential of the parent compound. The toxicity induced by various concentrations of the investigated compounds was in vitro evaluated by the activities of acetylcholinesterase, ATPases, antioxidant defense enzymes and lactate dehydrogenase, and malondialdehyde level in rat brain synaptosomes. Diazinon inhibited acetylcholinesterase and Na(+)/K(+)-ATPase in dose-dependent manner, while the inhibition of ecto-ATPase activity was less than 15% at all investigated concentrations. It did not demonstrate noteworthy prooxidative properties causing increase (up to 10%) in antioxidant enzymes activity and malondialdehyde level, as a marker of lipid peroxidation. Diazinon oxidation product, diazoxon was found as the most toxic investigated compound. Beside the expected strong inhibitory effect on acetylcholinesterase, it induced dose-dependent and almost complete inhibition of Na(+)/K(+)-ATPase and ecto-ATPase at the highest investigated concentration (0.1mM). Increasing diazoxon concentrations activated catalase (up to 30%), superoxide dismutase (up to 50%), glutathione peroxidase (up to 30%), and significantly increased malondialdehyde level (up to 50%). The investigated hydrolysis product of diazinon, 2-isopropyl-6-methyl-4-pyrimidinol did not remarkably alter the activities of acetylcholinesterase, Na(+)/K(+)-ATPase, catalase, glutathione peroxidase and lipid peroxidation level (up to about 10%). Although this diazinon metabolite has been known as non toxic, it induced superoxide dismutase stimulation up to 30%. Finally, even high concentrations of both diazinon and its metabolites did noticeably affect lactate dehydrogenase activity as a marker of synaptosomal integrity. The changes in investigated biochemical parameters in rat brain synaptosomes could serve as indicators of toxicity due to the exposure to thio organophosphates and/or their break-down products.
ESTHER : Colovic_2015_Toxicol.Lett_233_29
PubMedSearch : Colovic_2015_Toxicol.Lett_233_29
PubMedID: 25562544

Title : Acetylcholinesterase inhibitors: pharmacology and toxicology - Colovic_2013_Curr.Neuropharmacol_11_315
Author(s) : Colovic MB , Krstic DZ , Lazarevic-Pasti TD , Bondzic AM , Vasic VM
Ref : Curr Neuropharmacol , 11 :315 , 2013
Abstract : Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer's disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system. Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates detoxification is their degradation by corresponding phosphotriesterases.
ESTHER : Colovic_2013_Curr.Neuropharmacol_11_315
PubMedSearch : Colovic_2013_Curr.Neuropharmacol_11_315
PubMedID: 24179466

Title : Indirect electrochemical oxidation of organophosphorous pesticides for efficient detection via acetylcholinesterase test - Lazarevic-Pasti_2012_Pestic.Biochem.Physiol_104_236
Author(s) : Lazarevic-Pasti TD , Bondzic AM , Pasti IA , Vasic VM
Ref : Pesticide Biochemistry and Physiology , 104 :236 , 2012
Abstract : Organothiophosphorous pesticides diazinon, malathion, chlorpyrifos, azinphos-methyl and phorate, have been indirectly electrochemically oxidized in aqueous media using anodically evolved Cl2, Br2 or I2 as a pre-step for their detection via acetylcholinesterase-based test. The presence of single oxidation product, corresponding oxo-form, was confirmed by UPLC analysis, as well as its stability with respect to hydrolysis. Comparing different halogens, the best results were obtained using Br2 as the oxidant due to high reactivity of HOBr, which is formed upon chemical reaction of anodically formed Br2 with water. Limits of detection of five analyzed pesticides were lowered upon indirect electrochemical oxidation with Br2 for two orders of magnitude or more, comparing to unoxidized parental thio-forms. In fact, the lowest possible detection limits for all five pesticides using proposed analytical procedure were achieved, as being determined by detection limits of corresponding oxo forms. Comparison of here proposed electrochemical oxidation pre-step with earlier reported ones is provided and discussed.
ESTHER : Lazarevic-Pasti_2012_Pestic.Biochem.Physiol_104_236
PubMedSearch : Lazarevic-Pasti_2012_Pestic.Biochem.Physiol_104_236

Title : Single and simultaneous exposure of acetylcholinesterase to diazinon, chlorpyrifos and their photodegradation products - Colovic_2011_Pestic.Biochem.Physiol_100_16
Author(s) : Colovic MB , Krstic DZ , Uscumlic GS , Vasic VM
Ref : Pesticide Biochemistry and Physiology , 100 :16 , 2011
Abstract : In vitro inhibition of electric eel acetylcholinesterase (AChE) by single and simultaneous exposure to organophosphorus insecticides diazinon and chlorpyrifos, and their transformation products, formed due to photoinduced degradation, was investigated. Increasing concentrations of diazinon, chlorpyrifos and their oxidation products, diazoxon and chlorpyrifos-oxon, inhibited AChE in a concentration-dependent manner. IC50 (20 min) values, obtained from the inhibition curves, were (in mol/l): (5.1 +/- 0.3) 10-8, (4.3 +/- 0.2) 10-6 and (3.0 +/- 0.1) 10-8 for diazoxon, chlorpyrifos and chlorpyrifos-oxon, respectively, while maximal diazinon concentration was lower than its IC50 (20 min). Calculated KI values, in mol/l, of 7.9 10-7, 9.6 10-6 and 4.3 10-7 were obtained for diazoxon, chlorpyrifos and chlorpyrifos-oxon, respectively. However, 2-isopropyl-4-methyl-6-pyrimidinol (IMP) and 3,5,6-trichloro-2-pyridinol, diazinon and chlorpyrifos hydrolysis products, did not noticeably affect the enzyme activity at all investigated concentrations. Additive inhibition effect was achieved for lower concentrations of the inhibitors (diazinon/diazoxon -1 10-4/1 10-8 mol/l i.e., chlorpyrifos/chlorpyrifos-oxon -2 10-6/3 10-8 mol/l), while an antagonistic effect was obtained for all higher concentrations of the organophosphates. Inhibitory power of 1 10-4 mol/l diazinon irradiated samples can be attributed mostly to the formation of diazoxon, while the presence of non-inhibiting photodegradation product IMP did not affect diazinon and diazoxon inhibitory efficiencies.
ESTHER : Colovic_2011_Pestic.Biochem.Physiol_100_16
PubMedSearch : Colovic_2011_Pestic.Biochem.Physiol_100_16

Title : Spectrophotometric and electrochemical study of protolytic equilibria of some oximes-acetylcholinesterase reactivators - Cakar_1999_J.Pharm.Biomed.Anal_20_655
Author(s) : Cakar MM , Vasic VM , Petkovska LT , Stojic DL , Avramov-Ivic M , Milovanovic GA
Ref : J Pharm Biomed Anal , 20 :655 , 1999
Abstract : Newly synthesized oximes, mono and bis imidazole derivatives, which promise to be more effective acetylcholinesterase reactivators than standard antidotes used, were investigated by spectrophotometric and electrochemical methods. The electrochemical investigations confirmed the existence of overlapping equilibria, obtained by spectrophotometric methods. Dissociation constants of those oximes were also obtained by numerical treatment of overlapping equilibria, using the Lavendberg Marquardt least square method, and when compared with the same for some similar compounds, were found to be very effective acetylcholinesterase reactivators. The distribution of ionic forms of the investigated oximes, as a dependence of pH values, was calculated from the obtained values of dissociation constants. The results indicated that many oxime anions will be available at physiological pH 7.4 and a relative increased ability to reactivate inhibited acetylcholinesterase could be expected.
ESTHER : Cakar_1999_J.Pharm.Biomed.Anal_20_655
PubMedSearch : Cakar_1999_J.Pharm.Biomed.Anal_20_655
PubMedID: 10704134