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Reactivation kinetic studies of bis-pyridinium mono-oximes against nerve agents poisoning: An in vitro screening
S250
Abstracts / Toxicology Letters 258S (2016) S62–S324
P16-046 Evaluation of the in vitro antioxidant, cytotoxic and genotoxic/antigenotoxic effects of resveratrol G. Taner 1,∗ , S. Aydın 2 , Z. Aytac¸ 3 , A.A. Bas¸aran 4 , N. Bas¸aran 2 1
Department of Bioengineering, Faculty of Natural Sciences, Architecture and Engineering, Bursa Technical University, Bursa, Turkey 2 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey 3 Department of Biology, Faculty of Science, Gazi University, Ankara, Turkey 4 Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey It has been shown in many studies that natural compounds in plants known as secondary metabolites, have protective effects against genetic damage induced by oxidative stress. Among these compounds, resveratrol (RSV) is a stilbene group non-flavonoid polyphenol found in especially grapes, red fruits and seeds, roots, stems or leaves of many plants. Its health effects were investigated by many scientists since many years, and today it is one of the most studied phenolic compound. RSV has been suggested to exert anticarcinogenic, antifungal, antimicrobial and antioxidant effects. In this study, we aimed to determine the in vitro antioxidant, cytotoxic, genotoxic and antigenotoxic properties of RSV. Antioxidant capacity of RSV was measured by trolox equivalent antioxidant capacity assay (TEAC) and its potential cytotoxic effect was evaluated in Chinese hamster ovary (CHO) cells by neutral red uptake (NRU) method. At the non-cytotoxic concentrations, both genotoxic and antigenotoxic effects against hydrogen peroxide (H2 O2 ), which is known to have genotoxic potential and causes oxidative damage were assessed by micronucleus and comet assays in human lymphocytes. RSV showed antioxidant activity against oxidant ABTS at all tested concentrations. Low concentrations have been shown to have no cytotoxic and genotoxic effects, but at the high concentrations RSV alone show cytotoxic and genotoxic effects which causes DNA damage and micronucleus formation. On the other hand RSV reduced genotoxic effects of H2 O2 which may be due to its antioxidant properties. http://dx.doi.org/10.1016/j.toxlet.2016.06.1885 P16-047 The effect of bisphenol AF on lipid peroxidation and antioxidant enzymes activity in human erythrocytes ∗ , B. Bukowska, J. Michałowicz ´ A. Macczak
Department of Environmental Pollution Biophysics, University of Lodz, Lodz, Poland Bisphenols are chemical substances widely used in the manufacturing of polycarbonates, epoxy resins and thermal paper. Among these compounds, bisphenol A (BPA) is produced in the highest amounts, while in recent years an increased production of BPA analogues including bisphenol AF (BPAF) has been noted. The number of studies on the effect of BPAF on living organisms is very small, while there are only two studies on its impact on human erythrocytes. That is why, the aim of this study, was to assess the effect of BPAF on the lipid peroxidation and the activity of antioxidant enzymes, i.e. catalase, glutathione peroxidase and superoxide dismutase in human erythrocytes.
The results showed that BPAF in the concentrations of 25 g/ml and 100 g/ml after 4 h incubation and in the concentrations of 5 g/ml and 25 g/ml after 24 h incubation caused an increase in lipid peroxidation. BPAF decreased the activity of superoxide dismutase in the concentration of 100 g/ml after 4 h incubation and in the concentrations ranging from 0.5 to 25 g/ml after 24 h incubation. Moreover, BPAF in the concentrations of 25 g/ml and 100 g/ml after 4 h incubation and in the concentrations 0.5 g/ml and 5 g/ml after 24 h incubation caused changes in the activity of catalase, while it did not alter the activity of glutathione peroxidase. The obtained results suggest that BPAF can disrupt redox balance in human erythrocytes in the concentrations that may affect human organism during occupational exposure or subacute poisoning. http://dx.doi.org/10.1016/j.toxlet.2016.06.1886 P16-048 Reactivation kinetic studies of bis-pyridinium mono-oximes against nerve agents poisoning: An in vitro screening A.K. Sahu ∗ , B. Gupta, R. Sharma, K.K. Ghosh Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India Organophosphate compounds (OPC) include pesticides (e.g., chlorpyrifos, methamidophos) and nerve agents (e.g. sarin, tabun, VX) that are extremely toxic and perilous chemicals for common population as the number of accidental, homicidal and suicidal fatalities is estimated 300,000 per year worldwide. OPC attack on the serine hydroxyl group situated at active site of acetylcholinesterase (AChE) and irreversibly inhibits its catalytic activity. Hence the hydrolysis of neurotransmitter acetylcholine (ACh) is discontinued resulting in several sever disorders. Reactivation of AChE is the key therapeutic approach to reverse the ill effects of OP poisoning. Oximes are the universal choice for this therapeutic intervention. Only few oximes like 2-PAM, obidoxime are used clinically. In spite of widespread approach, no single oxime is available as universal reactivator against all kind of OP-poisoning, hence the search is continued. And in the past decades extensive research programs have been undertaken independently in various countries to develop and identify more effective oxime reactivators. In our present investigation we have studied the reactivation kinetics of a series of bis-pyridinium mono-oximes having different functionalities in one of the pyridinium ring with pesticides inhibited-AChE. Results were compared with the standard oximes as 2-PAM, obidoxime and TMB-4. Out of the studied compound butene linked mono-oxime with carboxylic functionality demonstrated good efficacy against tested OP. The results of this study give further importance of structure activity relationship for oxime reactivators, and the development of a next generation broad spectrum antidote. http://dx.doi.org/10.1016/j.toxlet.2016.06.1887
Abstracts / Toxicology Letters 258S (2016) S62–S324
P16-046 Evaluation of the in vitro antioxidant, cytotoxic and genotoxic/antigenotoxic effects of resveratrol G. Taner 1,∗ , S. Aydın 2 , Z. Aytac¸ 3 , A.A. Bas¸aran 4 , N. Bas¸aran 2 1
Department of Bioengineering, Faculty of Natural Sciences, Architecture and Engineering, Bursa Technical University, Bursa, Turkey 2 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey 3 Department of Biology, Faculty of Science, Gazi University, Ankara, Turkey 4 Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey It has been shown in many studies that natural compounds in plants known as secondary metabolites, have protective effects against genetic damage induced by oxidative stress. Among these compounds, resveratrol (RSV) is a stilbene group non-flavonoid polyphenol found in especially grapes, red fruits and seeds, roots, stems or leaves of many plants. Its health effects were investigated by many scientists since many years, and today it is one of the most studied phenolic compound. RSV has been suggested to exert anticarcinogenic, antifungal, antimicrobial and antioxidant effects. In this study, we aimed to determine the in vitro antioxidant, cytotoxic, genotoxic and antigenotoxic properties of RSV. Antioxidant capacity of RSV was measured by trolox equivalent antioxidant capacity assay (TEAC) and its potential cytotoxic effect was evaluated in Chinese hamster ovary (CHO) cells by neutral red uptake (NRU) method. At the non-cytotoxic concentrations, both genotoxic and antigenotoxic effects against hydrogen peroxide (H2 O2 ), which is known to have genotoxic potential and causes oxidative damage were assessed by micronucleus and comet assays in human lymphocytes. RSV showed antioxidant activity against oxidant ABTS at all tested concentrations. Low concentrations have been shown to have no cytotoxic and genotoxic effects, but at the high concentrations RSV alone show cytotoxic and genotoxic effects which causes DNA damage and micronucleus formation. On the other hand RSV reduced genotoxic effects of H2 O2 which may be due to its antioxidant properties. http://dx.doi.org/10.1016/j.toxlet.2016.06.1885 P16-047 The effect of bisphenol AF on lipid peroxidation and antioxidant enzymes activity in human erythrocytes ∗ , B. Bukowska, J. Michałowicz ´ A. Macczak
Department of Environmental Pollution Biophysics, University of Lodz, Lodz, Poland Bisphenols are chemical substances widely used in the manufacturing of polycarbonates, epoxy resins and thermal paper. Among these compounds, bisphenol A (BPA) is produced in the highest amounts, while in recent years an increased production of BPA analogues including bisphenol AF (BPAF) has been noted. The number of studies on the effect of BPAF on living organisms is very small, while there are only two studies on its impact on human erythrocytes. That is why, the aim of this study, was to assess the effect of BPAF on the lipid peroxidation and the activity of antioxidant enzymes, i.e. catalase, glutathione peroxidase and superoxide dismutase in human erythrocytes.
The results showed that BPAF in the concentrations of 25 g/ml and 100 g/ml after 4 h incubation and in the concentrations of 5 g/ml and 25 g/ml after 24 h incubation caused an increase in lipid peroxidation. BPAF decreased the activity of superoxide dismutase in the concentration of 100 g/ml after 4 h incubation and in the concentrations ranging from 0.5 to 25 g/ml after 24 h incubation. Moreover, BPAF in the concentrations of 25 g/ml and 100 g/ml after 4 h incubation and in the concentrations 0.5 g/ml and 5 g/ml after 24 h incubation caused changes in the activity of catalase, while it did not alter the activity of glutathione peroxidase. The obtained results suggest that BPAF can disrupt redox balance in human erythrocytes in the concentrations that may affect human organism during occupational exposure or subacute poisoning. http://dx.doi.org/10.1016/j.toxlet.2016.06.1886 P16-048 Reactivation kinetic studies of bis-pyridinium mono-oximes against nerve agents poisoning: An in vitro screening A.K. Sahu ∗ , B. Gupta, R. Sharma, K.K. Ghosh Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India Organophosphate compounds (OPC) include pesticides (e.g., chlorpyrifos, methamidophos) and nerve agents (e.g. sarin, tabun, VX) that are extremely toxic and perilous chemicals for common population as the number of accidental, homicidal and suicidal fatalities is estimated 300,000 per year worldwide. OPC attack on the serine hydroxyl group situated at active site of acetylcholinesterase (AChE) and irreversibly inhibits its catalytic activity. Hence the hydrolysis of neurotransmitter acetylcholine (ACh) is discontinued resulting in several sever disorders. Reactivation of AChE is the key therapeutic approach to reverse the ill effects of OP poisoning. Oximes are the universal choice for this therapeutic intervention. Only few oximes like 2-PAM, obidoxime are used clinically. In spite of widespread approach, no single oxime is available as universal reactivator against all kind of OP-poisoning, hence the search is continued. And in the past decades extensive research programs have been undertaken independently in various countries to develop and identify more effective oxime reactivators. In our present investigation we have studied the reactivation kinetics of a series of bis-pyridinium mono-oximes having different functionalities in one of the pyridinium ring with pesticides inhibited-AChE. Results were compared with the standard oximes as 2-PAM, obidoxime and TMB-4. Out of the studied compound butene linked mono-oxime with carboxylic functionality demonstrated good efficacy against tested OP. The results of this study give further importance of structure activity relationship for oxime reactivators, and the development of a next generation broad spectrum antidote. http://dx.doi.org/10.1016/j.toxlet.2016.06.1887