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Protective effects of saffron and crocin against biochemical markers of diazinon subacute toxicity
Abstracts / Toxicology Letters 196S (2010) S37–S351
tration of paraoxon was 0.026 nM. After that the samples were incubated for up to two hours forty-three minutes. At 43 min of reactivation at 37 ◦ C the percentage of activity was around 9% and at long time was around 32%. This spontaneous reactivation is clearly time-progressive. The results show the “ongoing inhibition” and “ongoing reactivation” may be taken into account in the kinetic models to analyze the interaction by paraoxon of soluble chicken peripheral nerve phenylvalerate esterases. doi:10.1016/j.toxlet.2010.03.1012
P308-028 Secondary (nosocomial) poisoning from organophosphates in health workers, fact or fiction? J. Anderson 1 , B. Rajapakse 2 , N. Buckley 1 1 2
Prince of Wales Clinical School, University of New South Wales, UK, South Asian Clinical Toxicology Research Collaboration, UK
There is international debate regarding the risk to health workers treating pesticide poisoning. Multiple papers have suggested risks from organophosphates (OP) in health workers but provide little evidence in support. In contrast, Sri Lankan health workers treat thousands of OP poisonings each year with limited protection and no reports of nosocomial poisoning. This ongoing study is prospectively assessing poisoning from organophosphates in health workers in Sri Lanka. So far 11 subjects (clinical assistants, researchers and doctors) employed from 6 to 18 months have been recruited from 2 sites. Baseline data includes previous history of exposure, pulse, BP, oximetry, spirometry, urine and blood samples (n = 11). Acetylcholinesterase (AChE), plasma cholinesterase (BChE) and dialkylphosphate urinary metabolites are measured as biomarkers of OP exposure. The same measurements as for baseline are collected for post-exposure/treatment data at 1, 4, and 24 h. Current data indicate all health workers had frequently treated OP poisonings and wore gloves but no protective gown or mask. 2/11 health workers reported occasions of mild symptoms after previous exposures including vertigo, tightness of chest and respiratory tract irritation, but none sought medical attention or took medication. Prospective findings to date include post exposure data from just one health worker who treated a deliberate chlorpyrifos ingestion. There was no significant change to either AChE or BChE, both sensitive biomarkers of exposure. [AChE;BChE % change from baseline at 1 h + 5.56; −11.7%; 4 h −3.7; −4.79%; 24 hrs −6.8; −4.79%]. There were no reported symptoms or change in observations. Health workers in Sri Lanka are at high risk of exposure to patients with severe organophosphate poisoning. To date this ongoing study has found no evidence to suggest this risk translates into any measurable adverse health effects that warrant greater precautions. doi:10.1016/j.toxlet.2010.03.1013
P308-029 Protective effects of saffron and crocin against biochemical markers of diazinon subacute toxicity S.A. Moallem, H. Hosseinzadeh, A. Timcheh-Hariri Mashhad University of Medical Sciences, Iran Diazinon is one of the most common organophosphate insecticides in the world. In addition to its inhibitory effect on choline esterase
S321
(ChE), it produces reactive oxygen species. Saffron, a common spice with many health benefits along with its main ingredient, crocin have been shown to possess potent antioxidant activity. The purpose of this study was to evaluate the protective effects of saffron and crocin against biochemical markers of diazinon subacute toxicity. Oral administration of diazinon (20 mg/kg/day) and intraperitonneal injection of saffron aqueous extract or crocin (50, 100 and 200 mg/kg/day) were used for four weeks. Diazinon resulted in reductions of serum total protein and albumin. In contrast to saffron, the high dose of crocin was able to prevent these reductions. Enzymatic studies showed that diazinon treatment caused increases in aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), creatine phosphokinase (CPK), creatine phosphokinase MB (CPK-MB) and gamma glutamyl transferase (GGT). Crocin at doses of 100 and 200 mg/kg/day reduced AST and at all doses reduced LDH, ALP, CPK and CPK-MB. Crocin at 50 and 100 mg/kg/day reduced GGT levels. Saffron did not affect AST, ALT and ALP but at 100 and 200 mg/kg/day reduced LDH, CPK and CPK-MB. Diazinon increased serum S100␣, TNF-␣ and F2␣-Isoprostan. Crocin at 100 mg/kg/day and saffron at 200 mg/kg/day were able to significantly reduce the levels of these biomarkers. As expected, diazinon caused a significant reduction in the activity of ChE. Crocin and saffron were not effective against this effect. Therefore, it is evident crocin and to some extent saffron were able to normalize changes induced in some biochemical markers as result of subacute toxicity of diazinon. As ChE was not affected in these studies, it is suggested that the antioxidant activities of crocin and saffron mediate their effects in protecting against diazinon toxicity. doi:10.1016/j.toxlet.2010.03.1014
P308-030 Determination of tissue blood partition coefficients for non-volatile herbicides and fungicides using negligible depletion solid phase microextraction (nd-SPME) R. Tremblay 1 , D. Kim 2 , J. Fisher 1 1 Environmental Health Science Department, University of Georgia, Athens, GA, USA, 2 Syngenta Crop Protection Inc., Greensboro, NC, USA
Partition coefficients (PC) are parameters used in physiologically based pharmacokinetic models to estimate the free concentration of chemicals in specific tissues and organs. PC values have been quantified for volatile compounds using air to blood or tissue ratios; however, the same method cannot be applied for nonvolatile compounds. The objective of this research project was to develop and apply an analytical method for measuring PCs of non-volatile compounds. Buffered water was used instead of air. Ultra-filtration filters used to separate the blood and tissues from the liquid were found to significantly retain compounds with Kow > 1. Instead, a negligible depletion solid phase microextraction (nd-SPME) method, not requiring filtration, was implemented. Only the free-phase compounds and not tissue-bound can partition to the SPME fiber coating. PC values were measured for a series of low volatility pesticides with water solubility ranging from 0.07 to 990 mg/L and Kow between 1.9 and 5.5. Tissue:blood PC values were quantified for liver, brain, skin, fat, kidneys and muscle of male Sprague–Dawley rats. Tissue and blood (0.01–0.5 mL) were added to 8.5 mL solutions spiked with the chemicals (0.07–20 ppm in phosphate buffered saline) and allowed to equilibrate for 4+ h at 37 ◦ C. Free concentrations were measured (3–8 replicates) by inserting a polydimethylsiloxane fiber (PDMS, 100 m thick, 1–4 mm length) directly in the solutions for 1 min. The extracted
tration of paraoxon was 0.026 nM. After that the samples were incubated for up to two hours forty-three minutes. At 43 min of reactivation at 37 ◦ C the percentage of activity was around 9% and at long time was around 32%. This spontaneous reactivation is clearly time-progressive. The results show the “ongoing inhibition” and “ongoing reactivation” may be taken into account in the kinetic models to analyze the interaction by paraoxon of soluble chicken peripheral nerve phenylvalerate esterases. doi:10.1016/j.toxlet.2010.03.1012
P308-028 Secondary (nosocomial) poisoning from organophosphates in health workers, fact or fiction? J. Anderson 1 , B. Rajapakse 2 , N. Buckley 1 1 2
Prince of Wales Clinical School, University of New South Wales, UK, South Asian Clinical Toxicology Research Collaboration, UK
There is international debate regarding the risk to health workers treating pesticide poisoning. Multiple papers have suggested risks from organophosphates (OP) in health workers but provide little evidence in support. In contrast, Sri Lankan health workers treat thousands of OP poisonings each year with limited protection and no reports of nosocomial poisoning. This ongoing study is prospectively assessing poisoning from organophosphates in health workers in Sri Lanka. So far 11 subjects (clinical assistants, researchers and doctors) employed from 6 to 18 months have been recruited from 2 sites. Baseline data includes previous history of exposure, pulse, BP, oximetry, spirometry, urine and blood samples (n = 11). Acetylcholinesterase (AChE), plasma cholinesterase (BChE) and dialkylphosphate urinary metabolites are measured as biomarkers of OP exposure. The same measurements as for baseline are collected for post-exposure/treatment data at 1, 4, and 24 h. Current data indicate all health workers had frequently treated OP poisonings and wore gloves but no protective gown or mask. 2/11 health workers reported occasions of mild symptoms after previous exposures including vertigo, tightness of chest and respiratory tract irritation, but none sought medical attention or took medication. Prospective findings to date include post exposure data from just one health worker who treated a deliberate chlorpyrifos ingestion. There was no significant change to either AChE or BChE, both sensitive biomarkers of exposure. [AChE;BChE % change from baseline at 1 h + 5.56; −11.7%; 4 h −3.7; −4.79%; 24 hrs −6.8; −4.79%]. There were no reported symptoms or change in observations. Health workers in Sri Lanka are at high risk of exposure to patients with severe organophosphate poisoning. To date this ongoing study has found no evidence to suggest this risk translates into any measurable adverse health effects that warrant greater precautions. doi:10.1016/j.toxlet.2010.03.1013
P308-029 Protective effects of saffron and crocin against biochemical markers of diazinon subacute toxicity S.A. Moallem, H. Hosseinzadeh, A. Timcheh-Hariri Mashhad University of Medical Sciences, Iran Diazinon is one of the most common organophosphate insecticides in the world. In addition to its inhibitory effect on choline esterase
S321
(ChE), it produces reactive oxygen species. Saffron, a common spice with many health benefits along with its main ingredient, crocin have been shown to possess potent antioxidant activity. The purpose of this study was to evaluate the protective effects of saffron and crocin against biochemical markers of diazinon subacute toxicity. Oral administration of diazinon (20 mg/kg/day) and intraperitonneal injection of saffron aqueous extract or crocin (50, 100 and 200 mg/kg/day) were used for four weeks. Diazinon resulted in reductions of serum total protein and albumin. In contrast to saffron, the high dose of crocin was able to prevent these reductions. Enzymatic studies showed that diazinon treatment caused increases in aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), creatine phosphokinase (CPK), creatine phosphokinase MB (CPK-MB) and gamma glutamyl transferase (GGT). Crocin at doses of 100 and 200 mg/kg/day reduced AST and at all doses reduced LDH, ALP, CPK and CPK-MB. Crocin at 50 and 100 mg/kg/day reduced GGT levels. Saffron did not affect AST, ALT and ALP but at 100 and 200 mg/kg/day reduced LDH, CPK and CPK-MB. Diazinon increased serum S100␣, TNF-␣ and F2␣-Isoprostan. Crocin at 100 mg/kg/day and saffron at 200 mg/kg/day were able to significantly reduce the levels of these biomarkers. As expected, diazinon caused a significant reduction in the activity of ChE. Crocin and saffron were not effective against this effect. Therefore, it is evident crocin and to some extent saffron were able to normalize changes induced in some biochemical markers as result of subacute toxicity of diazinon. As ChE was not affected in these studies, it is suggested that the antioxidant activities of crocin and saffron mediate their effects in protecting against diazinon toxicity. doi:10.1016/j.toxlet.2010.03.1014
P308-030 Determination of tissue blood partition coefficients for non-volatile herbicides and fungicides using negligible depletion solid phase microextraction (nd-SPME) R. Tremblay 1 , D. Kim 2 , J. Fisher 1 1 Environmental Health Science Department, University of Georgia, Athens, GA, USA, 2 Syngenta Crop Protection Inc., Greensboro, NC, USA
Partition coefficients (PC) are parameters used in physiologically based pharmacokinetic models to estimate the free concentration of chemicals in specific tissues and organs. PC values have been quantified for volatile compounds using air to blood or tissue ratios; however, the same method cannot be applied for nonvolatile compounds. The objective of this research project was to develop and apply an analytical method for measuring PCs of non-volatile compounds. Buffered water was used instead of air. Ultra-filtration filters used to separate the blood and tissues from the liquid were found to significantly retain compounds with Kow > 1. Instead, a negligible depletion solid phase microextraction (nd-SPME) method, not requiring filtration, was implemented. Only the free-phase compounds and not tissue-bound can partition to the SPME fiber coating. PC values were measured for a series of low volatility pesticides with water solubility ranging from 0.07 to 990 mg/L and Kow between 1.9 and 5.5. Tissue:blood PC values were quantified for liver, brain, skin, fat, kidneys and muscle of male Sprague–Dawley rats. Tissue and blood (0.01–0.5 mL) were added to 8.5 mL solutions spiked with the chemicals (0.07–20 ppm in phosphate buffered saline) and allowed to equilibrate for 4+ h at 37 ◦ C. Free concentrations were measured (3–8 replicates) by inserting a polydimethylsiloxane fiber (PDMS, 100 m thick, 1–4 mm length) directly in the solutions for 1 min. The extracted