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Effect of endosulfan on LDH level in tilapia
S238
Abstracts / Toxicology Letters 164S (2006) S1–S324
in lipid peroxidation (LPO) and carbonyl groups content and by normalization of the myeloperoxidase (MPO) activities. On the other hand, these improvements were not observed in kidney and spleen of DEX treated rats. Conversely, an increase of LPO and carbonyl groups content and aggravation of histological damages were observed. In addition, MPO activity increased in the spleen of DEX exposed rats beyond PQ and N-acetyl-d-glucosaminidase activity, a biomarker of renal tubular proximal damage, also augmented in the urine of these rats giving credit to an aggravation of the renal lesion caused by PQ. In spite of these apparent contradictory effects, the increased survival rate indicates that DEX treatment constitutes an important and valuable therapeutic tool to be used against PQ-induced toxicity. Acknowledgement: Ricardo Dinis-Oliveira, acknowledges FCT for his PhD grant (SFRH/BD/13707/2003). doi:10.1016/j.toxlet.2006.07.153 P17-10 Effect of endosulfan on LDH level in tilapia Ashok Rani, T.R. Ambili Lady Doak College, Madurai, Tamilnadu, India Demand for agricultural products is increasing day by day due to ever increasing human population. This inturn increases the stress on soil due to overdose of application of fertilizers and pesticides. Endosulfan, a banned pesticide in developed countries but still in use in developing countries is of importance as they reach the waterbody as run off from fields due to rain, etc. The fish forms the staple food and as a source of protein to economically weak human society. Detoxification of ingested pesticide is done by the activity of various enzymes. In the present dose and time dependent study, effect of endosulfan on LDH level is studied by spectrophotometric method using pyruvate as substrate. From the study, we find that the level is altered and that medium concentration of endosulfan produces more significant effect in kidney LDH and as the concentration and days increased, there was considerable increase in amount of LDH in muscle indicating bioaccumulation of endosulfan. doi:10.1016/j.toxlet.2006.07.154
P17-11 Pralidoxime kinetics in rats pre-treated with organic cationic transporters substrates Maya Kayouka, Pascal Houz´e, Claire Monier, Patricia Ris`ede, Frederic J. Baud INSERM U705, CNRS, UMR 7157; Universit´e Paris 5, France Pralidoxime methylsulate (PRX) is a nucleophilic agent used as antidote after intoxication with organophosphates. The efficacy of the antidote depends on its plasma concentrations that should be greater than 4 mg L−1 . PRX is rapidly (half life <60 min) eliminated in urine and may be handled by the kidney as a strong organic base (as thiamine or tetraethylammonium, TEA) and secreted by similar mechanisms. Strong bases are transported by organic cationic transporters (Oct1 and 2); thus, their co-administration with PRX may delay its secretion and increase its plasma levels. The aim of this study was to determine the effects of thiamine or TEA pre-treatments on PRX pharmacokinetic. Sprague–Dawley male rats were pre-treated by thiamine or TEA (75 mg kg−1 , IM). Animals were than treated with PRX (50 mg kg−1 , 30 min perfusion). Aiming at determining a dose–effect relationship, thiamine pre-treatment was performed at 15, 30 and 60 min; and at different doses (0.15, 1.5, 15 and 150 mg kg−1 , 15 min pre-treatment). TEA was injected at different times (15, 30 min, 1, 2, 4 and 6 h) before PRX infusion. Blood samples were collected during PRX infusion and 180 min post infusion. Plasma PRX concentrations were measured by liquid chromatography. Results are expressed as mean ± S.E.M. Thiamine induced a significant increase of PRX distribution volume and renal clearance, with a maximal effect at 15 min, with no half-life modification. Using 15 min pre-treatment, we observed a dose–effect relationship for thiamine. Only 1.5 and 15 mg kg−1 of thiamine reduced significantly Cmax and area under the curves and increased distribution volume and renal clearance. A pre-treatment with TEA induced an increase of beta half live, a decrease of renal clearance of PRX; distribution volume was not altered. A time effect relationship was also found with a maximal effect observed for 30 min pre-treatment. Our results support that PRX might be excreted via Oct1 and 2 because TEA decreased the urinary elimination of PRX without altering its distribution. Thiamine renal excretion is more complex implying different transporters. Our work suggests that thiamine alters the distribution of PRX in tissues without modifying its elimina-
Abstracts / Toxicology Letters 164S (2006) S1–S324
in lipid peroxidation (LPO) and carbonyl groups content and by normalization of the myeloperoxidase (MPO) activities. On the other hand, these improvements were not observed in kidney and spleen of DEX treated rats. Conversely, an increase of LPO and carbonyl groups content and aggravation of histological damages were observed. In addition, MPO activity increased in the spleen of DEX exposed rats beyond PQ and N-acetyl-d-glucosaminidase activity, a biomarker of renal tubular proximal damage, also augmented in the urine of these rats giving credit to an aggravation of the renal lesion caused by PQ. In spite of these apparent contradictory effects, the increased survival rate indicates that DEX treatment constitutes an important and valuable therapeutic tool to be used against PQ-induced toxicity. Acknowledgement: Ricardo Dinis-Oliveira, acknowledges FCT for his PhD grant (SFRH/BD/13707/2003). doi:10.1016/j.toxlet.2006.07.153 P17-10 Effect of endosulfan on LDH level in tilapia Ashok Rani, T.R. Ambili Lady Doak College, Madurai, Tamilnadu, India Demand for agricultural products is increasing day by day due to ever increasing human population. This inturn increases the stress on soil due to overdose of application of fertilizers and pesticides. Endosulfan, a banned pesticide in developed countries but still in use in developing countries is of importance as they reach the waterbody as run off from fields due to rain, etc. The fish forms the staple food and as a source of protein to economically weak human society. Detoxification of ingested pesticide is done by the activity of various enzymes. In the present dose and time dependent study, effect of endosulfan on LDH level is studied by spectrophotometric method using pyruvate as substrate. From the study, we find that the level is altered and that medium concentration of endosulfan produces more significant effect in kidney LDH and as the concentration and days increased, there was considerable increase in amount of LDH in muscle indicating bioaccumulation of endosulfan. doi:10.1016/j.toxlet.2006.07.154
P17-11 Pralidoxime kinetics in rats pre-treated with organic cationic transporters substrates Maya Kayouka, Pascal Houz´e, Claire Monier, Patricia Ris`ede, Frederic J. Baud INSERM U705, CNRS, UMR 7157; Universit´e Paris 5, France Pralidoxime methylsulate (PRX) is a nucleophilic agent used as antidote after intoxication with organophosphates. The efficacy of the antidote depends on its plasma concentrations that should be greater than 4 mg L−1 . PRX is rapidly (half life <60 min) eliminated in urine and may be handled by the kidney as a strong organic base (as thiamine or tetraethylammonium, TEA) and secreted by similar mechanisms. Strong bases are transported by organic cationic transporters (Oct1 and 2); thus, their co-administration with PRX may delay its secretion and increase its plasma levels. The aim of this study was to determine the effects of thiamine or TEA pre-treatments on PRX pharmacokinetic. Sprague–Dawley male rats were pre-treated by thiamine or TEA (75 mg kg−1 , IM). Animals were than treated with PRX (50 mg kg−1 , 30 min perfusion). Aiming at determining a dose–effect relationship, thiamine pre-treatment was performed at 15, 30 and 60 min; and at different doses (0.15, 1.5, 15 and 150 mg kg−1 , 15 min pre-treatment). TEA was injected at different times (15, 30 min, 1, 2, 4 and 6 h) before PRX infusion. Blood samples were collected during PRX infusion and 180 min post infusion. Plasma PRX concentrations were measured by liquid chromatography. Results are expressed as mean ± S.E.M. Thiamine induced a significant increase of PRX distribution volume and renal clearance, with a maximal effect at 15 min, with no half-life modification. Using 15 min pre-treatment, we observed a dose–effect relationship for thiamine. Only 1.5 and 15 mg kg−1 of thiamine reduced significantly Cmax and area under the curves and increased distribution volume and renal clearance. A pre-treatment with TEA induced an increase of beta half live, a decrease of renal clearance of PRX; distribution volume was not altered. A time effect relationship was also found with a maximal effect observed for 30 min pre-treatment. Our results support that PRX might be excreted via Oct1 and 2 because TEA decreased the urinary elimination of PRX without altering its distribution. Thiamine renal excretion is more complex implying different transporters. Our work suggests that thiamine alters the distribution of PRX in tissues without modifying its elimina-