• Toxicological Research
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• v.13 no.1_2
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• pp.87-94
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• 1997

This study was carried out to investigate toxicity of insecticide carbofuran and compensatory effects of phenobarbital sodium (PB) in vivo and in vitro. Sprague Dawley male rats were used as experimental animals and divided into carbofuran only administered group and simultaneous application group of carbofuran and PB. At 30 rain and 1, 3, 6, 12, 24, 48 and 96 hrs after each treatment, the animals were sacrificed by decapitation. Kidney were immediately removed, immersed in fixatives, and processed with routine method for light microscopic study. Paraffin sections were stained with H-E, PAM and PAS. $5.0\times 10^4$ cell/ml of NIH 3T3 fibroblast in each well of 24 multidish were cultured: After 24 hours, the cells were treated with solution of six groups; control group cultured in media only, carbofuran $MTT_50$ or $NR_50$ group cultured in the media containing carbofuran $MTT_50$ or $NR_50$ and four experimental groups cultured in the media containing carbofuran $NR_50$ plus various concentratins of PB. After the NIH 3T3 fibroblast of all groups were cultured in same condition for 48 hours, Tetrazolium MTT (MTT) and NR (neutral red) assay were performed to evaluate the cytotoxicity of cell organelles. Under the light microscope, atrophic change of renal corpuscles were frequently observed in 1 and 2 days after carbofuran treatment. The increase of the mesangium was apparent in 1 and 2 days after carbofuran treatment. Necrotic changes of the epithelium and loss of brush border of proximal tubules were most severe at 2 and 3 days after carbofuran treatment, respectively. In contrast, there were no evidences of the toxic effects on renal tissues at 48hrs in carbofuran-PB treated groups. Carbofuran $MTT_50$ and $NR_50$ were 78$\mu M$, 82.5$\mu M$ respectively. MTT and NR quantities were significantly increased in carbofuran-PB 100$\mu M$ treatment group and carbofuran-PB 100$\mu M$ treatment group. On the basis of these results, it is obvious that PB has compensatory effects against carbofuran toxicity.

• Applied Biological Chemistry
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• v.39 no.1
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• pp.77-83
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• 1996

Effects of insecticide carbofuran and Phenobarbital sodium(PB) or 3-methylcholanthrene(3-MC) on activities of several enzymes in israeli carps were investigated. Survival number of Israeli carp was the same as that of control when PB and 3-MC only was treated, individually and that was low compared to control when carbofuran only was treated. But survival rate of Israeli carp was high compared to individual treatment of carbofuran when combination treatment of carbofuran and PB or 3-MC was carried out. These results indicate that PB and 3-MC can intervene to detoxify carbofuran exposed to israeli carp. In in vivo test for the effect of this chemicals on activity of enzyme in israeli carp, activities of acetylcholinesterase(AChE) and glutathione S-transferase(GST) were inhibited in carbofuran treatment, but did not in combination treatment of carbofuran and P3 or 3-MC. Activities of UDP-glucuronosyltransfe-rase (UDPGT) and cytochrome P-450-dependent monooxygenase increased in individual or combined treatments of carbofuran and PB or 3-MC. These results suggest that a simultaneous application of carbofuran and PB or 3-MC is critical for the enhancement of activity of AChE, GST, UDPGT and monooxygenase and the protection of Israeli carp from carbofuran toxicity.

• The Korean Journal of Pesticide Science
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• v.3 no.3
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• pp.27-36
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• 1999

Effect of insecticide carbofuran and phenobarbital sodium(PB) or 3-methylcholanthrene(3-MC), they were orally administered by the chemicals, alone or in combination, on activities of several enzymes in rats were investigated. In in vivo test for the effect of this chemicals on activity of enzyme in rat, activities of acetylcholinesterase(AChE) and butyrylcholinesterase(BuCheE) were inhibited by $20{\sim}70%$ for 48 hrs after the oral administration of carbofuran alone of 3.8mg/kg, whereas those were lowered at the beginning, but recovered to the control level after 24 hrs, in case of the mixed administration of carbofuran+PB or carbofuran+3-MC. The activity of glutathione S-transferase(GST) was inhibited by more than 15 to 35% for an early period of 0.5 to 6 hrs, in the case of the administration of carbofuran alone, whereas that was slightly inhibited at the beginning, recovered almost to the control level after 3 hrs, and raised by mere than 20% above the control after 6 hrs, in case of the mixed administration of carbofuran+PB or carbofuran+3-MC. When carbofuran was administered alorig with PB or 3-MC, the activities of UDP-glucuronosyltransferase(UDPGT) and cytochrome P-450 were more than 2.6 to 2.8 times higher than that in the case of the administration of carbofuran alone for 6 hrs. These results suggest that a simultaneous application of carbofuran and PB or 3-MC is critical for the enhancentment of activity of GST, UDPGT and cytochrome P450 and the protection of rat from carbofuran toxicity.

• Korean Journal of Environmental Agriculture
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• v.21 no.1
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• pp.57-68
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• 2002

In order to elucidate the effect of phenobarbital sodium (PB) and 3-methylcholanthrene (3-MC) on metabolism of insecticide carbofuran in rat. Carbofuran metabolites and its formation rates were determined when orally administered $^{14}C$-carbofuran alone and its combination with PB or 3-MC to rat. $^{14}C$-carbofuran administered orally, alone or in combination with PB or 3-MC, was secreted rapidly within 48 hrs. That is, 79.9 to 81.1% of the original radioactivity was secreted into the urine and 5.7 to 6.5% into the feces. The secretion rate was faster in the combined administration than that in carbofuran alone. Metabolites of carbofuran in main organs, urine, feces and blood of rat were largely 3-hydroxycarbofuran, 3-ketocarbofuran, 3-hydroxycarbofuran phenol, 3-ketocarbofuran phenol, and carbofuran phenol, the major ones being 3-hydroxycarbofuran and 3-ketocarbofuran, respectively, in all administrations of carbofuran alone, carbofuran+PB and carbofuran+3-MC. In addition, formation rate of the two major metabolites detected in the urine was 17.4% and 12.8%, respectively, when carbofuran alone was administered. Meanwhile, when carbofuran was administered with PB or 3-MC, they were 8.6% and 23.5, repectively. These results indicate that the oral administration of PB or 3-MC can reduce carbofuran toxicity by fastening and stimulating the carbofuran metabolism in rat.

• Korean Journal of Environmental Agriculture
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• v.16 no.1
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• pp.61-66
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• 1997

This study was carried out to investigate the toxicological effects of carbofuran on the histological and fine structures in the kidney, liver, and brain of rat and also to clarify compensatory effects of phenobarbital sodium (PB) and 3-methylcholanthrene(3-MC) on the carbofuran toxicity. SPF albino rats were treated with carbofuran(3.8mg/kg), PB(60mg/kg), 3-MC(60mg/kg), carbofuran+PB, carbofuran+3-MC and subjected to the light microscopic study. In the kidney of rat, hemorrhage and extremely atropic change of renal corpuscles were frequently observed at 48 hrs after carbofuran treatment. Combination treatment groups of carbofuran and PB or 3-MC showed atrophic changes were largely recovered at 6 hrs, and the tissue findings of the kidney became similar to those of control group at 48 hrs after treatment. In the liver of rat treated only carbofuran, the degenerative and necrotic changes of hepatic lobules were frequently observed at 48 hrs after carbofuran treatment. Combination treatment of carbofuran and PB or 3-MC showed the hepatic lobules were similar to those of control groups at 6 hrs after the combination treatment. In the brain of rat treated with carbofuran alone, degenerative changes and dilation of capillary vessel of cerebral cortexes were observed at 48hrs after treatment. Combination treatment of carbofuran and PB or carbofuran and 3-MC showed the cerebral cortexes were similar to those of control groups at 6 hrs after the treatment. These results suggest that PB and 3-MC could regenerate the toxicity of carbofuran to the tissue of kidney, liver and brain of rat.

• The Korean Journal of Pharmacology
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• v.21 no.2
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• pp.128-141
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• 1985

To investigate the influence of phenobarbital sodium on the action of morphine and on the diurnal rhythms of both opiate receptor binding and ${\beta}-endorphin$ contents, the amount of specifically bound $(^3H)$-morphine and immunoreactive ${\beta}-endorphin$ were measured in the midbrain of phenobarbital-treated rats at 4h intervals in a day. Rats were housed and adapted to a controlled cycle of either 12 h light-12 h dark or 24 h constant dark. After 3 weeks of adaptation, 0.5 ml of physiological saline or phenobarbital sodium (20mg/kg/day, i.p.) were administered twice a day for 2 weeks. Highly significant diurnal rhythms of opiate receptor binding and ${\beta}-endorphin$ were present in rat midbrain. In control group, the peak of maximum $(^3H)$-morphine binding was observed at 22:00 h, whereas the peak of ${\beta}-endorphin$ content was found at 06:00 h. Even in the absence of time cues these diurnal rhythms persisted, but they were highly modified with respect to the wave form as well as differences in the timing of peak and nadir. In the phenobarbital-treated group, these diurnal rhythms were also modified in shape, phase and amplitude, as well as in timing of peak and nadir. In this group, 24 h mean of opiate receptor binding was significantly decreased, while the 24 h mean level of ${\beta}-endorphin$ content was highly increased. However, Kd values in all experimental groups did not change. This indicates that differences in binding were not due to changes in the affinity, but in the number of binding sites. Statistical analysis of regression line indicates that changes of receptor binding were closely correlated with the changes of ${\beta}-endorphin$ content. These results suggest that phenobarbital may influence the action of morphine by changing the number of opiate receptors and that the modification of diurnal rhythm of opiate receptor by the agent is possibly due to changes of ${\beta}-endorphin$ content.

• The Korean Journal of Pesticide Science
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• v.2 no.2
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• pp.29-38
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• 1998

In order to elucidate the effect of phenobarbital sodium(PB) and 3-methylcholanthrene(3-MC) on metabolism in vitro and toxicity of $^{14}C$-carbofuran in rat, they were administered by the chemicals, alone or in combination, and their survival ratios and metabolites were investigated. The $LD_{50}$(96 hrs) value of carbofuran to rats was 6.9 mg/kg. The toxicities of the major metabolites were in the decreasing order of 3-hydroxycarbofuran, 3-ketocarbofuran, 3-hydroxycarbofuran phenol and were much lower than that of the parent compound. When the rats were orally administered by the dose of carbofuran alone, 8.4 mg/kg, the survival ratio was 0%, whereas that was raised up to $60{\sim}80%$ with 20 mg/kg of PB or 3-MC, and 100% with 60 mg/kg of PB or 3-MC. Their metabolism in vitro occurred in the microsomal fraction. In case of carbofuran alone, the major metabolite was 3-hydroxycarbofuran. When carbofuran with PB or 3-MC, on the other hand, was treated, it was 3-ketocarbofuran. In addition, when the co-factor(NADP+G-6-P+G-6-P-DG) was added to the microsomal fraction(phase I system), and a mixture of NADPH+GSH to the 105,000g supernatant(phase II system) taken by carbofuran alone, each metabolites were produced by the maximum levels, respectively. In case of the carbofuran treatment with PB or 3-MC, the microsomal fraction of phase I system produced the maximum levels of metabolites, as in the treatment of carbofuran alone, whereas the 105,000g supernatant supplemented with the co-factor NADPH+FAD(phase II system) was brought about the maximum production of metabolites. The ratio of the formation of metabolites was 2 to 3 times higher in the combined treatment of carbofuran with PB or 3-MC than in the treatment of carbofuran alone.

• Toxicological Research
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• v.4 no.2
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• pp.107-115
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• 1988

The effects of altering the hepatic mixed-function oxidase(MFO) activities on the acute toxicity of parathion were examined in female rats. Phenobarbital sodium pretreatment (50mg/kg/day, i.p.) for 4 consecutive days has resulted in significant decreases in the toxicity of parathion (2 or 4 mg/kg, i.p.) as determined by lethality and cholinesterase activities wheras the toxicity arising from a single dose of CCl4(2 mmol/kg, i.p.) 24 hr prior to parathion challenge was potentiated.

• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1194-1201
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• 2004

Michael addition of certain nucleophiles on ${\alpha}$ , ${\beta}$-unsaturated ketones 1 led to the formation of adducts 2-7 as well as the reaction of arylidene derivatives with secondary amines afforded the amino compounds 9 and 11. Also, dialkylmalonates were treated with ${\alpha}$-cyano cinnamide to afford 13. On the other hand, double Michael cycloaddition of ethylcyanoacetate or tetrachlorophthalic anhydride to the suitable divinylketone were synthesized to produce 15-17. Selected compounds (13 and 6) were screened for muscle relaxant, anticonvulsant, and sedative activities using established pharmacological models. Their activities were compared with that of phenobarbital sodium taken as standard. Compound 6 was the most potent muscle relaxant while compounds 13a and 13c offered the highest anticonvulsant activity. Meanwhile compound 13c showed the highest potentiation of phenobarbital induced sleep in mice.

• Journal of Veterinary Clinics
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• v.20 no.4
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• pp.516-518
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• 2003

Six year-old female shihtzu was presented as primary epileptic seizure. We had been treated with high dose phenobarbital sodium (6.5 mg/kg), but could not achieved adequate control seizures. In an add-on therapy, the dog was given potassium bromide at a dose of 20 to 40 mg/kg daily for a period of 24 months. This dog has showed a greater than 50% reduction in seizure frequency. The therapeutic range of serum concentration of potassium bromide was from 0.7 to 1.3 mg/ml at 6weeks after treatment. To begin an add-on therapy with potassium bromide it can be recommended at a daily dose of 20 to 40 mg/kg.