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Electroanalysis of cisplatin–glutathione and cisplatin–DNA interactions
Abstracts / Toxicology Letters 180S (2008) S32–S246
Results: In the saline group, 12 of the 25 mice receiving amitriptyline + saline died. Kaplan-Meier estimates of the 24 h survival rate was 52%(13/25) for saline and 68%(17/25), 52%(13/25) and 40%(10/25) for DPCPX, CSC and DMSO groups, respectively. Median survival times were 1440, 1440,1440 and 44 min for saline, DPCPX, CSC and DMSO groups, respectively. There was no statistically significant difference in survival rates for amitriptyline poisoning between control and adenosine receptor antagonist treatment groups (p > 0.05). Power analysis demonstrated a 42% likelihood of finding a 20% difference (S1 = 50%, S2 = 70%, beta error 58%, alpha 5%). Conclusions: Adenosine antagonists, DPCPX or CSC, failed to increase survival rates of amitriptyline poisoning in mice. Future studies are needed with repeated doses of adenosine antagonists in amitriptyline poisoning with a higher statistical power. doi:10.1016/j.toxlet.2008.06.760 C25 Investigation of a role of metallothionein in resistance on platinum based cytostatics Dalibor Huska 1,∗ , Ivo Fabrik 1 , Jan Hrabeta 2 , Tomas Eckschlager 2 , Jiri Kukacka 2 , Richard Prusa 2 , Sona Krizkova 1 , Vojtech Adam 1 , Rene Kizek 1 1 2
Mendel University of Agriculture and Forestry, Brno, Czech Republic, Charles University, Prague, Czech Republic
In this work, we employed electroanalytical methods for determination of metallothionein (MT) in cisplatin or carboplatin sensitive and resistant neuroblastoma cell lines, blood serum of patients with head and neck cancer or retinoblastoma, and of rats treated with cisplatin with respect to discuss the role of MT in formation of resistance on treatment with heavy metal based cytostatics. Level of MT increases with higher dose of platinum based cytostatics at cells. Further we focused on determination of MT in blood serum of rats treated with cisplatin (two doses 1.05 mg and/or 2.1 mg of cisplatin per kg). The highest level of MT at rats treated with 1.05 mg cisplatin was determined after 4 h as 4.9 mol/l. In the case of the second experimental group, the maximum was reached even after 2 h of the treatment as 4.8 mol/l. In addition, we were interested in the effect of cisplatin or carboplatin treatment of patients with a tumour disease. At patients with tumour in head and neck area treated with cisplatin we observed that the level of MT was going higher due to administration of the drug. However, at retinoblastoma patients treated with carboplatin we observed various phenomena including decreasing, increasing or no changes in MT level. Acknowledgement: The financial support from GAAV IAA 401990701 is acknowledged. doi:10.1016/j.toxlet.2008.06.761 C26 The effect of psychiatric examinations in drug intoxication: MMPI, BDI, SCL-90-R Hoon Lim, Ho Jung Kim ∗ Soonchunhyang University, Bucheon, Republic of Korea Introduction: In South Korea, the patients admitted with drug intoxication in ED have recently been increased. We try to directly psychiatric examination to the patients with drug intoxication for
S133
rapidly getting the objective results and to use this information for treatment and insurance. Methods: The enrolled were normal cognitively patients admitted with drug intoxication for suicidal attempts from 1 January 2007 to 31 August 2007 in ED. They were treated with basic decontaminations as irrigation or activated charcoal or antidote and admitted the intensive care unit. In first admission date, we tried to perform the MMPI under a nurse’s or resident’s guidance and the results was sent to the clinical psychiatric department for interpretation and analysis. Results: The numbers of total enrolled patients were 50 (females 37, mean age 31). In drug informations, 22 were related with psychiatric drugs. 26 had a personal history with depression and 14 were just on impulsive. In results of MMPI, D < 60 and Ma < 30 was 27, Pd < 60 and Ma < 30 was 34. BDI T-score, be reflected on recent depression statues, was <60 in 24 and SCL-90-R was 18 in depression <60. Self-discharge rate was more in with depression history than none and there was analytic relationship in the results of MMPI (p = 0.004). Conclusions: D and Ma were objectively the effectiveness as the parameters of early detected the depression statues with drug intoxication. Pd and Ma were effective in detect the impulseness and correlated with personal history of depression. doi:10.1016/j.toxlet.2008.06.762 C27 Electroanalysis of cisplatin–glutathione and cisplatin–DNA interactions Ondrej Zitka 1,∗ , Dalibor Huska 1 , Vojtech Adam 1 , Libuse Trnkova 2 , Rene Kizek 1 1 2
Mendel University of Agriculture and Forestry, Brno, Czech Republic, Masaryk University, Brno, Czech Republic
Due to high reactivity of sulfhydryl group of glutathione (GSH) it is not a surprise that GSH can influence a treatment of diseases including cancer. An investigation of interactions of GSH with heavy metal based cytostatics like cisplatin can be one of the possible ways of studying of reasons how GSH can interrupt the cancer treatment. To investigate GS–cisplatin and DNA–cisplatin interactions, we employed electroanalytical techniques. Primarily, we attempted to characterize reduced GSH and oxidized GSSG glutathione with respect to reach the lowest detection limits. Under the most suitable conditions, the limits of GSH and GSSG were 100 pg/ml and 50 ng/ml, respectively. Then, the interactions between GSH and cisplatin have been investigated. The results obtained have been evaluated the formation of the complex by spectrometry. Besides that we studied DNA–cisplatin interaction. The average concentration of the drug bound to DNA was estimated as 8.1 ng of cisplatin per 500 ng of DNA. Finally, we utilized the electroanalytical techniques to investigate interactions between GS–cisplatin complex and DNA. Electrochemical detection represents an alternative method for determination of biologically active compounds. Here, we have shown the various electrochemical techniques could be suitable tools to monitor interaction between thiols, cytostatics and DNA. Acknowledgement: The financial IAA401990701 is acknowledged. doi:10.1016/j.toxlet.2008.06.763
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Results: In the saline group, 12 of the 25 mice receiving amitriptyline + saline died. Kaplan-Meier estimates of the 24 h survival rate was 52%(13/25) for saline and 68%(17/25), 52%(13/25) and 40%(10/25) for DPCPX, CSC and DMSO groups, respectively. Median survival times were 1440, 1440,1440 and 44 min for saline, DPCPX, CSC and DMSO groups, respectively. There was no statistically significant difference in survival rates for amitriptyline poisoning between control and adenosine receptor antagonist treatment groups (p > 0.05). Power analysis demonstrated a 42% likelihood of finding a 20% difference (S1 = 50%, S2 = 70%, beta error 58%, alpha 5%). Conclusions: Adenosine antagonists, DPCPX or CSC, failed to increase survival rates of amitriptyline poisoning in mice. Future studies are needed with repeated doses of adenosine antagonists in amitriptyline poisoning with a higher statistical power. doi:10.1016/j.toxlet.2008.06.760 C25 Investigation of a role of metallothionein in resistance on platinum based cytostatics Dalibor Huska 1,∗ , Ivo Fabrik 1 , Jan Hrabeta 2 , Tomas Eckschlager 2 , Jiri Kukacka 2 , Richard Prusa 2 , Sona Krizkova 1 , Vojtech Adam 1 , Rene Kizek 1 1 2
Mendel University of Agriculture and Forestry, Brno, Czech Republic, Charles University, Prague, Czech Republic
In this work, we employed electroanalytical methods for determination of metallothionein (MT) in cisplatin or carboplatin sensitive and resistant neuroblastoma cell lines, blood serum of patients with head and neck cancer or retinoblastoma, and of rats treated with cisplatin with respect to discuss the role of MT in formation of resistance on treatment with heavy metal based cytostatics. Level of MT increases with higher dose of platinum based cytostatics at cells. Further we focused on determination of MT in blood serum of rats treated with cisplatin (two doses 1.05 mg and/or 2.1 mg of cisplatin per kg). The highest level of MT at rats treated with 1.05 mg cisplatin was determined after 4 h as 4.9 mol/l. In the case of the second experimental group, the maximum was reached even after 2 h of the treatment as 4.8 mol/l. In addition, we were interested in the effect of cisplatin or carboplatin treatment of patients with a tumour disease. At patients with tumour in head and neck area treated with cisplatin we observed that the level of MT was going higher due to administration of the drug. However, at retinoblastoma patients treated with carboplatin we observed various phenomena including decreasing, increasing or no changes in MT level. Acknowledgement: The financial support from GAAV IAA 401990701 is acknowledged. doi:10.1016/j.toxlet.2008.06.761 C26 The effect of psychiatric examinations in drug intoxication: MMPI, BDI, SCL-90-R Hoon Lim, Ho Jung Kim ∗ Soonchunhyang University, Bucheon, Republic of Korea Introduction: In South Korea, the patients admitted with drug intoxication in ED have recently been increased. We try to directly psychiatric examination to the patients with drug intoxication for
S133
rapidly getting the objective results and to use this information for treatment and insurance. Methods: The enrolled were normal cognitively patients admitted with drug intoxication for suicidal attempts from 1 January 2007 to 31 August 2007 in ED. They were treated with basic decontaminations as irrigation or activated charcoal or antidote and admitted the intensive care unit. In first admission date, we tried to perform the MMPI under a nurse’s or resident’s guidance and the results was sent to the clinical psychiatric department for interpretation and analysis. Results: The numbers of total enrolled patients were 50 (females 37, mean age 31). In drug informations, 22 were related with psychiatric drugs. 26 had a personal history with depression and 14 were just on impulsive. In results of MMPI, D < 60 and Ma < 30 was 27, Pd < 60 and Ma < 30 was 34. BDI T-score, be reflected on recent depression statues, was <60 in 24 and SCL-90-R was 18 in depression <60. Self-discharge rate was more in with depression history than none and there was analytic relationship in the results of MMPI (p = 0.004). Conclusions: D and Ma were objectively the effectiveness as the parameters of early detected the depression statues with drug intoxication. Pd and Ma were effective in detect the impulseness and correlated with personal history of depression. doi:10.1016/j.toxlet.2008.06.762 C27 Electroanalysis of cisplatin–glutathione and cisplatin–DNA interactions Ondrej Zitka 1,∗ , Dalibor Huska 1 , Vojtech Adam 1 , Libuse Trnkova 2 , Rene Kizek 1 1 2
Mendel University of Agriculture and Forestry, Brno, Czech Republic, Masaryk University, Brno, Czech Republic
Due to high reactivity of sulfhydryl group of glutathione (GSH) it is not a surprise that GSH can influence a treatment of diseases including cancer. An investigation of interactions of GSH with heavy metal based cytostatics like cisplatin can be one of the possible ways of studying of reasons how GSH can interrupt the cancer treatment. To investigate GS–cisplatin and DNA–cisplatin interactions, we employed electroanalytical techniques. Primarily, we attempted to characterize reduced GSH and oxidized GSSG glutathione with respect to reach the lowest detection limits. Under the most suitable conditions, the limits of GSH and GSSG were 100 pg/ml and 50 ng/ml, respectively. Then, the interactions between GSH and cisplatin have been investigated. The results obtained have been evaluated the formation of the complex by spectrometry. Besides that we studied DNA–cisplatin interaction. The average concentration of the drug bound to DNA was estimated as 8.1 ng of cisplatin per 500 ng of DNA. Finally, we utilized the electroanalytical techniques to investigate interactions between GS–cisplatin complex and DNA. Electrochemical detection represents an alternative method for determination of biologically active compounds. Here, we have shown the various electrochemical techniques could be suitable tools to monitor interaction between thiols, cytostatics and DNA. Acknowledgement: The financial IAA401990701 is acknowledged. doi:10.1016/j.toxlet.2008.06.763
support
from
GAAV