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An adsorptive transfer technique coupled with brdicka reaction to reveal the importance of metallothionein in chemotherapy with platinum based cytostatics.

Krizkova S, Fabrik I, Huska D, Adam V, Babula P, Hrabeta J, Eckschlager T, Pochop P, Darsova D, Kukacka J, Prusa R, Trnkova L, Kizek R - Int J Mol Sci (2010)

Bottom Line: The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents.This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo.The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic.

ABSTRACT
The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents. Thanks to many clinical studies it is known that resistance of tumor cells to drugs is a frequent cause of chemotherapy failure. With regard to platinum based drugs, multidrug resistance can also be connected with increased expression of low-molecular weight protein metallothionein (MT). This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo. The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT. Further, we analyzed extracts of neuroblastoma cell lines treated with cisplatin or carboplatin. It is clear that neuroblastoma UKF-NB-4 cisplatin-resistant and cisplatin-sensitive cell lines unlikely respond to the presence of the platinum-based cytostatics cisplatin and carboplatin. Finally, we determined the level of MT in samples from rabbits treated with carboplatin and patients with retinoblastoma treated with the same drug.

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Related in: MedlinePlus

Time-dependent changes in concentrations of MT in the plasma of rabbits treated with carboplatin. The increase of MT levels is observed after injection of drug. PK RV (peripheral blood from right ventricle) has always higher MT concentration than PK LV (peripheral blood from right ventricle). Typical DP voltammogram of plasma analysis is shown on the right side.
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f6-ijms-11-04826: Time-dependent changes in concentrations of MT in the plasma of rabbits treated with carboplatin. The increase of MT levels is observed after injection of drug. PK RV (peripheral blood from right ventricle) has always higher MT concentration than PK LV (peripheral blood from right ventricle). Typical DP voltammogram of plasma analysis is shown on the right side.

Mentions: Retinoblastoma is one of the most frequent intraocular malignant tumors and it is the malignancy with the highest incidence in children. Retinoblastoma genesis is connected with gene mutation of both alleles of the retinoblastoma gene RB1 localized on chromosome 13q1.4. Its therapy is still very difficult, thus, new therapeutic possibilities as well as new ways of cytostatics application are intensively searched. One of these applications is direct injection of cytostatics—in this case especially carboplatin—into the eye. For this purpose, carboplatin was applied to experimental animals and consequently MT level was determined using automated electrochemical detection. Figure 6 shows the changes in MT levels according to the length of the carboplatin treatment. At the beginning, the MT level was about 3.5 μM in healthy rabbits. After carboplatin application, a significant increase in the MT level was determined in all experimental animals up to 5 μM. An enhanced MT level was detected for the following seven days in all experimental animals. A slight decrease in MT level was observed 14 days after carboplatin application. From the obtained results, it clearly follows that MT level was induced by carboplatin application directly into the eyes and can be probably connected with the resistance origination.


An adsorptive transfer technique coupled with brdicka reaction to reveal the importance of metallothionein in chemotherapy with platinum based cytostatics.

Krizkova S, Fabrik I, Huska D, Adam V, Babula P, Hrabeta J, Eckschlager T, Pochop P, Darsova D, Kukacka J, Prusa R, Trnkova L, Kizek R - Int J Mol Sci (2010)

Time-dependent changes in concentrations of MT in the plasma of rabbits treated with carboplatin. The increase of MT levels is observed after injection of drug. PK RV (peripheral blood from right ventricle) has always higher MT concentration than PK LV (peripheral blood from right ventricle). Typical DP voltammogram of plasma analysis is shown on the right side.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3100849&req=5

f6-ijms-11-04826: Time-dependent changes in concentrations of MT in the plasma of rabbits treated with carboplatin. The increase of MT levels is observed after injection of drug. PK RV (peripheral blood from right ventricle) has always higher MT concentration than PK LV (peripheral blood from right ventricle). Typical DP voltammogram of plasma analysis is shown on the right side.
Mentions: Retinoblastoma is one of the most frequent intraocular malignant tumors and it is the malignancy with the highest incidence in children. Retinoblastoma genesis is connected with gene mutation of both alleles of the retinoblastoma gene RB1 localized on chromosome 13q1.4. Its therapy is still very difficult, thus, new therapeutic possibilities as well as new ways of cytostatics application are intensively searched. One of these applications is direct injection of cytostatics—in this case especially carboplatin—into the eye. For this purpose, carboplatin was applied to experimental animals and consequently MT level was determined using automated electrochemical detection. Figure 6 shows the changes in MT levels according to the length of the carboplatin treatment. At the beginning, the MT level was about 3.5 μM in healthy rabbits. After carboplatin application, a significant increase in the MT level was determined in all experimental animals up to 5 μM. An enhanced MT level was detected for the following seven days in all experimental animals. A slight decrease in MT level was observed 14 days after carboplatin application. From the obtained results, it clearly follows that MT level was induced by carboplatin application directly into the eyes and can be probably connected with the resistance origination.

Bottom Line: The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents.This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo.The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic.

ABSTRACT
The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents. Thanks to many clinical studies it is known that resistance of tumor cells to drugs is a frequent cause of chemotherapy failure. With regard to platinum based drugs, multidrug resistance can also be connected with increased expression of low-molecular weight protein metallothionein (MT). This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo. The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT. Further, we analyzed extracts of neuroblastoma cell lines treated with cisplatin or carboplatin. It is clear that neuroblastoma UKF-NB-4 cisplatin-resistant and cisplatin-sensitive cell lines unlikely respond to the presence of the platinum-based cytostatics cisplatin and carboplatin. Finally, we determined the level of MT in samples from rabbits treated with carboplatin and patients with retinoblastoma treated with the same drug.

Show MeSH
Related in: MedlinePlus