<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Hypoxic cancer cells are more aggressive and responsible for more efficient metastasis and recurrence. It seems worth-while, hence, to supplement current cytostatic drugs therapy (i.e. cisplatin) with hypoxia cytotoxic agents (i.e. tirapazamine), the toxicity of which is activated by hypoxia. Cisplatin and tirapazamine can change a redox equilibrium and consequently lead to changes in cell metabolism, fibrosis and apoptosis. The aim of this study was to evaluate the cisplatin/tirapazamine toxicological synergism. In doing so we tested selected kidney oxidative stress parameters, as well as nephrotoxicity markers, in plasma and urine. Once a week for 6 weeks, rats received intraperitoneally two doses of tirapazamine (5 or 10 mg/kg bw), 2 hours before cisplatin (2 mg/kg bw) was applied. Our results show that Tirapazamine (TP) had no significant adverse effect on the redox balance, oxidative stress and kidney function in rats receiving cisplatin (CP). However, TP significantly increased protein concentration in the kidneys of rats. In all tested groups, a significant decrease in NADH concentration in kidneys was recorded, which could indicate disorder in the cell metabolism. TP also was found to have prevented bacterial infection caused by CP. In summary, there was no nephrotoxic synergy of TP with CP at an unacceptable level.</p></abstract>

Hypoxic cancer cells are more aggressive and responsible for more efficient metastasis and recurrence. It seems worth-while, hence, to supplement current cytostatic drugs therapy (i.e. cisplatin) with hypoxia cytotoxic agents (i.e. tirapazamine), the toxicity of which is activated by hypoxia. Cisplatin and tirapazamine can change a redox equilibrium and consequently lead to changes in cell metabolism, fibrosis and apoptosis. The aim of this study was to evaluate the cisplatin/tirapazamine toxicological synergism. In doing so we tested selected kidney oxidative stress parameters, as well as nephrotoxicity markers, in plasma and urine. Once a week for 6 weeks, rats received intraperitoneally two doses of tirapazamine (5 or 10 mg/kg bw), 2 hours before cisplatin (2 mg/kg bw) was applied. Our results show that Tirapazamine (TP) had no significant adverse effect on the redox balance, oxidative stress and kidney function in rats receiving cisplatin (CP). However, TP significantly increased protein concentration in the kidneys of rats. In all tested groups, a significant decrease in NADH concentration in kidneys was recorded, which could indicate disorder in the cell metabolism. TP also was found to have prevented bacterial infection caused by CP. In summary, there was no nephrotoxic synergy of TP with CP at an unacceptable level.

Effect of tirapazamine on selected kidney parameters in rats treated with cisplatin

Current Issues in Pharmacy and Medical Sciences

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Hypoxic cancer cells are more aggressive and responsible for more efficient metastasis and recurrence. It seems worth-while, hence, to supplement current...

Effect of tirapazamine on selected kidney parameters in rats treated with cisplatin

Publié en ligne: 06 avr. 2019

Pages: 18 - 22

Reçu: 19 mars 2018

Accepté: 28 mai 2018

DOI: https://doi.org/10.2478/cipms-2019-0004

Mots clés
Cisplatin, Tirapazamine, | Nephrotoxicity

© 2019 Marcin Sysa et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Effect of tirapazamine on selected kidney parameters in rats treated with cisplatin

Publié en ligne: 06 avr. 2019

Pages: 18 - 22

Reçu: 19 mars 2018

Accepté: 28 mai 2018

DOI: https://doi.org/10.2478/cipms-2019-0004

Mots clésCisplatin, Tirapazamine, | Nephrotoxicity

© 2019 Marcin Sysa et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Mots clés
Cisplatin, Tirapazamine, | Nephrotoxicity