Doxorubicin increases the susceptibility of brain mitochondria to Ca(2+)-induced permeability transition and oxidative damage

Susana Cardoso, Renato X. Santos, Cristina Carvalho, Sónia Correia, Gonçalo C. Pereira, Susana S. Pereira, Paulo J. Oliveira, Maria S. Santos, Teresa Proença, Paula I. Moreira*

*Corresponding author for this work

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

This study was aimed at investigating the effects of subchronic administration of doxorubicin (DOX) on brain mitochondrial bioenergetics and oxidative status. Rats were treated with seven weekly injections of vehicle (sc, saline solution) or DOX (sc, 2 mg kg−1), and 1 week after the last administration of the drug the animals were sacrificed and brain mitochondrial fractions were obtained. Several parameters were analyzed: respiratory chain, phosphorylation system, induction of the permeability transition pore (PTP), mitochondrial aconitase activity, lipid peroxidation markers, and nonenzymatic antioxidant defenses. DOX treatment induced an increase in thiobarbituric acid-reactive substances and vitamin E levels and a decrease in reduced glutathione content and aconitase activity. Furthermore, DOX potentiated PTP induced by Ca2+. No statistical differences were observed in the other parameters analyzed. Altogether our results show that DOX treatment increases the susceptibility of brain mitochondria to Ca2+-induced PTP opening and oxidative stress, predisposing brain cells to degeneration and death.
Original languageEnglish
Pages (from-to)1395-1402
Number of pages8
JournalFree Radical Biology and Medicine
Volume45
Issue number10
Early online date14 Aug 2008
DOIs
Publication statusPublished - 15 Nov 2008

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Mitochondria
Doxorubicin
Permeability
Brain
Aconitate Hydratase
Phosphorylation
Oxidative stress
Thiobarbituric Acid Reactive Substances
Electron Transport
Vitamin E
Sodium Chloride
Energy Metabolism
Lipid Peroxidation
Glutathione
Rats
Animals
Oxidative Stress
Antioxidants
Lipids
Injections

Keywords

  • Brain
  • Doxorubicin
  • Mitochondria
  • Oxidative stress
  • Permeability transition pore
  • Free radicals

Cite this

Doxorubicin increases the susceptibility of brain mitochondria to Ca(2+)-induced permeability transition and oxidative damage. / Cardoso, Susana; Santos, Renato X.; Carvalho, Cristina; Correia, Sónia; Pereira, Gonçalo C.; Pereira, Susana S.; Oliveira, Paulo J.; Santos, Maria S.; Proença, Teresa; Moreira, Paula I.

In: Free Radical Biology and Medicine, Vol. 45, No. 10, 15.11.2008, p. 1395-1402.

Research output: Contribution to journalArticle

Cardoso, S, Santos, RX, Carvalho, C, Correia, S, Pereira, GC, Pereira, SS, Oliveira, PJ, Santos, MS, Proença, T & Moreira, PI 2008, 'Doxorubicin increases the susceptibility of brain mitochondria to Ca(2+)-induced permeability transition and oxidative damage', Free Radical Biology and Medicine, vol. 45, no. 10, pp. 1395-1402. https://doi.org/10.1016/j.freeradbiomed.2008.08.008
Cardoso, Susana ; Santos, Renato X. ; Carvalho, Cristina ; Correia, Sónia ; Pereira, Gonçalo C. ; Pereira, Susana S. ; Oliveira, Paulo J. ; Santos, Maria S. ; Proença, Teresa ; Moreira, Paula I. / Doxorubicin increases the susceptibility of brain mitochondria to Ca(2+)-induced permeability transition and oxidative damage. In: Free Radical Biology and Medicine. 2008 ; Vol. 45, No. 10. pp. 1395-1402.
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abstract = "This study was aimed at investigating the effects of subchronic administration of doxorubicin (DOX) on brain mitochondrial bioenergetics and oxidative status. Rats were treated with seven weekly injections of vehicle (sc, saline solution) or DOX (sc, 2 mg kg−1), and 1 week after the last administration of the drug the animals were sacrificed and brain mitochondrial fractions were obtained. Several parameters were analyzed: respiratory chain, phosphorylation system, induction of the permeability transition pore (PTP), mitochondrial aconitase activity, lipid peroxidation markers, and nonenzymatic antioxidant defenses. DOX treatment induced an increase in thiobarbituric acid-reactive substances and vitamin E levels and a decrease in reduced glutathione content and aconitase activity. Furthermore, DOX potentiated PTP induced by Ca2+. No statistical differences were observed in the other parameters analyzed. Altogether our results show that DOX treatment increases the susceptibility of brain mitochondria to Ca2+-induced PTP opening and oxidative stress, predisposing brain cells to degeneration and death.",
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AU - Santos, Maria S.

AU - Proença, Teresa

AU - Moreira, Paula I.

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N2 - This study was aimed at investigating the effects of subchronic administration of doxorubicin (DOX) on brain mitochondrial bioenergetics and oxidative status. Rats were treated with seven weekly injections of vehicle (sc, saline solution) or DOX (sc, 2 mg kg−1), and 1 week after the last administration of the drug the animals were sacrificed and brain mitochondrial fractions were obtained. Several parameters were analyzed: respiratory chain, phosphorylation system, induction of the permeability transition pore (PTP), mitochondrial aconitase activity, lipid peroxidation markers, and nonenzymatic antioxidant defenses. DOX treatment induced an increase in thiobarbituric acid-reactive substances and vitamin E levels and a decrease in reduced glutathione content and aconitase activity. Furthermore, DOX potentiated PTP induced by Ca2+. No statistical differences were observed in the other parameters analyzed. Altogether our results show that DOX treatment increases the susceptibility of brain mitochondria to Ca2+-induced PTP opening and oxidative stress, predisposing brain cells to degeneration and death.

AB - This study was aimed at investigating the effects of subchronic administration of doxorubicin (DOX) on brain mitochondrial bioenergetics and oxidative status. Rats were treated with seven weekly injections of vehicle (sc, saline solution) or DOX (sc, 2 mg kg−1), and 1 week after the last administration of the drug the animals were sacrificed and brain mitochondrial fractions were obtained. Several parameters were analyzed: respiratory chain, phosphorylation system, induction of the permeability transition pore (PTP), mitochondrial aconitase activity, lipid peroxidation markers, and nonenzymatic antioxidant defenses. DOX treatment induced an increase in thiobarbituric acid-reactive substances and vitamin E levels and a decrease in reduced glutathione content and aconitase activity. Furthermore, DOX potentiated PTP induced by Ca2+. No statistical differences were observed in the other parameters analyzed. Altogether our results show that DOX treatment increases the susceptibility of brain mitochondria to Ca2+-induced PTP opening and oxidative stress, predisposing brain cells to degeneration and death.

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