Apoptogenic effect of fentanyl on freshly isolated peripheral blood lymphocytes

Giovanna Delogu, Sonia Moretti, Adriana Antonucci, Maurizio Marandola, Guglielmo Tellan, Patrizio Sale, Roberta Carnevali, Giuseppe Famularo

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Opiods may trigger the apoptotic death of widely ranging cell types, and apoptosis contributes to the immune deficiency of critically ill patients and subjects experiencing surgical trauma. There is evidence that an altered mitochondrial membrane potential constitutes an early and irreversible step in the death-signaling pathway of apoptosis. This study investigated whether fentanyl, a opioid widely used in the management of these patients, may induce apoptosis of T cells by altering their mitochondrial membrane potential. Methods: Peripheral blood lymphocytes were cultured in the presence of 30 ng fentanyl for 60 (time 1), 90 (time 2), and 120 (time 3) minutes, respectively. The cells then were processed for assessment of mitochondrial membrane potential by means of flow cytometry and confocal scanning microscopy. Furthermore, production of reactive oxygen species, expression of the Fas-Fas L pro-apoptotic pathway, and apoptosis frequency were measured by means of flow cytometry. Control cells were incubated for the same times in the complete culture medium without the drug. Results: Flow cytometry analysis showed a significantly increased rate (p <0.05) of lymphocytes with disrupted mitochondria! membrane potential after incubation with fentanyl for 90 and 120 minutes, as compared with both control cells and lymphocytes cultured in the presence of fentanyl for 60 minutes. In addition, as early as 60 minutes after exposure to fentanyl, cells displayed a disrupted mitochondrial membrane potential when this was assayed by means of confocal laser scanning. These findings were associated with increased production of reactive oxygen species. The frequency of apoptotic lymphocytes was markedly increased (p <0.05) after 120 minutes of incubation, as compared with untreated cells and cells exposed to fentanyl for only 60 and 90 minutes. Expression of Fas-FasL was not substantially affected by exposure to fentanyl. Conclusions: Fentanyl may induce a time-dependent apoptosis of lymphocytes by altering their mitochondrial redox metabolism.

Original languageEnglish
Pages (from-to)75-81
Number of pages7
JournalThe Journal of trauma
Volume57
Issue number1
Publication statusPublished - Jul 2004

Fingerprint

Fentanyl
Lymphocytes
Mitochondrial Membrane Potential
Apoptosis
Flow Cytometry
Reactive Oxygen Species
Critical Illness
Confocal Microscopy
Membrane Potentials
Opioid Analgesics
Oxidation-Reduction
Culture Media
Cultured Cells
Mitochondria
Lasers
T-Lymphocytes
Wounds and Injuries
Pharmaceutical Preparations

Keywords

  • Apoptosis
  • Critically ill patient
  • Fentanyl
  • Lymphocyte
  • Mitochondria
  • Mitochondria membrane potential
  • Opioids
  • Programmed cell death
  • Reactive oxygen species
  • Surgical trauma

ASJC Scopus subject areas

  • Surgery

Cite this

Delogu, G., Moretti, S., Antonucci, A., Marandola, M., Tellan, G., Sale, P., ... Famularo, G. (2004). Apoptogenic effect of fentanyl on freshly isolated peripheral blood lymphocytes. The Journal of trauma, 57(1), 75-81.

Apoptogenic effect of fentanyl on freshly isolated peripheral blood lymphocytes. / Delogu, Giovanna; Moretti, Sonia; Antonucci, Adriana; Marandola, Maurizio; Tellan, Guglielmo; Sale, Patrizio; Carnevali, Roberta; Famularo, Giuseppe.

In: The Journal of trauma, Vol. 57, No. 1, 07.2004, p. 75-81.

Research output: Contribution to journalArticle

Delogu, G, Moretti, S, Antonucci, A, Marandola, M, Tellan, G, Sale, P, Carnevali, R & Famularo, G 2004, 'Apoptogenic effect of fentanyl on freshly isolated peripheral blood lymphocytes', The Journal of trauma, vol. 57, no. 1, pp. 75-81.
Delogu G, Moretti S, Antonucci A, Marandola M, Tellan G, Sale P et al. Apoptogenic effect of fentanyl on freshly isolated peripheral blood lymphocytes. The Journal of trauma. 2004 Jul;57(1):75-81.
Delogu, Giovanna ; Moretti, Sonia ; Antonucci, Adriana ; Marandola, Maurizio ; Tellan, Guglielmo ; Sale, Patrizio ; Carnevali, Roberta ; Famularo, Giuseppe. / Apoptogenic effect of fentanyl on freshly isolated peripheral blood lymphocytes. In: The Journal of trauma. 2004 ; Vol. 57, No. 1. pp. 75-81.
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abstract = "Background: Opiods may trigger the apoptotic death of widely ranging cell types, and apoptosis contributes to the immune deficiency of critically ill patients and subjects experiencing surgical trauma. There is evidence that an altered mitochondrial membrane potential constitutes an early and irreversible step in the death-signaling pathway of apoptosis. This study investigated whether fentanyl, a opioid widely used in the management of these patients, may induce apoptosis of T cells by altering their mitochondrial membrane potential. Methods: Peripheral blood lymphocytes were cultured in the presence of 30 ng fentanyl for 60 (time 1), 90 (time 2), and 120 (time 3) minutes, respectively. The cells then were processed for assessment of mitochondrial membrane potential by means of flow cytometry and confocal scanning microscopy. Furthermore, production of reactive oxygen species, expression of the Fas-Fas L pro-apoptotic pathway, and apoptosis frequency were measured by means of flow cytometry. Control cells were incubated for the same times in the complete culture medium without the drug. Results: Flow cytometry analysis showed a significantly increased rate (p <0.05) of lymphocytes with disrupted mitochondria! membrane potential after incubation with fentanyl for 90 and 120 minutes, as compared with both control cells and lymphocytes cultured in the presence of fentanyl for 60 minutes. In addition, as early as 60 minutes after exposure to fentanyl, cells displayed a disrupted mitochondrial membrane potential when this was assayed by means of confocal laser scanning. These findings were associated with increased production of reactive oxygen species. The frequency of apoptotic lymphocytes was markedly increased (p <0.05) after 120 minutes of incubation, as compared with untreated cells and cells exposed to fentanyl for only 60 and 90 minutes. Expression of Fas-FasL was not substantially affected by exposure to fentanyl. Conclusions: Fentanyl may induce a time-dependent apoptosis of lymphocytes by altering their mitochondrial redox metabolism.",
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AU - Moretti, Sonia

AU - Antonucci, Adriana

AU - Marandola, Maurizio

AU - Tellan, Guglielmo

AU - Sale, Patrizio

AU - Carnevali, Roberta

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AB - Background: Opiods may trigger the apoptotic death of widely ranging cell types, and apoptosis contributes to the immune deficiency of critically ill patients and subjects experiencing surgical trauma. There is evidence that an altered mitochondrial membrane potential constitutes an early and irreversible step in the death-signaling pathway of apoptosis. This study investigated whether fentanyl, a opioid widely used in the management of these patients, may induce apoptosis of T cells by altering their mitochondrial membrane potential. Methods: Peripheral blood lymphocytes were cultured in the presence of 30 ng fentanyl for 60 (time 1), 90 (time 2), and 120 (time 3) minutes, respectively. The cells then were processed for assessment of mitochondrial membrane potential by means of flow cytometry and confocal scanning microscopy. Furthermore, production of reactive oxygen species, expression of the Fas-Fas L pro-apoptotic pathway, and apoptosis frequency were measured by means of flow cytometry. Control cells were incubated for the same times in the complete culture medium without the drug. Results: Flow cytometry analysis showed a significantly increased rate (p <0.05) of lymphocytes with disrupted mitochondria! membrane potential after incubation with fentanyl for 90 and 120 minutes, as compared with both control cells and lymphocytes cultured in the presence of fentanyl for 60 minutes. In addition, as early as 60 minutes after exposure to fentanyl, cells displayed a disrupted mitochondrial membrane potential when this was assayed by means of confocal laser scanning. These findings were associated with increased production of reactive oxygen species. The frequency of apoptotic lymphocytes was markedly increased (p <0.05) after 120 minutes of incubation, as compared with untreated cells and cells exposed to fentanyl for only 60 and 90 minutes. Expression of Fas-FasL was not substantially affected by exposure to fentanyl. Conclusions: Fentanyl may induce a time-dependent apoptosis of lymphocytes by altering their mitochondrial redox metabolism.

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KW - Reactive oxygen species

KW - Surgical trauma

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