Idelalisib induces apoptosis in the lymphoid tissues and impairs lung function in mice

Junu A. George, Zainab Alshebli, Asma Alneyadi, Noura Al Mukhaini, Suhail Al-Salam, Manjusha Sudhadevi, Abdul Kader Souid, Ahmed R. Alsuwaidi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Idelalisib, an inhibitor of the phosphatidylinositol-3-kinase p110δ subunit (PI3Kδ), is approved for treating lymphoid malignancy. The drug is associated with hematopoietic and pulmonary toxicities, which limit its clinical use. However, the toxicity mechanisms are not completely elucidated. In this study, mice were intraperitoneally injected with idelalisib (40 or 80 µg/g) or dimethyl sulfoxide for five days every week for up to four weeks to evaluate the changes in the thymus, spleen, and pulmonary functions. Idelalisib treatment induced thymic involution, decreased CD4+/CD8+ T-cell population, and increased CD4-/CD8- T-cell population. In the spleen, idelalisib dose dependently decreased the lymphocyte viability and cell count. Idelalisib-treated mice exhibited enhanced cleaved caspase-3 expression in the thymus, spleen, and lung tissues. Idelalisib augmented thoracic and airway resistance and decreased thoracic compliance. Thus, PI3Kδ has physiological roles in T-cell development and airway function. Monitoring drug toxicity is important for developing follow-up compounds that target PI3Kδ signalling.

Original languageEnglish
Pages (from-to)88-97
Number of pages10
JournalJournal of Chemotherapy
Volume32
Issue number2
DOIs
Publication statusPublished - Feb 17 2020

Keywords

  • PI3K delta
  • airway resistance
  • caspase-3
  • idelalisib
  • spleen
  • thymus

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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