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

被引:8
作者
George, Junu A. [1 ]
Alshebli, Zainab [1 ]
Alneyadi, Asma [1 ]
Al Mukhaini, Noura [1 ]
Al-Salam, Suhail [2 ]
Sudhadevi, Manjusha [2 ]
Souid, Abdul-Kader [1 ]
Alsuwaidi, Ahmed R. [1 ]
机构
[1] United Arab Emirates Univ, Dept Paediat, Coll Med & Hlth Sci, Khalifa Bin Zayed St,POB 17666, Al Ain, U Arab Emirates
[2] United Arab Emirates Univ, Dept Pathol, Coll Med & Hlth Sci, Al Ain, U Arab Emirates
关键词
PI3K delta; idelalisib; thymus; spleen; airway resistance; caspase-3; PHARMACOLOGICAL INHIBITION; P110-DELTA; CELL; DIFFERENTIATION;
D O I
10.1080/1120009X.2019.1708153
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Idelalisib, an inhibitor of the phosphatidylinositol-3-kinase p110 delta subunit (PI3K delta), 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 mu g/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, PI3K delta has physiological roles in T-cell development and airway function. Monitoring drug toxicity is important for developing follow-up compounds that target PI3K delta signalling.
引用
收藏
页码:88 / 97
页数:10
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