Pulmonary Side Effects Associated With Abemaciclib the Antibreast Cancer Drug in Female Mice

This study investigated the potential lung-related side effects of abemaciclib in virgin female mice. Animals were divided into four groups: Group 1 (control) received clean drinking water; Group 2 received abemaciclib orally (50 mg/kg/day) for 28 days; Group 3 was given a single dose of 7,12-dimethylbenz(a)anthracene (DMBA, 50 mg/kg) to induce mammary carcinoma; and Group 4 received DMBA followed by abemaciclib treatment (50 mg/kg/day for 28 days) starting 10 days post-induction. Biochemical, histopathological, and immunohistochemical analyses were performed, including hormonal assays, liver enzymes, kidney biomarkers, oxidative stress markers (malondialdehyde [MDA] and catalase [CAT]), and adiponectin/TNF-α expression. DMBA administration significantly elevated estrogen, progesterone, liver enzymes, kidney biomarkers, and MDA, while reducing CAT activity. Abemaciclib treatment decreased estrogen and progesterone levels but further increased liver enzymes, kidney biomarkers, MDA, and reduced CAT. Breast histopathology in the DMBA group revealed invasive ductal adenocarcinoma with strong desmoplastic reaction, whereas abemaciclib treatment reduced tumor size and stromal reaction. Lung tissue of the DMBA group showed severe inflammation, epithelial hyperplasia, and dysplasia. Abemaciclib-treated lungs exhibited interstitial inflammation, fibrosis, and vascular thrombosis, indicating aggravated pulmonary changes. Immunohistochemically, DMBA reduced adiponectin expression in the breast, which was restored by abemaciclib. Conversely, TNF-α expression in the lung was increased by DMBA and further elevated after abemaciclib. In summary, DMBA successfully induced mammary carcinoma and lung toxicity. While abemaciclib reduced breast tumor burden, it was associated with exacerbated pulmonary toxicity, suggesting the need for careful evaluation of its lung-related side effects.