Methotrexate (MTX) is frequently used to treat a variety of autoimmune diseases and malignancies, but its use is restricted due to a number of side effects, including lung damage. For the first time, this study attempts to assess the potential protective advantages of atomoxetine (ATOM) against MTX-induced lung damage in rats. MTX was used to cause lung damage. A total of 24 male Wistar albino rats were used in this study. Animals were randomly allocated to four experimental groups of six rats each: (Ⅰ) Control group, (Ⅱ) ATOM group, (Ⅲ) MTX group, and (Ⅳ) MTX+ATOM group. Malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels in the lungs were measured. ELISA was used to measure the levels of lung IL-10, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2). NF-κB p65 and caspase-3 were evaluated using immunohistochemistry. Toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MYD88) protein expression levels were assessed using the Western blot technique. A histopathological study of lung tissues was performed. Lung MDA, IL-6, TNF-α, and Bax levels were significantly increased by MTX, while GSH, SOD, IL-10, and Bcl-2 levels were significantly decreased. Additionally, this led to the overexpression of the proteins TLR4 and MYD88. Additionally, the MTX group had higher immunopositivity for both NF-κB p65 and caspase-3. All of the aforementioned biochemical and histological abnormalities were greatly improved with ATOM. ATOM significantly improved MTX-induced pulmonary injury by suppressing TLR4/MYD88/NF-κB p65 and caspase-3-mediated apoptotic signaling pathways.
Mohyeldin et al. (2026) studied this question.