Work

Piracetam attenuates cyclophosphamide-evoked pulmonary injury in rats; the role of AMPK/NF-κB/NLRP3/caspase-1 and caspase-3 mediated apoptosis signaling cascades

Year: 2026

Type: article

Abstract: Cyclophosphamide (CP) is often employed in the treatment of numerous malignancies and autoimmune diseases, although it is accompanied by numerous side effects. Piracetam (PIRA) is used as a nootropic agent and reported to possess antioxidant, anti-inflammatory, and anti-apoptotic properties in addition to its established cognitive-enhancing effects. This study aimed to investigate the potential protective effects of PIRA against CP-induced lung damage in rats. CP was utilized to provoke pulmonary damage. Molecular docking was performed to predict the binding affinity of piracetam for NF-κB p65, NLRP3, caspase-1, caspase-3, and AMPK. Arterial blood gas parameters (PaO₂ and PaCO₂) were assessed to evaluate pulmonary gas-exchange function. The lung contents of MDA, GSH, and CAT activity were measured. Levels of lung IL-18, IL-1β, TNF-α, and caspase-1 were evaluated using ELISA. Immunohistochemistry was employed to evaluate NF-κB p65 and caspase-3. The Western blot technique was utilized to evaluate the protein expression of NLRP3 and p-AMPK. Lung Bax and Bcl-2 gene expression was assessed using qRT-PCR. The histological examination of lung tissues was conducted. Molecular docking revealed favorable binding affinities of piracetam. CP caused a notable reduction in PaO₂ and elevation in PaCO₂, alongside a notable increase in lung MDA, IL-18, IL-1β, TNF-α, caspase-1, and Bax levels, with a substantial reduction in GSH, CAT, p-AMPK, and Bcl-2. CP administration also led to the upregulation of NLRP3 protein. Additionally, the immunopositivity of both NF-κB p65 and caspase-3 was elevated in the CP group. PIRA markedly ameliorated all previously described functional, biochemical, and histopathological anomalies. PIRA pretreatment significantly improved CP-induced pulmonary injury, an effect associated with suppression of NF-κB/NLRP3/caspase-1 and caspase-3 signaling and with increased p-AMPK expression.

Source: Scientific Reports

DOI: 10.1038/s41598-026-73683-5