Vinpocetine alleviated lung injury induced by cyclophosphamide in rats via modulation of NLRP3 inflammasome, NF-kB, and apoptotic pathways.

Cyclophosphamide (CP) acts widely as a potent anticancer and immunosuppressant agent. However, due to its adverse side effects, such as lung injury, its therapeutic applications are limited. This study investigated the efficacy of vinpocetine (Vinpo), a cerebral-protective agent, in reducing CP-induced lung injury in rat models. Rats were given oral Vinpo (10 and 20 mg/kg) daily for 14 days. On day seven, a single intraperitoneal injection of CP (200 mg/kg) was also administered. Twenty-four hours after the last Vinpo dose, the severity of lung injury, oxidative stress, antioxidant status markers, and pro-inflammatory and apoptotic markers were evaluated. The increased lung/body weight ratio and the infiltration of inflammatory cells in the lung tissues, in addition to a rise in the total content of protein and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluid (BALF), were indicative of injury to the lung. The biochemical analysis was validated by histopathological investigation. In CP-intoxicated animals, the lungs demonstrated increased oxidative stress, indicated by elevated levels of malondialdehyde (MDA) and total nitrate/nitrite (NOx), coupled with reduced antioxidant levels of glutathione (GSH). Furthermore, CP initiated NLRP3 inflammasome activation, subsequently activating procaspase-1, which led to NF-κB activation and an increase in inflammatory cytokines (IL-1β, TNF-α, IL-6). This process was associated with the induction of apoptosis, as indicated by elevated caspase-3 levels and decreased Bcl-2 expression. Conversely, improvements in the biochemical and histological markers indicated that Vinpo therapy effectively preserved lung function. Our findings indicate that vinpo alleviated CP-induced pulmonary damage by inhibiting the ROS/NLRP3/NF-κB pathway and suppressing apoptotic pathways.