Osajin attenuates diazinon-induced pulmonary toxicity in rats

Diazinon (DZN) is an organophosphate insecticide whose widespread agricultural and veterinary use raises continuing concerns about non-target organ toxicity. While its hepatic and neurological effects have been extensively documented, the molecular basis of DZN-induced pulmonary injury - and whether plant-derived isoflavones can counteract it - remains poorly defined. The present study examined the lung-protective potential of Osajin (OSJ), an isoflavone isolated from Maclura pomifera fruits, against DZN-induced pulmonary toxicity. 35 male Sprague-Dawley rats were randomly allocated into five groups: Healthy, OSJ (200 mg/kg), DZN (20 mg/kg), DZN + OSJ-100, and DZN + OSJ-200. All compounds were administered orally for 28 consecutive days. Pulmonary tissues were processed for biochemical, molecular, and histopathological analyses. Quantitative analyses included biochemical and ELISA assays (n = 7 per group), as well as Western blot and qRT-PCR (n = 3 per group). DZN exposure produced lipid peroxidation (elevated MDA) accompanied by suppression of GSH and SOD activity, alongside transcriptional activation of ER stress markers (Eif2α, Atf4, Xbp1, Chop) and inflammatory mediators (Tlr4, Il10, NF-κB, TNF-α, IL-1β, iNOS, COX-2). Apoptotic balance was disrupted, with BAX and Caspase-3 elevated and BCL2 reduced. Protein data suggested that OSJ partially mitigated these cytokines, potentially showing less efficiency against IL-6 and especially mature IL-1β. Histopathology revealed alveolar disruption, leukocyte infiltration, hemorrhage, and tissue degeneration. These alterations were less pronounced in OSJ-treated groups in a dose-dependent manner, with the 200 mg/kg dose providing substantial but not complete restoration of redox homeostasis, attenuation of inflammatory and apoptotic signaling, and preservation of pulmonary architecture. These findings position OSJ as a potential candidate warranting further investigation against organophosphate-induced lung injury.