Can, IsmailBozkurt, IlyasSenocak, Esra AktasKaraarslan, TubaAlat, OmercanHalici, Mesut BunyamiGur, Cihan2026-03-152026-03-1520262008-38662008-3874https://hdl.handle.net/20.500.12514/10506https://doi.org/10.22038/ijbms.2025.90102.19424Objective(s): Diazinon (DZN), a widely used organophosphate pesticide, induces pulmonary toxicity through oxidative stress, inflammation, endoplasmic reticulum (ER) stress, and apoptosis. This study investigated the potential protective effects of protocatechuic acid (PCA) against DZN-induced lung injury in rats. Materials and Methods: Thirty-five adult rats were randomly assigned to five groups (n = 7): Control, DZN (20 mg/kg), PCA100 (100 mg/kg), DZN + PCA50, and DZN + PCA100. Lung tissues were evaluated histopathologically, and oxidative stress markers (GSH, SOD, CAT, and GPx) and inflammatory mediators (TNF-alpha, IL-1 beta, IL-6, NF-kappa B, COX-2, and iNOS) were measured by ELISA. The protein levels of Keap-1, Nrf2, and HO-1 were assessed via Western blotting. Expression of ER stress-related genes (XBP-1, eIF2, ATF4, CHOP) and apoptotic markers (Bax, Bcl-2, caspase-3, -6, -9) was analyzed by qRT-PCR. Results: DZN exposure caused severe histopathological damage and significantly increased oxidative, inflammatory, ER stress, and apoptotic responses. PCA administration, particularly at 100 mg/kg, markedly improved lung morphology, normalized antioxidant enzyme levels, reduced cytokine production and NF-kappa B activation, and downregulated ER stress and apoptosis-related genes. PCA also enhanced Bcl-2 expression and activated the Nrf2/HO-1 signaling pathway. Conclusion: PCA exerts dose-dependent protective effects against DZN-induced pulmonary toxicity by modulating oxidative stress, inflammation, ER stress, and apoptosis. These findings suggest that PCA may serve as a promising therapeutic candidate for mitigating pesticide-related lung injury.en10.22038/ijbms.2025.90102.19424info:eu-repo/semantics/closedAccessDiazinonApoptosisStressInflammationEndoplasmic ReticulumProtocatechuic AcidArticle