Protocatechuic acid mitigates diazinon-induced lung injury in rats through modulation of oxidative stress, inflammatory, Keap-1/Nrf-2/HO-1 and ER stress-mediated apoptotic pathways
Karaarslan, Tuba, Alat, Omercan, Can, Ismail, Senocak, Esra Aktas, Gur, Cihan, Bozkurt, Ilyas, Alhilal, Mohammad, Halici, Mesut Bunyami
Objective(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.<br /> 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.<br /> 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.<br /> 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.
- Dergi
- IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES
- Yıl
- 2026
- Cilt
- 29
- Sayı
- 2
- Sayfa
- 261-270
- ISSN
- 2008-3866
- eISSN
- 2008-3874
- DOI
- 10.22038/ijbms.2025.90102.19424
- WoS UID
- WOS:001682361800011