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
IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, vol.29, no.2, pp.261-270, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 29 Issue: 2
- Publication Date: 2026
- Doi Number: 10.22038/ijbms.2025.90102.19424
- Journal Name: IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Index Islamicus, Directory of Open Access Journals
- Page Numbers: pp.261-270
- Ataturk University Affiliated: Yes
Abstract
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.
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.