Tabriz University of Medical Sciences Pharmaceutical Sciences 1735-403X 32 4 2026 10 31 Preventive Potential of Crocus sativus L. (Saffron) Hydro-Alcoholic Extract and Safranal Against Systemic Inflammatory and Oxidative Alterations Caused by Paraquat in Rats 556 565 10.34172/ps.43498 EN Mahboobeh Ghasemzadeh Rahbardar https://orcid.org/0000-0002-5491-572X Arghavan Memarzia Seyedeh Zahra Ghasemi Mohammad Hossein Boskabady https://orcid.org/0000-0001-5736-9755 Journal Article 10.34172/ps.43498 2025 11 15 2026 06 08 Introduction: Paraquat (PQ) is a toxic herbicide that induces systemic inflammation and oxidative stress. Saffron (Crocus sativus L.) (CS) and its constituent safranal possess antioxidant and anti-inflammatory properties, while pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, may also protect against inflammatory and oxidative injury. However, their preventive effects against PQ-induced systemic toxicity, alone or in combination, remain unclear. The present study aimed to investigate whether saffron, safranal, and pioglitazone and their combination can prevent systemic inflammation and oxidative stress resulting from PQ inhalation. Methods: Ten groups of male Wistar rats (n=7) were included in the experiment. The control animals (Ctrl) were exposed to saline, while the other groups to inhaled PQ aerosol (54 mg/m³, eight times in alternate days). The PQ-exposed rats then received different treatments as: saline (PQ group), two doses of CS hydro-alcoholic extract (CS-L, CS-H), two doses of safranal (Saf-L, Saf-H), pioglitazone (Pio), a combination of Pio with CS-L (Pio + CS), or Saf-L (Pio + Saf), or dexamethasone (Dexa). During the 16-days of PQ exposure, pioglitazone was delivered through intraperitoneal injection, whereas the other agents were administered orally during PQ exposure for 16 days. Measurements included total and differential white blood cell (WBC) counts, serum levels of catalase (CAT), superoxide dismutase (SOD), thiol, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10). Data normality was assessed using the Kolmogorov–Smirnov test; group comparisons were performed by one-way ANOVA followed by Tukey’s post hoc test. Results: PQ inhalation significantly increased differential and total WBC counts, IL-10, TNF-α, and MDA levels, while decreasing CAT, SOD, and thiol levels (P<0.001). Treatment with CS, Saf, Pio + CS, Pio + Saf, Pio, and Dexa significantly mitigated these effects (P<0.05–0.001). Pio + CS and Pio+ Saf demonstrated stronger improvements in most variables compared to individual treatments. Conclusion: Briefly, CS, Saf, and Pio mitigated PQ-induced systemic oxidative stress and inflammation in a preventive manner. Additionally, a synergistic effect was observed with Pio+ CS and Pio+Saf, potentially involving PPARγ-mediated pathways in the beneficial properties of CS and Saf.