The effects of safranal and pioglitazone alone and their combination on inhaled paraquat (PQ)-induced systemic oxidative stress and inflammation as well as behavioral changes were examined in rats. In this study, animals were exposed to saline (Ctrl) or PQ (PQ groups) aerosols. PQ exposed animals were treated with dexamethasone, 0.8 and 3.2 mg/kg/day safranal (Saf-L and Saf-H), 5 mg/kg/day pioglitazone (Pio), and Saf-L + Pio for 16 days during PQ exposure period. PQ group showed increased numbers of total and differential WBCs in blood and bronchoalveolar lavage fluid (BALF), increased malondialdehyde (MDA), in the serum BALF and brain reduced thiol, catalase (CAT), and superoxide dismutase (SOD) levels compared to the control group (for all, p < 0.001). The escape latency and traveled distance were enhanced, but the time spent in the target quadrant in the probe day and the latency to enter the dark room 3, 24, 48, and 72 h after receiving an electrical shock, (in the shuttle box test) were decreased in the PQ group (p < 0.05 to P < 0.001). In all treated groups, all measure values were improved compared to PQ group (p < 0.05 to p < 0.001). In combination treated group of Saf-L + Pio, most measured values were more improved than the Saf-L and Pio groups (p < 0.05 to p < 0.001). Saf and Pio improved PQ-induced changes similar to dexamethasone but the effects produced by combination treatments of Saf-L + Pio were more prominent than Pio and Saf-L alone, suggesting a potentiating effect for the combination of the two agents.

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http://dx.doi.org/10.1016/j.toxicon.2024.107687DOI Listing

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