Black Cumin Oil Alleviates Hepatic Injury Induced by Fipronil in Rats via Inhibiting NLRP3 Signaling Pathway

Fipronil (Fipro), a wide-spectrum insecticide, is commonly used in veterinary practice, but it is linked to notable liver toxicity. Nigella sativa (black cumin) seed (BCS) is recognized for its potential anti-inflammatory and antioxidant properties. Thus, our work aimed to assess the potential protective roles of BCS oil against Fipro-induced hepatic damage, with a focus on modulating oxidative stress, suppressing pyroptosis, and regulating miRNA-103-3p. Therefore, forty male albino rats were randomly assigned to four equal groups: control, BCS alone (200 mg/kg orally), Fipro alone (9.7 mg/kg orally), and combined BCS + Fipro. Treatments were administered for 60 days. Molecular docking analysis identified that nigellicine is the most potent BCS-derived ligand for both NOD-like receptor protein 3 (NLRP3) and tumor necrosis factors-α (TNF-α), followed closely by nigellimine N-oxide. The results revealed that BCS oil significantly restored hepatic function indices as aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total bilirubin, albumin, total protein and lipid profile markers in Fipro-intoxicated rats. Furthermore, BCS oil downregulated hepatic oxidative stress markers such as malondialdehyde (MDA), while upregulating antioxidant defenses including superoxide dismutase (SOD) and glutathione (GSH). Moreover, pyroptotic mediators (NLRP3, caspase-1, and GSDMD), and interleukins (IL-1β, IL-18) and TNF-α were markedly downregulated, without any significant change in apoptosis-associated speck-like protein (ASC) and miRNA-103-3p. Additionally, histopathological and immunohistochemical examinations confirmed severe disruption of hepatic architecture and reduced IL-1β expression in the Fipro group. In conclusion, BCS oil exhibits strong hepatoprotective effects against liver injury induced by Fipro via anti-inflammatory, antioxidant and anti-pyroptotic mechanisms, highlighting its therapeutic potential in pesticide-related hepatic damage and warranting further research for clinical and environmental health applications.