Hepatoprotective effects of carvacrol nano-phytosomes against lead toxicity: Restoration of tissue architecture via NF-κB/NLRP3 suppression and antioxidant enhancement.

The objective of the current study was to assess the hepatoprotective properties of nano-phytosomes (CRV-PNPs) loaded with carvacrol (CRV) in response to lead (Pb)- triggered liver injury. Male Wistar rats were assigned to six groups: Control, CRV, CRV-PNPs, Pb, Pb/CRV, and Pb/CRV-PNPs. Pb intoxication led to considerable blood profile disruption; in addition, it lowered serum total protein and its fractions. Pb also provoked an oxidative stress cascade, indicated by reductions in catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and glutathione (GSH) levels, coinciding with a marked increase in malondialdehyde (MDA) concentrations. Pb also increased the inflammatory mediators (NF-κB, TNF-α, IL-1β, IL-6, NLRP3). Compared to crude CRV, CRV-PNPs provided significantly better protection against Pb-induced hepatotoxicity by restoring hematological indices and liver function, correcting dyslipidemia, and attenuating histopathological alterations. This protective efficacy was associated with improved antioxidant enzyme activity, diminished oxidative damage, and reduced inflammatory response by downregulating key mediators. Molecular docking revealed that CRV has a strong affinity for antioxidant and inflammatory proteins. The CRV-PNPs exhibited a better protective effect against Pb-induced hepatic damage than crude CRV, which might be attributed to improved stability, solubility, and bioavailability, as well as multiple protective mechanisms.