Cadmium-induced hepatotoxicity in Mice- Prophylactic supplementation of quercetin exerts hepatoprotective effect by modulating PI3K/Akt/NF-κB signaling pathway

The previous literature has confirmed the hepatoprotective properties of Quercetin. This current study seeks to examine the pre-protective function of Quercetin in Cadmium (Cd)-induced liver damage, along with its modulation of the PI3K/Akt/NF-κB signaling pathway. A total of 60 male C57BL/6J mice were randomly assigned to four groups: control (C), quercetin (Q, 100 mg/kg/day), Cd(Cd, 2.5 mg/kg/day), and quercetin and Cd(Q+Cd).Before receiving chloride treatment, quercetin was administered intragastrically for 4 weeks. Biochemical parameters, oxidative stress parameters and pro-inflammatory cytokines were examined. We used histological analysis to track changes in the liver's histology. Western blot analysis was used to assess the expression of apoptotic components and criticalproteins in the PI3K/Akt/NF-κB pathway to identify the pre-protective effects. We discovered that the body weight of the Cd-treated mice dramatically rose after 4 weeks of quercetin pre-administration, and the Cd concentration in serum significantly decreased. By examining the levels of the blood liver indicators alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH), quercetin enhanced Cd-induced liver dysfunction. Additionally, it was demonstrated that quercetin reduced Cd-mediated liver injury in mice by assessing the activity of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) concentrations and the histological alterations. By monitoring Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), quercetin successfully reduced the inflammatory cytokines that the Cd metal caused in the liver. Additionally, in the liver tissues of Cd-mediated, quercetin could enhance the expression of Bcl-2 and decrease the expression of p-Akt, p-PI3K, Bax, Caspase-9, Caspase-3, NF-κB. This study demonstrates that quercetin pre-administration could reduce Cd-mediated liver damage by blocking the PI3K/Akt and NF-κB pathways.