PERK Signaling Pathway Mediates the Hepatoprotective Effects of Naringenin Against Cadmium-Induced Liver Injury in Rats.

Cadmium (Cd), a heavy metal element with extensive industrial applications, exhibits significant toxicological risks in biological systems (Zhu et al. 2019). Naringenin (Nar), a bioactive flavonoid possessing potent antioxidant properties, demonstrates ameliorative effects against Cd toxicity. 24 male SD rats were randomly allocated into four groups: Control group; Cd group; Cd + Nar group; Nar group. Determination of biochemical indicators, antioxidant indicators; reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot were used to detect the expression levels of related mRNA and protein. Cd exposure reduced rat body weight and increased liver-to-body weight ratio, along with elevations in ALT, AST, GSH, and MDA. Conversely, Cd + Nar treatment increased body weight, reduced liver organ coefficient, and decreased these biomarkers. HE staining revealed expanded hepatic sinusoids in the Cd group. RT-qPCR and Western blot showed Cd upregulated GRP78, PERK, and CHOP expression at both mRNA and protein levels, while Cd + Nar treatment attenuated these increases. Cd activates the PERK signaling pathway through ERS and causes liver damage. Nar can reduce liver toxicity. The mechanism may be related to the inhibition of PERK activation by Nar.