Sinapic Acid Ameliorates Cadmium-Induced Hepatotoxicity: Modulation of Oxidative Stress, Inflammation, and Apoptosis.

Background/Objectives: Cadmium (Cd) is a harmful metal commonly used in industry. Numerous clinical diseases, including osteomalacia, testicular damage, renal and hepatic failure, and pulmonary edema, are associated with Cd exposure. The current study evaluated the protective effect of Sinapic acid (SA) against Cd-induced hepatotoxicity by investigating different mechanistic pathways interfering with Cd-related liver injury. Methods: Forty rats were randomly assigned to four groups as follows; group 1 served as negative control and received saline, group 2 received saline for 14 days and CdCl(2) (3.5 mg/kg IP) as a single dose on day 14, groups 3 and 4 were treated with SA (20, 40 mg/kg PO), respectively, for 14 days and injected with CdCl(2) (3.5 mg/kg IP) on day 14. Serum was collected to evaluate liver function. Liver samples were collected for histopathological examination and the assessment of markers related to oxidative stress, inflammation, and apoptosis. Results: Acute Cd administration elevated liver enzymes and induced pathological changes in liver specimens, with the concurrent release of inflammatory markers and reduced antioxidant capabilities. Pretreatment with SA improved liver function and Cd-induced histopathological changes and elevated the activities of antioxidant enzymes. SA ameliorated inflammation, as evidenced by decreased expression of NF-κB, TNF-α, TLR-4, and COX-2, iNOS, and IL-1β levels along with suppression of mTOR, JNK, ERK, BAX, and Bcl-2. Conclusions: The present data suggest that SA represents a promising protective agent against Cd-induced hepatic injury by attenuating oxidative stress, inflammation, and apoptosis.