Protective Effects of Oral Pharmaceutical Solution of Fucoxanthin Against Paracetamol-Induced Liver Injury: Modulation of Drug-Metabolizing Enzymes, Oxidative Stress, and Apoptotic Pathways in Rats

Paracetamol (PAC) overdose causes acute liver injury through oxidative stress, inflammation, and apoptosis. While N-acetyl cysteine (NAC) is the standard treatment, fucoxanthin (FUC), a carotenoid from brown seaweed, has shown hepatoprotective effects in animal studies, but its role in PAC toxicity is unclear. Compared to NAC, this study assessed the hepatoprotective potential of oral FUC solution towards PAC-induced injury to the rat's liver. FUC was formulated as a pharmaceutical solution and characterized via UV-VIS spectroscopy. Six groups of male Wistar rats each contain five animal which are in total thirty rats: negative control (NC), positive control (PC, 2 g/kg PAC), NAC (1200 mg/kg), and three oral FUC doses (100, 200, and 500 mg/kg) for seven days, with PAC administered on day-8. Liver tissues were analyzed for oxidative stress, gene expression, and histology. FUC solution was clear with absorbance at 433 nm. PAC caused 30% mortality (p < 0.01 vs. others). NAC reduced ALT (56%), AST (78%), ALP (28%), and increased TP by 25% (p < 0.001 vs. PC). FUC at 500 mg/kg (F500) was superior, reducing ALT (82%), AST (93%), ALP (40%), and increasing TP (35%) (p < 0.001 vs. NAC). PAC increased oxidative stress, CYP2E1/CYP3A2 expression, apoptosis markers, and suppressed Nrf2/AMPK/AKT1. F500 improved antioxidants, reduced oxidative stress, and apoptosis, enhanced the Nrf2/AMPK pathway, and downregulated CYP2E1/CYP3A2 (p < 0.01). FUC, particularly at 500 mg/kg, offers significant hepatoprotection against PAC-induced liver injury by modulating drug metabolizing enzymes and enhancing antioxidant defences, warranting further research.