Investigation of the Effects of Artemisinin on Acetaminophen-Induced Acute Liver Toxicity.

Paracetamol (PARA) is a widely used antipyretic and analgesic drug; however, overdose is a major cause of hepatotoxicity. Although N-acetylcysteine (NAC) is the standard antidote, its limitations necessitate the investigation of alternative therapeutic approaches. Artemisinin (ART), a natural compound with antioxidant and anti-inflammatory properties, was evaluated for its hepatoprotective potential in a paracetamol-induced acute liver injury model. Biochemical liver function parameters (ALT, AST), oxidative stress markers (SOD, GSH, MDA), molecular markers (TNF-α, IL-1β, iNOS, NF-κB, CYP2E1 mRNA expression), and histopathological changes were assessed using spectrophotometric assays, quantitative real-time PCR (qPCR), and histological staining methods. PARA administration significantly increased ALT and AST levels compared to the CONTROL group (p < 0.001). Among the treatment groups, PARA + ART 14 significantly reduced these enzyme levels compared to the PARA group (p < 0.001). ART treatment also increased antioxidant parameters (SOD, GSH) and decreased MDA levels compared to the PARA group (p < 0.001), with effects comparable to PARA + NAC. Inflammation- and oxidative stress-related gene expressions were significantly elevated in the PARA group versus CONTROL (p < 0.001), whereas PARA + ART 14 significantly downregulated all markers (p < 0.001). Histopathological findings supported the biochemical and molecular results, showing partial improvement in PARA + ART 7 and more pronounced recovery in PARA + ART 14, while no significant improvement was observed in PARA + ART 35. These findings suggest that ART may exert dose-dependent hepatoprotective effects against paracetamol-induced liver injury by modulating oxidative stress and inflammatory responses. Further studies are needed to determine the optimal therapeutic dose and confirm its clinical potential.