Hepatoprotective and antioxidant effects of safflower oil in a rat model of paracetamol-induced acute toxic hepatitis

Background Drug-induced liver injury (DILI) is a major cause of acute liver failure, highlighting the need for effective hepatoprotective agents. Natural products with antioxidant properties represent promising therapeutic options. This study aimed to evaluate the hepatoprotective, antioxidant, and anti-inflammatory effects of cold-pressed safflower oil in a rat model of paracetamol-induced acute toxic hepatitis. Methods Acute toxic hepatitis was induced in male Wistar rats by intragastric administration of paracetamol at a dose of 1000 mg/kg for two consecutive days. This dosing regimen was selected based on established experimental models of acute toxic hepatitis that reliably induce liver injury while maintaining animal survival. Safflower oil was administered orally at a dose of 10 mL/kg for 14 days. Hepatic injury was evaluated by assessing serum biochemical markers, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase; oxidative stress parameters (malondialdehyde); antioxidant enzyme activities (superoxide dismutase and catalase); inflammatory cytokine levels (IL-1β, IL-6, IL-4, and TNF-α); and histopathological changes in liver tissue. Statistical analyses were performed using parametric or non-parametric methods, as appropriate. Results Paracetamol administration caused significant liver injury, evidenced by elevated serum aminotransferase and alkaline phosphatase activities, increased malondialdehyde levels, suppression of antioxidant enzyme activity, and marked histopathological damage. Treatment with safflower oil significantly reduced aspartate aminotransferase and alkaline phosphatase levels and attenuated oxidative stress, as indicated by decreased malondialdehyde concentrations and restoration of superoxide dismutase and catalase activities (p < 0.05). Inflammatory cytokine levels were partially normalised following safflower oil treatment, with significant reductions in IL-1β, IL-6, and IL-4, while TNF-α remained elevated. Histological examination confirmed reduced hepatocellular degeneration, necrosis, inflammatory infiltration, and early fibrotic changes in treated animals compared with the untreated model group. Conclusions Cold-pressed safflower oil exhibits significant hepatoprotective, antioxidant, and anti-inflammatory effects in paracetamol-induced acute toxic hepatitis. These effects are associated with suppression of oxidative stress, modulation of inflammatory responses, normalisation of liver enzyme activity, and preservation of hepatic histoarchitecture. Safflower oil may represent a promising natural adjunctive agent for the prevention and management of toxic liver injury.