Boldine treatment protects acetaminophen‐induced liver inflammation and acute hepatic necrosis in mice

<jats:title>Abstract</jats:title><jats:p>Drug‐induced liver injury (DILI) is a frequent cause responsible for acute liver failure (ALF). Acetaminophen (APAP) is a known hepatotoxin predictably causing intrinsic DILI. At high doses, APAP causes acute liver necrosis and responsible for ALF and liver transplant cases in 50% and 20% of patients, respectively, in the United States alone. Oxidative stress and glutathione depletion are implicated in APAP‐induced liver necrosis. Boldine, a plant‐derived compound is shown to have promising antioxidant potential. Therefore, this study investigates the protective effect of boldine against APAP‐induced acute hepatic necrosis in mice. A single toxic dose of APAP (300 mg/kg b.w. p.o.) was administered in overnight‐fasted mice to induce acute liver necrosis. Separately, APAP + boldine and APAP + <jats:italic>N</jats:italic>‐acetylcysteine (NAC) simultaneous treatments were also given. Serum transaminases and reduced glutathione, enzymic antioxidants, tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and, IL‐6 were evaluated in liver tissue. Acute APAP intoxication significantly elevated serum marker enzymes of hepatotoxicity. APAP administration increased lipid peroxidation, TNF‐α, IL‐1β, and IL‐6 protein expressions. The enzymic antioxidants and reduced glutathione levels were decreased in liver tissue of APAP intoxicated mice. Boldine and NAC simultaneous treatments prevented APAP‐induced oxidative stress, inflammation, and necrosis. The results of this study suggest the crucial role of boldine to protect against APAP induced hepatotoxicity by virtue of its antioxidant and anti‐inflammatory properties.</jats:p>