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 + N‐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.

中文翻译：

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Boldine治疗可保护对乙酰氨基酚引起的小鼠肝脏炎症和急性肝坏死

药物性肝损伤（DILI）是导致急性肝衰竭（ALF）的常见原因。对乙酰氨基酚（APAP）是一种可引起内在DILI的已知肝毒素。高剂量时，仅在美国，APAP会导致急性肝坏死，分别导致50％和20％的ALF和肝移植病例。氧化应激和谷胱甘肽耗竭与APAP诱发的肝坏死有关。Boldine是一种植物来源的化合物，具有潜在的抗氧化潜力。因此，本研究调查了丁氨酸对APAP诱导的小鼠急性肝坏死的保护作用。在过夜禁食的小鼠中给予单次毒性剂量的APAP（300 mg / kg bwpo），以诱导急性肝坏死。分别是APAP +布丁和APAP +  N还给予了乙酰半胱氨酸（NAC）同时治疗。在肝组织中评估了血清转氨酶和还原型谷胱甘肽，酶抗氧化剂，肿瘤坏死因子-α（TNF-α），白介素-1β（IL-1β）和IL-6。急性APAP中毒可明显提高肝毒性血清标志物酶的水平。APAP给药可增加脂质过氧化，TNF-α，IL-1β和IL-6蛋白表达。APAP中毒小鼠肝组织中的酶促抗氧化剂和降低的谷胱甘肽水平降低。Boldine和NAC同时治疗可防止APAP诱导的氧化应激，炎症和坏死。这项研究的结果表明，由于其抗氧化剂和抗炎特性，其在防止APAP诱导的肝毒性中起着至关重要的作用。