乙醯氨酚為西方國家常見之非處方鎮痛解熱家庭用藥，卻頻繁地導致急性肝臟衰竭或中毒死亡的藥物，美國FDA曾對其使用提出警告，並調降每日最高的使用量，但乙醯氨酚中毒事件仍舊頻繁。隨著工業發展及生產需求的增加，人們的睡眠逐漸被剝奪，睡眠剝奪可能會影響多重器官的功能、免疫力下降與痛覺敏感度的增加。褪黑激素一種新興的助眠劑也是一種強力抗氧化劑，曾被用於預防乙醯氨酚的肝毒性研究。本研究目的：探討睡眠剝奪後服用乙醯氨酚對肝臟造成的影響；評估褪黑激素對睡眠剝奪後服用乙醯氨酚之肝臟損傷的保護作用；進一步釐清睡眠剝奪後服用乙醯氨酚所造成的急性肝臟損傷之原因及褪黑激素對急性肝臟損傷的保護作用。睡眠剝奪實驗以改良式多平台水槽，以兩天睡眠剝奪(12小時/天)、一天休息的循環共8天，將雄性小鼠隨機分組，進行睡眠剝奪後，以口服方式給予小鼠67、103或206 mg/kg之乙醯氨酚，檢視對肝臟造成的影響；預先於小鼠腹腔注射1或10 mg/kg褪黑激素，相隔1小時後以肝損傷指標有激烈反應的劑量進行肝損傷誘導，採集血液與肝臟並分析血清生化值、氧化壓力、發炎反應、凋亡與壞死相關蛋白以及肝臟病理切片。結果顯示，睡眠剝奪後使用206 mg/kg乙醯氨酚，顯著增加部分小鼠的肝臟損傷指標GPT與Bax蛋白表現量並出現肝臟組織壞死呈現急性肝臟損傷的現象；預先注射10 mg/kg褪黑激素則顯著減少部分小鼠的肝臟損傷指標GOT、GPT與Bcl 2蛋白表現量以及肝臟組織壞死等急性肝臟損傷的現象。綜合上述實驗結果：睡眠剝奪可能為乙醯氨酚中毒事件之修飾因子，褪黑激素具有保護小鼠免於睡眠剝奪後給予乙醯氨酚導致的急性肝臟損傷之潛力，然確切機制尚待進一步探討。

Acetaminophen (APAP) is commonly used as an effective analgesic and antipyretic agent. Although APAP does not possess adverse effect in therapeutic doses, it causes acute liver injury at overdose. U.S. Food and Drug Administration has raised warnings using APAP for physical malaise. However, the number of hospitalized patients using APAP do not decrease; which is still unclear. Sleep deprivation is known to cause mild liver injury, in addition, therapeutic dose of APAP may synergistically enhance liver injury. Therefore, the aim of this study is to investigate the effect of therapeutic APAP for physical malaise on acute liver injury during sleep deprivation and the protective effect of melatonin on APAP-induced adverse effect. A cycle of two-day sleep deprivation (from 7:30 am to 7:30 pm) and one-day sleep for 8 days was performed by modified multiple platform method. Melatonin and APAP were given on the eighth day. In the first experiment, mice were randomly assigned into six groups, control, sleep deprivation, sleep deprivation with APAP (67, 103, 206 mg/kg) and APAP alone (206 mg/kg) group. In the second experiment, mice were randomly assigned into four groups, control, sleep deprivation with APAP (206 mg/kg) and sleep deprivation with APAP (206 mg/kg) pretreatment with melatonin (1, 10 mg/kg). After 8 days, blood and liver were collected. Sleep deprivation with APAP (206 mg/kg) increased GPT, Bax expression and necrosis area in liver. In addition, pretreatment with melatonin (10 mg/kg) decreased GOT, GPT, Bcl 2 expression and necrosis area in liver. In conclusion, sleep deprivation may be a modifying factor in the acetaminophen poisoning incident. Furthermore, melatonin may attenuate sleep deprivation-acetaminophen associated acute liver injury.

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