Abstract：
The most important problem with acetaminophen is its hepatotoxicity. N-acetylcysteine (NAC) is used to treat the hepatotoxicity of acetaminophen. Due to the structural similarities of this compound with amifostine, we decided to test the effect of this substance and its metabolite, WR-1065, on the hepatotoxicity of acetaminophen.
The single-dose method contained 1. Control; 2. Acetaminophen (1 g/kg, gavage); 3-5. Acetaminophen + amifostine (100, 200, 400 mg/kg, i.p.); 6-8. Acetaminophen + WR-1065 (50, 100, 200 mg/kg, i.p.); and 9. Acetaminophen + NAC (100, 200 mg/kg, i.p.). The multiple-dose method included the same groups: amifostine (50, 100, 200 mg/kg), WR-1065 (25, 50, 100 mg/kg), and NAC (100 mg/kg). Then, animals were sacrificed, and blood samples were collected for measuring ALT, AST, ALP, and T-Bil, liver tissue for histopathological examination, MDA, and GSH amounts.
Acetaminophen increased the levels of MDA, T-Bil, ALT, AST, and ALP, decreased GSH levels, and augmented necrosis, neutrophils, lymphocytes, and macrophages in the port space in single-dose and multiple-dose studies. Amifostine and WR-1065 significantly reduced the levels of MDA, T-Bil, ALT, AST, ALP, increased GSH content, and ameliorated histopathological alterations in a single-dose and multiple-dose method compared to the acetaminophen group. Moreover, NAC caused a significant decrease in the levels of MDA, T-Bil, ALT, AST, and ALP, and reduced GSH amounts in single-dose and multiple-dose studies.
Amifostine and WR-1065 as antioxidant and hepatoprotective compounds are effective in reducing acetaminophen-induced hepatotoxicity with a similar effect to NAC and can be administered as an adjunct in the treatment of acetaminophen overdose.
The single-dose method contained 1. Control; 2. Acetaminophen (1 g/kg, gavage); 3-5. Acetaminophen + amifostine (100, 200, 400 mg/kg, i.p.); 6-8. Acetaminophen + WR-1065 (50, 100, 200 mg/kg, i.p.); and 9. Acetaminophen + NAC (100, 200 mg/kg, i.p.). The multiple-dose method included the same groups: amifostine (50, 100, 200 mg/kg), WR-1065 (25, 50, 100 mg/kg), and NAC (100 mg/kg). Then, animals were sacrificed, and blood samples were collected for measuring ALT, AST, ALP, and T-Bil, liver tissue for histopathological examination, MDA, and GSH amounts.
Acetaminophen increased the levels of MDA, T-Bil, ALT, AST, and ALP, decreased GSH levels, and augmented necrosis, neutrophils, lymphocytes, and macrophages in the port space in single-dose and multiple-dose studies. Amifostine and WR-1065 significantly reduced the levels of MDA, T-Bil, ALT, AST, ALP, increased GSH content, and ameliorated histopathological alterations in a single-dose and multiple-dose method compared to the acetaminophen group. Moreover, NAC caused a significant decrease in the levels of MDA, T-Bil, ALT, AST, and ALP, and reduced GSH amounts in single-dose and multiple-dose studies.
Amifostine and WR-1065 as antioxidant and hepatoprotective compounds are effective in reducing acetaminophen-induced hepatotoxicity with a similar effect to NAC and can be administered as an adjunct in the treatment of acetaminophen overdose.
摘要：
目的：对乙酰氨基酚最重要的问题是其肝毒性。N-乙酰半胱氨酸(NAC)用于治疗对乙酰氨基酚的肝毒性。由于该化合物与氨磷汀的结构相似性,我们决定测试这种物质及其代谢物的作用，WR-1065，对乙酰氨基酚的肝毒性。
方法：单剂量方法包含1。控制；2.对乙酰氨基酚（1克/千克，灌胃)；3-5。对乙酰氨基酚+氨磷汀（100、200、400mg/kg，i.p.）；6-8。对乙酰氨基酚+WR-1065(50,100,200mg/kg,i.p.)；和9。对乙酰氨基酚+NAC（100，200mg/kg，i.p.）。多剂量方法包括相同的组：氨磷汀（50、100、200mg/kg），WR-1065(25,50,100mg/kg),和NAC(100mg/kg)。然后，动物被处死，收集血样用于测量ALT，AST,ALP,还有T-Bil,用于组织病理学检查的肝组织，MDA,和GSH金额。
结果：对乙酰氨基酚增加丙二醛水平，T-Bil,ALT,AST,ALP,GSH水平下降，和扩大的坏死，中性粒细胞，淋巴细胞，单剂量和多剂量研究中端口空间的巨噬细胞。氨磷汀和WR-1065显著降低MDA水平,T-Bil,ALT,AST,ALP,GSH含量增加，与对乙酰氨基酚组相比，单剂量和多剂量方法改善了组织病理学改变。此外，NAC引起MDA水平的显著降低,T-Bil,ALT,AST,ALP,单剂量和多剂量研究中的GSH含量降低。
结论：氨磷汀和WR-1065作为抗氧化剂和肝保护化合物可有效减少对乙酰氨基酚诱导的肝毒性，具有与NAC相似的作用，并且可以作为辅助治疗对乙酰氨基酚过量。
方法：单剂量方法包含1。控制；2.对乙酰氨基酚（1克/千克，灌胃)；3-5。对乙酰氨基酚+氨磷汀（100、200、400mg/kg，i.p.）；6-8。对乙酰氨基酚+WR-1065(50,100,200mg/kg,i.p.)；和9。对乙酰氨基酚+NAC（100，200mg/kg，i.p.）。多剂量方法包括相同的组：氨磷汀（50、100、200mg/kg），WR-1065(25,50,100mg/kg),和NAC(100mg/kg)。然后，动物被处死，收集血样用于测量ALT，AST,ALP,还有T-Bil,用于组织病理学检查的肝组织，MDA,和GSH金额。
结果：对乙酰氨基酚增加丙二醛水平，T-Bil,ALT,AST,ALP,GSH水平下降，和扩大的坏死，中性粒细胞，淋巴细胞，单剂量和多剂量研究中端口空间的巨噬细胞。氨磷汀和WR-1065显著降低MDA水平,T-Bil,ALT,AST,ALP,GSH含量增加，与对乙酰氨基酚组相比，单剂量和多剂量方法改善了组织病理学改变。此外，NAC引起MDA水平的显著降低,T-Bil,ALT,AST,ALP,单剂量和多剂量研究中的GSH含量降低。
结论：氨磷汀和WR-1065作为抗氧化剂和肝保护化合物可有效减少对乙酰氨基酚诱导的肝毒性，具有与NAC相似的作用，并且可以作为辅助治疗对乙酰氨基酚过量。
