Antioxidative effect of melatonin, ascorbic acid and N-acetylcysteine on caerulein-induced pancreatitis and associated liver injury in rats

瞄准：在老鼠在导致 caerulein 的胰腺炎和联系肝损伤上处于导致胰腺炎的肝的损坏和象 melatonin，抗坏血酸和 N 乙酰半胱氨酸那样的抗氧化剂代理人的效果调查氧化损害的角色。方法：38 只女 Wistar 老鼠被使用。尖锐胰腺炎(AP ) 被 caerulein 的二 i.p 注射在 2-h 间隔导致(在 100 microg/kg b.wt 的全部的剂量) 。另外的二个组收到了另外的 melatonin (20 mg/kg b.wt ) 或包含 L (+) 维生素酸(14.3 mg/kb.wt.) 和 N 乙酰半胱氨酸(181 mg/kg b.wt ) 的抗氧化剂混合物立即在 caerulein 的每注射前的 i.p。老鼠被斩首杀头 12 h 在 caerulein 的最后注射以后牺牲。胰腺、肝的氧化压力标记被变化在在织物抗氧化剂酶层次，过氧化氢酶(猫) 和谷胱甘肽过氧化物酶(GPx ) 作为 malondialdehyde (MDA ) 和变化测量的类脂化合物过氧化物的数量评估。组织病理学说的检查用获得系统被执行。结果：肝的房间退化，细胞内部的空泡形成，脉管的拥挤，正弦曲线膨胀和炎性浸润的度显示出在 caerulein 和 caerulein + melatonin 之间的有效差量(P = 0.001 ) ，并且 careulein 和 caerulein + L (+) 维生素酸 +N 乙酰半胱氨酸组(P = 0.002 ) 。ciner 房间退化，胰腺的浮肿，细胞内部的空泡形成和炎性浸润的度显示出在 caerulein 和 caerulein + melatonin 之间的有效差量(P = 0.004 ) ，并且 careulein 和 caerulein + L (+) 维生素酸 +N 乙酰半胱氨酸组(P = 0.002 ) 。 导致Caerulein 胰腺并且肝损坏伴有织物 MDA 层次的重要增加( P = 0.01 ， P = 0.003 ，分别地)而在猫的重要减少( P = 0.002 ， P = 0.003 ，分别地)并且 GPx 活动( P = 0.002 ， P = 0.03 ，分别地)。Melatonin 和 L (+) 维生素 acid+N 乙酰半胱氨酸管理显著地减少了在胰的 MDA 层次(P=0.03， P=0.002，分别地) 并且肝(P = 0.007， P = 0.01，分别地) 。这些代理人的管理增加了胰腺、肝的猫和 GPx 活动。Melatonin 显著地增加了胰腺、肝的猫(P = 0.002， P = 0.001，分别地) 并且 GPx 活动(P = 0.002， P = 0.001 ) 。另外， L (+) 维生素酸 +N 乙酰半胱氨酸显著地增加了胰腺的 GPx (P = 0.002 ) 并且肝的猫和 GPx 活动(P = 0.001， P = 0.007，分别地).CONCLUSION：氧化损害不仅在 AP 的致病而且处于导致胰腺炎的肝的损坏起一个重要作用。抗氧化剂代理人象 melatonin 和抗坏血酸 +N 乙酰半胱氨酸那样，能够限制经由恢复织物抗氧化剂酶活动在 AP 期间生产的胰腺、肝的损坏。

AIM： To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats. METHODS： Thirty-eight female Wistar rats were used. Acute pancreatitis （AP） was induced by two i.p. injections of caerulein at 2-h intervals （at a total dose of 100 μg/kg b.wt）. The other two groups received additional melatonin （20 mg/kg b.wt） or an antioxidant mixture containing L（＋）-ascorbic acid （14.3 mg/kb.wt.） and N-acetyl cysteine （181 mg/kg b.wt.） i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein. Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde （MDA） and changes in tissue antioxidant enzyme levels, catalase （CAT） and glutathione peroxidase （GPx）. Histopathological examination was performed using scoring systems. RESULTS： The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein＋melatonin （P= 0.001）, and careulein and caerulein ＋ L（＋）- ascorbic acid ＋N-acetyl cysteine groups （P= 0.002）. The degree of aciner cell degeneration, pancreatic edema, intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein ＋ melatonin （P=0.004）, and careulein and caerulein ＋ L（＋）-ascorbic acid ＋N-acetyl cysteine groups （P=0.002）. Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels （P= 0.01, P= 0.003, respectively） whereas a significant decrease in CAT （P= 0.002, P=0.003, respectively） and GPx activities （P= 0.002, P= 0.03, respectively）. Melatonin and L（＋）-ascorbic acid ＋N-acetyl cysteine administration significantly decreased MDA levels in pancreas （P= 0.03, P= 0.002, respectively） and liver （P= 0.007, P= 0.01, respectively）. Administration of these agents increased pancreatic and hepatic CAT and GPx activities. Melatonin significantly increased pancreatic and hepatic CAT （P= 0.002, P= 0.001, respectively） and GPx activities （P=0.002, P=0.001）. Additionally, L（＋）-ascorbic acid＋N-acetyl cysteine significantly increased pancreatic GPx （P= 0.002） and hepatic CAT and GPx activities （P= 0.001, P= 0.007, respectively） CONCLUSION： Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage. Antioxidant agents such as melatonin and ascorbic acid＋N-acetyl cysteine, are capable of limiting pancreatic and hepatic damage produced during AP via restoring tissue antioxidant enzyme activities.