The Effects of MK-801 on Central Nervous Antioxidative Stress System in Rats with Obstructive Jaundice_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHANGLi-chao ¹ , CAOHui-fang ² , WANGChen-yu ³ , LIUBo ⁴ , ZHOUYuan-long ¹ , KANGJian-sheng ¹ , HOUSen-lin ¹ , QIAOZhan-ying ¹ ,  LIUHuai-jun ⁵

1. Department of Biliary Track Minimally Invasive Surgery, The Second Hospital of Hebei Medical University, Shijiazhaung 050000, Hebei Province, China;
2. Department of Rehabilitation, The Second Hospital of Hebei Medical University, Shijiazhaung 050000, Hebei Province, China;
3. Medical Administration Division, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075061, Hebei Province, China;
4. Surgical Oncology, The Second Hospital of Hebei Medical University, Shijiazhaung 050000, Hebei Province, China;
5. Medical Imaging Department, The Second Hospital of Hebei Medical University, Shijiazhaung 050000, Hebei Province, China;

Corresponding author：

LIUHuai-jun, Email: rockboyyu@126.com

Keywords：

Dizocilpine maleate; Oxidative stress; Obstructive jaundice; Ruclear factor E2 related factor

DOI：

10.7507/1007-9424.20160110

Video：

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Objective To investigate the effects of MK-801 on antioxidant system activity in the central nervous system of rats with obstructive jaundice. Methods Twenty rats were divided into four groups: sham operation group, control group, MK-801 low dose group, and MK-801 high dose group. The control group, MK-801 low dose group, and MK-801 high dose group were the obstructive jaundice model groups (OJ groups). From the first day after operation, MK-801 low dose group were processed intraperitoneal injection of MK-801 0.025 mg/(kg·d) and MK-801 high dose group were processed intraperitoneal injection of MK-801 0.25 mg/(kg·d). Meanwhile, sham operation group and control group were injected the same volume of normal saline everyday for 10 days. Three days after operation, rats' tail vein blood were collected for examining the direct bilirubin DBIL) and total bile acids (TBA) in order to determine whether the model were successfully established. And malondialdehyde (MDA), catalase (CAT), total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC) were determined on the 10th day to evaluate the oxdative status of the rats. Results ①Obstructive jaundice model was established successfully.②The content of MDA in control group, MK-801 low dose group and MK-801 high dose group were significantly increased than the sham operation group, and there was statistical difference (P < 0.05). The content of MDA decreased in MK-801groups compared with the control group (P < 0.05).③Compared with the sham operation group, the activity of CAT in control group decreased significantly (P < 0.05). The activity of CAT in the MK-801 groups increased compared with the control group with significant difference (P < 0.05). There was no statistical difference on the activity of CAT between MK-801 low dose group and high dose group (P > 0.05).④Compared with sham operation group, the activity of T-SOD was decreased significantly in control group with statistical significance (P < 0.05). The activity of T-SOD were increased in the MK-801 groups compared with control group with significant difference (P < 0.05), but the activity of T-SOD was decreased significantly in the high dose group than the low dose group (P < 0.05).⑤In the Oj groups, the T-AOC were significantly increased compared with the sham operation group, and there was statistical significance (P < 0.05). The T-AOC in MK-801 groups were increased compared with the control group with statistical significance (P < 0.05), but there was no statistical difference between the MK-801 groups. Conciusions Oxidative stress exists when obstructive jaundice occurs, and obstructive jaundice can aggravate the oxidative stress damage in the rats' central nervous system and cause increasing expression of enzymes such as CAT which enhance antioxidant capacity of the whole body. MK-801 can decrease lipid peroxidation, and increase activity of CAT and SOD as well as T-AOC in CNS of jaundice rats. But High dose of MK-801 has no better effect than low dose of MK-801. On the contrary, activity of T-SOD decrease in the high dose group than in the low dose group. Further research is needed on the specific mechanism.

Citation： ZHANGLi-chao, CAOHui-fang, WANGChen-yu, LIUBo, ZHOUYuan-long, KANGJian-sheng, HOUSen-lin, QIAOZhan-ying, LIUHuai-jun. The Effects of MK-801 on Central Nervous Antioxidative Stress System in Rats with Obstructive Jaundice. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(4): 411-415. doi: 10.7507/1007-9424.20160110 Copy

1.	Kawano H, Minagawa K, Wakahashi K, et al. Successful management of obstructive jaundice due to gallstones with eculizumab in a patient with paroxysmal nocturnal hemoglobinuria. Intern Med, 2012, 51(18): 2613-2616.
2.	Peter G, Shaheer R, Narayanan P, et al. Hepatic artery aneurysm: a rare case of obstructive jaundice with severe hemobilia. Ann Gast roenterol, 2014, 27(3): 288-289.
3.	Xin KY, Yee LS, Yong TT, et al. Obstructive jaundice due to intradu ctal tumour thrombus in recurrent hepatocellular carcinoma: what is the optimal therapeutic approach? Hepatogastroenterology, 2014, 61(135): 1863-1866.
4.	Wang L, Yu WF. Obstructive jaundice and perioperative manage ment. Acta Anaesthesiol Taiwan, 2014, 52(1): 22-29.
5.	Grojean S, Koziel V, Vert P, et al. Bilirubin induces apoptosis via activation of NMDA receptors in developing rat brain neurons. Exp Neurol, 2000, 166(2): 334-341.
6.	余水平, 李坚, 侯冰宗, 等.急慢性大鼠梗阻性黄疸模型的建立.世界华人消化杂志, 2011, 19(12): 1285-1289.
7.	Zhang RP, Zhang XP, Ruan YF, et al. Protective effect of Radix Astragali injection on immune organs of rats with obstructive jaundice and its mechanism. World J Gastroenterol, 2009, 15(23): 2862-2869.
8.	Oruç MT, Ozmen MM, Han U. A new technique for inducing and releasing obstructive jaundice in rats. Eur Surg Res, 2009, 43(4): 354-359.
9.	Hatipoglu S, Yildiz H, Bulbuloglu E, et al. Protective effects of intravenous anesthetics on kidney tissue in obstructive jaundice. World J Gastroenterol, 2014, 20(12): 3320-3326.
10.	Zhou YX, Ni Y, Liu YB, et al. Histone preconditioning protects against obstructive jaundice-induced liver injury in rats. Exp Ther Med, 2014, 8(1): 15-20.
11.	Aydin S, Aytac E, Uzun H, et al. Effects of Ganoderma lucidum on obstructive jaundice-induced oxidative stress. Asian J Surg, 2010, 33(4): 173-180.
12.	Singh S, Koiri RK, Trigun SK. Acute and chronic hyperammonemia modulate antioxidant enzymes differently in cerebral cortex and cerebellum. Neurochem Res, 2008, 33(1): 103-113.
13.	Xu C, Lv PH, Huang XE, et al. Analysis of different ways of drainage for obstructive jaundice caused by hilar cholangiocarcinoma. Asian Pac J Cancer Prev, 2014, 15(14): 5617-5620.
14.	He FL, Wang L, Zhao HW, et al. Transjugular intrahepatic portosy stemic shunt for severe jaundice in patients with acute Budd-Chiari syndrome. World J Gastroenterol, 2015, 21(8): 2413241-8.
15.	Gargaglia E, Totti V, Ligabue G, et al. Acute obstructive jaundice: a possible clinical manifestation of IPMT. Case report and review of the literature. Ann Ital Chir, 2014, 85(4): 377-384.
16.	Grintzalis K, Papapostolou I, Assimakopoulos SF, et al. Time-related alterations of superoxide radical levels in diverse organs of bile duct-ligated rats. Free Radic Res, 2009, 43(9): 803-808.
17.	Zarkua NÉ. Differential diagnostic strategy in obstructive jaundice. Vestn Khir Im I I Grek, 2013, 172(1): 38-44.
18.	Cruz A, Túnez I, Martínez R, et al. Melatonin prevents brain oxidative stress induced by obstructive jaundice in rats. J Neurosci Res, 2007, 85(16): 3652-3656.
19.	Xu F, Dai CL, Peng SL, et al. Polymyxin B protects against hepatic ischemia/reperfusion injury in a rat model of obstructive jaundice. Inflammation, 2014, 37(4): 1015-1021.
20.	Ahlfors CE, Parker AE. Evaluation of a model for brain bilirubin uptake in jaundiced newborns. Pediatr Res, 2005, 58(6): 1175-1179.
21.	Worsley JB. Hyperbilirubinemia guidelines and unintended harms. Pediatrics, 2004, 114(4): 1134-1135.
22.	Palmela I, Cardoso FL, Bernas M, et al. Elevated levels of bilirubin and long-term exposure impair human brain microvascular endothelial cell integrity. Curr Neurovasc Res, 2011, 8(2): 153-169.
23.	Smirnova NG, Chefu SG, Kovalenko AL, et al. Effect of hepatopro tector remaxol infusion on liver function in obstructive jaundice model in rats. Eksp Klin Farmakol, 2010, 73(9): 24-27.
24.	Shila S, Kolilavani V, Subathra M, et al. Brain regional responses in antioxidant system to alpha-lipoic acid in arsenic intoxicated rat. Toxicology, 2005, 210(1): 25-36.
25.	Dai G, Chen Y, Gu F, et al. Effects of electroacupuncture on the contents of NO, ET and T-AOC in the brain tissues of the cerebral hemorrhage model rats. J Tradit Chin Med, 2005, 25(1): 62-65.
26.	Moran M, Oruc MT, Ozmen MM, et al. Effect of erythropoietin on oxidative stress and liver injury in experimental obstructive jaundice. Eur Surg Res, 2009, 43(2): 228-234.
27.	Zhang C, Zhang M, Sun Y, et al. Effect of dibutyl phthalate and di-(2-ethylhexyl) phthalate on urine SOD activity and MDA content in rats. Nan Fang Yi Ke Da Xue Xue Bao, 2012, 32(2): 160-164.
28.	Lu X, Wang C, Liu B. The role of Cu/Zn-SOD and Mn-SOD in the immune response to oxidative stress and pathogen challenge in the clam Meretrix meretrix. Fish Shellfish Immunol, 2015, 42(1): 58-65.
29.	Yu C, Wang P, Li S, et al. The protective effect of Cu/Zn-SOD against oxidative stress after PTEN deletion. Cancer Invest, 2011, 29(4): 253-256.

1. Kawano H, Minagawa K, Wakahashi K, et al. Successful management of obstructive jaundice due to gallstones with eculizumab in a patient with paroxysmal nocturnal hemoglobinuria. Intern Med, 2012, 51(18): 2613-2616.
2. Peter G, Shaheer R, Narayanan P, et al. Hepatic artery aneurysm: a rare case of obstructive jaundice with severe hemobilia. Ann Gast roenterol, 2014, 27(3): 288-289.
3. Xin KY, Yee LS, Yong TT, et al. Obstructive jaundice due to intradu ctal tumour thrombus in recurrent hepatocellular carcinoma: what is the optimal therapeutic approach? Hepatogastroenterology, 2014, 61(135): 1863-1866.
4. Wang L, Yu WF. Obstructive jaundice and perioperative manage ment. Acta Anaesthesiol Taiwan, 2014, 52(1): 22-29.
5. Grojean S, Koziel V, Vert P, et al. Bilirubin induces apoptosis via activation of NMDA receptors in developing rat brain neurons. Exp Neurol, 2000, 166(2): 334-341.
6. 余水平, 李坚, 侯冰宗, 等.急慢性大鼠梗阻性黄疸模型的建立.世界华人消化杂志, 2011, 19(12): 1285-1289.
7. Zhang RP, Zhang XP, Ruan YF, et al. Protective effect of Radix Astragali injection on immune organs of rats with obstructive jaundice and its mechanism. World J Gastroenterol, 2009, 15(23): 2862-2869.
8. Oruç MT, Ozmen MM, Han U. A new technique for inducing and releasing obstructive jaundice in rats. Eur Surg Res, 2009, 43(4): 354-359.
9. Hatipoglu S, Yildiz H, Bulbuloglu E, et al. Protective effects of intravenous anesthetics on kidney tissue in obstructive jaundice. World J Gastroenterol, 2014, 20(12): 3320-3326.
10. Zhou YX, Ni Y, Liu YB, et al. Histone preconditioning protects against obstructive jaundice-induced liver injury in rats. Exp Ther Med, 2014, 8(1): 15-20.
11. Aydin S, Aytac E, Uzun H, et al. Effects of Ganoderma lucidum on obstructive jaundice-induced oxidative stress. Asian J Surg, 2010, 33(4): 173-180.
12. Singh S, Koiri RK, Trigun SK. Acute and chronic hyperammonemia modulate antioxidant enzymes differently in cerebral cortex and cerebellum. Neurochem Res, 2008, 33(1): 103-113.
13. Xu C, Lv PH, Huang XE, et al. Analysis of different ways of drainage for obstructive jaundice caused by hilar cholangiocarcinoma. Asian Pac J Cancer Prev, 2014, 15(14): 5617-5620.
14. He FL, Wang L, Zhao HW, et al. Transjugular intrahepatic portosy stemic shunt for severe jaundice in patients with acute Budd-Chiari syndrome. World J Gastroenterol, 2015, 21(8): 2413241-8.
15. Gargaglia E, Totti V, Ligabue G, et al. Acute obstructive jaundice: a possible clinical manifestation of IPMT. Case report and review of the literature. Ann Ital Chir, 2014, 85(4): 377-384.
16. Grintzalis K, Papapostolou I, Assimakopoulos SF, et al. Time-related alterations of superoxide radical levels in diverse organs of bile duct-ligated rats. Free Radic Res, 2009, 43(9): 803-808.
17. Zarkua NÉ. Differential diagnostic strategy in obstructive jaundice. Vestn Khir Im I I Grek, 2013, 172(1): 38-44.
18. Cruz A, Túnez I, Martínez R, et al. Melatonin prevents brain oxidative stress induced by obstructive jaundice in rats. J Neurosci Res, 2007, 85(16): 3652-3656.
19. Xu F, Dai CL, Peng SL, et al. Polymyxin B protects against hepatic ischemia/reperfusion injury in a rat model of obstructive jaundice. Inflammation, 2014, 37(4): 1015-1021.
20. Ahlfors CE, Parker AE. Evaluation of a model for brain bilirubin uptake in jaundiced newborns. Pediatr Res, 2005, 58(6): 1175-1179.
21. Worsley JB. Hyperbilirubinemia guidelines and unintended harms. Pediatrics, 2004, 114(4): 1134-1135.
22. Palmela I, Cardoso FL, Bernas M, et al. Elevated levels of bilirubin and long-term exposure impair human brain microvascular endothelial cell integrity. Curr Neurovasc Res, 2011, 8(2): 153-169.
23. Smirnova NG, Chefu SG, Kovalenko AL, et al. Effect of hepatopro tector remaxol infusion on liver function in obstructive jaundice model in rats. Eksp Klin Farmakol, 2010, 73(9): 24-27.
24. Shila S, Kolilavani V, Subathra M, et al. Brain regional responses in antioxidant system to alpha-lipoic acid in arsenic intoxicated rat. Toxicology, 2005, 210(1): 25-36.
25. Dai G, Chen Y, Gu F, et al. Effects of electroacupuncture on the contents of NO, ET and T-AOC in the brain tissues of the cerebral hemorrhage model rats. J Tradit Chin Med, 2005, 25(1): 62-65.
26. Moran M, Oruc MT, Ozmen MM, et al. Effect of erythropoietin on oxidative stress and liver injury in experimental obstructive jaundice. Eur Surg Res, 2009, 43(2): 228-234.
27. Zhang C, Zhang M, Sun Y, et al. Effect of dibutyl phthalate and di-(2-ethylhexyl) phthalate on urine SOD activity and MDA content in rats. Nan Fang Yi Ke Da Xue Xue Bao, 2012, 32(2): 160-164.
28. Lu X, Wang C, Liu B. The role of Cu/Zn-SOD and Mn-SOD in the immune response to oxidative stress and pathogen challenge in the clam Meretrix meretrix. Fish Shellfish Immunol, 2015, 42(1): 58-65.
29. Yu C, Wang P, Li S, et al. The protective effect of Cu/Zn-SOD against oxidative stress after PTEN deletion. Cancer Invest, 2011, 29(4): 253-256.

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The Effects of MK-801 on Central Nervous Antioxidative Stress System in Rats with Obstructive Jaundice

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