Preventive effect of N-acetyl-L-cysteine on oxidative stress and cognitive impairment in hepatic encephalopathy following bile ductligation |
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| Institution: | 1. Division of General Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;2. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;3. Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan;4. Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan;5. Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan;6. Cheng-Hsin General Hospital, Taipei, Taiwan;1. Divisions of General Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC;2. Divisions of Gastroenterology and Hepatology, Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC;3. Divisions of Endoscopy Center for Diagnosis and Treatment, Taipei Veterans, General Hospital, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC;4. Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC;5. Institute of Pharmacology, National, Yang-Ming University School of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC;6. Cheng-Hsin General Hospital, Taipei, Taiwan, ROC;1. Department of Gastroenterology, Ningxia People''s Hospital, 301 Zhengyuan North Street, Jinfeng District, 750021 Yinchuan, Ningxia, PR China;2. Endoscopy Center, Ningxia People''s Hospital, Yinchuan, PR China;1. Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman 76198-13159, Iran;2. Quchan Higher Health Education Center, Mashhad University of Medical Sciences, Mashhad, Iran;3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;4. Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran;1. Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran;2. Department of Physiology, The Medical School, Shiraz University of Medical Sciences, Shiraz, 71365-1689, Iran;3. Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, 71365-1689, Iran;4. Department of Anatomy, The Medical School, Shiraz University of Medical Sciences, Shiraz, Iran |
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| Abstract: | Oxidative stress caused by ammonia toxicity is known to play a key role in the pathogenesis of hepatic encephalopathy (HE). The present study was designed to evaluate the protective effect of N-acetyl-L-cysteine (NAC) supplementation in a bile duct ligation (BDL)-induced model of HE. Three weeks after BDL, rats developed biliary fibrosis which was supported by liver function tests, ammonia levels, and hydroxyproline content. Impaired cognitive and motor functions were observed along with decreased acetylcholinesterase activity in the brain of BDL rats. Cerebral cortex and cerebellum of BDL animals showed an increase in lipid peroxidation and reduction in total and nonprotein thiols along with reduction in antioxidant enzymes. Histopathological examination of cortex and cerebellum of BDL rats showed astrocytic swelling, inflammation, necrosis, and white matter edema. One week after BDL surgery, animals administered with NAC at a daily dose 100 mg/kg for 2weeks showed significant improvement in the activity of liver marker enzymes and restored structural morphology of liver. NAC was able to ameliorate spatial memory and motor coordination deficits observed in BDL rats. NAC supplementation decreased lipid peroxidation and was also able to restore the activity of antioxidant enzymes as well as structural deficits observed in the cortex and cerebellum of BDL animals. The results clearly demonstrate that the protective effect of NAC in an experimental model of HE is mediated through attenuation of oxidative stress, suggesting a therapeutic role for NAC in individuals withHE. |
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