Lipoic Acid Attenuates Cholestasis Induced Cerebral Injury in Rats

Cholestasis is characterized by an abnormal accumulation of bile acids, which is caused by defectiveness in the process of bile acid transport. It is believed that oxidative stress is a likely mediator for cholestatic damage and antioxidant therapy is a recommended therapeutic strategy. The aim of this study was to evaluate protective effect o alpha lipoic acid as an anti oxidant agent on cerebral injury after bile act ligation in rats. forty five adult male wistar rats were randomly assigned to three groups each containing fifteen rats as follows: sham operation (SO) (control), bile duct ligation (BDL), and BDL+LA (25mg/kg). After fourteen day’s cerebral tissue sampled for pathologic and biochemical studies. Levels of SOD and GPx antioxidant enzymes were higher in BDL+LA group comparing to BDL group significantly, histologic damage and MDA levels were higher in BDL group comparing to BDL+LA group significantly (P<0.05). In our study LA treatment in BDL rats improved cellular SOD and GPx levels and reduced MDA levels in BDL+LA group comparing to BDL group. The findings of our present study showed that LA, with its potent free radical scavenging and antioxidant properties, seems to be a highly promising agent in protecting cerebral tissue against oxidative damage. [Mohammad Mehdi Hosseinian Zakaria, Babak Hajipour, Mohammad Taghizadieh, Ghafour Mousavi, Ali Khodadadi. Lipoic Acid Attenuates Cholestasis Induced Cerebral Injury in Rats. Life Sci J 2013;10(5s):539-545] (ISSN:1097-8135). http://www.lifesciencesite.com. 95

[1]  N. Başaran,et al.  Protective effects of curcumin against oxidative stress parameters and DNA damage in the livers and kidneys of rats with biliary obstruction. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[2]  Samuel S. Lee,et al.  Protective effects of erythropoietin on cirrhotic cardiomyopathy in rats. , 2012, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[3]  Xing Wu,et al.  Alpha-lipoic acid pre- and post-treatments provide protection against in vitro ischemia-reperfusion injury in cerebral endothelial cells via Akt/mTOR signaling , 2012, Brain Research.

[4]  S. Vasdev,et al.  Role of the immune system in hypertension: modulation by dietary antioxidants. , 2011, The International journal of angiology : official publication of the International College of Angiology, Inc.

[5]  A. Khodadadi,et al.  Anti-Oxidative Effect of Lipoic Acid in Spinal Cord Ischemia/Reperfusion , 2010, Medical Principles and Practice.

[6]  R. Hughes,et al.  Changing face of hepatic encephalopathy: role of inflammation and oxidative stress. , 2010, World journal of gastroenterology.

[7]  J. Sheen,et al.  The interaction between high ammonia diet and bile duct ligation in developing rats: assessment by spatial memory and asymmetric dimethylarginine , 2010, International Journal of Developmental Neuroscience.

[8]  O. Simonetti,et al.  Lipoic acid effects on established atherosclerosis. , 2010, Life sciences.

[9]  S. Rivera-Mancía,et al.  Morphological changes of rat astrocytes induced by liver damage but not by manganese chloride exposure , 2009, Metabolic Brain Disease.

[10]  Y. Tain,et al.  Melatonin Ameliorates Bile Duct Ligation-Induced Systemic Oxidative Stress and Spatial Memory Deficits in Developing Rats , 2009, Pediatric Research.

[11]  H. Kırımlıoğlu,et al.  Effect of resveratrol and melatonin on oxidative stress enzymes, regeneration, and hepatocyte ultrastructure in rats subjected to 70% partial hepatectomy. , 2008, Transplantation proceedings.

[12]  F. Groenendaal,et al.  Anti-oxidant strategies. , 2007, Seminars in fetal & neonatal medicine.

[13]  P. Varalakshmi,et al.  Effect of DL-alpha-lipoic acid on cyclophosphamide induced lysosomal changes in oxidative cardiotoxicity. , 2007, Life sciences.

[14]  M. Vacca,et al.  Parallel intestinal and liver injury during early cholestasis in the rat: modulation by bile salts and antioxidants. , 2007, Free radical biology & medicine.

[15]  D. Butterfield,et al.  Roles of amyloid beta-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer's disease and mild cognitive impairment. , 2007, Free radical biology & medicine.

[16]  J. Sastre,et al.  Mitochondrial function in liver disease. , 2007, Frontiers in bioscience : a journal and virtual library.

[17]  Omar Cauli,et al.  Brain edema and inflammatory activation in bile duct ligated rats with diet‐induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis , 2006, Hepatology.

[18]  E. Coskun,et al.  Neuroprotective effects of L-carnitine and vitamin E alone or in combination against ischemia-reperfusion injury in rats. , 2006, The Journal of surgical research.

[19]  C. Vagianos,et al.  Evidence for intestinal oxidative stress in patients with obstructive jaundice , 2006, European journal of clinical investigation.

[20]  C. Georgiou,et al.  Brain Oxidative Stress Induced by Obstructive Jaundice in Rats , 2006, Journal of neuropathology and experimental neurology.

[21]  U. Çakatay.  Pro-oxidant actions of alpha-lipoic acid and dihydrolipoic acid. , 2006, Medical hypotheses.

[22]  A. Bilska,et al.  Lipoic acid - the drug of the future? , 2005, Pharmacological reports : PR.

[23]  Z. Gong,et al.  Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats. , 2005, World journal of gastroenterology.

[24]  N. Chatauret,et al.  Alterations in soluble guanylate cyclase content and modulation by nitric oxide in liver disease , 2004, Neurochemistry International.

[25]  T. Minor,et al.  The effects of allopurinol and SOD on lipid peroxidation and energy metabolism in the liver after ischemia in an aerobic/anaerobic persufflation , 2004, Surgery Today.

[26]  N. Gürbüz,et al.  Protective effect of polyunsaturated phosphatidylcholine on liver damage induced by biliary obstruction in rats. , 2003, Journal of pediatric surgery.

[27]  Yau-Huei Wei,et al.  Oxidative-Stress-Related Changes in the Livers of Bile-Duct-Ligated Rats , 2003, Journal of Biomedical Science.

[28]  Xiongwei Zhu,et al.  Is oxidative damage the fundamental pathogenic mechanism of Alzheimer's and other neurodegenerative diseases? , 2002, Free radical biology & medicine.

[29]  L. Packer,et al.  Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. , 2002, Toxicology and applied pharmacology.

[30]  D. Butterfield,et al.  The glial glutamate transporter, GLT‐1, is oxidatively modified by 4‐hydroxy‐2‐nonenal in the Alzheimer's disease brain: the role of Aβ1–42 , 2001, Journal of neurochemistry.

[31]  M. Smith,et al.  Chemistry and biochemistry of oxidative stress in neurodegenerative disease. , 2001, Current medicinal chemistry.

[32]  A. Bomzon,et al.  Evidence of a systemic phenomenon for oxidative stress in cholestatic liver disease , 2000, Gut.

[33]  N. Dhalla,et al.  Status of myocardial antioxidants in ischemia-reperfusion injury. , 2000, Cardiovascular research.

[34]  K. Okinaga,et al.  Impaired Kupffer cell function and effect of immunotherapy in obstructive jaundice. , 2000, The Journal of surgical research.

[35]  M. Orellana,et al.  Bile duct ligation and oxidative stress in the rat: effects in liver and kidney. , 2000, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[36]  G. Gores,et al.  Hepatocyte apoptosis after bile duct ligation in the mouse involves Fas. , 1999, Gastroenterology.

[37]  R. Marchioli.  Antioxidant vitamins and prevention of cardiovascular disease: laboratory, epidemiological and clinical trial data. , 1999, Pharmacological research.

[38]  J. Boyer,et al.  Molecular pathogenesis of cholestasis. , 2012, The New England journal of medicine.

[39]  M. Mattson,et al.  Increased Sensitivity to Mitochondrial Toxin-Induced Apoptosis in Neural Cells Expressing Mutant Presenilin-1 Is Linked to Perturbed Calcium Homeostasis and Enhanced Oxyradical Production , 1998, The Journal of Neuroscience.

[40]  L. Packer.  α-Lipoic Acid: A Metabolic Antioxidant Which Regulates NF-κB Signal Transduction and Protects Against Oxidative Injury , 1998 .

[41]  Z. Canturk,et al.  Cytoprotective effects of alpha tocopherol against liver injury induced by extrahepatic biliary obstruction. , 1998, East African medical journal.

[42]  J. Féher,et al.  Oxidative stress in the liver and biliary tract diseases. , 1998, Scandinavian journal of gastroenterology. Supplement.

[43]  M. Mattson,et al.  Roles of Lipid Peroxidation in Modulation of Cellular Signaling Pathways, Cell Dysfunction, and Death in the Nervous System , 1998, Reviews in the neurosciences.

[44]  H. Tritschler,et al.  The Roles of Oxidative Stress and Antioxidant Treatment in Experimental Diabetic Neuropathy , 1997, Diabetes.

[45]  A Bast,et al.  The pharmacology of the antioxidant lipoic acid. , 1997, General pharmacology.

[46]  D. Agrawal,et al.  Morphological and biochemical characterization and analysis of apoptosis. , 1997, Journal of pharmacological and toxicological methods.

[47]  D D Breimer,et al.  The blood-brain barrier in neuroinflammatory diseases. , 1997, Pharmacological reviews.

[48]  L. Packer,et al.  Neuroprotection by the Metabolic Antioxidant α-Lipoic Acid , 1997 .

[49]  S W Schalm,et al.  Subclinical Hepatic Encephalopathy , 1996, Seminars in liver disease.

[50]  H. Tritschler,et al.  Alpha-lipoic acid: antioxidant potency against lipid peroxidation of neural tissues in vitro and implications for diabetic neuropathy. , 1996, Free radical biology & medicine.

[51]  H. Tritschler,et al.  Lipoic Acid Improves Nerve Blood Flow, Reduces Oxidative Stress, and Improves Distal Nerve Conduction in Experimental Diabetic Neuropathy , 1995, Diabetes Care.

[52]  G. Gores,et al.  Increases of intracellular magnesium promote glycodeoxycholate-induced apoptosis in rat hepatocytes. , 1994, The Journal of clinical investigation.

[53]  M Raes,et al.  Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. , 1994, Free radical biology & medicine.

[54]  Y. Furukawa.  [Histological changes in the brain due to experimental obstructive jaundice]. , 1991, Nihon Geka Gakkai zasshi.

[55]  H. H. Draper,et al.  Malondialdehyde determination as index of lipid peroxidation. , 1990, Methods in enzymology.

[56]  H. J. G. Gundersen,et al.  The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis , 1988, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[57]  F. Paoletti,et al.  A sensitive spectrophotometric method for the determination of superoxide dismutase activity in tissue extracts. , 1986, Analytical biochemistry.

[58]  M. Uchiyama,et al.  Effects of antioxidants on the TBA reaction of various rat liver homogenates. , 1983, Biochemical medicine.

[59]  W. Valentine,et al.  Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. , 1967, The Journal of laboratory and clinical medicine.

[60]  L. Reed,et al.  Crystalline alpha-lipoic acid; a catalytic agent associated with pyruvate dehydrogenase. , 1951, Science.