Neuroprotective effects of pre-treament with L-carnitine and Acetyl-L-carnitine on ischemic injury in vivo and in vitro

International Journal of Molecular Sciences

Volumn 13, Issue 2, 2012, Pages 2078-2090

  Zhang, Rui ^a   Zhang, Hong ^b   Zhang, Zhongxia ^a   Wang, Tao ^c   Niu, Jingya ^a   Cui, Dongsheng ^a   Xu, Shunjiang ^a  

^a HEBEI MEDICAL UNIVERSITY   (China)

^b Handan City Hospital for Infectious Diseases   (China)

^c Handan county Hospital   (China)

Author keywords

Acetyl L carnitine; Ischemia; L carnitine; Neuroprotection; Oxygen glucose deprivation

Indexed keywords

ADENOSINE TRIPHOSPHATASE; CARNITINE; LEVACECARNINE; MALONALDEHYDE; SUPEROXIDE DISMUTASE; ACETYLCARNITINE; NEUROPROTECTIVE AGENT; OXYGEN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BRAIN INFARCTION SIZE; BRAIN ISCHEMIA; CELL VIABILITY; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME INDUCTION; IN VITRO STUDY; IN VIVO STUDY; MALE; MIDDLE CEREBRAL ARTERY OCCLUSION; NEUROPROTECTION; NONHUMAN; RAT; ANIMAL; CEREBRAL ARTERY DISEASE; COMPLICATION; DRUG EFFECTS; METABOLISM; PATHOLOGY; PC12 CELL LINE; SPRAGUE DAWLEY RAT;

RATTUS;

ACETYLCARNITINE; ANIMALS; APOPTOSIS; BRAIN ISCHEMIA; CARNITINE; INFARCTION, MIDDLE CEREBRAL ARTERY; MALE; MALONDIALDEHYDE; NEUROPROTECTIVE AGENTS; OXYGEN; PC12 CELLS; RATS; RATS, SPRAGUE-DAWLEY; SUPEROXIDE DISMUTASE;

EID: 84863273465     PISSN: None     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms13022078     Document Type: Article

References (32)

1. Murray, C.J.; Lopez, A.D. Mortality by cause for eight regions of the world: Global burden of disease study. Lancet 1997, 349, 1269-1276.
2. Deshpande, J.K.; Siesjo, B.K.; Wieloch, T. Calcium accumulation and neuronal damage in the rat hippocampus following cerebral ischemia. J. Cereb. Blood Flow Metab. 1987, 7, 89-95.
3. MacManus, J.P.; Buchan, A.M.; Hill, I.E.; Rasquinha, I.; Preston, E. Global ischemia can cause DNA fragmentation indicative of apoptosis in rat brain. Neurosci. Lett. 1993, 164, 89-92.
4. Leist, M.; Jaattela, M. Four deaths and a funeral: From caspases to alternative mechanisms. Nat. Rev. Mol. Cell Biol. 2001, 2, 589-598.
5. Picconi, B.; Barone, I.; Pisani, A.; Nicolai, R.; Benatti, P.; Bernardi, G.; Calvani, M.; Calabresi, P. Acetyl-L-carnitine protects striatal neurons against in vitro ischemia: The role of endogenous acetylcholine. Neuropharmacology 2006, 50, 917-923.
6. Zivin, J.A. Neuroprotective therapies in stroke. Drugs 1997, 54, 83-88, discussion 88-89.
7. Flanagan, J.L.; Simmons, P.A.; Vehige, J.; Willcox, M.D.; Garrett, Q. Role of carnitine in disease. Nutr. Metab. (Lond.) 2010, 7, 30-43.
8. Virmani, A.; Binienda, Z. Role of carnitine esters in brain neuropathology. Mol. Aspects Med. 2004, 25, 533-549.
9. Wainwright, M.S.; Kohli, R.; Whitington, P.F.; Chace, D.H. Carnitine treatment inhibits increases in cerebral carnitine esters and glutamate detected by mass spectrometry after hypoxia-ischemia in newborn rats. Stroke 2006, 37, 524-530.
10. Zanelli, S.A.; Solenski, N.J.; Rosenthal, R.E.; Fiskum, G. Mechanisms of ischemic neuroprotection by acetyl-L-carnitine. Ann. N.Y. Acad. Sci. 2005, 1053, 153-161.
11. Slivka, A.; Silbersweig, D.; Pulsinelli, W. Carnitine treatment for stroke in rats. Stroke 1990, 21, 808-811.
12. Turkyilmaz, C.; Turkyilmaz, Z.; Onal, E.; Atalay, Y.; Soylemezoglu, F.; Celasun, B. L-Carnitine pre-treatment reduces apoptotic cell death in seven-day-old rats hypoxia ischemia. Restor. Neurol. Neurosci. 2010, 28, 817-824.
13. Jalal, F.Y.; Bohlke, M.; Maher, T.J. Acetyl-L-carnitine reduces the infarct size and striatal glutamate outflow following focal cerebral ischemia in rats. Ann. N.Y. Acad. Sci. 2010, 1199, 95-104.
14. Sitprija, V. Altered fluid, electrolyte and mineral status in tropical disease, with an emphasis on malaria and leptospirosis. Nat. Clin. Pract. Nephrol. 2008, 4, 91-101.
15. Llansola, M.; Felipo, V. Carnitine prevents NMDA receptor-mediated activation of MAP-kinase and phosphorylation of microtubule-associated protein 2 in cerebellar neurons in culture. Brain Res. 2002, 947, 50-56.
16. Breitkreutz, R.; Babylon, A.; Hack, V.; Schuster, K.; Tokus, M.; Bohles, H.; Hagmuller, E.; Edler, L.; Holm, E.; Droge, W. Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases. Br. J. Cancer 2000, 82, 399-403.
17. Ferrari-Toninelli, G.; Maccarinelli, G.; Uberti, D.; Buerger, E.; Memo, M. Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexole. BMC Pharmacol. 2010, 10, doi:10.1186/1471- 2210-10-2.
18. Garrett, Q.; Xu, S.; Simmons, P.A.; Vehige, J.; Flanagan, J.L.; Willcox, M.D. Expression and localization of carnitine/organic cation transporter OCTN1 and OCTN2 in ocular epithelium. Invest. Ophthalmol. Vis. Sci. 2008, 49, 4844-4849.
19. Inazu, M.; Takeda, H.; Maehara, K.; Miyashita, K.; Tomoda, A.; Matsumiya, T. Functional expression of the organic cation/carnitine transporter 2 in rat astrocytes. J. Neurochem. 2006, 97, 424-434.
20. Muneer, P.M.A.; Alikunju, S.; Szlachetka, A.M.; Mercer, A.J.; Haorah, J. Ethanol impairs glucose uptake by human astrocytes and neurons: Protective effects of acetyl-L-carnitine. Int. J. Physiol. Pathophysiol. Pharmacol. 2011, 3, 48-56.
21. Scafidi, S.; Fiskum, G.; Lindauer, S.L.; Bamford, P.; Shi, D.; Hopkins, I.; McKenna, M.C. Metabolism of acetyl-L-carnitine for energy and neurotransmitter synthesis in the immature rat brain. J. Neurochem. 2010, 114, 820-831.
22. Singh, G.; Siddiqui, M.A.; Khanna, V.K.; Kashyap, M.P.; Yadav, S.; Gupta, Y.K.; Pant, K.K.; Pant, A.B. Oxygen glucose deprivation model of cerebral stroke in PC-12 cells: Glucose as a limiting factor. Toxicol. Mech. Methods 2009, 19, 154-160.
23. Hota, K.B.; Hota, S.K.; Chaurasia, O.P.; Singh, S.B. Acetyl-L-carnitine-mediated neuroprotection during hypoxia is attributed to ERK1/2-Nrf2-regulated mitochondrial biosynthesis. Hippocampus 2011, doi: 10.1002/hipo.20934.
24. Yuan, J. Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke. Apoptosis 2009, 14, 469-477.
25. Qi, J.; Hong, Z.Y.; Xin, H.; Zhu, Y.Z. Neuroprotective effects of leonurine on ischemia/reperfusion-induced mitochondrial dysfunctions in rat cerebral cortex. Biol. Pharm. Bull. 2010, 33, 1958-1964.
26. Siktar, E.; Ekinci, D.; Beydemir, S.; Gulcin, I.; Gunay, M. Protective role of L-carnitine supplementation against exhaustive exercise induced oxidative stress in rats. Eur. J. Pharmacol. 2011, 668, 407-413.
27. Kim, W.; Kim, D.W.; Yoo, D.Y.; Chung, J.Y.; Hwang, I.K.; Won, M.H.; Choi, S.Y.; Jeon, S.W.; Jeong, J.H.; Hwang, H.S.; et al. Neuroprotective effects of PEP-1-Cu, Zn-SOD against ischemic neuronal damage in the rabbit spinal cord. Neurochem. Res. 2011, 37, 307-313.
28. Haorah, J.; Floreani, N.A.; Knipe, B.; Persidsky, Y. Stabilization of superoxide dismutase by acetyl-L-carnitine in human brain endothelium during alcohol exposure: Novel protective approach. Free Radic. Biol. Med. 2011, 51, 1601-1609.
29. Derin, N.; Izgut-Uysal, V.N.; Agac, A.; Aliciguzel, Y.; Demir, N. L-Carnitine protects gastric mucosa by decreasing ischemia-reperfusion induced lipid peroxidation. J. Physiol. Pharmacol. 2004, 55, 595-606.
30. Shuaib, A.; Waqaar, T.; Wishart, T.; Kanthan, R.; Howlett, W. Acetyl-L-carnitine attenuates neuronal damage in gerbils with transient forebrain ischemia only when given before the insult. Neurochem. Res. 1995, 20, 1021-1025.
31. Lin, T.N.; He, Y.Y.; Wu, G.; Khan, M.; Hsu, C.Y. Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke 1993, 24, 117-121.
32. SPSS, version 16.0; IBM Corporation: Armonk, NY, USA, 2008.