Prevention of paclitaxel-evoked painful peripheral neuropathy by acetyl-l-carnitine: Effects on axonal mitochondria, sensory nerve fiber terminal arbors, and cutaneous Langerhans cells

Experimental Neurology

Volumn 210, Issue 1, 2008, Pages 229-237

  Jin, Hai Wei ^a   Flatters, Sarah J L ^b   Xiao, Wen Hua ^a   Mulhern, Howard L ^c   Bennett, Gary J ^a  

^a MCGILL UNIVERSITY   (Canada)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

Allodynia; Chemotherapy; Hyperalgesia; Langerhans cell; Neuroprotection; Neurotoxicity

Indexed keywords

LEVACECARNINE; PACLITAXEL;

AFFERENT NERVE GROUP 1; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL ACTIVATION; CELL COUNT; CELL VACUOLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; INCIDENCE; LANGERHANS CELL; MALE; MITOCHONDRION; MITOCHONDRION SWELLING; NERVE DEGENERATION; NERVE FIBER C; NEUROPATHIC PAIN; NEUROPROTECTION; NONHUMAN; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; RAT; SENSORY NERVE;

ACETYLCARNITINE; ANIMALS; AXONS; BEHAVIOR, ANIMAL; DISEASE MODELS, ANIMAL; DRUG INTERACTIONS; LANGERHANS CELLS; MALE; MICROSCOPY, ELECTRON, TRANSMISSION; MITOCHONDRIA; PACLITAXEL; PAIN; PERIPHERAL NERVOUS SYSTEM DISEASES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, SENSORY; SKIN;

EID: 39249083334     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2007.11.001     Document Type: Article

References (65)

1. Andre N., Braguer D., Brasseur G., Goncalves A., Lemesle-Meunier D., Guise S., Jordan M.A., and Briand C. Paclitaxel induces release of cytochrome c from mitochondria isolated from human neuroblastoma cells. Cancer Res. 60 (2000) 5349-5353
2. Authier N., Gillet J.P., Fialip J., Eschalier A., and Coudore F. Description of a short-term Taxol-induced nociceptive neuropathy in rats. Brain Res. 887 (2000) 239-249
3. Bertamini M., Marzani B., Guarneri R., Guarneri P., Bigini P., Mennini T., and Curti D. Mitochondrial oxidative metabolism in motor neuron degeneration (mnd) mouse central nervous system. Eur. J. Neurosci. 16 (2002) 2291-2296
4. Binienda Z.K., Ali S.F., Virmani A., Amato A., Salem N., and Przybyla B.D. Co-regulation of dopamine D1 receptor and uncoupling protein-2 expression in 3-nitropropionic acid-induced neurotoxicity: neuroprotective role of l-carnitine. Neurosci. Lett. 410 (2006) 62-65
5. Byers M.R. Sensory innervation of periodontal ligament of rat molars consists of unencapsulated Ruffini-like mechanoreceptors and free nerve endings. J. Comp. Neurol. 231 (1985) 500-518
6. Byers M.R., and Yeh Y. Fine structure of subepithelial "free" and corpuscular trigeminal nerve endings in anterior hard palate of the rat. Somatosens. Res. 1 (1984) 265-279
7. Calabrese V., Ravagna A., Colombrita C., Scapagnini G., Guagliano E., Calvani M., Butterfield D.A., and Stella A.M.G. Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2. J. Neurosci. Res. 79 (2005) 509-521
8. Cavaletti G., Tredici G., Braga M., and Tazzari S. Experimental peripheral neuropathy induced in adult rats by repeated intraperitoneal administration of taxol. Exp. Neurol. 133 (1995) 64-72
9. Cavaletti G., Cavalletti E., Montaguti P., Oggioni N., De Negri O., and Tredici G. Effect on the peripheral nervous system of the short-term intravenous administration of paclitaxel in the rat. Neurotoxicol. 18 (1997) 137-145
10. Cavaletti G., Cavalletti E., Oggioni N., Sottani C., Minoia C., D'Incalci M., Zucchetti M., Marmiroli P., and Tredici G. Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration. Neurotoxicol 21 (2000) 389-393
11. Carre M., Andre N., Carles G., Borghi H., Brichese L., Briand C., and Braguer D. Tubulin is an inherent component of mitochondrial membranes that interacts with the voltage-dependent anion channel. J. Biol. Chem. 277 (2002) 33664-33669
12. Chen H., and Chan D.C. Critical dependence of neurons on mitochondrial dynamics. Curr. Opin. Cell. Biol. 18 (2006) 453-459
13. Chiechio S., Copani A., De Petris L., Morales M.E., Nicoletti F., and Gereau R.W. Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of l-acetylcarnitine. Mol. Pain 2 (2006) 20
14. Cliffer K.D., Siuciak J.A., Carson S.R., Radley H.E., Park J.S., Lewis D.R., Zlotchenko E., Nguyen T., Garcia K., Tonra J.R., Stambler N., Cedarbaum J.M., Bodine S.C., Lindsay R.M., and DiStefano P.S. Physiological characterization of taxol-induced large-fiber sensory neuropathy in the rat. Ann. Neurol. 43 (1998) 46-55
15. DeGrandis D., and Mirandi C. Acetyl-l-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomized, double-blind, placebo-controlled study. Drugs R&D 3 (2002) 223-231
16. Djouhri L., and Lawson S.N. A-beta-fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals. Brain Res. Rev. 46 (2004) 131-145
17. Dougherty P.M., Cata J.P., Cordella J.V., Burton A., and Weng H.R. Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain 109 (2004) 132-142
18. Evtodienko Y.V., Teplova V.V., Sidash S.S., Ichas F., and Mazat J.P. Microtubule-active drugs suppress the closure of the permeability transition pore in tumour mitochondria. FEBS Lett. 393 (1996) 86-88
19. Fernandez E., Pallini R., Lauretti L., Marchese E., Bozzini V., Sbriccoli A., and Rossi G.F. Levocarnitine acetyl promotes the regeneration of peripheral sensory axons and reduces the hypertrophy of axotomized spinal cord motoneurons in rats. Drugs Exp. Clin. Res. 17 (1991) 563-570
20. Flatters S.J.L., and Bennett G.J. Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy. Pain 109 (2004) 150-161
21. Flatters S.J.L., and Bennett G.J. Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: evidence for mitochondrial dysfunction. Pain 122 (2006) 247-257
22. Flatters S.J.L., Xiao W.H., and Bennett G.J. Acetyl-l-carnitine prevents and reduces paclitaxel-induced painful neuropathy. Neurosci. Lett. 397 (2006) 219-223
23. Friz I.B., and Yue K.T. Long-chain carnitine acyltransferase and the role of acylcarnitine derivatives in the catalytic increase of fatty acid oxidation induced by carnitine. J. Lipid Res. 58 (1963) 279-288
24. Ghelardini C., Galeotti N., Calvani M., Mosconi L., Nicolai R., and Bartolini A. Acetyl-l-carnitine induces muscarinic antinocieption in mice and rats. Neuropharmacol. 43 (2002) 1180-1187
25. Ghirardi O., Vertechy M., Vesci L., Canta A., Nicolini G., Galbiati S., Ciogli C., Quattrini G., Pisano C., Cundari S., and Rigamonti L.M. Chemotherapy-induced allodinia: neuroprotective effect of acetyl-l-carnitine. In Vivo 19 (2005) 631-637
26. Hart A.M., Terenghi G., Kellerth J.O., and Wiberg M. Sensory neuroprotection, mitochondrial preservation, and therapeutic potential of N-acetyl-cysteine after nerve injury. Neurosci. 125 (2004) 91-101
27. Hart A.M., Wilson A.D., Montovani C., Smith C., Johnson M., Terenghi G., and Youle M. Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy. AIDS 18 (2004) 1549-1560
28. Hart A.M., Wiberg M., Youle M., and Terenghi G. Systemic acetyl-l-carnitine eliminates sensory neuronal loss after peripheral axotomy: a new clinical approach in the management of peripheral nerve trauma. Exp. Brain Res. 145 (2002) 182-189
29. Heppelmann B., Gallar J., Trost B., Schmidt R.F., and Belmonte C. Three-dimensional reconstruction of scleral cold thermoreceptors of the cat eye. J. Comp. Neurol. 441 (2001) 148-154
30. Heppelmann B., Messlinger K., Neiss W.F., and Schmidt R.F. Mitochondria in fine afferent nerve fibres of the knee joint in the cat: a quantitative electron-microscopical examination. Cell Tissue Res. 275 (1994) 493-501
31. Higgins C.M., Jung C., and Xu Z. ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes. BMC Neurosci. 4 (2003) 16
32. Jimenez-Andrade J.M., Peters C.M., Mejia N.A., Ghilardi J.R., Kuskowski M.A., and Mantyh P.W. Sensory neurons and their supporting cells located in the trigeminal, thoracic and lumbar ganglia differentially express markers of injury following intravenous administration of paclitaxel in the rat. Neurosci. Lett. 405 (2006) 62-67
33. Kidd J.F., Pilkington M.F., Schell M.J., Fogarty K.E., Skepper J.N., Taylor C.W., and Thorn P. Paclitaxel affects cytosolic calcium signals by opening the mitochondrial permeability transition pore. J. Biol. Chem. 277 (2002) 6504-6510
34. Lauria G., Cornblath D.R., Johansson O., McArthur J.C., Mellgren S.I., Nolano M., Rosenberg N., and Sommer C. EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur. J. Neurol. 12 (2005) 747-758
35. Lauria G., Lombardi R., Borgna M., Penza P., Bianchi R., Savino C., Canta A., Nicolini G., Marmiroli P., and Cavaletti G. Intraepidermal nerve fiber density in rat foot pad: neuropathologic-neurophysiologic correlation. J. Peripher. Nerv. Syst. 10 (2005) 202-208
36. Lowitt S., Malone J.I., Salem A.F., Korthals J., and Benford S. Acetyl-l-carnitine corrects the altered peripheral nerve function of experimental diabetes. Metabolism 44 (1995) 677-680
37. Mansour H.H. Protective role of carnitine ester against radiation-induced oxidative stress in rats. Pharmacol. Res. 54 (2006) 165-171
38. Nogales E., Wolf S.G., Khan I.A., Luduena R.F., and Downing K.H. Structure of tubulin at 6.5 A and location of the taxol-binding site. Nature 375 (1995) 424-427
39. Pacifici L., Bellucci A., Piovesan P., Maccari F., Gorio A., and Ramacci M.T. Counteraction on experimentally induced diabetic neuropathy by levocarnitine acetyl. Int. J. Clin. Pharmacol. Res. 12 (1992) 231-236
40. Pastorino J.G., Snyder J.W., Serroni A., Hoek J.B., and Farber J.L. Cyclosporin and carnitine prevent the anoxic death of cultured hepatocytes by inhibiting the mitochondrial permeability transition. J. Biol. Chem. 268 (1993) 13791-13798
41. Patacchioli F.R., Amenta F., Ramacci M.T., Taglialatela G., Maccari S., and Angelucci L. Acetyl-l-carnitine reduces the age-dependent loss of glucocorticoid receptors in the rat hippocampus: an autoradiographic study. J. Neurosci. Res. 23 (1989) 462-466
42. Peters C.M., Jimenez-Andrade J.M., Jonas B.M., Sevcik M.A., Koewler N.J., Ghilardi J.R., Wong G.Y., and Mantyh P.W. Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells. Exp. Neurol. 203 (2007) 42-54
43. Piovesan P., Quatrini G., Pacifici L., Taglialatela G., and Angelucci L. Acetyl-l-carnitine restores choline acetyltransferase activity in the hippocampus of rats with partial unilateral fimbria-fornix transection. Int. J. Dev. Neurosci. 13 (1995) 13-19
44. Pisano C., Pratesi G., Laccabue D., Zunino F., Lo Giudice P., Bellucci A., Pacifici L., Camerini B., Vesci L., Castorina M., Cicuzza S., Tredici G., Marmiroli P., Nicolini G., Galbiati S., Calvani M., Carminati P., and Cavaletti G. Paclitaxel and cisplatin-induced neurotoxicity: a protective role of acetyl-l-carnitine. Clin. Cancer Res 9 (2003) 5756-5767
45. Polomano R.P., and Bennett G.J. Chemotherapy-evoked painful peripheral neuropathy. Pain Med. 2 (2001) 8-14
46. Polomano R., Clark U., Mannes A.J., and Bennett G.J. A painful peripheral neuropathy in rat produced by the chemotherapeutic drug, paclitaxel. Pain 94 (2001) 293-304
47. Rebouche C.J. Kinetics, pharmacokinetics, and regulation of l-carnitine and acetyl-l-carnitine metabolism. Ann. N.Y. Acad. Sci. 1033 (2004) 30-41
48. Sayed-Ahmed M.M., Mansour H.H., Gharib O.A., and Hafez H.F. Acetyl-l-carnitine modulates bleomycin-induced oxidative stress and energy depletion in lung tissues. J. Egypt. Natl. Cancer Inst. 16 (2004) 237-243
49. Siau C., and Bennett G.J. Dysregulation of neuronal calcium homeostasis in chemotherapy-evoked painful peripheral neuropathy. Anesth. Analg. 102 (2006) 1485-1490
50. Siau C., Xiao W.H., and Bennett G.J. Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of epidermal innervation and activation of Langerhans cells. Exp. Neurol 201 (2006) 507-514
51. Sima A.A., Calvani M., Mehra M., Amato A., and Acetyl-l-Carnitine Study Group. Acetyl-l-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care 28 (2005) 89-94
52. Sima A.A., Ristic H., Merry A., Kamijo M., Lattimer S.A., Stevens M.J., and Greene D.A. Primary preventive and secondary interventionary effects of acetyl-l-carnitine on diabetic neuropathy in the bio-breeding Worcester rat. J. Clin. Invest. 97 (1996) 1900-1907
53. Starkov A.A., Markova O.V., Mokhova E.N., Arrigoni-Martelli E., and Bobyleva V.A. Fatty acid-induced Ca(2+)-dependent uncoupling and activation of external pathway of NADH oxidation are coupled to cyclosporin A-sensitive mitochondrial permeability transition. Biochem. Mol. Biol. Int. 32 (1994) 1147-1155
54. Taglialatela G., Navarra D., Cruciani R., Ramacci M.T., Alema G.S., and Angelucci L. Acetyl-l-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats. Exp. Gerontol. 29 (1994) 55-66
55. Varbiro G., Veres B., Gallyas F., and Sumegi B. Direct effect of Taxol on free radical formation and mitochondrial permeability transition. Free Radic. Biol. Med. 31 (2001) 548-558
56. Virmani M.A., Biselli R., Spadoni A., Rossi S., Corsico N., Calvani M., Fattorossi A., De Simone C., and Arrigoni-Martelli E. Protective actions of l-carnitine and acetyl-l-carnitine on the neurotoxicity evoked by mitochondrial uncoupling or inhibitors. Pharmacol. Res. 32 (1995) 383-389
57. Virmani A., Gaetani F., and Binienda Z. Effects of metabolic modifiers such as carnitines, coenzyme Q10, and PUFAs against different forms of neurotoxic insults: metabolic inhibitors, MPTP, and methamphetamine. Ann. N.Y. Acad. Sci. 1053 (2005) 183-1891
58. Wang C., Sadovova N., Ali H.K., Duhart H.M., Fu X., Zou X., Patterson T.A., Binienda Z.K., Virmani A., Paule M.G., Slikker W., and Ali S.F. l-carnitine protects neurons from 1-methyl-4-phenylpyridinium-induced neuronal apoptosis in rat forebrain culture. Neurosci. 144 (2007) 46-55
59. Wilkinson K.D., Lee K.M., Deshpande S., Duerksen-Hughes P., Boss J.M., and Pohl J. The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Science 246 (1989) 670-673
60. Wilson A.D., Hart A., Brannstrom T., Wiberg M., and Terenghi G. Delayed acetyl-l-carnitine administration and its effect on sensory neuronal rescue after peripheral nerve injury. J. Plast. Reconstr. Aesthet. Surg. 60 (2007) 114-118
61. Wilson A.D., Hart A., Brannstrom T., Wiberg M., and Terenghi G. Primary sensory neuronal rescue with systemic acetyl-l-carnitine following peripheral axotomy. A dose-response analysis. Br. J. Plast. Surg. 56 (2003) 732-739
62. Xiao W.H., and Bennett G.J. Chemotherapy-evoked neuropathic pain: abnormal spontaneous discharge in A-fiber and C-fiber primary afferent neurons and its suppression by acetyl-l-carnitine. Pain (2007) 10.1016/j.pain.2007.06.01
63. Youle M., Osio M., and ALCAR Study Group. A double-blind, parallel-group, placebo-controlled, multicentre study of acetyl l-carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV-1 infection. HIV Med. 8 (2007) 241-250
64. Zanelli S.A., Solenski N.J., Rosenthal R.E., and Fiskum G. Mechanisms of ischemic neuroprotection by acetyl-l-carnitine. Ann. N.Y. Acad. Sci. 1053 (2005) 153-161
65. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16 (1983) 109-110