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Erschienen in: Journal of Neural Transmission 1/2012

01.01.2012 | Basic Neurosciences, Genetics and Immunology - Original Article

The effect of selegiline on total scavenger capacity and liver fat content: a preliminary study in an animal model

verfasst von: Gabor Bekesi, Zsolt Tulassay, Gabriella Lengyel, Zsuzsa Schaff, Dezso Szombath, Julia Stark, Istvan Marczell, Peter Nagy-Repas, Ildiko Adler, Elek Dinya, Karoly Racz, Kalman Magyar

Erschienen in: Journal of Neural Transmission | Ausgabe 1/2012

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Abstract

Selegiline is a selective irreversible inhibitor of the B-type of monoamine oxidase (MAO-B). The spectrum of its pharmacological activity is wide, possesses antioxidant, antiapoptotic and neuroprotective properties and, additionally, we found it is effective on the total scavenger capacity (TSC), and the regulation of fat content in rat liver kept on lipid-rich diet. Our aim was to clarify whether the oral treatment with selegiline is protective on oxidative damage of Sprague–Dawley adult rats in vivo. Four groups of rats (five animals in a group) were examined: (1) lipid-rich diet, (2) normal rat food, (3) lipid-rich diet + selegiline and (4) normal rat food + selegiline. Selegiline solution (2.5 µg/ml) was supplied with the drinking water, which was freely available for the animals. Regarding the drinking habit of the rats (20–30 ml/day), the daily dose was roughly equal with that used in the human therapy (5–10 mg/day). TSC was determined both at the beginning (0 day) and at the end of the study (28 days), when the blood samples were taken for chemiluminometric assay. Fat content of the liver was determined in the freshly frozen tissue by Sudan staining. TSC was increased in both the selegiline-treated groups. Selegiline treatment prevented the increase of liver fat in the group fed with lipid-rich diet. Our results led us to the conclusion that prolonged selegiline administration can raise the antioxidant capacity of the animals and prevents the accumulation of fat in their livers.
Literatur
Zurück zum Zitat Adolfsson R, Gottfries CG, Oreland L, Wiberg A, Winblad B (1980) Increased activity of brain and platelet monoamine oxidase in dementia of Alzheimer type. Life Sci 27:1029–1034PubMedCrossRef Adolfsson R, Gottfries CG, Oreland L, Wiberg A, Winblad B (1980) Increased activity of brain and platelet monoamine oxidase in dementia of Alzheimer type. Life Sci 27:1029–1034PubMedCrossRef
Zurück zum Zitat Birkmayer W, Riederer P, Youdim MBH, Linauer W (1975) Potentiation of anti akinetic effect after l-dopa treatment by an inhibitor of MAO-B, deprenil. J Neural Trans 36:303–326CrossRef Birkmayer W, Riederer P, Youdim MBH, Linauer W (1975) Potentiation of anti akinetic effect after l-dopa treatment by an inhibitor of MAO-B, deprenil. J Neural Trans 36:303–326CrossRef
Zurück zum Zitat Birkmayer W, Riederer P, Ambrozi L, Youdim MBH (1977) Implications of combined treatment with madopar and l-deprenil in Parkinsons-disease—long-term study. Lancet 1:439–443PubMedCrossRef Birkmayer W, Riederer P, Ambrozi L, Youdim MBH (1977) Implications of combined treatment with madopar and l-deprenil in Parkinsons-disease—long-term study. Lancet 1:439–443PubMedCrossRef
Zurück zum Zitat Birkmayer W, Knoll J, Riederer P, Youdim MB (1983) (−)-Deprenyl leads to prolongation of l-dopa efficacy in Parkinson’s disease. Mod Probl Pharmacopsychiatry 19:170–176PubMed Birkmayer W, Knoll J, Riederer P, Youdim MB (1983) (−)-Deprenyl leads to prolongation of l-dopa efficacy in Parkinson’s disease. Mod Probl Pharmacopsychiatry 19:170–176PubMed
Zurück zum Zitat Birkmayer W, Knoll J, Riederer P, Youdim MBH, Hars V, Marton J (1985) Increased life expectancy resulting from addition of l-deprenyl to madopar treatment in Parkinsons-disease—a longterm study. J Neural Trans 64:113–127CrossRef Birkmayer W, Knoll J, Riederer P, Youdim MBH, Hars V, Marton J (1985) Increased life expectancy resulting from addition of l-deprenyl to madopar treatment in Parkinsons-disease—a longterm study. J Neural Trans 64:113–127CrossRef
Zurück zum Zitat Blazovics A, Kovacs A, Lugasi A, Hagymasi K, Biro L, Feher J (1999) Antioxidant defense in erythrocytes and plasma of patients with active and quiescent Crohn disease and ulcerative colitis: a chemiluminescent study. Clin Chem 45:895–896PubMed Blazovics A, Kovacs A, Lugasi A, Hagymasi K, Biro L, Feher J (1999) Antioxidant defense in erythrocytes and plasma of patients with active and quiescent Crohn disease and ulcerative colitis: a chemiluminescent study. Clin Chem 45:895–896PubMed
Zurück zum Zitat Braillon A, Capron JP, Hervé MA, Degott C, Quenum C (1985) Liver in obesity. Gut 26:133–139PubMedCrossRef Braillon A, Capron JP, Hervé MA, Degott C, Quenum C (1985) Liver in obesity. Gut 26:133–139PubMedCrossRef
Zurück zum Zitat Carrillo MC, Kanai S, Nokubo M, Kitani K (1991) (−) deprenyl induces activities of both superoxide dismutase and catalase but not of glutathione peroxidase in the striatum of young male rats. Life Sci 48:517–521PubMedCrossRef Carrillo MC, Kanai S, Nokubo M, Kitani K (1991) (−) deprenyl induces activities of both superoxide dismutase and catalase but not of glutathione peroxidase in the striatum of young male rats. Life Sci 48:517–521PubMedCrossRef
Zurück zum Zitat Day CP, James OF (1998) Steatohepatitis: a tale of two “hits”? Gastroenterology 114:842–845PubMedCrossRef Day CP, James OF (1998) Steatohepatitis: a tale of two “hits”? Gastroenterology 114:842–845PubMedCrossRef
Zurück zum Zitat Fromenty B, Pessayre D (1995) Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity. Pharmacol Ther 67:101–154PubMedCrossRef Fromenty B, Pessayre D (1995) Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity. Pharmacol Ther 67:101–154PubMedCrossRef
Zurück zum Zitat Glover V, Gibb C, Sandler M (1986) The role of MAO in MPTP toxicity—a review. J Neural Transm Suppl 20:65–76PubMed Glover V, Gibb C, Sandler M (1986) The role of MAO in MPTP toxicity—a review. J Neural Transm Suppl 20:65–76PubMed
Zurück zum Zitat Javitch JA, D’Amato RJ, Strittmatter SM, Snyder SH (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1, 2, 3, 6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci USA 82:2173–2177PubMedCrossRef Javitch JA, D’Amato RJ, Strittmatter SM, Snyder SH (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1, 2, 3, 6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci USA 82:2173–2177PubMedCrossRef
Zurück zum Zitat Jenei V, Zor K, Magyar K, Jakus J (2005) Increased cell–cell adhesion, a novel effect of R-(−)-deprenyl. J Neural Transm 112:1433–1445PubMedCrossRef Jenei V, Zor K, Magyar K, Jakus J (2005) Increased cell–cell adhesion, a novel effect of R-(−)-deprenyl. J Neural Transm 112:1433–1445PubMedCrossRef
Zurück zum Zitat Knoll J, Magyar K (1972) Some puzzling pharmacological effects of monoamine oxidase inhibitors. Adv Biochem Psychopharmacol 5:393–408PubMed Knoll J, Magyar K (1972) Some puzzling pharmacological effects of monoamine oxidase inhibitors. Adv Biochem Psychopharmacol 5:393–408PubMed
Zurück zum Zitat Knoll J, Ecseri Z, Kelemen K, Nievel J, Knoll B (1965) Phenylisopropylmethylpropinylamine (E-250), a new spectrum psychic energizer. Arch Int Pharmacodyn Ther 155:154–164PubMed Knoll J, Ecseri Z, Kelemen K, Nievel J, Knoll B (1965) Phenylisopropylmethylpropinylamine (E-250), a new spectrum psychic energizer. Arch Int Pharmacodyn Ther 155:154–164PubMed
Zurück zum Zitat Magyar K (1993) Pharmacology of monoamine oxidase type-B inhibitors. In: Szelényi I (ed) Inhibitors of Monoamine Oxidase B. Pharmacology and clinical use in neurodegenerative disorders. Birkhauser Verlag, Basel, pp 125–143 Magyar K (1993) Pharmacology of monoamine oxidase type-B inhibitors. In: Szelényi I (ed) Inhibitors of Monoamine Oxidase B. Pharmacology and clinical use in neurodegenerative disorders. Birkhauser Verlag, Basel, pp 125–143
Zurück zum Zitat Magyar K, Szende B (2004) (−)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and anti-apoptotic properties. Neurotoxicology 25:233–242PubMedCrossRef Magyar K, Szende B (2004) (−)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and anti-apoptotic properties. Neurotoxicology 25:233–242PubMedCrossRef
Zurück zum Zitat Magyar K, Vizi ES, Ecseri Z, Knoll J (1967) Comparative pharmacological analysis of the optical isomers of phenyl-isopropyl-methyl-propinylamine (E-250). Acta Physiol Acad Sci Hung 32:377–387PubMed Magyar K, Vizi ES, Ecseri Z, Knoll J (1967) Comparative pharmacological analysis of the optical isomers of phenyl-isopropyl-methyl-propinylamine (E-250). Acta Physiol Acad Sci Hung 32:377–387PubMed
Zurück zum Zitat Magyar K, Szende B, Lengyel J, Tekes K (1996) The pharmacology of B-type selective monoamine oxidase inhibitors; milestones in (−)-deprenyl research. J Neural Transm Suppl 48:29–43PubMed Magyar K, Szende B, Lengyel J, Tekes K (1996) The pharmacology of B-type selective monoamine oxidase inhibitors; milestones in (−)-deprenyl research. J Neural Transm Suppl 48:29–43PubMed
Zurück zum Zitat Magyar K, Szende B, Jenei V, Tabi T, Palfi M, Szoko E (2010) R-deprenyl: pharmacological spectrum of its activity. Neurochem Res 35:1922–1932PubMedCrossRef Magyar K, Szende B, Jenei V, Tabi T, Palfi M, Szoko E (2010) R-deprenyl: pharmacological spectrum of its activity. Neurochem Res 35:1922–1932PubMedCrossRef
Zurück zum Zitat Milgram NW, Racine RJ, Nellis P, Mendonca A, Ivy GO (1990) Maintenance on l-deprenyl prolongs life in aged male rats. Life Sci 47:415–420PubMedCrossRef Milgram NW, Racine RJ, Nellis P, Mendonca A, Ivy GO (1990) Maintenance on l-deprenyl prolongs life in aged male rats. Life Sci 47:415–420PubMedCrossRef
Zurück zum Zitat Olanow CW, Hauser RA, Gauger L, Malapira T, Koller W, Hubble J, Bushenbark K, Lilienfeld D, Esterlitz J (1995) The effect of deprenyl and levodopa on the progression of Parkinson’s disease. Ann Neurol 38:771–777PubMedCrossRef Olanow CW, Hauser RA, Gauger L, Malapira T, Koller W, Hubble J, Bushenbark K, Lilienfeld D, Esterlitz J (1995) The effect of deprenyl and levodopa on the progression of Parkinson’s disease. Ann Neurol 38:771–777PubMedCrossRef
Zurück zum Zitat Ricci A, Mancini M, Strocchi P, Bongrani S, Bronzetti E (1992) Deficits in cholinergic neurotransmission markers induced by ethylcholine mustard aziridinium (AF64A) in the rat hippocampus: sensitivity to treatment with the monoamine oxidase-B inhibitor l-deprenyl. Drugs Exp Clin Res 18:163–171PubMed Ricci A, Mancini M, Strocchi P, Bongrani S, Bronzetti E (1992) Deficits in cholinergic neurotransmission markers induced by ethylcholine mustard aziridinium (AF64A) in the rat hippocampus: sensitivity to treatment with the monoamine oxidase-B inhibitor l-deprenyl. Drugs Exp Clin Res 18:163–171PubMed
Zurück zum Zitat Riederer P, Youdim MB (1986) Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with l-deprenyl. J Neurochem 46:1359–1365PubMedCrossRef Riederer P, Youdim MB (1986) Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with l-deprenyl. J Neurochem 46:1359–1365PubMedCrossRef
Zurück zum Zitat Ross SB (1976) Long-term effects of N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurones in the rat brain and heart. Br J Pharmacol 58:521–527PubMed Ross SB (1976) Long-term effects of N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurones in the rat brain and heart. Br J Pharmacol 58:521–527PubMed
Zurück zum Zitat Ross SB, Renyl AL (1976) On the long-lasting inhibitory effect of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP 4) on the active uptake of noradrenaline. J Pharm Pharmacol 28:458–459PubMedCrossRef Ross SB, Renyl AL (1976) On the long-lasting inhibitory effect of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP 4) on the active uptake of noradrenaline. J Pharm Pharmacol 28:458–459PubMedCrossRef
Zurück zum Zitat Tatton WG, Chalmers-Redman RM (1996) Modulation of gene expression rather than monoamine oxidase inhibition: (−)-deprenyl-related compounds in controlling neurodegeneration. Neurology 47:S171–S183PubMed Tatton WG, Chalmers-Redman RM (1996) Modulation of gene expression rather than monoamine oxidase inhibition: (−)-deprenyl-related compounds in controlling neurodegeneration. Neurology 47:S171–S183PubMed
Zurück zum Zitat Tatton WG, Ju WY, Holland DP, Tai C, Kwan M (1994) (−)-Deprenyl reduces PC12 cell apoptosis by inducing new protein synthesis. J Neurochem 63:1572–1575PubMedCrossRef Tatton WG, Ju WY, Holland DP, Tai C, Kwan M (1994) (−)-Deprenyl reduces PC12 cell apoptosis by inducing new protein synthesis. J Neurochem 63:1572–1575PubMedCrossRef
Zurück zum Zitat Tatton WG, Wadia JS, Ju WY, Chalmers-Redman RM, Tatton NA (1996) (−)-Deprenyl reduces neuronal apoptosis and facilitates neuronal outgrowth by altering protein synthesis without inhibiting monoamine oxidase. J Neural Transm Suppl 48:45–59PubMed Tatton WG, Wadia JS, Ju WY, Chalmers-Redman RM, Tatton NA (1996) (−)-Deprenyl reduces neuronal apoptosis and facilitates neuronal outgrowth by altering protein synthesis without inhibiting monoamine oxidase. J Neural Transm Suppl 48:45–59PubMed
Zurück zum Zitat Tatton WG, Chalmers-Redman RM, Elstner M, Leesch W, Jagodzinski FB, Stupak DP, Sugrue MM, Tatton NA (2000) Glyceraldehyde-3-phosphate dehydrogenase in neurodegeneration and apoptosis signaling. J Neural Transm Suppl (60):77–100 Tatton WG, Chalmers-Redman RM, Elstner M, Leesch W, Jagodzinski FB, Stupak DP, Sugrue MM, Tatton NA (2000) Glyceraldehyde-3-phosphate dehydrogenase in neurodegeneration and apoptosis signaling. J Neural Transm Suppl (60):77–100
Zurück zum Zitat Tatton WG, Chalmers-Redman RM, Ju WJ, Mammen M, Carlile GW, Pong AW, Tatton NA (2002) Propargylamines induce antiapoptotic new protein synthesis in serum- and nerve growth factor (NGF)-withdrawn, NGF-differentiated PC-12 cells. J Pharmacol Exp Ther 301:753–764PubMedCrossRef Tatton WG, Chalmers-Redman RM, Ju WJ, Mammen M, Carlile GW, Pong AW, Tatton NA (2002) Propargylamines induce antiapoptotic new protein synthesis in serum- and nerve growth factor (NGF)-withdrawn, NGF-differentiated PC-12 cells. J Pharmacol Exp Ther 301:753–764PubMedCrossRef
Zurück zum Zitat Thyagarajan S, Meites J, Quadri SK (1995) Deprenyl reinitiates estrous cycles, reduces serum prolactin, and decreases the incidence of mammary and pituitary tumors in old acyclic rats. Endocrinology 136:1103–1110PubMedCrossRef Thyagarajan S, Meites J, Quadri SK (1995) Deprenyl reinitiates estrous cycles, reduces serum prolactin, and decreases the incidence of mammary and pituitary tumors in old acyclic rats. Endocrinology 136:1103–1110PubMedCrossRef
Zurück zum Zitat Youdim MB, Weinstock M (2002) Novel neuroprotective anti-Alzheimer drugs with anti-depressant activity derived from the anti-Parkinson drug, rasagiline. Mech Ageing Dev 123:1081–1086PubMedCrossRef Youdim MB, Weinstock M (2002) Novel neuroprotective anti-Alzheimer drugs with anti-depressant activity derived from the anti-Parkinson drug, rasagiline. Mech Ageing Dev 123:1081–1086PubMedCrossRef
Zurück zum Zitat Youdim MB, Wadia A, Tatton W, Weinstock M (2001) The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo. Ann NY Acad Sci 939:450–458PubMedCrossRef Youdim MB, Wadia A, Tatton W, Weinstock M (2001) The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo. Ann NY Acad Sci 939:450–458PubMedCrossRef
Zurück zum Zitat Zangar RC, Novak RF (1997) Effects of fatty acids and ketone bodies on cytochromes P450 2B, 4A, and 2E1 expression in primary cultured rat hepatocytes. Arch Biochem Biophys 337:217–224PubMedCrossRef Zangar RC, Novak RF (1997) Effects of fatty acids and ketone bodies on cytochromes P450 2B, 4A, and 2E1 expression in primary cultured rat hepatocytes. Arch Biochem Biophys 337:217–224PubMedCrossRef
Metadaten
Titel
The effect of selegiline on total scavenger capacity and liver fat content: a preliminary study in an animal model
verfasst von
Gabor Bekesi
Zsolt Tulassay
Gabriella Lengyel
Zsuzsa Schaff
Dezso Szombath
Julia Stark
Istvan Marczell
Peter Nagy-Repas
Ildiko Adler
Elek Dinya
Karoly Racz
Kalman Magyar
Publikationsdatum
01.01.2012
Verlag
Springer Vienna
Erschienen in
Journal of Neural Transmission / Ausgabe 1/2012
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI
https://doi.org/10.1007/s00702-011-0666-x

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