title: Antitumor effect of L-deprenyl in rats with carcinogen-induced mammary tumors.
abstract: Deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, has a wide range of pharmacological properties that are beneficial therapeutically in the treatment of human neurodegenerative diseases. Recent studies have demonstrated that deprenyl possesses a neuroprotective function that is not dependent on its MAO-B inhibitory activity. The focus of the present study was to investigate whether prolonged treatment of young Sprague-Dawley female rats with deprenyl before and after 9,10-dimethyl-1,2-benzanthracene (DMBA) administration would inhibit the development of mammary tumors by exerting a neuroprotective effect on the tuberoinfundibular dopaminergic (TIDA) neurons in the medial basal hypothalamus (MBH). For this purpose, the concentrations of catecholamines, indoleamine and their metabolites were measured in the MBH by high-performance liquid chromatography (HPLC) at the end of the treatment period. Female Sprague-Dawley rats (28-29 days old) were treated intraperitoneally with saline, or 0.25 or 2.5 mg of deprenyl/kg b.w. daily for 4 weeks prior to the administration of DMBA. Following the administration of DMBA, the rats were treated with saline or deprenyl daily for 27 weeks. At the end of the treatment period, there was a significant reduction in the tumor incidence and tumor number in rats that received 2.5 mg/kg deprenyl before and after the administration of DMBA and also in rats that were treated with 2.5 mg/ kg deprenyl following DMBA. There also was a significant decrease in tumor number in rats that were treated with 0.25 mg/kg deprenyl during the entire treatment period of 31 weeks. Body weight increased throughout the treatment period with no significant differences between the groups. Treatment of rats with 2.5 mg of deprenyl following the administration of DMBA and also during the entire treatment period resulted in a significant decrease in the concentrations of the metabolites of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in the MBH, but there were no significant alterations in the concentrations of NE, DA and 5-HT in the MBH. These results suggest that the administration of deprenyl blocked the development of mammary tumors in part by inhibiting the metabolism of catecholamines and indoleamine and possibly by conferring a neuroprotective effect on the TIDA neurons in the MBH, especially at 0.25 mg/kg of deprenyl.
authors.affiliation: Department of Neurobiology and Anatomy, University of Rochester School of Medicine, NY 14642, USA. Srinivasan_ThyagaRajan@urmc.rochester.edu
authors.forename: S
authors.initials: S
authors.lastname: ThyagaRajan
authors.forename: S Y
authors.initials: SY
authors.lastname: Felten
authors.forename: D L
authors.initials: DL
authors.lastname: Felten
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000008:administration & dosage / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D012642:Selegiline; D012701:Serotonin; D015127:9,10-Dimethyl-1,2-benzanthracene; D004298:Dopamine; D009638:Norepinephrine