title: Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.
abstract: Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage.
authors: Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Avenida Universitária, 1105, Criciúma, SC 88806-000, Brazil.
authors: Cinara L
authors: CL
authors: Gonçalves
authors: Gislaine T
authors: GT
authors: Rezin
authors: Gabriela K
authors: GK
authors: Ferreira
authors: Isabela C
authors: IC
authors: Jeremias
authors: Mariane R
authors: MR
authors: Cardoso
authors: Samira S
authors: SS
authors: Valvassori
authors: Bruna J P
authors: BJ
authors: Munhoz
authors: Gabriela D
authors: GD
authors: Borges
authors: Bruno N
authors: BN
authors: Bristot
authors: Daniela D
authors: DD
authors: Leffa
authors: Vanessa M
authors: VM
authors: Andrade
authors: João
authors: J
authors: Quevedo
authors: Emilio L
authors: EL
authors: Streck
mesh_terms: D000367:Age Factors; D000662:Amphetamines / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D020552:Comet Assay; D004247:DNA / Q000097:blood / Q000235:genetics; D004249:DNA Damage; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000662:Amphetamines; D004247:DNA; C026013:fenproporex
references: Int J Dev Neurosci. 2011 Dec;29(8):937-42
references: 21723935
references: Addict Biol. 2010 Jan;15(1):96-9
references: 19878142
references: Braz J Med Biol Res. 1996 Aug;29(8):1025-30
references: 9181085
references: J Psychiatry Neurosci. 2008 Nov;33(6):516-24
references: 18982174
references: Ann Intern Med. 1993 Oct 1;119(7 Pt 2):707-13
references: 8363202
references: Free Radic Biol Med. 1994 Jan;16(1):99-109
references: 8300000
references: Behav Pharmacol. 2007 Sep;18(5-6):471-81
references: 17762515
references: J Psychiatr Res. 2010 Oct;44(14):903-9
references: 20334877
references: J Nutr Biochem. 2006 Mar;17(3):145-56
references: 16426829
references: Mol Biotechnol. 2004 Mar;26(3):249-61
references: 15004294
references: Mutat Res. 2001 May;488(2):151-69
references: 11344042
references: Mutagenesis. 2006 Jul;21(4):219-24
references: 16775218
references: Nature. 2000 Apr 6;404(6778):635-43
references: 10766250
references: Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1140-9
references: 16115017
references: Metab Brain Dis. 2012 Dec;27(4):453-8
references: 22832793
references: Neuroreport. 1998 Sep 14;9(13):2989-93
references: 9804303
references: Hum Exp Toxicol. 2010 Mar;29(3):187-97
references: 20051455
references: Mutat Res. 2006 Jun 16;605(1-2):78-86
references: 16697250
references: Appetite. 2006 Jan;46(1):6-10
references: 16229924
references: Obes Rev. 2003 Feb;4(1):25-42
references: 12608525
references: Mutagenesis. 2008 May;23(3):143-51
references: 18283046
references: Can J Physiol Pharmacol. 1986 Jun;64(6):724-8
references: 3756624
references: Hum Exp Toxicol. 2005 Aug;24(8):403-8
references: 16138731
references: J Chromatogr B Biomed Sci Appl. 2000 Jan 28;738(1):107-18
references: 10778932
references: J Gen Intern Med. 2009 Mar;24(3):430-3
references: 19096898
references: Brain Res. 2006 Jun 30;1097(1):224-9
references: 16730669
references: Pharmacol Res. 2009 Jan;59(1):57-61
references: 18973814
references: Nature. 2000 Apr 6;404(6778):661-71
references: 10766253
references: Exp Cell Res. 1988 Mar;175(1):184-91
references: 3345800
references: Mutagenesis. 2008 May;23(3):153-62
references: 18252696
references: Mutagenesis. 2008 May;23(3):191-205
references: 18326867
references: Mutat Res. 2000 Nov 20;455(1-2):155-66
references: 11113474
references: J Anal Toxicol. 1999 May-Jun;23(3):187-94
references: 10369328
references: Biochem Soc Trans. 1996 Nov;24(4):1023-7
references: 8968505
references: Nature. 2000 Apr 6;404(6778):672-7
references: 10766254
references: J Forensic Sci. 2006 Mar;51(2):407-10
references: 16566781
references: J Psychiatry Neurosci. 2006 Sep;31(5):326-32
references: 16951735
references: Obes Surg. 2003 Jun;13(3):329-30
references: 12852397
references: Nitric Oxide. 1999 Jun;3(3):235-43
references: 10442855
references: Mutagenesis. 2008 May;23(3):183-90
references: 18256034
references: Am J Physiol Cell Physiol. 2007 Feb;292(2):C670-86
references: 17020935
references: Environ Mol Mutagen. 2000;35(3):206-21
references: 10737956