Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats
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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.
KeywordsFenproporex DNA damage Peripheral blood Rats
This research was supported by grants from Programa de Pós-graduação em Ciências da Saúde—Universidade do Extremo Sul Catarinense (UNESC), Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina NENASC project, Conselho Nacional de Desenvolvimento Científico e Tecnológico (PRONEX—FAPESC/CNPq), and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT).
Conflict of interest
The authors declare no conflict of interest.
- 2.World Health Organization (2006) Obesity and overweight. Media Center, Fact Sheet N_311Google Scholar
- 17.Rezin GT, Scaini G, Ferreira GK, Cardoso MR, Gonçalves CL, Constantino LS, Deroza PF, Ghedim FV, Valvassori SS, Resende WR, Quevedo J, Zugno AI, Streck EL (2012) Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex. Metab Brain Dis 27:453–458PubMedCrossRefGoogle Scholar
- 31.Andreazza AC, Kauer-Sant’Anna M, Frey BN, Stertz L, Zanotto C, Ribeiro L, Giasson K, Valvassori SS, Réus GZ, Salvador M, Quevedo J, Gonçalves CA, Kapczinski F (2008) Effects of mood stabilizers on DNA damage in an animal model of mania. J Psychiatry Neurosci 33:516–524PubMedCentralPubMedGoogle Scholar
- 35.Pereira P, Gianesini J, da Silva Barbosa C, Cassol GF, Von Borowski RG, Kahl VF, Cappelari SE, Picada JN (2009) Neurobehavioral and genotoxic parameters of duloxetine in mice using the inhibitory avoidance task and comet assay as experimental models. Pharmacol Res 59(1):57–61PubMedCrossRefGoogle Scholar
- 43.Frenzilli G, Ferrucci M, Giorgi FS, Blandini F, Nigro M, Ruggieri S, Murri L, Paparelli A, Fornai F (2007) DNA fragmentation and oxidative stress in the hippocampal formation: a bridge between 3,4-methylenedioxymethamphetamine (ecstasy) intake and long-lasting behavioral alterations. Behav Pharmacol 18(5–6):471–481PubMedCrossRefGoogle Scholar