title: Hypothalamic energy metabolism is impaired by doxorubicin independently of inflammation in non-tumour-bearing rats.
abstract: We sought to explore the effects of doxorubicin on inflammatory profiles and energy metabolism in the hypothalamus of rats. To investigate these effects, we formed two groups: a control (C) group and a Doxorubicin (DOXO) group. Sixteen rats were randomly assigned to either the control (C) or DOXO groups. The hypothalamus was collected. The levels of interleukin (IL)-1β, IL-6, IL-10, TNF-α and energy metabolism (malate dehydrogenase, complex I and III activities) were analysed in the hypothalamus. The DOXO group exhibited a decreased body weight (p < 0.01). Hypothalamic malate dehydrogenase activity was reduced when compared with control (p < 0.05). In addition, pro-inflammatory cytokine levels were unchanged. Therefore, our results demonstrate that doxorubicin leads to an impairment of \hypothalamic energy metabolism, but do not affect the inflammatory pathway. SIGNIFICANCE PARAGRAPH: The hypothalamus is a central organ that regulates a great number of functions, such as food intake, temperature and energy expenditure, among others. Doxorubicin can lead to deep anorexia and metabolic chaos; thus, we observed the effect of this chemotherapeutic drug on the inflammation and metabolism in rats after the administration of doxorubicin in order to understand the central effect in the hypothalamus. Drug treatment by doxorubicin is used as a cancer therapy; however the use of this drug may cause harmful alterations to the metabolism. Thus, further investigations are needed on the impact of drug therapy over the long term.
authors.affiliation: Exercise and Immunometabolism Research Group, Department of Physical Education, Universidade Estadual Paulista (UNESP), Presidente Prudente, SP, Brazil.
authors.forename: Barbara M M
authors.initials: BM
authors.lastname: Antunes
authors.affiliation: Exercise and Immunometabolism Research Group, Department of Physical Education, Universidade Estadual Paulista (UNESP), Presidente Prudente, SP, Brazil.
authors.forename: Fabio Santos
authors.initials: FS
authors.lastname: Lira
authors.affiliation: Departamento de Clínica Médica, Faculdade de Ciências Médicas (FCM), Universidade do Estadual de Campinas, Campinas, São Paulo, Brazil.
authors.forename: Gustavo Duarte
authors.initials: GD
authors.lastname: Pimentel
authors.affiliation: Immunometabolism Research Group, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: José Cesar
authors.initials: JC
authors.lastname: Rosa Neto
authors.affiliation: Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, Limeira, São Paulo, Brazil.
authors.forename: Andrea Maculano
authors.initials: AM
authors.lastname: Esteves
authors.affiliation: Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Lila Missae
authors.initials: LM
authors.lastname: Oyama
authors.affiliation: Laboratório de Fisiologia e Bioquímica do Exercício, Unidade de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil.
authors.forename: Cláudio Teodoro
authors.initials: CT
authors.lastname: de Souza
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Santa Catarina, Brazil.
authors.forename: Cinara Ludvig
authors.initials: CL
authors.lastname: Gonçalves
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Santa Catarina, Brazil.
authors.forename: Emilio Luiz
authors.initials: EL
authors.lastname: Streck
authors.affiliation: Faculty of Physical Education, University of Campinas (FEF-UNICAMP), São Paulo, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Rodrigues
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, Santos, São Paulo, Brazil.
authors.forename: Ronaldo Vagner
authors.initials: RV
authors.lastname: dos Santos
authors.affiliation: Sport Psychology Laboratory, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Marco Túlio
authors.initials: MT
authors.lastname: de Mello
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D007031:Hypothalamus / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; D004317:Doxorubicin; D008291:Malate Dehydrogenase
keywords: cancer; doxorubicin; energy metabolism; hypothalamus; inflammation