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Chronic rapamycin treatment decreases hepatic IL-6 protein, but increases autophagy markers as a protective effect against the overtraining-induced tissue damage.
Pinto, Ana P; da Rocha, Alisson L; Marafon, Bruno B; Nogueira, Jonatas E; Branco, Luiz G S; Pauli, José R; de Moura, Leandro P; Cintra, Dennys E; Ropelle, Eduardo R; da Silva, Adelino S R.
Afiliação
  • Pinto AP; Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
  • da Rocha AL; Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
  • Marafon BB; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, Brazil.
  • Nogueira JE; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, Brazil.
  • Branco LGS; Department of Basic and Oral Biology, Dental School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
  • Pauli JR; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, Brazil.
  • de Moura LP; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, Brazil.
  • Cintra DE; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, Brazil.
  • Ropelle ER; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, Brazil.
  • da Silva ASR; Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
Clin Exp Pharmacol Physiol ; 49(8): 893-902, 2022 08.
Article em En | MEDLINE | ID: mdl-35637552
Regular endurance exercise is a non-pharmacological strategy to protect the liver against diseases. Conversely, exercise may be harmful when excessive, the so-called overtraining. As expected, mice who underwent an overtraining protocol presented higher levels of proinflammatory cytokines in the serum and liver. Based on the relationship among overtraining, inflammation and mammalian target of rapamycin complex 1 (mTORC1) upregulation, the present study verified if animals submitted to an overtraining protocol, but with inhibition of the mTOR pathway via rapamycin injections could mitigate the liver and serum inflammation. Once autophagy can be linked to the improvement of hepatic dysfunction, we also investigated if the inhibition of mTORC1 by rapamycin can improve hepatic autophagy. The animals were randomized into four groups: control (CT; sedentary mice), overtraining by downhill running (OT; mice submitted to the downhill running-based overtraining protocol), overtraining by downhill running with chronic administration of rapamycin (OT/Rapa; mice submitted to the downhill running-based overtraining protocol with intraperitoneal injections of rapamycin) and aerobic (AER; submitted to aerobic training protocol). The serum and liver of the animals were used for biochemical analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunoblotting. The main results are (a) OT and OT/Rapa protocols decreased the performance; (b) the protein levels of interleukin 6 (IL-6) were higher for the OT group; the OT/Rapa group reduced the autophagic genes, increased the microtubule-associated protein light chain 3 II/I (LC3II/LC3I) protein ratio and decreased the sequestosome 1 (SQSTM1) protein. In conclusion, rapamycin appears efficiently to increase the autophagy proteins and decrease IL-6 protein in the liver of overtraining mice.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-6 / Sirolimo Limite: Animals Idioma: En Revista: Clin Exp Pharmacol Physiol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Austrália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-6 / Sirolimo Limite: Animals Idioma: En Revista: Clin Exp Pharmacol Physiol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Austrália