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Mitochondrial dysfunction and cardiac ischemia/reperfusion injury are attenuated by nandrolone: Role of JAK-STAT3 pathway.
Domingos, Ainá E; Seara, Fernando A C; Oliveira, Dahienne F; Maciel, Leonardo; Barbosa, Raiana A Q; Barcellos, Luciane C; Pinto, Verônica S; Fortunato, Rodrigo S; Nascimento, Jose H M.
Afiliação
  • Domingos AE; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Seara FAC; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto de Ciências Biológicas e da Saúde, Universidade Federal Rural do Rio de Janeiro, Seropédica, Brazil; Programa de Pós-graduação Multicêntrico em Ciências Fisiológicas, Sociedade Brasi
  • Oliveira DF; Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Maciel L; Campus Professor Geraldo Cidade, Universidade Federal do Rio de Janeiro, Duque de Caxias, Brazil.
  • Barbosa RAQ; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Barcellos LC; Escola de Educação Física e Desportos, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Pinto VS; Escola de Educação Física e Desportos, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Fortunato RS; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Nascimento JHM; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: jhmn@biof.ufrj.br.
Steroids ; 197: 109247, 2023 09.
Article em En | MEDLINE | ID: mdl-37149242
ABSTRACT

AIM:

To investigate the effect of acute treatment with the anabolic steroid (AS) nandrolone decanoate in mitochondrial homeostasis and JAK-STAT3 signaling during the progression of cardiac ischemia/reperfusion injury (IR).

METHODS:

Male Wistar rats (2 months old) were randomly allocated into four experimental groups Control (CTRL), IR, AS, and AS + AG490. All animals were euthanized 3 days after a single intramuscular injection of nandrolone at 10 mg/kg (AS and AS + AG490 groups) or vehicle (CTRL and IR groups). Baseline mRNA expression of antioxidant enzymes superoxide dismutase (SOD) 1 and 2, glutathione peroxidase, catalase, and myosin heavy chain (MHC) α and ß were compared between CTRL and AS groups. Isolated hearts were submitted to ex vivo ischemia and reperfusion, except for hearts from the CTRL group. Before the IR protocol, the JAK-STAT3 inhibitor AG490 was perfused in hearts from the AS + AG490 group. Heart samples were collected during reperfusion to investigate the effects on mitochondrial function. Results Antioxidant enzyme mRNA expression was unaffected, whereas the AS group exhibited decreased ß- MHC/α-MHC ratio versus the CTRL group. Compared to the IR group, the AS group exhibited better recovery of post-ischemic left ventricular (LV) end-diastolic pressure and LV-developed pressure levels, while infarct size significantly decreased. Furthermore, mitochondrial production, transmembrane potential, and swelling were improved, whereas ROS formation was decreased versus the IR group. These effects were prevented by the perfusion of JAK-STAT3 inhibitor AG490.

CONCLUSION:

These findings suggest that acute nandrolone treatment can provide cardioprotection by recruiting the JAK-STAT3 signaling pathway and mitochondrial preservation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão Miocárdica / Nandrolona Tipo de estudo: Guideline Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão Miocárdica / Nandrolona Tipo de estudo: Guideline Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article