Mitochondrial dysfunction and cardiac ischemia/reperfusion injury are attenuated by nandrolone: Role of JAK-STAT3 pathway

• Published in: Steroids Vol. 197; p. 109247
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2023
• Subjects: Anabolic steroid; Ischemia/reperfusion; JAK/STAT; Mitochondria; AMPK-PGC-1α; MOPS; MHC; FCCP; peak VO2; JAK/STAT; Ischemia/reperfusion; mPTP; GPX; LVEDP; BSA; DHT; Mitochondria; TMRM; ANOVA; GRIM-19; KHS; Anabolic steroid; JAK-STAT; IR; SOD; EGTA; AS; CTRL; Δψm; LVDP; ROS; Bcl2; GAPDH
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2023.109247

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•Acute nandrolone treatment decreased the susceptibility to cardiac IR injury;•Cardioprotection elicited by nandrolone is triggered by JAK/STAT3 pathway;•IR-induced mitochondrial damage was attenuated by nandrolone.
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).
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 β 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 β- 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.
These findings suggest that acute nandrolone treatment can provide cardioprotection by recruiting the JAK-STAT3 signaling pathway and mitochondrial preservation.