Nandrolone decanoate induces heart injury via oxidative damage and mitochondrial apoptotic pathway by regulation of TLR4/NF-κB/NLRP3 axis in male rats: The rescue effect of N-acetylcysteine

Myocardial apoptosis is a leading cause of damage in cardiac tissues of nandrolone (ND) treatment. However, its molecular mechanism is not fully understood. This study aims to investigate the effect of ND with or without N −acetylcysteine (NAC) treatment on oxidative damage and TLR4/NF-κB /NLRP3 signaling pathway in the heart of male rats. Eighteen male Wistar rats with a weight range of 220 ± 10 g were selected. They were divided into three groups (n = 6): control (C) group, ND group, NAC + ND group. After six weeks of treatment, the TUNEL staining indicated that ND increased the number of apoptotic cells in the hearts of male rats. The molecular analysis demonstrated that ND exposure resulted in increased protein levels of cytochrome c, c-Caspase-3/p-Caspase-3 ratio, p53, TLR4, NF-κB, NLRP3, and 8-OHdG with a concomitant up-regulation of LDH and CK-MB enzymes activity in the heart tissue compared to the C group. Our findings suggested that ND can cause damage to heart tissue via induction of DNA damage, apoptosis, and probably TLR4/NF-κB/NLRP3 signaling pathway plays a crucial role in this process. It also demonstrates that these negative effects of ND can be reduced by using NAC treatment as an antioxidant and anti-inflammatory agent.