Nandrolone decanoate induces liver damage via TGF-β/Smad3/miR-29 and regulation of FAT/CD36, PTP1B, HNF4A expression in male rats: Rescue effect of N-acetylcysteine.

Anabolic-androgenic steroid (AAS) abuse is associated with damage to various organs, including the liver. However, the underlying molecular mechanisms remain unclear. This study was conducted to elucidate the effect of nandrolone decanoate on liver injury, both alone and in combination with N-acetylcysteine (NAC), and its related mechanisms. Twenty-four male Wistar rats were randomly subdivided into three groups: Control (Con), Nandrolone (10 mg/kg) (ND), and Nandrolone + NAC (ND+NAC: 150 mg/kg daily). After 6 weeks, nandrolone treatment led to increased levels of triglycerides, cholesterol, LDL, AST, ALT, and ALP, along with a decreased HDL level compared to the control group. ND administration also elevated the expression of PTP1B, HNF4A, and FAT/CD36 genes, as well as protein levels of MMP-2, MMP-9, TGF-β1, SMAD-3, and SREBP-1. miRNA-29b levels decreased in liver tissue following nandrolone exposure, as determined by RT-PCR. Moreover, histopathological examination showed increased fibrosis after ND treatment. Consumption of NAC along with ND partially ameliorated gene and protein expression alterations and fibrotic changes, and improved the undesirable lipid profile and liver enzyme levels compared to the ND group. These findings indicate that ND-induced liver abnormalities may be partly associated with lipid homeostasis changes mediated by overexpression of the aforementioned genes and proteins. They also demonstrate that these effects can be reduced by using NAC as an antioxidant and anti-inflammatory agent.