RETRACTED: Sulforaphane restores oxidative stress induced by di-N-butylphthalate in testicular Leydig cells with low basal reactive oxygen species levels.

To investigate the role and therapeutic potential of Nuclear factor erythroid-related factor 2 (Nrf2) in oxidative stress induced by di-N-butylphthalate (DBP) in testicular Leydig cells. Levels of reactive oxygen species (ROS) and Nrf2 in testicles from offspring of mice fed with DBP were studied. Basal ROS and Nrf2 level in mouse TM3 testicular Leydig cells were studied. Cells were treated with silencing or overexpression of Nrf2 in the presence and absence of DBP. Oxidative profiles were examined. Expressions of antioxidant genes downstream of Nrf2 were studied. Therapeutic effect of Nrf2 inducer sulforaphane (SFN) was evaluated. Leydig cells with low basal Nrf2 and ROS are more vulnerable to DBP. DBP-induced intracellular oxidative stress to a similar extent with Nrf2 knockdown. Nrf2 level was increased together with its target genes, hemeoxygenase 1, quinone 1, and peroxiredoxin 6, after DBP stimulation. Endogenous Nrf2 of Leydig cells was upregulated to battle against ROS. Upregulation of Nrf2 by SFN not only restored the intracellular oxidative toxicity but also cell proliferation and testosterone secretion in response to DBP. SFN restores oxidative stress induced by DBP in testicular Leydig cells with low basal ROS.