Knocking down the transcript of NF-kappaB modulates the reciprocal regulation of endogenous antioxidants and feeding behavior in phenylpropanolamine-treated rats

Abstract

It has been reported that oxidative stress, antioxidants, and neuropeptide Y (NPY) are involved in regulating the feeding behavior of phenylpropanolamine (PPA), a sympathomimetic drug. This study explored whether transcription factor NF-κB is involved in this effect. Rats were treated daily with PPA for 4 days. Changes in hypothalamic NF-κB, NPY, superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels during PPA treatment were assessed and compared. Results showed that NF-κB, SOD, and GPx increased, with a maximal response on Day 2, while the food intake and NPY decreased with the biggest reduction on Day 2 during PPA treatment. To further determine whether NF-κB was involved, intracerebroventricular infusion of antisense oligonucleotide was performed at 1 h before daily PPA in free-moving rats. Cerebral NF-κB knockdown could modify PPA anorexia and the expressions of NPY, SOD, and GPx. It is suggested that hypothalamic NF-κB participates in the reciprocal regulation of NPY and antioxidants, which mediated the appetite-suppressing effect of PPA. Results may further the understanding of the molecular mechanisms of PPA.