The protective and therapeutic effects of 5-androstene3ß, 17ß-diol (ADIOL) in abdominal post-operative adhesions in rat: Suppressing TLR4/NFκB/HMGB1/TGF1 ß/α SMA pathway.

ABSTRACT

Neurosteroid, 5-androstenediol (ADIOL) had been experimentally applied to protect against many diseases as it had anti-oxidant, anti-inflammatory, and anti-apoptotic effects. In our study, we investigate its role in abdominal postoperative adhesion (APA) formations. Our results demonstrate that ADIOL alleviates APA formation after induction by cecal abrasion (CA) model in the male rat. Interestingly, per administration of ADIOL before APA induction leads to inhibit oxidative stress by increasing superoxide dismutase (SOD) and decreasing Malondialdehyde (MAD) levels to a similar level to the sham group, in addition inhibiting inflammatory pathway by decreasing toll-like receptor 4 (TLR4), nuclear factor kappa-B (NFκB), and High mobility group box 1 (HMGB1) to a similar level to the sham group, furthermore decreasing Transforming growth factor beta 1 (TGFß1) and alpha Smooth muscle -actin (α SMA) levels to similar levels in the sham group. While administration of ADIOL after APA induction lead to decrease adhesions formation by decreasing oxidative stress (↓MDA and ↑SOD levels), inflammatory markers (↓TLR4, ↓NFκB, and ↓HMGB1levels), and collagen deposition by (↓TGF1 ß and↓α SMA levels) is the highly significant manner to those levels in CA model but also significant to those levels in the sham group. Concluded that, pre-administration of ADIOL before APA induction was more effective than its administration after adhesions formations.