Effects of Alpha-Lipoic Acid on TGF-β1 and Urotensin-II Levels in Glucocorticoid-Induced Osteonecrosis in Rats

Abstract

Background: Osteonecrosis (ON) is a serious health problem, which dramatically reduces the quality of life. Objectives: In the present study on the rat model of glucocorticoids (GCs) -induced ON, we explored the influence of alpha-lipoic acid on serum levels of TGF-β1 and urotensin-II (U-II) and on histological alteration with respect to fatty degeneration and osteocyte necrosis. Methods: A total of 32 male Wistar albino rats were equally assigned to four groups, including control, methylprednisolone acetate (MPA), alpha-lipoic acid (ALA), and MPA with ALA (MP1 + ALA). The animals in MPA group subcutaneously received 15 mg/kg/week during 2 weeks, whereas 100 mg/kg/day ALA was intraperitoneally administered to ALA group during 4 weeks. The MPA + ALA group had both treatments with the same doses. ON was confirmed and graded histologically. Lipid peroxidation and DNA damage levels were immunohistochemically assessed in rats’ bones. Results: After histopathological examinations, ALA injection attenuated oxidative stress levels through reducing both 8-OHdG-and 4-HNE-positive cells in the femoral head region (P < 0.05). The U-II and TGF-β1 protein levels significantly decreased after ALA treatment in MPA injected animals (P < 0.05, P < 0.01, respectively). Moreover, there was a strong correlation between U-II and TGF-β1 protein levels (P = 0.019, r = 0.884). Conclusions: This study is novel with regard to showing the therapeutic effects of ALA on GC-induced ON in rats as well as the strong correlation between the expression levels of U-II and TGF-β1 proteins. In this regard, ALA may be a therapeutic agent in the treatment of ON patients.