Abstract
BackgroundThe objective of this study was to investigate the protective effects of molecular hydrogen, a novel and selective antioxidant, on steroid-induced osteonecrosis (ON) in a rabbit model.MethodsSixty rabbits were randomly divided into two groups (model group and hydrogen group). Osteonecrosis was induced according to an established protocol of steroid-induced ON. Rabbits in the hydrogen group were treated with intraperitoneal injections of molecular hydrogen at 10 ml/kg body weight for seven consecutive days. Plasma levels of total cholesterol, triglycerides, soluble thrombomodulin(sTM), glutathione(GSH) and malondialdehyde(MDA) were measured before and after steroid administration. The presence or absence of ON was examined histopathologically. Oxidative injury and vascular injury were assessed in vivo by immunohistochemical staining of 8-hydoxy-2-deoxyguanosine(8-OHdG) and MDA, and ink artery infusion angiography. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays were performed to measure apoptosis.ResultsThe incidence of steroid-induced ON was significantly lower in hydrogen group (28.6%) than that in model group (68.0%). No statistically differences were observed on the levels of total cholesterol and triglycerides. Oxidative injury, vascular injury and apoptosis were attenuated in the hydrogen group compared with those in the model group in vivo.ConclusionsThese results suggested that molecular hydrogen prevents steroid-induced osteonecrosis in rabbits by suppressing oxidative injury, vascular injury and apoptosis.
Highlights
The objective of this study was to investigate the protective effects of molecular hydrogen, a novel and selective antioxidant, on steroid-induced osteonecrosis (ON) in a rabbit model
In addition to Methylpednisolone acetate (MPSL), the hydrogen group received intraperitoneal injections of molecular hydrogen at 10 ml/kg body weight for seven consecutive days starting from the day of MPSL administration, which was based on the period of greatest susceptibility to steroid-induced oxidative injury suggested by Ichiseki et al [11, 28]
The incidence of osteonecrosis was significantly lower in the hydrogen group than that in the model group (Pearson’s chi-square test, P < 0.01)
Summary
The objective of this study was to investigate the protective effects of molecular hydrogen, a novel and selective antioxidant, on steroid-induced osteonecrosis (ON) in a rabbit model. As most of the affected patients are young individuals and the surgical prognosis of steroid-induced ON is generally poor, it is highly desirable to develop a strategy to prevent its occurrence. It is generally accepted that microcirculatory disturbances within bone underlie the development of steroid-induced ON [4]. To clarify the pathophysiology of steroid-induced ON and develop promising methods to prevent its occurrence, a number of preclinical animal ON models have been established including traumatic ON(surgical vascular deprivation, physical and chemical insult–induced traumatic ON) and non-traumatic ON(spontaneous, steroidinduced or steroid-associated, lipopolysaccharide-induced or their combination-induced, horse serum-induced and alcohol-induced) [5]. Many researchers described steroidinduced ON models in rabbits by administering methylprednisolone intramuscularly, which had an advantage
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