Edaravone, a novel free radical scavenger, prevents steroid-induced osteonecrosis in rabbits

Li, Guangyi; Feng, Yong; Cheng, Tak Sum; Yin, Jiewei; Zhang, Changqing

doi:10.1093/rheumatology/kes313

Cited by 15 publications

(25 citation statements)

References 33 publications

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“…Consistently, pretreatment with edaravone was able to rescue the impaired endogenous antioxidant enzymes superoxide dismutase and catalase, which are responsible for the detoxification of deleterious oxygen radicals. Subsequently, edaravone maintained the levels of reduced glutathione in γ-irradiated human blood lymphocytes, which is consistent with the previous study (Li et al 2013).…”

Section: Discussionsupporting

confidence: 92%

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Chen

Liu

Dong

et al. 2015

Cell Stress and Chaperones

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Radiation-induced cellular injury is attributed primarily to the harmful effects of free radicals, which play a key role in irradiation-induced apoptosis. In this study, we investigated the radioprotective efficacy of edaravone, a licensed clinical drug and a powerful free radical scavenger that has been tested against γ-irradiation-induced cellular damage in cultured human peripheral blood lymphocytes in studies of various diseases. Edaravone was pre-incubated with lymphocytes for 2 h prior to γ-irradiation. It was found that pretreatment with edaravone increased cell viability and inhibited generation of γ-radiation-induced reactive oxygen species (ROS) in lymphocytes exposed to 3 Gy γ-radiation. In addition, γ-radiation decreased antioxidant enzymatic activity, such as superoxide dismutase and glutathione peroxidase, as well as the level of reduced glutathione. Conversely, treatment with 100 μM edaravone prior to irradiation improved antioxidant enzyme activity and increased reduced glutathione levels in irradiated lymphocytes. Importantly, we also report that edaravone reduced γ-irradiation-induced apoptosis through downregulation of Bax, upregulation of Bcl-2, and consequent reduction of the Bax:Bcl-2 ratio. The current study shows edaravone to be an effective radioprotector against γ-irradiation-induced cellular damage in lymphocytes in vitro. Finally, edaravone pretreatment significantly reduced DNA damage in γ-irradiated lymphocytes, as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment) (p<0.05). Thus, the current study indicates that edaravone offers protection from radiation-induced cytogenetic alterations.

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Section: Discussionsupporting

confidence: 92%

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Chen

Liu

Dong

et al. 2015

Cell Stress and Chaperones

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“…Edaravone, a novel free radical scavenger, is demonstrated to prevent steroid-induced osteonecrosis by suppressing the accumulation of lipid peroxidative products and oxidative DNA damage [41]. For MSCs, oxidative stress is regarded as a crucial mediator for adipogenic differentiation under GC's administration [42].…”

Section: Discussionmentioning

confidence: 99%

Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study

et al. 2014

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“…GC treatment may have a systemic influence on the vascular system and BMSC pool ( 40 , 41 ). Thus, an increasing number of studies focus on systemic administration of drugs to prevent or treat ONFH ( 42 – 44 ).…”

Section: Introductionmentioning

confidence: 99%

Valproic acid prevents glucocorticoid‑induced osteonecrosis of the femoral head of rats

et al. 2018

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Abstract. Glucocorticoids (Gcs) are the most common cause of atraumatic osteonecrosis of the femoral head (ONFH) because their effect compromises the osteogenic capability of bone marrow-derived mesenchymal stem cells (BMScs). Valproic acid (VPA) is a widely used anti-epileptic and anti-convulsant drug. Previous studies have reported that VPA promotes osteogenic differentiation of MScs in vitro and osteogenesis in vivo as a histone deacetylase (HdAc) inhibitor. The purpose of the present study was to investigate the efficacy of VPA as a precautionary treatment of ONFH after Gc treatment in rats. In vitro, the effect of VPA, dexamethasone or a combination treatment of the two on the proliferation and osteogenic differentiation of human BMScs was assessed using a cell counting Kit-8 and apoptosis assays, and by measuring the expression of proteins associated with osteogenesis. In vivo, a Gc-induced ONFH model was established in rats and VPA was added during Gc treatment to investigate the preventive effect of VPA against ONFH. Rat BMScs were also extracted to investigate the osteogenic capacity. The results of micro-computed tomography scanning, angiography of the femoral head and histological and immunohistochemical analyses indicated that 11 of 15 rats induced with methylprednisolone (MP) presented with ONFH, while only 2 of 15 rats treated with a combination of MP and VPA developed ONFH. VPA produced beneficial effects on subchondral bone trabeculae in the femoral head with significant preservation of bone volume and blood supply, as well as improved osteogenic capability of BMScs compared with those in rats treated with Gc alone. In conclusion, VPA attenuated the inhibitory effect of Gc on BMSc proliferation and osteogenesis by inhibiting apoptosis and elevating the expression of proteins associated with osteogenesis, which may contribute to the prevention of Gc-induced ONFH in rats.

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Edaravone, a novel free radical scavenger, prevents steroid-induced osteonecrosis in rabbits

Abstract: Edaravone exerted beneficial effects on reducing incidence of steroid-induced ON by suppressing the accumulation of lipid peroxidative products and oxidative DNA damage in endothelial cells and haematopoietic cells.

Cited by 15 publications

References 33 publications

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study

Valproic acid prevents glucocorticoid‑induced osteonecrosis of the femoral head of rats

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