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BACKGROUND: Oxidative stress plays an important role in femoral head necrosis. Platelet-rich plasma (PRP) contains growth factors that can accelerate fracture healing. PRP combined with core decompression can promote recovery from non-traumatic femoral head necrosis. OBJECTIVE: To investigate whether PRP combined with core decompression can inhibit oxidative stress in steroid-induced avascular necrosis of the femoral head model via Keap1/Nrf2/HO-1 signaling pathway. METHODS: Forty New Zealand rabbits were randomly divided into normal group, model group, control group and PRP group, with 10 rabbits in each group. In the model and PRP groups, a model of steroid-induced femoral head necrosis was established in a sterile environment. At 4 weeks after operation, the rabbits in the PRP group were injected with 0.4 mL of 3% PRP after core decompression. The control group received core decompression treatment, and the control and model groups were raised normally. After 14 weeks, the experimental animals were sacrificed. Hematoxylin-eosin staining was used to observe the pathological changes of bone marrow cavity and the vacancy rate of bone lacunae in the femoral head of each group. Total antioxidant capacity, superoxide dismutase, glutathione peroxidase, reduced glutathione, and malondialdehyde were detected. TUNEL was used to detect bone cell apoptosis in the femoral head. Immunofluorescence staining was used to determine the distribution of Keap1 and Nrf2. Western blot was used to measure Keap1, Nrf2, and H0-1 protein expression in the femoral head. Approval was obtained from the Animal Ethics Committee of the Affiliated Hospital of Qinghai University, approval No. qhdx-201908374. RESULTS AND CONCLUSION: (1) Compared with the normal group, the trabecular bone in model group was thinned with structure disorder. Compared with the model group, the trabecular bone structure in control group was restored, and the number of vacant bone lacunae was reduced (P < 0.05). Compared with the control group, the animals treated with PRP combined with core decompression were further improved, the trabecular bone structure was further improved, and the number of vacant bone lacunae was further reduced (P < 0.05). Whereas there was no significant difference between the PRP group and normal group (P > 0.05). (2) The total antioxidant capacity and serum levels of superoxide dismutase, glutathione peroxidase, and reduced glutathione in the model group were significantly lower than those in normal animals (P < 0.05), while the MDA concentration was significantly higher than that in the normal group (P < 0.05). These oxidative stress indexes were slightly improved in the control group compared with the model group (P > 0.05), while these indexes were significantly improved in the PRP group than the model and control groups (P < 0.05). (3) The expression of Kesp1 in the model group was significantly lower than that of the normal group (P < 0.05), and the expression of Nrf2 and HQ-1 protein was significantly higher than that of the normal group (P < 0.05). The expression of Keap1 in the PRP group was lower than that of the model and control groups (P < 0.05), and the expression of Nrf2 and HQ-1 was significantly higher than that of the model and control groups (P < 0.05). Therefore, PRP can effectively inhibit oxidative stress in the process of steroid-induced femoral head necrosis, which may be caused by activating the Keap1/Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

A series of novel β-elemene dimer derivatives were synthesized and evaluated for their antioxidant activities. The results indicated that most of the target compounds showed more potent cytoprotective effects than positive control vitamin E. In particular, dimer D5 exhibited the strongest antioxidant activity, which was significantly superior to the active compound D1 obtained in our previous study. Besides, D5 did not produce obvious cytotoxicity in normal human umbilical vein endothelial cells (HUVECs) and increased the viability of HUVECs injured by H 2 O 2 in a concentration-dependent manner. Further studies suggested that the cytoprotective action of D5 might be mediated, at least in part, by increasing the intracellular superoxide dismutase activity and nitric oxide secretion as well as decreasing the intracellular malonyldialdehyde content and lactate dehydrogenase release. Furthermore, D5 observably inhibited ROS generation and prevented H 2 O 2 -induced apoptosis in HUVECs possibly via inhibiting the activation of the MAPK signaling pathway.