Objective To investigate the possibility of mitochondria-dependent apoptosis as a mechanism of early steroid-induced avascular necrosis of femoral head (SANFH) in rats and vitamin E as a possible prevention strategy. Methods Seventy-two male Sprague Dawley rats were randomly divided into control group, model group, and intervention group, with 24 rats in each group. The rats in control group were not treated as normal control. The rats in model group and intervention group were established early SANFH models by lipopolysaccharide combined with methylprednisolone injection. At the same time, the rats in intervention group were injected with vitamin E (40 mg/kg) every day for 7 days. At 2, 4, and 8 weeks after the final injection, the bilateral femoral heads were harvested and observed by HE staining, TUNEL assay, immunohistochemical staining, and Western blot. The rate of empty lacunae, apoptotic index, and the expressions of Caspase-9, Caspase-3, and cytochrome-c (Cyt-c) proteins were calculated. Results According to histological staining, there were significant differences in the rate of empty lacunae between intervention group and control group at 8 weeks (P<0.05) and between intervention group and model group at 4 and 8 weeks (P<0.05). The apoptotic index of intervention group was significantly lower than that of model group at each time point (P<0.05). And there was significant difference between the intervention group and the control group at 8 weeks (P<0.05). According to immunohistochemistry staining and Western blot, the expressions of Cyt-c, Caspase-9, and Caspase-3 all significantly decreased in intervention group than those in model group at each time point (P<0.05); and the differences were significant between intervention group and control group at 8 weeks (P<0.05). Conclusion Vitamin E can delay the progression of early SANFH by reducing mitochondrial dependent osteocyte apoptosis.
Objective To observe the therapeutic effect of thermosensitive hydrogel containing curcumin-vitamin E (VE) complex (hereinafter referred to as “curcumin-VE hydrogel”) on radiation-induced oral mucositis in mice. Methods Curcumin-VE hydrogel was prepared using the synthesized curcumin-VE complex as the carrier and poloxam as the substrate. The structure of curcumin-VE complex was characterized by Fourier transform infrared spectrometer, the microstructure of curcumin-VE hydrogel was determined by scanning electron microscope, and the gelation temperature was determined by rheometer, gel swelling and degradation were tested and gel adhesion was determined using a universal testing machine. Thirty healthy male BALB/C mice with specific pathogen free grade were randomly divided into three groups, with ten mice in each group. The radiation group and radiation+hydrogel group were modeled by a single high dose of radiation (25 Gy), while the control group had anesthesia but no radiation. The control group and radiation group were given daily feed and water 7 days after radiation. In addition to daily feed and water, the radiation+hydrogel group was given curcumin-VE hydrogel twice a day. The mice were sacreficed on the 8th day after radiation. The weight changes of each group were recorded after radiation. The ulceration area of tongue was measured by toluidine blue. The tongue of mouse were pathologically observed. The activities of superoxide dismutase, catalase (CAT), and glutathione peroxidase and the level of malondialdehyde in tongue tissue were determined. The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in tongue tissue were determined by enzyme linked immunosorbent assay. The distribution and positive expression of phosphorylated histone H2AX (γ-H2AX) and nuclear factor-erythroid 2-related factor 2 were determined by immunohistochemistry. Results Curcumin-VE hydrogel had a porous network structure and the gelation temperature was 30℃, the swelling rate was close to 300%, the gel degradation rate was up to 95% after 48 h, and the adhesion strength was 12.748 kPa. Compared with the radiation group, the weight of mice in the radiation+hydrogel group increased (P<0.05), the ulcer area decreased (P<0.05); the activity of CAT increased (P<0.05); the levels of TNF-α, IL-1β and IL-6 decreased (P<0.05); the expression of γ-H2AX was down-regulated (P<0.05). Conclusion Curcumin-VE hydrogel can delay or weaken the process of radiation-induced oral mucositis by reducing the DNA damage caused by radiation, inhibiting the production of reactive oxygen species, and effectively reducing the level of inflammation in tongue tissue.