RESUMEN
BACKGROUND: Radiation-induced skin injury is a common complication of radiotherapy. The RHIZOMA COPTIDIS and COPTIS CHINENSIS aqueous extract (RCE) can ameliorate radiation-induced skin injury in our clinical observation. But, the protective mechanism of RHIZOMA COPTIDIS and COPTIS CHINENSIS in radiation-induced skin injury remains unclear. METHODS: In this experiment, we developed a radiation-induced skin injury rat model to study the mechanism. The animals were randomly divided into control group, treatment group, radiation group, and treatment and radiation group. 5 rats in each group were separately executed on 2 d and 49 d post-radiation. The semi-quantitative skin injury score was used to measure skin reactions by unblinded observers, and hematoxylin and eosin staining was used to evaluate the damage areas by irradiation. The MDA content, SOD activity of skin and serum were measured to detect the oxidative stress. RESULTS: Acute skin reactions were caused by a single dose of 45 Gy of ß-ray irradiation, and the skin injury could be found in all rats receiving irradiation based on the observation of HE staining of skin at different time-points, while RCE could significantly ameliorate those changes. The MDA content in serum and skin of control rats was 4.13±0.12 mmol/ml and 4.95±0.35 mmol/mgprot on 2 d post-radiation. The rats receiving radiation showed an increased content of MDA (5.54±0.21 mmol/ml and 7.10±0.32 mmol/mgprot), while it was 4.57±0.21 mmol/ml and 5.95±0.24 mmol/mgprot after treated with RCE (p<0.05). Similar changes of the MDA content could be seen on 49 d post-radiation. However, the SOD activity of rats receiving radiation decreased compared with control group on both time-points, which was inhibited by RCE (p<0.05). Meanwhile, no valuable changes could be found between control group and treatment group on 2 d and 49 d. CONCLUSIONS: Our study provides evidences for the radioprotective role of RCE against radiation-induced skin damage in rats by modulating oxidative stress in skin, which may be a useful therapy for radiation-induced skin injury.
Asunto(s)
Coptis/química , Medicamentos Herbarios Chinos/administración & dosificación , Traumatismos por Radiación/tratamiento farmacológico , Rizoma/química , Animales , Coptis chinensis , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Traumatismos por Radiación/enzimología , Traumatismos por Radiación/metabolismo , Traumatismos por Radiación/prevención & control , Ratas , Piel/efectos de los fármacos , Piel/enzimología , Piel/metabolismo , Piel/efectos de la radiación , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: Saikosaponin-d (SSd), a monomer terpenoid purified from the Chinese herbal drug Radix bupleuri, has multiple effects, including anticancer properties. However, the effect of SSd on tumors exposed to radiation is largely unknown. To investigate the radiosensitizing effect of SSd and its possible mechanism, we combined SSd with radiation therapy to treat SMMC-7721 hepatocellular carcinoma cells under oxia and hypoxia. METHODS: Cell growth, apoptosis, and cell cycle distribution were examined after treatment with SSd alone, radiation alone, and their combinations under oxia and hypoxia. The protein and mRNA levels of p53, Bcl2, and BAX were measured using western blot analysis and RT-PCR, respectively. RESULTS: Treatment with SSd alone and radiation alone inhibited cell growth and increased apoptosis rate at the concentration used. These effects were enhanced when SSd was combined with radiation. Moreover, SSd potentiated the effects of radiation to induce G0/G1 arrest in SMMC-7721 cells, and reduced the G2/M-phase population under hypoxia. However, under oxia, SSd only potentiated the effects of radiation to induce G0/G1 arrest, but not G2/M-phase arrest. These effects of SSd alone, radiation alone, and their combination, were accompanied by upregulated expression of p53 and BAX and downregulation of Bcl2 expression under oxia and hypoxia. CONCLUSION: SSd potentiates the effects of radiation on SMMC-7721 cells; thus, it is a promising radiosensitizer. The radiosensitizing effect of SSd may contribute to its effect on the G0/G1 and G2/M checkpoints of the cell cycle.