• Biomolecules & Therapeutics
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• 제20권4호
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• pp.357-370
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• 2012

Radiation therapy, the most commonly used for the treatment of brain tumors, has been shown to be of major significance in tumor control and survival rate of brain tumor patients. About 200,000 patients with brain tumor are treated with either partial large field or whole brain radiation every year in the United States. The use of radiation therapy for treatment of brain tumors, however, may lead to devastating functional deficits in brain several months to years after treatment. In particular, whole brain radiation therapy results in a significant reduction in learning and memory in brain tumor patients as long-term consequences of treatment. Although a number of in vitro and in vivo studies have demonstrated the pathogenesis of radiation-mediated brain injury, the cellular and molecular mechanisms by which radiation induces damage to normal tissue in brain remain largely unknown. Therefore, this review focuses on the pathophysiological mechanisms of whole brain radiation-induced cognitive impairment and the identification of novel therapeutic targets. Specifically, we review the current knowledge about the effects of whole brain radiation on pro-oxidative and pro-inflammatory pathways, matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) system and extracellular matrix (ECM), and physiological angiogenesis in brain. These studies may provide a foundation for defining a new cellular and molecular basis related to the etiology of cognitive impairment that occurs among patients in response to whole brain radiation therapy. It may also lead to new opportunities for therapeutic interventions for brain tumor patients who are undergoing whole brain radiation therapy.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.267-274
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• 2013

A beneficial radioprotective agent has been used to treat the radiation-induced lung injury. This study was performed to investigate whether curcumin, which is known to have anti-inflammatory and antioxidant properties, could ameliorate radiation-induced pulmonary inflammation and fibrosis in irradiated lungs. Rats were given daily doses of intragastric curcumin (200 mg/kg) prior to a single irradiation and for 8 weeks after radiation. Histopathologic findings demonstrated that macrophage accumulation, interstitial edema, alveolar septal thickness, perivascular fibrosis, and collapse in radiation-treated lungs were inhibited by curcumin administration. Radiation-induced transforming growth factor-${\beta}1$ (TGF-${\beta}1$), connective tissue growth factor (CTGF) expression, and collagen accumulation were also inhibited by curcumin. Moreover, western blot analysis revealed that curcumin lowered radiation-induced increases of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), TNF receptor 1 (TNFR1), and cyclooxygenase-2 (COX-2). Curcumin also inhibited the nuclear translocation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) p65 in radiation-treated lungs. These results indicate that long-term curcumin administration may reduce lung inflammation and fibrosis caused by radiation treatment.

• Archives of Plastic Surgery
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• 제48권1호
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• pp.127-130
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• 2021

Rectovaginal fistula, which can arise after an injury to the vaginal canal or rectum, is a troublesome obstacle for patients' everyday life. In most cases, it can be covered with a local flap, but previous radiation therapy increases the recurrence rate, making it especially difficult to cure. As the application of stromal vascular fraction (SVF) obtained from enzymatically digested autologous adipose tissue has become increasingly common, several reports have advocated its effectiveness for the treatment of refractory wounds. In light of the angiogenic, regenerative characteristics of SVF, it was incorporated as a treatment option in two cases of rectovaginal fistula discussed here. As described in this report, irradiated rectovaginal fistulas in rectal cancer patients were successfully treated with SVF injection, and we suggest SVF as a feasible treatment option for cases of rectovaginal fistula that would otherwise be very difficult to cure.

• 한국수산과학회지
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• 제42권2호
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• pp.131-138
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• 2009

The radioprotect effects of fractinated fucoidan, derived from Undaria pinnatifida sporophylls, were examined in lung injured rats treated with partial body irradiation. The right lung of Sprague-Dawley rats, eight separately grouped by including radiation only control group (ROG) and fucoidan+radiation treated group (FRG), were treated with various fraction of Undaria-derived fucoidan every other day by intraperitoneal injection 6 days prior to irradiation and during monitoring at 24 hours, 48 hours, 2 weeks, 4 weeks and 12-weeks post-irradiation of 6 Mev/2 Gy. The rats were euthanized at completion of the treatment. Tissue samples from the injured lung, fixed in formaldehyde using lung perfusion prior to extraction, were H/E stained for histological analysis using optical microscopy. Interstitial congestion (IC), hemorrhage in alveolar sac (HM), number of macrophage (MP) and alveolar wall thickness (AWT) as a measure of early indication of fibrosis were measured. AWTs in 24 hrs post-irradiation rats increased in comparison with $2.49{\pm}0.06{\mu}m$ of control group by $3.67{\pm}0.09{\mu}m$, $3.21{\pm}0.08{\mu}m$ (p=0.013), $2.98{\pm}0.08{\mu}m$ (p=0.00) in ROG, F1-fucoidan+radiation, and F3-fucoidan+radiation group, respectively. AWT of the ROG was further increased by $4.30{\pm}0.13{\mu}m$ in the 12 weeks post-irradiation group, but AWT on average was $2.56{\pm}0.05{\mu}m$ in the FRG. MP in the 24 hrs post-irradiation group markedly increased in comparison with $2.6{\pm}0.34/0.14\;mm^2$ of the control group by $8.0{\pm}1.48/0.14\;mm^2$ in the ROG, but it was only $3.6{\pm}0.48/0.14\;mm^2$ in F3-FRG. MP in the 12 weeks post-irradiation group was $7.2{\pm}1.28/0.14\;mm^2$ in ROG, but it was $2.8{\pm}0.37/0.14\;mm^2$ or $2.4{\pm}0.4/0.14\;mm^2$ (p<0.05) in the FRG. In addition, increased IC and HM in ROG were relatively smaller in FRG of the 24 hr and 12 weeks post-irradiation rats. In conclusion, Undaria pinnatifida sporophylls-derived fucoidan fractions exhibited radioprotectant activity on injured rat lung subjected to X-ray irradiation. However, success was variable according to the fractions and also time of injection post injury.

• 방사선산업학회지
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• 제7권1호
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• pp.81-85
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• 2013

This study was conducted to investigate the effect of fermented blackberry drinks (BD) on carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Male Sprague-Dawley rats were randomly divided into four groups with 6 rats per group: control, $CCl_4$, $CCl_4$ plus BD $3ml\;kg^{-1}$, and $CCl_4$ plus BD $6ml\;kg^{-1}$. We found that the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly increased and the activity of antioxidant enzyme glutathione peroxidase (GPx) in the liver was decreased in rats treated with $CCl_4$ alone when compared with the control group. However, the administration of BD attenuated the levels of serum AST and ALT in $CCl_4$-treated rats. Moreover, the administration of BD significantly increased the activity of GPx in $CCl_4$-treated rat livers. Taken together, these results suggest that BD could protect the liver from $CCl_4$-induced hepatic damage.

• 한국방사선학회논문지
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• 제10권6호
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• pp.375-379
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• 2016

방사선장해 극복을 위한 조직공학실험에서는 다양한 실험방법이 존재한다. 그중에서도 방사선 장해모델을 구현함에 있어서 쥐는 가장 많이 사용되는 실험동물이다. 이번 실험에서는 쥐 피부를 벗긴 후 일정한 두께로 만든 후에 피부 두께에 따른 방사선량을 측정하였다. 또한 쥐의 피부 두께에 따른 방사선 흡수선량을 유추해 날수 있는 수식을 도식화 하였다. 결론적으로 이러한 수식을 적용한다면 방사선장해극복을 위한 조직공학 연구에서 사용하는 다양한 지지체삽입시에 지지체가 받을 수 있는 방사선량의 정도를 유추해 낼 수 있으며 이것을 통하여 쥐 피부두께 피하에 관한 체내 (in-vitro)실험모델 구현 시 방사선량의 정보를 제공하고자 한다. 따라서 이번 연구의 결과를 기반으로 사용한다면 방사선이 노출된 쥐의 피하조직 체내 (in-vitro) 조직공학 실험에서 효과적으로 사용 될 수 있을 것이다.

• Tuberculosis and Respiratory Diseases
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• 제47권5호
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• pp.650-659
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• 1999

목 적: 산소를 이용하는 세포들은 반응성 산소기(reactive oxygen species, ROS)로 부터 자신을 보호하는 기전을 가지고 있는데, thioredoxin system으로부터 전자를 받아 과산화물을 물로 환원시키는 생화학적 성질을 가진 효모 단백질을 발견하여 이를 thioredoxin peroxidase(TPX)로 명명하였다. 이는 효모 뿐 아니라 체내 여러 장기에 고루 분포되어 있으며, 특허 종양세포에서 유리되는 반응생 산소기를 제거함으로써 종양세포의 발생(initiation), 성장(promotion) 및 전이(metastasis)를 억제하는 역할을 할 것으로 알려져 있으며, 폐암, 유방암 등의 종양세포내에서의 발현이 증가되는 것으로 보고되었다. 한편, 폐암의 치료에 있어서 방사선 치료는 폐암의 국소적 치료 및 증상 경감을 위해 중요한 위치를 차지하고 있으나, 폐의 방사선 치료에 있어 가장 중요한 장애요인은 치료후 발생하는 폐실질의 섬유화로서 방사선 조사후의 산소유리가(free radical) 손상 등에 의한 것으로 알려져 있으며, 이런 섬유화에 관여하는 인자 및 방어기전에 대한 연구는 미흡한 실정이다. 이에 저자 등은 방사선 조사 후에 백서의 폐조직에서 thioredoxin peroxidase의 아형 및 catalase등이 방사선 조사로 인한 폐손상의 방어기전에 어떤 역할을 하는지 알아보기 위하여 다음과 같은 연구를 시행하였다. 대상 및 방법: 백서 18마리를 각각 3마리씩 6개 군으로 나누었고, 그 중 15마리에 900cGY와 방사선을 조사하였다. 방사선 조사를 받은 백서를 조사직후, 1주후, 2주후, 3주후 및 6주후에 희생시켜 폐조직을 얻었고, 이들 폐조직과 대조군 3마리의 폐조직을 H&E 염색하여 폐섬유화의 정도를 관찰함과 동시에 TPX 아형 및 catalase에 대한 항체로 Western blot analysis를 시행하여 각각의 단백질의 발현정도를 비교하였다. 결 과: 대조군과 비교하여 볼 때 폐조직에서 H&E 염색상 방사선 조사후 시기별로 폐섬유화의 정도가 점차로 진행됨을 볼 수 있었으나, thioredoxin peroxidase 5가지 아형(TPX-A & B, HS22, MER5, HORF-06) 모두 방사선 조사전과 조사후, 시간경과에 따른 면역반응대(immunoreactive band)의 차이를 보이지는 않았다. Catalase 역시 면역반응대의 차이를 보이지 않았다. 결 론: 체내 여러장기, 특히 폐장에 많이 분포하고, 폐암세포에 의한 반응성 산소기(reactive oxygen species)에 의하여 발현이 증가되는 것으로 알려진 thioredoxin peroxidase가 방사선 조사후에 발생한 백서의 폐섬유화에서는 그 발현의 정도가 변하지 않는 것으로 미루어 방사선으로 인한 폐손상의 복원과정에는 관여하지 않는 것으로 생각된다.

• Journal of Radiation Protection and Research
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• 제40권1호
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• pp.65-72
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• 2015

방사선 노출에 따른 피부손상의 기본이론들은 정립되어 있지만, 정확한 기전에 관해서는 알려지지 않은 실정이다. 본 연구에서는 감마선 조사 후 용량 및 시간에 따라 돼지 피부의 장애를 육안 및 조직학적인 변화를 통해 평가하고 cyclooxygenase(COX)-2 발현 정도를 비교하고자 하였다. 미니돼지의 등 쪽 피부에 20-70 Gy 감마선을 국소조사 후 12 주 동안 육안적인 변화를 관찰하고 생검을 통해 조직학적인 변화를 관찰하였다. 방사선 조사 후 피부의 기저세포층에서의 세포자멸사와 표피층의 두께 변화를 평가하였고 COX-2 발현 정도를 면역염색을 통하여 비교하였다. 방사선 조사 후 피부 장애는 용량이 증가할수록 피부손상이 더욱 심하였으며 초기에 발적 소견을 보이다가 50 Gy 이상 조사군에서는 미란과 궤양으로 이어졌다. 조직학적인 변화는 육안적인 소견과 일치하였다. 방사선 조사 후 3일부터 기저세포에서 세포자멸사가 관찰되었으며 기저세포수의 감소가 유발되었으며 이러한 변화는 용량이 증가할수록 더욱 증가하였다. 방사선 조사 후 표피층의 두께는 3일 무렵에 일시적으로 증가하다가 점차 감소하였으며 20, 30, 40 Gy 조사 군에서는 다시 회복되는 소견이 관찰되었으나 50, 70 Gy 조사 군에서는 다시 회복되지 못하고 표피창의 두께 소실을 보였다. 방사선 조사 후 피부에서의 COX-2 발현은 피부손상정도와 일치하게 관찰되었다. 방사선 조사 후 COX-2 발현은 방사선의 용량이 증가할수록 발현이 증가하였고 시간이 증가할수록 증가하였다. 이러한 조직학적인 변화와 함께 방사선 손상을 일으키는 신호전달에 관여하는 COX-2 발현이 방사선조사 용량에 비례하여 증가하며 이러한 단백질의 발현은 피부손상과 관련성이 높은 것으로 사료된다.

• Journal of Plant Biology
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• 제11권1호
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• pp.7-14
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• 1968

Buckwheat seeds produced in previous year (1965) in an experimental pot culture in which nine levels of P-32 ranging from $1.4{\times}10-4 to 3.3{\times}104$\mu$c/pot(as of 27 July 1965)$, with the same specific activity, had been applied to the corresponding pots respectively, were used this year(1996) in water and soil culture as well as in germination test to investigate the feature and extent of possible residual effects of P-32 incorporated upon germination and plant growth, and the following results were obtained: 1. Under the given experimental conditions both stimulative and inhibitory effects of radiation were observed. 2. The germination rate of the seeds was lower at the higher level of P-32 aplication ranging from $3.0{\times}103 to 3.3{\times}104$\mu$c/pot$ and higher at 0.2 $\mu$c P/pot than the control. 3. Among the seeds produced at the higher level of application about 80% was failed to germinate, owing to the radiation injury. The remaining 80% was failed to germinate, owing to the radiation injury. The remaining 80% survived the damaging effect and showed vigorous growth and increased yield. The latter group of seeds thus proved themselves to be more radioresistant than the former. 4. The survived seeds produced later more straw and root on dry weight basis. The higher the level of P-32 applied, the stronger the stimulative effect showed in vegetative growth. 5. No radiation effect on linear growth of the plants was observed in the soil culture. 6. The dry weight of straw produced showed little difference at the moderate range compared with that of control in the soil culture. At high level of application, i.e. over $\mu$c P32/pot, however, the production was increased by 12-37% of control. 7. As for the dry weight of root harvested, the P-32 treatment over 24$\mu$c P32/pot produced 82-155% more than the control, whereas little difference was observed under 2.2$\mu$c P32/pot. 8. The seed production increased in general by the P-32 treatments. Particularly at the moderate level of application the rate of increase amounted to 70% of the control. 9. Those individual plants which survived damaging effects of radiation at the germinating stage shwoed remarkable stimulative effects both in vegetative and in reproductive stage of growth.

• Nutrition Research and Practice
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• 제12권1호
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• pp.41-46
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• 2018

BACKGROUND/OBJECTIVES: Exposure of the normal lung tissue around the cancerous tumor during radiotherapy causes serious side effects such as pneumonitis and pulmonary fibrosis. Radioprotectors used during cancer radiotherapy could protect the patient from side effects induced by radiation injury of the normal tissue. Delphinidin has strong antioxidant properties, and it works as the driving force of a radioprotective effect by scavenging radiation-induced reactive oxygen species (ROS). However, no studies have been conducted on the radioprotective effect of delphinidin against high linear energy transfer radiation. Therefore, this study was undertaken to evaluate the radioprotective effects of delphinidin on human lung cells against a proton beam. MATERIALS/METHODS: Normal human lung cells (HEL 299 cells) were used for in vitro experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay assessed the cytotoxicity of delphinidin and cell viability. The expression of radiation induced cellular ROS was measured by the 2'-7'-dicholordihydrofluorescein diacetate assay. Superoxide dismutase activity assay and catalase activity assay were used for evaluating the activity of corresponding enzymes. In addition, radioprotective effects on DNA damage-induced cellular apoptosis were evaluated by Western blot assay. RESULTS: Experimental analysis, including cell survival assay, MTT assay, and Western blot assay, revealed the radioprotective effects of delphinidin. These include restoring the activities of antioxidant enzymes of damaged cells, increase in the levels of pro-survival protein, and decrease of pro-apoptosis proteins. The results from different experiments were compatible with each to provide a substantial conclusion. CONCLUSION: Low concentration ($2.5{\mu}M/mL$) of delphinidin administration prior to radiation exposure was radioprotective against a low dose of proton beam exposure. Hence, delphinidin is a promising shielding agent against radiation, protecting the normal tissues around a cancerous tumor, which are unintentionally exposed to low doses of radiation during proton therapy.