방사선 조사로 인한 폐렴은 흉부 방사선 치료를 받은 환자에게 흔히 수반되는 합병증으로 그간 이를 예방 혹은 감소시키기 위한 연구가 시행되어 왔다. curcumin은 기존의 연구에서 항염증 작용과 항산화 작용을 가지는 것으로 밝혀진 물질로 이번 연구는 방사선 조사로 유도된 폐렴을 가진 쥐 모형에서 curcumin이 폐 염증에 대해 어떤 효과를 보이는지 알아보기 위해 시행되었다. 체중 250-270g 내외의 6주령 Sprague-Dawley 수컷 흰쥐를 사용하였으며 실험 동물을 무작위로 A. 정상 대조군(N=5), B. 방사선 조사군(N=11) C. curcumin 치료 +방사선 조사군(N =11), D. curcumin 복용군(N=5)의 4군으로 나누었다. B와 C군은 18Gy용량으로 1회 흉부 방사선 조사를 시행하였고 C와 D군은 방사선 조사 1주 전부터 조사 후 8주째까지 총 9주에 걸쳐 200mg/kg의 curcumin을 주 5회 경구로 투여하였다. 방사선 조사 후 8주째에 쥐의 우측 폐를 채취하여 Western blot를 통해 ...
방사선 조사로 인한 폐렴은 흉부 방사선 치료를 받은 환자에게 흔히 수반되는 합병증으로 그간 이를 예방 혹은 감소시키기 위한 연구가 시행되어 왔다. curcumin은 기존의 연구에서 항염증 작용과 항산화 작용을 가지는 것으로 밝혀진 물질로 이번 연구는 방사선 조사로 유도된 폐렴을 가진 쥐 모형에서 curcumin이 폐 염증에 대해 어떤 효과를 보이는지 알아보기 위해 시행되었다. 체중 250-270g 내외의 6주령 Sprague-Dawley 수컷 흰쥐를 사용하였으며 실험 동물을 무작위로 A. 정상 대조군(N=5), B. 방사선 조사군(N=11) C. curcumin 치료 +방사선 조사군(N =11), D. curcumin 복용군(N=5)의 4군으로 나누었다. B와 C군은 18Gy용량으로 1회 흉부 방사선 조사를 시행하였고 C와 D군은 방사선 조사 1주 전부터 조사 후 8주째까지 총 9주에 걸쳐 200mg/kg의 curcumin을 주 5회 경구로 투여하였다. 방사선 조사 후 8주째에 쥐의 우측 폐를 채취하여 Western blot를 통해 tumor necrosis factor α (TNF α), TNF α receptor-1(TNF αR-1), cyclo-oxygenase2 (Cox-2), tumor gross factor-β (TGF-β), nuclear transcription factor kappa B (NF-κB) 및 microsomal prostaglandin E synthase-1 (mPGES-1) 발현을 확인하였고 좌측 폐를 채취하여 세포 병리학적 변화를 확인하였으며 쥐의 혈액을 함께 채취하여 TGF-β를 측정하여 네 군 간에 비교하였다. 방사선 조사 8주 후 curcumin 치료 + 방사선 조사군은 방사선 단독 조사군에 비해 폐포 대식세포 의 침윤, 폐포 상피 세포의 증식 및 비후와 혈관 주변 조직의 섬유화 소견이 감소되었으며 폐 조직에서 시행한 Western blot상 Cox-2와 TNF αR-1의 발현이 낮았다. 뿐만 아니라 면역 조직학염색법을 이용해 확인한 Cox-2와 TGF-β, NF-κB와 mPGES-1의 발현 정도가 방사선만 조사하였던 군에 비해 감소되어 있었고 혈중 TGF-β수치도 낮게 측정되었다. 이러한 결과는 Curcumin의 경구 주입이 방사선 조사로 유도된 폐렴을 가진 쥐 모형에서 폐 염증을 감소시킨다는 것을 시사한다.
방사선 조사로 인한 폐렴은 흉부 방사선 치료를 받은 환자에게 흔히 수반되는 합병증으로 그간 이를 예방 혹은 감소시키기 위한 연구가 시행되어 왔다. curcumin은 기존의 연구에서 항염증 작용과 항산화 작용을 가지는 것으로 밝혀진 물질로 이번 연구는 방사선 조사로 유도된 폐렴을 가진 쥐 모형에서 curcumin이 폐 염증에 대해 어떤 효과를 보이는지 알아보기 위해 시행되었다. 체중 250-270g 내외의 6주령 Sprague-Dawley 수컷 흰쥐를 사용하였으며 실험 동물을 무작위로 A. 정상 대조군(N=5), B. 방사선 조사군(N=11) C. curcumin 치료 +방사선 조사군(N =11), D. curcumin 복용군(N=5)의 4군으로 나누었다. B와 C군은 18Gy용량으로 1회 흉부 방사선 조사를 시행하였고 C와 D군은 방사선 조사 1주 전부터 조사 후 8주째까지 총 9주에 걸쳐 200mg/kg의 curcumin을 주 5회 경구로 투여하였다. 방사선 조사 후 8주째에 쥐의 우측 폐를 채취하여 Western blot를 통해 tumor necrosis factor α (TNF α), TNF α receptor-1(TNF αR-1), cyclo-oxygenase2 (Cox-2), tumor gross factor-β (TGF-β), nuclear transcription factor kappa B (NF-κB) 및 microsomal prostaglandin E synthase-1 (mPGES-1) 발현을 확인하였고 좌측 폐를 채취하여 세포 병리학적 변화를 확인하였으며 쥐의 혈액을 함께 채취하여 TGF-β를 측정하여 네 군 간에 비교하였다. 방사선 조사 8주 후 curcumin 치료 + 방사선 조사군은 방사선 단독 조사군에 비해 폐포 대식세포 의 침윤, 폐포 상피 세포의 증식 및 비후와 혈관 주변 조직의 섬유화 소견이 감소되었으며 폐 조직에서 시행한 Western blot상 Cox-2와 TNF αR-1의 발현이 낮았다. 뿐만 아니라 면역 조직학염색법을 이용해 확인한 Cox-2와 TGF-β, NF-κB와 mPGES-1의 발현 정도가 방사선만 조사하였던 군에 비해 감소되어 있었고 혈중 TGF-β수치도 낮게 측정되었다. 이러한 결과는 Curcumin의 경구 주입이 방사선 조사로 유도된 폐렴을 가진 쥐 모형에서 폐 염증을 감소시킨다는 것을 시사한다.
Radiation therapy (RT) is a widely used therapeutic modality for inoperable solid tumors and hematologic malignancies involving the lungs and mediastinum with chemotherapy. But unfortunately, inclusion of normal lung tissue into the radiation field is inevitable; although the degree of severity can ...
Radiation therapy (RT) is a widely used therapeutic modality for inoperable solid tumors and hematologic malignancies involving the lungs and mediastinum with chemotherapy. But unfortunately, inclusion of normal lung tissue into the radiation field is inevitable; although the degree of severity can vary among patients, radiation-induced lung injury is fairly common in patients receiving radiation therapy. According to previous research, RT-induced lung injury occurred in 3-25% of patients with lung cancer and 2-20% of those with breast cancer and lymphoma. RT-induced pneumonitis was manifested by cough, shortness of breath commonly, and impairment of pulmonary function and respiratory failure in severe and progressive cases. The finding that increasing morbidity - even mortality in severe cases- in patient having RT-induced lung injury after thoracic irradiation is generally accepted, and to minimize this deleterious effect is a principal factor in the successful treatment of patients receiving radiotherapy. In the last few years, many efforts to prevent or ameliorate radiation-induced lung injury have been tried. One of these is to apply the minimum dosage of radiation and to increase selectivity of the treatment field to avoid including normal lung into the therapeutic irradiation zone. Another approach is to use a radioprotective agent. Previous reports have shown that supplemental vitamin A in the diet inhibits RT-induced lung fibrosis and oral erdostein diminishes the RT-induced alveolitis in rat models. And it is reported that amiofostine and N-acetyl cysteine reduce radiation-induced lung toxicities in patients with non-small cell lung cancer. Although the pathogenesis of RT-induced lung injury is not understood clearly at the molecular level, many investigators reported that radiation induces release of oxygen-free radicals and expression of several cytokines, chemokines and adhesion molecules, and these recruit the inflammatory cells to the alveolar septum, interstitium and perivascular structures. The alveolar septum and interstitium were sequentially thickened by accumulation of leukocytes and macrophages and proliferation of type Ⅱpneumocytes. Moreover, the collagen materials deposited into the interstitium, vascular wall thickening and the luminal occlusion were happened. Many researchers have insisted that tumor growth factor β (TGF-β) is a key cytokine in the pathogenesis of RT-induced lung injury. It is known to display many diverse actions in the process of organ growth and development, immune modulation and response to injury. The potent fibrinogenic action of TGF-β was exhibited in damaged lung tissue after thoracic irradiation and caused late radiation-related lung fibrosis. Anscher and co-workers have suggested the possibility for finding a new radioprotective agent in their recent study. They found that the blocking of the TGF-β pathway with its specific antibody induces amelioration of tissue damage in radiation-induced lung injury in rats. Tumor necrosis factor-α (TNF-α) is known to be another important cytokine in sites injured by radiation. The gravity of TNF-α is increased after a study has demonstrated recently that it plays an important role in up-regulation of nuclear factor kappa B (NF-κB) in pathogenesis of radiation pneumonitis. NF-kB is a multifunctional cytokine and cell cycle regulator, and it is activated by free radicals, inflammatory stimuli, carcinogens and ultraviolet (UV) light or radiation. Recent studies have reported that NF-kB activation enhanced transcription of the pro-inflammatory cytokines and cell adhesion molecules such as metalloproteinases (MMPs), Cox-2 and nitric oxide (NO) synthase and intercellular adhesion molecule (I-CAM). Sequentially, the release of these pro-inflammatory cytokines causes the suppression of apoptosis and promotes cellular proliferation and inflammation. A similar sequence of events happens in lung tissue damaged by thoracic irradiation, activated NF-κB up-regulated by TNF-α enhances Cox-2 expression. The finding that TGF-β, NF-κB and Cox-2 play a key role in pathogenesis in radiation-induced lung injury is an important clue about the blocking of this pathway as a new treatment approach. Curcumin〔1,7-bis(4-hydroxy-3-methoxy phenyl)-1, 6-heptadiene-3, 5-dione〕is a natural polyphenol in turmeric derived from the rhizome of the Indian plant Curcuma longa, a member of the ginger family. It has a yellow color and unique flavor and is used as a spice or coloring agent in Asian countries. Curcumin was shown to exert potential anti-inflammatory effects by inhibiting pro-inflammatory cytokine and chemokine production through blood monocytes and lung inflammatory cells and also to modulate the expression of adhesion molecules. Interestingly, the suppressive effect of curcumin has occurred through the inhibition of the NF-κB pathways and other pro-inflammatory signaling pathways including the mitogen-activated protein kinase (MAPK) pathway in recent studies. However, the effect of curcumin on RT-induced pneumonitis that these cytokines act mainly in pathogenesis has not been studied. The author hypothesized that curcumin could reduce pulmonary inflammation through suppression of pro-inflammatory cytokines such as TGF-β, NF-κB and Cox-2, which play a key role in radiation-induced pneumonitis. Therefore, this study was performed to evaluate the effect of curcumin on pulmonary inflammation in RT-induced pneumonitis rat models.
Radiation therapy (RT) is a widely used therapeutic modality for inoperable solid tumors and hematologic malignancies involving the lungs and mediastinum with chemotherapy. But unfortunately, inclusion of normal lung tissue into the radiation field is inevitable; although the degree of severity can vary among patients, radiation-induced lung injury is fairly common in patients receiving radiation therapy. According to previous research, RT-induced lung injury occurred in 3-25% of patients with lung cancer and 2-20% of those with breast cancer and lymphoma. RT-induced pneumonitis was manifested by cough, shortness of breath commonly, and impairment of pulmonary function and respiratory failure in severe and progressive cases. The finding that increasing morbidity - even mortality in severe cases- in patient having RT-induced lung injury after thoracic irradiation is generally accepted, and to minimize this deleterious effect is a principal factor in the successful treatment of patients receiving radiotherapy. In the last few years, many efforts to prevent or ameliorate radiation-induced lung injury have been tried. One of these is to apply the minimum dosage of radiation and to increase selectivity of the treatment field to avoid including normal lung into the therapeutic irradiation zone. Another approach is to use a radioprotective agent. Previous reports have shown that supplemental vitamin A in the diet inhibits RT-induced lung fibrosis and oral erdostein diminishes the RT-induced alveolitis in rat models. And it is reported that amiofostine and N-acetyl cysteine reduce radiation-induced lung toxicities in patients with non-small cell lung cancer. Although the pathogenesis of RT-induced lung injury is not understood clearly at the molecular level, many investigators reported that radiation induces release of oxygen-free radicals and expression of several cytokines, chemokines and adhesion molecules, and these recruit the inflammatory cells to the alveolar septum, interstitium and perivascular structures. The alveolar septum and interstitium were sequentially thickened by accumulation of leukocytes and macrophages and proliferation of type Ⅱpneumocytes. Moreover, the collagen materials deposited into the interstitium, vascular wall thickening and the luminal occlusion were happened. Many researchers have insisted that tumor growth factor β (TGF-β) is a key cytokine in the pathogenesis of RT-induced lung injury. It is known to display many diverse actions in the process of organ growth and development, immune modulation and response to injury. The potent fibrinogenic action of TGF-β was exhibited in damaged lung tissue after thoracic irradiation and caused late radiation-related lung fibrosis. Anscher and co-workers have suggested the possibility for finding a new radioprotective agent in their recent study. They found that the blocking of the TGF-β pathway with its specific antibody induces amelioration of tissue damage in radiation-induced lung injury in rats. Tumor necrosis factor-α (TNF-α) is known to be another important cytokine in sites injured by radiation. The gravity of TNF-α is increased after a study has demonstrated recently that it plays an important role in up-regulation of nuclear factor kappa B (NF-κB) in pathogenesis of radiation pneumonitis. NF-kB is a multifunctional cytokine and cell cycle regulator, and it is activated by free radicals, inflammatory stimuli, carcinogens and ultraviolet (UV) light or radiation. Recent studies have reported that NF-kB activation enhanced transcription of the pro-inflammatory cytokines and cell adhesion molecules such as metalloproteinases (MMPs), Cox-2 and nitric oxide (NO) synthase and intercellular adhesion molecule (I-CAM). Sequentially, the release of these pro-inflammatory cytokines causes the suppression of apoptosis and promotes cellular proliferation and inflammation. A similar sequence of events happens in lung tissue damaged by thoracic irradiation, activated NF-κB up-regulated by TNF-α enhances Cox-2 expression. The finding that TGF-β, NF-κB and Cox-2 play a key role in pathogenesis in radiation-induced lung injury is an important clue about the blocking of this pathway as a new treatment approach. Curcumin〔1,7-bis(4-hydroxy-3-methoxy phenyl)-1, 6-heptadiene-3, 5-dione〕is a natural polyphenol in turmeric derived from the rhizome of the Indian plant Curcuma longa, a member of the ginger family. It has a yellow color and unique flavor and is used as a spice or coloring agent in Asian countries. Curcumin was shown to exert potential anti-inflammatory effects by inhibiting pro-inflammatory cytokine and chemokine production through blood monocytes and lung inflammatory cells and also to modulate the expression of adhesion molecules. Interestingly, the suppressive effect of curcumin has occurred through the inhibition of the NF-κB pathways and other pro-inflammatory signaling pathways including the mitogen-activated protein kinase (MAPK) pathway in recent studies. However, the effect of curcumin on RT-induced pneumonitis that these cytokines act mainly in pathogenesis has not been studied. The author hypothesized that curcumin could reduce pulmonary inflammation through suppression of pro-inflammatory cytokines such as TGF-β, NF-κB and Cox-2, which play a key role in radiation-induced pneumonitis. Therefore, this study was performed to evaluate the effect of curcumin on pulmonary inflammation in RT-induced pneumonitis rat models.
AI-Helper
※ AI-Helper는 부적절한 답변을 할 수 있습니다.