beta-irradiation (166Ho patch)-induced skin injury in mini-pigs: effects on NF-kappaB and COX-2 expression in the skin

In the present study, the detrimental effect of beta-emission on pig skin was evaluated. Skin injury was modeled in mini-pigs by exposing the animals to 50 and 100 Gy of beta-emission delivered by 166Ho patches. Clinicopathological and immunohistochemical changes in exposed skin were monitored for 18 weeks after beta-irradiation. Radiation induced desquamation at 2~4 weeks and gradual repair of this damage was evident 6 weeks after irradiation. Changes in basal cell density and skin depth corresponded to clinically relevant changes. Skin thickness began to decrease 1 week after irradiation, and the skin was thinnest 4 weeks after irradiation. Skin thickness increased transiently during recovery from irradiation-induced skin injury, which was evident 6~8 weeks after irradiation. Epidermal expression of nuclear factor-kappa B (NF-kappaB) differed significantly between the untreated and irradiated areas. One week after irradiation, cyclooxygenase-2 (COX-2) expression was mostly limited to the basal cell layer and scattered among these cells. High levels of COX-2 expression were detected throughout the full depth of the skin 4 weeks after irradiation. These findings suggest that NF-kappaB and COX-2 play roles in epidermal cell regeneration following beta-irradiation of mini-pig skin.

Analysis of the physical activity effects and measurement of pro-inflammatory cytokines in irradiated lungs in rats / Análise dos efeitos da atividade física e mensuração de citocinas pró-inflamatórias em pulmões irradiados em ratos

PURPOSE: To study if the pre-radiotherapy physical activity has radio-protective elements, by measuring the radio-induced activation of pro-inflammatory cytokines as interleukin-6 (il-6), transforming growth factor -β (tgf -β), tumor necrosis factor -α (tnf-α) and protein beta kinase β (ikkβ), through western blotting analysis. METHODS: A randomized study with 28 Wistar hannover rats, males, with a mean age of 90 days and weighing about 200 grams. The animals were divided into three groups: (GI, GII and GIII). GIII group were submitted to swimming for eight weeks (zero load, three times a week, about 30 minutes). Then, the groups (except the control group) were submitted to irradiation by cobalt therapy, single dose of 3.5 gray in the whole body. All animals were sacrificed by overdose of pentobarbital, according to the time for analysis of cytokines, and then a fragment of the lower lobe of the right lung went to western blotting analysis. RESULTS: The cytokines IKK β, TNF-α and IL-6 induced by radiation in the lung were lower in the exercised animals. However, exercise did not alter the radiation-induced increase in tgf-β. CONCLUSION: The results show a lower response in relation to inflammatory cytokines in the group that practiced the exercise pre-radiotherapy, showing that exercise can protect tissues from tissue damage due to irradiation.

OBJETIVO: Verificar se a radioterapia pré-atividade física tem elementos de rádio-proteção, medindo-se a ativação de citocinas pró-inflamatórias como a interleucina-6 (IL-6), fator transformador de crescimento - β (TGF - β), fator de necrose tumoral - α (TNF-α) e quinase de proteína beta β (IKK β), por meio da análise blotting ocidental. MÉTODOS: Um estudo randomizado empregando 28 ratos Wistar Hannover, machos, com idade média de 90 dias e pesando cerca de 200 gramas. Os animais foram divididos em três grupos: (GI, GII e GIII). Os animais do grupo GIII foram submetidos à natação durante oito semanas (carga zero, três vezes por semana, cerca de 30 minutos). Então, os grupos (exceto o grupo controle) foram submetidos à irradiação por cobalto terapia, dose única de 3,5 cinza em todo o corpo. Todos os animais foram sacrificados por overdose de pentobarbital, de acordo com o tempo de análise de citocinas, em seguida, um fragmento do lobo inferior do pulmão direito foi a análise de mata-borrão ocidental. RESULTADOS: As citocinas IKK β, TNF-α e IL-6 induzidas por radiação no pulmão foram menores nos animais que se exercitaram. No entanto, o exercício não alterou o aumento induzido pela radiação na TGF-β. CONCLUSÃO: Os resultados mostraram uma menor resposta em relação às citocinas inflamatórias no grupo que praticou o exercício físico pré-radioterapia, evidenciando que o exercício pode proteger os tecidos das lesões teciduais decorrentes da irradiação.

Increased Expression of EMMPRIN and VEGF in the Rat Brain after Gamma Irradiation

The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to play a key regulatory role in pathological angiogenesis. A elevated activation of vascular endothelial growth factor (VEGF) following radiation injury has been shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes in a rat model of radiation injury following GKS and examined potential associations between EMMPRIN and VEGF expression. Adult male rats were subjected to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and VEGF expression were markedly upregulated in the target area at 8-12 weeks after GKS compared with the control group by western blot, immunohistochemistry, and RT-PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated that increased EMMPRIN expression was correlated with increased VEGF levels in a temporal manner. This is the first study to show that EMMPRIN and VEGF may play a role in radiation injuries of the central nervous system after GKS.

The effects of Ligustrazine on the expression of bFGF and bFGFR in bone marrow in radiation injured mice / 华中科技大学学报（医学）（英德文版）

To study the expression of the bFGF and its receptor in the mouse bone marrow by treatment with acute radioactive injury and Ligustrazine, 56 mice were divided into 3 groups: normal group, radiation-injured group and Ligustrazine group. After irradiation by 6.0 Gy 60Co gamma-ray, each mouse was orally given 0.1 ml Ligustrazine twice a day for 13 days in Ligustrazine group, and each mouse in radiation injured group was orally given equal amount of saline. On the 3rd, 7th, 14th day after irradiation, bone marrow mono-nuclear cells (BMMNC) were counted, and the expression levels of bPGF and bFGFR in bone marrow were evaluated by immunohistochemistry and flow cytometry analysis respectively. On the 3rd, 7th, 14th day after irradiation, expression of bFGF in bone marrow were significantly lower than in normal group (P<0.05 or P<0.01). Expressions of bFGF and bFGFR were much higher in Ligustrazine treated group than that in the control group (P<0.05 or P<0.01). Ligustrazine potentiate the expression of bFGF and bFGFR in bone marrow MNC to recover the bone marrow hematopoiesis inductive microenvironment, which is one of the mechanisms by which Ligustrazine rebuild the bone marrow hematopoiesis after acute radioactive injury.