The role of bacteria and its derived biomaterials in cancer radiotherapy

Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics. It has made significant progress in breaking the limitations of monotherapy and effectively eradicating tumors, especially when combined with traditional therapy, such as radiotherapy. According to their different biological characteristics, bacteria and their derivatives can not only improve the sensitivity of tumor radiotherapy but also protect normal tissues. Moreover, genetically engineered bacteria and bacteria-based biomaterials have further expanded the scope of their applications in radiotherapy. In this review, we have summarized relevant researches on the application of bacteria and its derivatives in radiotherapy in recent years, expounding that the bacteria, bacterial derivatives and bacteria-based biomaterials can not only directly enhance radiotherapy but also improve the anti-tumor effect by improving the tumor microenvironment (TME) and immune effects. Furthermore, some probiotics can also protect normal tissues and organs such as intestines from radiation via anti-inflammatory, anti-oxidation and apoptosis inhibition. In conclusion, the prospect of bacteria in radiotherapy will be very extensive, but its biological safety and mechanism need to be further evaluated and studied.

The probable radioprotective role of Acacia nilotica L. against biochemical and cytogenetic disorders induced in gamma irradiated male rats

Gum Arabic (Acacia nilotica L.) is a respected plant that has many nutrients and curative practices. It hinders, improves, or manages many disorders. The radio-protective activity of Acacia nilotica was investigated against γ-rays-induced testicle damage in rats. Twenty-four rats were correspondingly distributed into 4 groups; control, Acacia nilotica (15mg/kg, daily for 30 days), γ-irradiated (5Gy γ-rays, single dose) and Acacia nilotica plus γ-rays treated groups. The plasma testosterone and total antioxidant status (TAS) were estimated. Lipid peroxidation; malondialdehyde (MDA), reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), also glutathione peroxidase (GPx), catalase (CAT), tumor necrosis factor-α (TNF-α) with interleukin-1ß (IL-1ß), were determined in the testicle tissues. A testis weight, sperm count and motility, peripheral-blood and bone-marrow micronuclei (PMN and BMN), and frequency of chromosomal aberrations (CAs) were scored. A significant decline in the levels of plasma testosterone with TAS observed in the γ-irradiated rats. The results also showed significantly increased levels of testicle MDA, inflammatory markers, PMN, BMN and CAs frequencies and decrease in testes weight, sperm count and motility and levels of testicle antioxidants markers in gamma irradiated group. All these biochemical and fertility indices results were significantly enhanced in the Acacia nilotica plus γ-rays treated groups. However, the possible alleviate activity of Acacia nilotica on γ-rays-induced testicle injury in rats has not previously conversed, and this is the topic of this study.

Research Advance in Ionizing Radiation Protection and Repair of Polysaccharide / 中国药师

Ionizing radiation can directly attack biological macromolecules including DNA, protein and lipids. Radiation can also damage cells indirectly by the formation of lots of free radicals through the radiolysis of surrounding water molecules. As the result, ion-izing radiation may make serious injury in human immune system, reproductive system and nervous system. Several synthetic radiopro-tectors have been used in clinic. However, most of them have some undesirable side effects. Hence, natural radioprotectors with high efficiency and low toxicity have been the focus of radioprotection field in recent years. In the paper, the recent research progress in the protection and repair effects of polysaccharides on radiation damage was reviewed.

Radiomodulation by Hoechst 33258 against radiation- induced damage in murine splenocytes.

In this study modulatory effect of Hoechst 33258 on radiation induced membrane related signaling events which ultimately leads to apoptosis has been investigated. Splenocytes from swiss albino mice were irradiated in air at room temperature in a gamma chamber (240 TBq 60Co Model 4000 A) at the dose-rate of 0.052 Gys-1. Membrane lipid peroxidation, fluidity, specific activities of antioxidant enzymes, levels of nitric oxide, glutathione and apoptosis in presence and absence of different concentrations of Hoechst 33258 has been assayed. DNA binding activity of nuclear factor kappa B and activator protein–1 was also assayed by electrophoretic mobility shift assay. Modulatory effect of Hoechst 33258 was examined at 3 and 5 Gy using different concentrations (10, 20 and 30 µM). Hoechst 33258 was found to inhibit radiation induced peroxidative damage and fluidity and lowered the level of nitric oxide and apoptosis - as evident by DNA ladder assay and FACS, indicating free radicals scavenging potential. Dot plot diagramme clearly showed that 30 µM Hoechst 33258 caused 14% and 19% decrease in apoptotic cells at 3 Gy and 5 Gy of radiation respectively (compared to irradiated control group). Further DNA binding activity of nuclear factor kappa B and activator protein–1 was also inhibited but the antioxidant potential of the cells was enhanced. These findings support that Hoechst 33258 protects the cell from undergoing apoptosis. Hoechst 33258 may have interacted and has an ability to protect splenocytes against radiation induced apoptosis through modulation of membrane-related signaling events and antioxidant status.

The Radioprotective Effect and Mechanism of Captopril on Radiation Induced-Heart Damage in Rats / 대한방사선종양학회지

PURPOSE: Captopril (angiotension converting enzyme inhibitor) is known to have a radioprotective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotective effect and mechanism of captopril in the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. MATERIALS AND METHODS: The histopathological changes and immunohistochemical stains (TNF alpha, TGFbeta1, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. RESULTS: In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema (p=0.082) and fibrin deposit (p=0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit (p=0.047) in the atrium, and the interstitial fibrin deposit (p=0.019) and edema (p=0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of TNF-alpha, TGF-beta1, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial TNF-alpha and TGF-beta1 in the radiation alone group continuously increased. The expressions of TNF-alpha, TGF-beta1 and PDGF were decreased in the combined group at 2 weeks. At 8 weeks, the expressions of TNF-alpha in the atrial and ventricular pericardia were markedly reduced (p=0.049, p=0.009). CONCLUSIONS: This study revealed that the early heart damage induced by radiation can be reduced by the addition of captopril in a rat model. The expressions of TNF-alpha, TGF-beta1 and PDGF were further decreased in the combined compared to the radiation alone group at both 2 and 8 weeks. From these results, it may be concluded that these cytokines probably play roles in the radioprotective mechanism of captopril from the radiation-induced heart toxicity, similarly to in other organs.

The Radioprotective Effect and Mechanism of Captopril on Radiation Induced Lung Damage in Rat / 대한방사선종양학회지

PURPOSE: It was reported that Captopril (angiotensin converting enzyme inhibitor) had an effect to reduce the pneumonitis and pulmonary fibrosis induced by radiation in rat. We performed this study to investigate the radioprotective effect and mechanism of Captopril. METHODS AND MATERIALS: The comparison was made between the radiation only group and the combined Captopril and radiation group by examining histopathologic findings and immunohistochemical stains (TNFalpha and TGFbeta1) at 2 and 8 weeks after irradiation. Each group has 8 to 10 rats (Sprague-Dawley). 12.5 Gy of X-ray was irradiated to the left hemithorax in a single fraction. Captopril (50 mg/kg/d) mixed with water was given per oral and continuously from 1 week prior to irradiation up to 8th week of the experiment. RESULT: In the combined Captopril and radiation group, the histopathologic changes which were hemorrhage into alveolar space, changes of alveolar epithelium, bronchial epithelium and blood vessels, and perivascular edema were less severe than in the radisation only group at 2 weeks. At 8 weeks, the alveolar epithelial changes and perivascular edema were less prominant in the combined Captopril and radiation group. At 2 weeks, the TNFalpha expression of the combined Captopril and radiation group was markedly decreased at the alveolar epithelium (p<0.01), lymphoid tissue (p=0.06) and the macrophage of alveolar space (p<0.01) compared with the radiation only group. Furthermore the TGFbeta1 expression was significantly prominant at the alveolar epithelium (p<0.02) and the macrophage in alveolar space (p< 0.02). At 8 weeks, the expression of TNFalpha and TGFbeta1 of most sites, except TGFbeta1 of the macrophage of alveolar space (p=0.09), showed no significant difference between 2 groups. CONCLUSION: This study revealed that early lung damage induced by irradiation was reduced with the addition of Captopril in the latent and early pneumonitis phase. The expression of TNFalpha and TGFbeta1 at 2 weeks and TGFbeta1 at 8 weeks was further decreased in the combined Captopril and radiation group than the radiation only group. From these results, it may be concluded that the proinflammatoy cytokine (TNFalpha) and fibrogenic cytokine (TGFbeta1) probably play the role of the radioprotective mechanism in Captopril.

Histomorphologic Change of Radiation Pneumonitis in Rat Lungs : Captopril Reduces Rat Lung Injury Induced by Irradiation / 대한방사선종양학회지

PURPOSE: To assess the histomorphologic changes in the rat lung injury induced by radiation, to determine whether captopril reduces the rat lung injury and to evaluate change in TNF-alpha and TGF-beta in rat lung damage by radiation and captopril. METHODS AND MATERIAL: Right lungs in male Sprague-Dawley rats were divided irradiation alone (10, 20, 30 Gy) or radiation (same dose with radiation alone group) with captopril (500 mg/L). Radiation alone group were sacrificed at twelve hours and eleven weeks after radiation and radiation with captopril group (captopril group) were sacrificed at eleven weeks after radiation with captopril. We examined the light microscope and electron microscopic features in the groups. RESULTS: In radiation alone group, there were patch parenchymal collapse and consolidation at twelve hours after radiation. The increase of radiation dose shows more prominent the severity and broader the affected areas. Eleven weeks after radiation, the severity and areas of fibrosis had increased in proportion to radiation dose given in the radiation alone group. There was notable decrease of lung fibrosis in captopril group than in radiation alone group. The number of mast cells rapidly increased with increase of radiation dose in radiation alone group and the degree of increase of mast cell number and severity of collagen accumulation more decreased in captopril group than in radiation alone group. In radiation alone group, expression of TNF-alpha and TGF-beta increased according to increase of radiation dose at twelve hours after radiation in both group. At eleven weeks after radiation, expression of TGF-beta increased according to increase of radiation dose in radiation group but somewhat decreased in captopril group. In the captopril group the collagen deposition increased but less dense than those of radiation alone group. The severity of perivascular thickening, capillary change, the number and degranulation of mast cells more decreased in the captopril group than in the radiation alone group. CONCLUSION: It is concluded that the effect of captopril in the rat lungs after radiation was considered to be due to its effect on inhibition of mast cells and reduction of collagen deposition, and captopril may be protect in lung damage after radiation. We observed expression of TNF-alpha and TGF-beta increased at the early phase after radiation and expression of TGF-beta increased in proportion to increase of radiation dose at the chronic phase after radiation. This results will contribute to future investigation in reduction mechanism of captopril in lung damage after radiation.

Effect of Radiotherapy on the Ascorbate (vitamin C) Levels in Whore Blood and Plasmas / 대한치료방사선과학회지

The role of ascorbate as an antioxidant in the prevention and cure of disease that result from free radicals has been of considerable interest and controversy lately. As an antioxidant, we can expect it to protect against radiation damage caused by free radicals that are produced when radiation, especially sparsely ionizing radiation, interacts with living tissues. The plasma and whole blood concentration of ascorbate was analyzed before and just after the radiation therapy for the purpose of estimating the consumption amount of ascorbate during radiotherapy. Whole blood ascorbate was decreased from 1.82 mg/dl to 1.58 mg/dl, plasma ascorbate was decreased from 1.13 mg/dl to 1.08 mg/dl, and urine ascorbate was decreased from 9.33 mg/dl to 6.96 mg/dl after radiotherapy. Although the difference was not significant statistically, further human study should be followed to define the role of ascorbate as a radioprotector.

Radioprotective Effect of Mesna on Mouse Testis / 대한치료방사선과학회지

Mesna has been used with ifosfamide to prevent urotoxicity in the treatment of testicular cancers. This drug also protected the toxicities of adriamycin without compromising cytostatic activity. With n idea of radioprotective role of sulfhydryl group of radioprotectors and of mesna decreasing the toxic effect of adriamycin which produces free radicals, mesna and radiation were administered to mice to study the protective effect of this drug and to identify the difference in regenerative capacity of the germ cells in the testis between radiation-treated and both mesna- and radiation-treated groups. The shape and numbers of spermatogenic cells in the seminiferous tubules were examined every week after irradiation. In both groups, initial reduction and later recovery in germ seel numbers and shape was observed. The lowest germ cell number was found around three weeks after irradiation. Mean germ cell number of the mesna-treated group was significantly higher than radiation-treated group at all observed periods (p<0.05). More competent regeneration was present in mesna-treated group. These results suggest that mesna protect the testis from radiation injury. Further study will be necessary to identify whether mesna protects other tissues from radiation and it does not hamper tumor control.