Celecoxib A Selective COX-2 Inhibitor Mitigates Fibrosis but not Pneumonitis Following Lung Irradiation: A Histopathological Study

Background: Lung is one of the radiosensitive and late responding organs, and is an important target for ionizing radiation. Radiation-induced pneumonitis and fibrosis are major consequences of lung exposure to a high dose of radiation and pose threats to the lives of exposed people. Mitigation of lung injury following an accidental radiation event or for patients with lung cancer is one of the most interesting issues in radiobiology. In the current study, we aimed to determine whether celecoxib, the most common cyclooxygenase-2 (COX-2) inhibitor, is able to mitigate pneumonitis and fibrosis following lung irradiation or not. Materials and methods: 20 male mice were assigned to 4 groups: control, celecoxib treatment, radiation, and radiation plus celecoxib. Irradiation was performed with a dose of 18 Gy cobalt-60 (60Co) gamma rays. Celecoxib treatment (50 mg/kg) started 24 h after irradiation and continued four times per week for 4 weeks. Results: Irradiation of lung led to remarkable infiltration of macrophages, lymphocytes, mast cells and neutrophils. Also, a mild increase in fibrosis markers including accumulation of collagen, and alveolar and vascular thickening, was observed. Post-exposure treatment with celecoxib was able to mitigate fibrosis as well as alveolar and vascular changes, however, it was unable to mitigate pneumonitis markers. Conclusion: Celecoxib showed that it may have an anti-fibrosis effect following exposure of mice lung to radiation, although it was unable to prevent pneumonitis.

Protective Effect of Selenium-L-methionine on Radiation-induced Acute Pneumonitis and Lung Fibrosis in Rat

Background: In this study, we aimed to detect the changes in the level of interleukin (IL)-4 and IL-13 cytokines and their downstream genes including interleukin-13 receptor subunit alpha-2 (IL13Ra2), interleukin-4 receptor subunit alpha-1 (IL4Ra1), dual oxidase 1 (DUOX1) and dual oxidase 2 (DUOX2). The protective effects of Selenium-L-methionine on radiation-induced histopathological damages and changes in the level of these cytokines and genes were detected. Methods: Four groups of 20 rats (5 rats in each) namely, control; Selenium-L-methionine, radiation and radiation plus Selenium-L-methionine were used in this study. 4 mg/kg of Selenium-Lmethionine was administered 1 day before irradiation and five consecutive days after irradiation. Irradiation was done using a dose of 15 Gy 60Co gamma rays at 109 cGy/min. All rats were sacrificed 10 weeks after irradiation for detecting changes in IL-4 and IL-13 cytokines, the expressions of IL13Ra2, IL4Ra1, Duox1 and Duox2 and histopathological changes. Results: The level of IL-4 but not IL-13 increased after irradiation. This was associated with increased expression of IL4Ra1, Duox1 and Duox2, in addition to changes in morphological properties. Selenium-L-methionine could attenuate all injury markers following lung irradiation. Conclusion: Selenium-L-methionine can protect lung tissues against toxic effects of ionizing radiation. It is possible that the modulation of immune responses and redox interactions are involved in the radioprotective effect of this agent.

Evaluation on The Supplementation of Fermented Garlic Extract in Protecting Human Lymphocytes In Vitro From The Negative Impact of Gamma-Rays

Garlic (Allium sativum) contains a wide range of phytocompounds that produce various responses in human body. However the knowledge on the potential of fermented form of garlic in protecting negative impacts of radiation is very limited. In this research in vitro efficacy of fermented garlic in protecting negative impact of gamma ray was studied using cytogenetic test. A set of culture of human lymphocytes was irradiated with 60Co gamma rays at dose of 2 Gy (dose rate of 2 Gy/min) and fermented garlic extract at four working concentrations of 0, 125, 250 and 500 mg/mL were added to these cells and then were incubated at 37oC for 48 hrs. Colcemid was added at 3 hr before harvest to collect metaphase cells and it was done by standard methodology for cytogenetic analysis. The fermented garlic extract significantly (p<0.05) did not exhibited antigenotoxic effect of gamma rays and its effectiveness was same as in control (without extract treatment) group. In contrary all concentration of chemicals (125, 250 and 500 mg/mL) were seemingly tend to induce higher number of dicentric and fragment chromosomes than control under microscopic observation. Mitotic index of the cell that was determined with programmed metaphase finder also did not influenced by garlic addition. It was concluded that aqueous garlic extract did not possesses its efficacy in protecting impact of ionizing radiation.