Effect of curcumin on γ-ray-induced cell response.

The purpose of the present study is to evaluate the effect of curcumin as a natural compound against radiation induced γ-foci and stable chromosome aberrations. Whole blood samples form three human volunteers were pretreated with curcumin at different concentrations (0.5, 10, 20 and 100 µg/ml). After 1-hour incubation, the lymphocytes were exposed to γ-rays (0.05, 0.5, 1 and 2 Gy). Radiation induced changes in cells were quantified using γ-H2AX/53BP1 assay and FISH analysis. Our results have shown that curcumin significantly reduced the frequency of both γ-foci and translocations. We found concentration-dependent increase of curcumin protective effect on γ-H2AX/53BP1 foci formation at all radiation doses. Concerning the translocations, after 0.05 and 0.5 Gy γ-rays the values of genomic frequencies are comparable within each dose and we did not observe any impact of curcumin. The most protective effect after 1 Gy exposure was found at 100 µg/ml curcumin. At 2 Gy irradiation, the maximum protection was achieved at 0.5 and 10 µg/ml of curcumin. Concentrations of 20 and 100 µg/ml also prevent lymphocytes but to less extent. Our in vitro study indicates radioprotective efficacy of curcumin against γ-ray induced damages in human lymphocytes. This observation suggests that curcumin may play a role to protect patients undergoing radiological procedures.

Inflammatory profile dysregulation in nuclear workers occupationally exposed to low-dose gamma radiation.

Chronic inflammation is a common denominator linking a wide range of health conditions, including tissue response to radiation exposure. This pilot study investigates whether inflammatory cytokines-interleukins IL-6, -8, -10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor α (TNFα)-can be used as early biomarkers of radiation-induced adverse health effects in occupationally exposed individuals. The study included 33 workers externally exposed to gamma radiation from the nuclear industry with cumulated doses from 0.11 to 190 mSv and 42 non-exposed controls of comparable age and socio-economic status. IL-6, IL-8, MCP-1, TNFα and IL-10 were analyzed by enzyme-linked assay (ELISA) in blood plasma samples. Total antioxidant status (TAS) of blood plasma was determined by a colorimetric assay. The radiation-exposed and control groups measured significantly different levels of MCP-1, TNFα and IL-10. Seventy-five percent of radiation workers had either high MCP-1 levels or low IL-10 levels and 30% had all three cytokines dysregulated. Approximately 50% of workers showed upregulated antioxidant status, which appeared to compensate the pro-inflammatory cytokine shift in these individuals. In contrast, only 2% of the control subjects were found to have three dysregulated cytokines, and all of them measured within the normal TAS range. The present study may represent an important step towards the establishment of a reliable set of biomarkers for health-risk estimation in population cohorts exposed to low radiation doses.

The soluble receptor ST2 is positively associated with occupational exposure to radiation.

Purpose Radiation exposure, besides the risk of cancer, may also increase the risk of non-cancer diseases, including cardiovascular disease (CVD). This study investigates whether the soluble form of the ST2 receptor (sST2), an emerging prognostic marker in patients with CVD, can be used to monitor the CVD risk in individuals occupationally exposed to radiation. Materials and methods sST2 in blood plasma from 69 individuals, 45 workers from the nuclear industry and 24 controls, was analyzed using enzyme-linked assay (ELISA). Total antioxidant status (TAS) of blood plasma and levels of reactive oxygen species (ROS) in lymphocytes were determined by colorimetric and fluorescence assays. Results The data suggest a 5-fold increase in the number of subjects with sST2 levels above the clinical threshold and a 10-fold increase in the number of subjects with TAS levels outside the reference range in the exposed group when compared to the group of non-exposed individuals. The strongest up-regulation of TAS was measured in the group of younger workers with cumulative doses not exceeding 50 mSv. Conclusion The present study may represent an initial step towards the establishment of sST2 as a biomarker for CVD risk estimation in the context of radiation exposure.

Proteasome inhibition protects human peripheral blood mononuclear cells from radiation-induced oxidative stress.

PURPOSE: The study aimed to analyze the impact of the proteasome inhibitors MG132 (N-carbobenzyoxyl-L-leucyl-L-leucyl-L-leucinal), lactacystin and celastrol on manganese superoxide dismutase (MnSOD), catalase and glutathione-S-transferase-π (GST-π), and on the heat shock protein 70 (Hsp70) in human peripheral blood mononuclear cells (PBMC), exposed to ionizing radiation. MATERIALS AND METHODS: Changes in protein levels were analyzed by Western blot. Cellular viability, proteasome activity, level of oxidative stress and apoptosis were determined by standard colorimetric and fluorescence assays. RESULTS: MG132 and lactacystin induced an increase in the intracellular levels of Hsp70. MnSOD was up-regulated by MG132 and celastrol, and GST-π was up-regulated by MG132 and lactacystin. Notably, the proteasome inhibitors significantly modified the protein levels in the irradiated cells and dramatically reduced the intracellular pool of oxidative species. The combined effect of radiation and proteasome inhibition was a dose-dependent up-regulation of the antioxidant enzymes and Hsp70. CONCLUSIONS: All three proteasome inhibitors showed antioxidant effects in PBMC and up-regulated the antioxidant enzymes MnSOD, catalase and GST-π and the stress protein Hsp70, modifying the early radiation response, and conferring protection against the effects of ionizing radiation.