Arash Ghasemi

Radiosensitization Effects of a Zataria multiflora Extract on Human Glioblastoma Cells.

BACKGROUND Although radiotherapy is one of the most effective strategies in the treatment of cancers, it is associated with short and long term side effects on normal tissues. Zataria multiflora Boiss (Laminacea) (ZM) has several biological properties such as antioxidant and anti-inflammation activities.Here we investigated cell killing effects of a hydroalcoholic Zataria multiflora extract on cell death induced by ionizing radiation in a human glioblastoma cell line (A172) and human non-malignant fibroblasts (HFFF2) in vitro. MATERIALS AND METHODS A172 and HFFF2 cells were treated with a hydroalcoholic extract of dried aerial parts of Zataria multiflora at different concentrations (25, 50, 100, 150 and 200 μg/ml) and then exposed to ionizing radiation (IR). Cell proliferation and DNA fragmentation were evaluated. Thymol content in the extract was analyzed and quantified by HPLC methods. RESULTS A172 cell proliferation was significantly inhibited by ZM. The percentage cell survival was 91.8 ± 8.57 for cells treated with 200 μg/ml of ZM extract alone while it was 76.0 ± 4.27 and 66.2 ± 8.42 for cells treated with ZM and exposed to IR at doses of 3 Gy and 6Gy, respectively. Radiation-induced apoptosis in A172 cells was significantly increased following treatment with ZM at doses of 200 μg/ml. ZM extract did not exhibit any enhanced cell killing effects and apoptosis caused by IR on HFFF2 cells. CONCLUSIONS These data show selective radiosensitization effects of ZM in A172 cells apparently due to increased radiation-induced apoptosis.

Atorvastatin mitigates testicular injuries induced by ionizing radiation in mice

BACKGROUND Radiotherapy in patients with pelvis malignancy causes testes irradiation and resulted in testicular damages. Atorvastatin (ATV) in the low-dose is considered as antioxidant and anti-inflammatory properties. OBJECTIVE This experimental study was investigated protective effects of ATV on irradiation-induced testicular injury. MATERIAL AND METHODS Sixty male balb/c mice were randomly divided into 6 groups: 1: control, 2: irradiated (IR), 3, 4 and 5: IR plus ATV (10, 20 and 50mg/kg), 6: only ATV (50mg/kg). The ATV treated groups were received ATV for 7days via oral gavage before IR. Irradiated groups exposed to 2Gy whole body X-ray on day 8. Biochemical, histological and immunohistological parameters were evaluated for radioprotective effect of ATV. RESULTS In the ATV pretreatment in irradiated mice, MDA levels were significantly decreased compared with the IR group. The effect of all three doses of ATV caused reduced MDA level, but ATV to dose of 50mg/kg had more effect than other doses of ATV. Significant decrease in the concentration of testosterone was observed in only irradiated mice compared with the ATV plus irradiated. In addition, the histological examination showed Johnsen Score in the IR group was lower compared to ATV pretreated groups. ATV significantly reduced caspase-3 immunoreactivity induced by irradiation. CONCLUSION The results from this study suggest that ATV at low dose has a protective effect against irradiation-induced testicular damage. This result provides a new indication of ATV for protection of testis during radiation therapy in treatment of cancer patients.

Celecoxib mitigates genotoxicity induced by ionizing radiation in human blood lymphocytes

Ionizing radiation causes DNA damage and chromosome abbreviations on normal cells. The radioprotective effect of celecoxib (CLX) was investigated against genotoxicity induced by ionizing radiation in cultured human blood lymphocytes. Peripheral blood samples were collected from human volunteers and were incubated at different concentrations at 1, 5, 10 and 50 μM of CLX for two hours. At each dose point, the whole blood was exposed in vitro to 150 cGy of X-ray, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronucleus frequency in cytokinesis blocked binucleated lymphocytes. Incubation of the whole blood with CLX exhibited a significant decrease in the incidence of micronuclei in lymphocytes induced by ionizing radiation, as compared with similarly irradiated lymphocytes without CLX treatment. The maximum reduction on the frequency of micronuclei was observed at 50 μM of CLX (65% decrease). This data may have an important possible application for the protection of human lymphocytes from the genetic damage induced by ionizing irradiation in human exposed to radiation.

Radioprotective Effect of Achillea millefolium L Against Genotoxicity Induced by Ionizing Radiation in Human Normal Lymphocytes.

The radioprotective effect of Achillea millefolium L (ACM) extract was investigated against genotoxicity induced by ionizing radiation (IR) in human lymphocytes. Peripheral blood samples were collected from human volunteers and incubated with the methanolic extract of ACM at different concentrations (10, 50, 100, and 200 μg/mL) for 2 hours. At each dose point, the whole blood was exposed in vitro to 2.5 Gy of X-ray and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cell. Antioxidant capacity of the extract was determined using free radical-scavenging method. The treatment of lymphocytes with the extract showed a significant decrease in the incidence of micronuclei binucleated cells, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection and decrease in frequency of micronuclei were observed at 200 μg/mL of ACM extract which completely protected genotoxicity induced by IR in human lymphocytes. Achillea millefolium extract exhibited concentration-dependent radical-scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. These data suggest that the methanolic extract of ACM may play an important role in the protection of normal tissues against genetic damage induced by IR.

Radiosensitizing Effect of Cerium Oxide Nanoparticles on Human Leukemia Cells

BACKGROUND Radiotherapy is an important protocol in the treatment of cancers, but radioresistance of cancerous cells is a challenge in cancer treatment. OBJECTIVE The aim of this study was to evaluate the radiosensitizing effect of Cerium oxide Nanoparticles (CNPs) on human promyelocytic leukemia cells (HL-60). METHOD HL-60 cells were treated with CNPs at different concentrations (10-100 μg/ml) and exposed to Ionizing Radiation (IR). The genotoxicity effects of CNPs or/and IR were assessed by micronuclei assay in HL-60 cells. RESULTS It was found that CNPs increased the frequencies of micronuclei in HL-60 cells. CNPs pretreatment to irradiation significantly increased the IR-induced micronuclei incidences in HL-60 cells. The present study demonstrates CNPs to be an effective sensitizer on DNA damage induced by IR in HL-60 cells. CONCLUSION These findings suggest the potential application of CNPs as a highly effective radiosensitizer for the treatment of leukemia.

Radioprotective effect of atorvastatin against ionizing radiation-induced nephrotoxicity in mice

Abstract Purpose: Kidneys are exposed to ionizing radiation during radiotherapy in patients with abdominal malignancy. The aim of this study is to investigate the protective effect of atorvastatin (ATV) against ionizing radiation-induced nephrotoxicity in mice. Materials and methods: Sixty male BALB/c mice were randomly divided into six groups (10 mice per group); control, irradiation (IR), IR plus ATV (10, 20 and 50 mg/kg) and only ATV (50 mg/kg). ATV groups received ATV for seven days via oral gavage before exposure to IR. Animals were exposed to 2 Gy whole body of X-ray on day 8. After exposure to IR, biochemical, histological and immunohistological assays were performed. Results: ATV significantly decreased the level of oxidative stress biomarkers in irradiated mice in comparison with IR alone. A significant reduction in the urea and creatinine levels was observed in ATV plus IR group compared to IR alone. Tubular degeneration, glomerular atrophy, interstitial expansion and fibrosis were observed in irradiated mice. Tubular degeneration and atrophy in the kidneys of IR plus ATV group were less than IR group. In addition, pre-treated animal with ATV significantly showed reduction in caspase-3 immunoreactivity. Conclusion: ATV has significant protective effect against radiation-induced nephrotoxicity in mice and is a promising medication for protection of patients during radiotherapy.

Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes

Purpose Mefenamic acid (MEF) as a non-steroidal anti-inflammatory drug is used as a medication for relieving of pain and inflammation. Radiation-induced inflammation process is involved in DNA damage and cell death. In this study, the radioprotective effect of MEF was investigated against genotoxicity induced by ionizing radiation in human blood lymphocytes. Materials and Methods Peripheral blood samples were collected from human volunteers and incubated with MEF at different concentrations (5, 10, 50, or 100 µM) for two hours. The whole blood was exposed to ionizing radiation at a dose 1.5 Gy. Lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis blocked binucleated lymphocyte. Results A significant decreasing in the frequency of micronuclei was observed in human lymphocytes irradiated with MEF as compared to irradiated lymphocytes without MEF. The maximum decreasing in frequency of micronuclei was observed at 100 µM of MEF (38% decrease), providing maximal protection against ionizing radiation. Conclusion The radioprotective effect of MEF is probably related to anti-inflammatory property of MEF on human lymphocytes.

Cerium oxide nanoparticles sensitize non-small lung cancer cell to ionizing radiation

Radiotherapy is an important strategy for cancer treatment, but resistance of tumor cells to ionizing radiation (IR) still remains a main challenging issue related to radiotherapy. The aim of this study was to evaluate the sensitizing effect of cerium oxide nanoparticles (CNPs) on non-small lung cancer (A-549) cells exposure to IR. A-549 cells were treated with CNPs and exposed to IR at dose 2 Gy. The radiosensitizing effect of CNPs was evaluated by clonogenic assay and flowcytometry. The findings of this study showed that CNPs reduced the frequencies of A-549 colony when these cells were exposed to IR. CNPs treatment prior exposure to IR significantly increased the IR-induced apoptotic incidences in A-549 cells. The present study demonstrates that CNPs to be an effective sensitizer on apoptosis and cell death induced by IR in A-549 cells.

Radioprotective Effect of Cerium Oxide Nanoparticles Against Genotoxicity Induced by Ionizing Radiation on Human Lymphocytes

BACKGROUND Ionizing radiation induces DNA damage on normal cell results in apoptosis and cell deaths. OBJECTIVES The radioprotective effects of cerium oxide nanoparticles (CNPs) on genotoxicity, apoptosis and necrosis induced by Ionizing Radiation (IR) in human healthy lymphocytes as highly radiosensitive cells were investigated. MATERIALS AND METHODS Lymphocytes were prepared from three volunteers and then treated with CNPs at different concentrations and exposed to IR at dose 1.5 Gy. The radioprotective effects of CNPs were assessed by micronucleus (MN) assay and flow cytometry. Interleukin-1 was quantified in treated samples. RESULTS It was found that CNPs reduced the percentage of MN induced by IR in lymphocytes up to 73%. CNPs treatment significantly reduced IR-induced apoptotic and necrotic incidences in human lymphocytes. CNPs significantly reduced IL-1β produced in cell environment exposed to IR. The present study demonstrated that CNPs may be an effective radioprotector against DNA damage and apoptosis induced by IR mainly through mitigation of pro-inflammatory process in lymphocytes. CONCLUSION This result provides a new potential indication of CNPs for protection of normal cells during radiation therapy in the treatment of cancer or unwanted radiation exposure.

The effectiveness of Zataria extract mouthwash for the management of radiation-induced oral mucositis in patients: a randomized placebo-controlled double-blind study

AbstractObjectivesOral mucositis (OM) is a common debilitating complication of chemoradiotherapy treatment of head and neck cancers. This randomized placebo-controlled double-blind clinical trial study was performed to evaluate the effectiveness of Zataria multiflora (ZM) extract mouthwash in the prevention and reduction of OM related to local radiotherapy in the treatment of head and neck cancer patients.MethodsSixty-three patients with head and neck cancers, who underwent a conventional fractionated radiotherapy regimen, were entered into the study. Patients gargled the ZM mouthwash or a placebo before the beginning of the treatment three times daily and before each radiotherapy session. The assessment of OM was conducted according to WHO and Oral Mucositis Assessment Scale.ResultsThe OM intensity trends in the ZM group during these weeks of treatment were detected 3.152 times less frequently than in the placebo group. A twofold decrease in the incidence of grades 3–4 OM was observed in the ZM group compared to the placebo. The use of the ZM mouthwash affected the incidence of grades 3–4 OM to a relative risk ratio of 0.432. The pain score was significantly decreased in the ZM group compared to the placebo group.ConclusionThe present study revealed that ZM mouthwash effectively decreases the severity of OM and mouth pain in patients with head and neck cancer treated with radiotherapy.Clinical relevanceThe use of ZM mouthwash effectively decreases the severity of oral complications induced by ionizing radiation in patients during radiotherapy and resulted in high oral quality care. Graphical abstractᅟ