The effect of ionizing radiation on the fetal bone development in pregnant rats: Role of melatonin.

Radiation has been widely used in many business sectors over the last century. Our study investigated the possible teratogenic effects of radiation on the bones of rat fetuses and the protective effect of melatonin against these effects. In this study, 15 pregnant female Wistar albino rats were used. These rats were divided into four groups: the control group, melatonin group (10 mg/kg/day), radiation group (0.5 gray), radiation (0.5 gray) + melatonin group (10 mg/kg/day), and sham group (1 mm hanks/day). The skeletal system development of fetuses was examined with double skeletal and scanning electron microscope (SEM), histopathological methods. In our study, fetal weight, placental weight, and fetal morphometric values were found to be statistically significantly decreased in the radiation group compared to the control group (p < .05). In immünohistochemistry (IHC) analysis, alkaline phosphatase, and tartrate-resistant acid phosphatase) concentrations were found to be significantly lower in the radiation group compared to the other groups. In the SEM analysis, it was observed that the amount of calcium and sodium decreased when the radiation group was compared with the other groups. As a result, when exposed to ionizing radiation during pregnancy, melatonin has a protective feature against the negative effects of radiation on the bone development of fetuses. RESEARCH HIGHLIGHTS: In our study, fetuses obtained from pregnant rats exposed to ionizing radiation were examined. In this study, the effect of melatonin on bone development in fetuses exposed to gray ionizing radiation was investigated. There are few studies on our subject in the literature. We believe that our findings will contribute to other planned studies.

Investigation of the anti-oxidative and anti-inflammatory effects of melatonin on experimental liver damage by radiation.

Radiotherapy is one of the inevitable treatment approaches for several types of cancer. We aimed to show the protective and therapeutic effects of daily use of melatonin on liver tissues subjected to a single dose of 10 Gy (gamma-ray) total body radiation. Rats were divided into 6 groups, of which 10 were in each: control, sham, melatonin, radiation, radiation+melatonin, and melatonin+radiation. The rats received 10 Gy of external radiation throughout their entire bodies. The rats were given 10 mg/kg/day of melatonin intraperitoneally before or after radiation treatment, depending on the group. Histological methods, immunohistochemical analysis (Caspase-3, Sirtuin-1, α-SMA, NFΚB-p65), biochemical analysis by ELISA (SOD, CAT, GSH-PX, MDA, TNF-α, TGF-ß, PDGF, PGC-1α) and the Comet assay as a marker of DNA damage were applied to the liver tissues. Histopathological examinations showed structural changes in the liver tissue of the radiation group. Radiation treatment increased the immunoreactivity of Caspase-3, Sirtuin-1 and α-SMA, but these effects were relatively attenuated in the melatonin-treated groups. The melatonin+radiation group had statistically significant results close to those of the control group, in terms of Caspase-3, NFΚB-p65 and Sirtuin-1 immunoreactivity. In melatonin treated groups, hepatic biochemical markers, MDA, SOD, TNF-α, TGF-ß levels, and DNA damage parameters were decreased. Administration of melatonin before and after radiation has beneficial effects, but using it before radiation may be more efficient. Accordingly, daily melatonin usage could mitigate ionizing radiation induced damage.

Protective effect of pycnogenol against gamma radiation-induced lung injury in rat: DNA damage, lipid peroxidation, antioxidant levels, and histopathological changes.

Background and Objective: The study aims to evaluate the histopathological changes, enzymatic alterations, and DNA damage in rat lungs induced by whole-body gamma irradiation as well as evaluation of the protective effect of pycnogenol. Materials and Methods: A hundred adult male rats were equally divided into ten groups including control, four antioxidants, γ-irradiation, four antioxidant + γ-irradiations. This study began the day before radiation treatment and continued for 3 days. The pycnogenol was dissolved 5% dimethyl sulfoxide and then administered orally through a gastric tube at a dose of 37.5 mg/kg, 75 mg/kg, 150 mg/kg, and 300 mg/kg in 24, 48, and 72 h before irradiation. Irradiation was applied with a whole-body irradiation dose of 900 cGy in one fraction. DNA damage, histopathological changes, catalase (CAT), and superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in lung tissue of rats were evaluated 3 days after irradiation. Results: CAT and SOD activities were found to be significantly lower in the irradiation group than control (P < 0.001). CAT and SOD activities were higher in the antioxidant + γ-irradiation group than both irradiation and control groups. MDA levels were significantly higher in the irradiation group compared to control (P < 0.001), whereas MDA levels decreased in the antioxidant + γ-irradiation group compared to the irradiation group. The antioxidant groups were significantly increased comet parameters depend on pycnogenol doses compared to control. The antioxidant + γ-irradiation was decreased comet parameter compared to γ-irradiation. As a result of the histopathologically, the antioxidant groups were different than the control group that in the areas of alveolar sacs and connective tissue areas were seen hemorrhage areas similar to the irradiation group. Conclusion: We demonstrate that 300 mg/kg of pycnogenol might provide significant protection against deleterious effects from whole-body ionizing radiation on the lung tissue. P300+ γ-ray group was significantly reduced radiation-induced lung injury and was possible to observe significantly preservation.

Hepatotoxicity and renal toxicity induced by radiation and the protective effect of quercetin in male albino rats.

PURPOSE: Although radiation is one of the basic methods commonly used in cancer treatment, it inevitably enters the field of treatment in healthy tissues and is adversely affected by the acute and chronic side effects of radiation. This study evaluated the possible protective effects of quercetin, an antioxidant agent, against liver and kidney damage in rats exposed to a whole-body single dose of radiation (10 Gy of gamma-ray). MATERIALS AND METHODS: The study groups were formed as control, sham, quercetin, radiation, quercetin + radiation and radiation + quercetin using 60 male Wistar albino (200-250 g, 3 months old) rats, including 10 rats in each group. The gamma-ray provided by the Co60 teletherapy machine was given to the whole body as external irradiation. According to the groups, quercetin was administered to rats at 50 mg/kg/day via oral gavage before or after radiation administration. The rats were sacrificed the day after irradiation and the extracted tissue samples from all groups were compared histologically and immunohistochemically. DNA damage was determined by the neutral comet assay technique. Also, malondialdehyde (MDA) and glutathione peroxidase (GSH) were evaluated in liver and kidney tissues by the ELISA method. RESULTS: Histopathological changes were observed altered morphology of liver and kidney tissues in the radiation groups. Sinusoidal dilatations, vacuolization, and hepatic parenchyma necrosis in the liver, while in kidneys, glomerular shrinkage, widened Bowman's space, tubular dilatation, and inflammation were evident. TNF-α, IL1-α, HIF1-α, and caspase 3 immunoreactivities in tissues were determined by immunohistochemistry. High caspase 3 positive cell number confirmed apoptosis, the comet parameters were decreased in the quercetin + radiation group. When compared to the control group, the exposure to radiation showed a marked elevation in MDA which was accompanied by high GSH. This damage was reduced in the quercetin + radiation group. CONCLUSIONS: With the results obtained from the study; Quercetin is thought to have a protective potential against radiation-induced liver and kidney damage due to its radioprotective effect.

The study of sirtuins in breast cancer patients before and after radiotherapy

Background/aim: Targeting the new and unique proteins is an important medical strategy for treating breast cancer. It is quite important to find out proteins that have a role in the development of cancer. Sirtuins (SIRT) are well related in different physiological activities and connected with cancer. We aimed to determine the effect of radiotherapy on SIRT1 and SIRT2, which have not been yet been clarified as a tumor suppressor or promoter. Materials and methods: Twenty-two women with nonmetastatic breast cancer enrolled in the study. Blood samples were taken before and after radiotherapy, soluble SIRT1 and SIRT2 levels were determined with ELISA kits. Results: There was no difference in SIRT1 levels before and after radiotherapy (p = 0.548). SIRT2 levels were significantly found to be decreased after radiotherapy (p = 0.042). There was a strong and positive correlation before radiotherapy (p < 0.001), and a moderate and positive correlation after radiotherapy (p = 0.007) between SIRT1 and SIRT2. Conclusion: These results suggest that SIRT2 may provide a new strategy for follow-up of breast cancer treatment. Additionally, by emphasizing the importance of SIRT2 in breast cancer, it opens ways to provide grounds for the development of the next generation of SIRT2-specific radiotracers. Finally, the most important thing, in fact, the positive correlation between SIRT1 and SIRT2 both before and after radiotherapy, appears to be clear evidence suggesting more oncogenic roles of sirtuins.

The different doses of radiation therapy-induced damage to the ovarian environment in rats.

PURPOSE: The sequelae of premature loss of ovarian function can undoubtedly have undesirable effects for a woman although radiotherapy is one of the most relevant treatment modalities for various types of malignancies. The aim of this study was to determine the effect of different doses of radiation on ovarian folliculogenesis, inflammation, and apoptotic markers. MATERIALS AND METHODS: For this purpose, 40 healthy Wistar albino female rats divided into four groups: 1) Control group; 2) those that were exposed to total body 1 Gy of gamma rays; 3) those that were exposed to the total body 5 Gy of gamma rays, and 4) those that were exposed to total body 10 Gy of gamma rays. External irradiation to the total body was given with gamma irradiation delivered by the Co60 teletherapy machine. The day after radiation application the rats were sacrificed and the ovaries were removed in all groups. Histopathologic examination, follicle counting, and classification were performed in the ovarian tissues. The expression of AMH, TNF-α, IL1-ß, Bax, and Bcl-2 was detected. The stained sections were examined for caspase 3 positive apoptotic cell numbers. RESULTS: The recorded results revealed that increased radiation dose induced obvious ovarian injuries that were indicated by histopathological, and immunohistochemical alterations, including elevation of ovarian injury markers. A significantly lower number of total and primordial follicles was detected with increasing radiation dose compared with the control group. According to our immunohistochemical results, 10 Gy of gamma rays group had the lowest AMH expression levels, while had the highest TNF-α, IL1-ß expression level compared to the control group. When the groups were evaluated in terms of apoptosis, it was seen that the number of caspase 3 positive cells and Bax immunoreactivity intensity increased with radiation dose. In contrast, Bcl-2 immunoreactivity intensity decreased with increasing radiation dose compared with the control group. CONCLUSIONS: We demonstrate here that dose rate plays an important role when estimating the relation between exposure to an increased dose of ionizing radiation and the risk of ovarian disease. According to these results, certain factors have to be optimized before introducing them into clinics.

Whole abdominal field versus standard field radiotherapy plus concomitant and adjuvant chemotherapy for patients with locally advanced gastric cancer.

PURPOSE: To compare standard radiotherapy field (SRTF) with whole abdomen irradiation (WAI), used in conjunction with adjuvant chemotherapy following curative surgery in patients with gastric cancer. METHODS AND MATERIAL: Ninety patients were included in the study and divided into two treatment arms. In the first treatment arm, SRTF, including 45 Gy radiation to the primary tumor and regional lymph nodes, was performed in 45 patients. In the second treatment arm, a total of 45.2 Gy RT was delivered; 20 Gy to the whole abdomen followed by 25.2 Gy RT to the tumor and regional lymph nodes, in 45 patients. An intravenous bolus dose of 250 mg/m(2)/week 5-fluorouracil (5-FU) was administered concomitantly with RT in both treatment arms. Patients who completed concomitant chemoradiotherapy, received adjuvant treatment, including 4 cycles of 5-FU (425 mg/m(2)) and folinic acid (20 mg/m(2)) in 4 week intervals. RESULTS: Median age was 56 years (range: 22-81), 89% of the patients (n = 80) had serosal involvement, 78% (n = 70) were node positive. The rate of hematological (40% vs. 16%, p = 0.010) and gastrointestinal toxicities (80% vs. 53%, p = 0.010) were higher, and performance loss (60% vs. 29%, p = 0.003) was greater in the second treatment arm. Number of patients who experienced Grade 3 and Grade 4 gastrointestinal toxicities (especially diarrhea) were higher in the second treatment arm (4% vs. 16%, p = 0.049). The median follow-up was 19 months (range: 7-96). The median 5-year survival was 29% and 17%, locoregional control was 30% and 25%, and disease-free survival was 27% and 16% in the first and second treatment arms, respectively. There was no significant difference between the treatment groups in terms of survival, locoregional control and disease-free survival rates (p > 0.05). CONCLUSION: Whole abdomen irradiation was not found to be superior to standard field radiotherapy used in conjunction with adjuvant chemotherapy in gastric cancer.

Prognostic significance of CD9 expression in locally advanced gastric cancer treated with surgery and adjuvant chemoradiotherapy.

The tetraspanin transmembrane protein CD9 plays an important role in inhibiting cell motility in numerous neoplastic cell lines, including lung, gastric, pancreatic, and bladder carcinomas. The prognostic importance of CD9 in the survival of gastric carcinoma patients has not been examined to date, and in the present study, we attempted to define its prognostic value. The study included 49 (35 men and 14 women) patients with locally advanced (stages II-IV) gastric cancer. The median age was 55 years (range, 22-73 years). Surgery was the initial treatment for all patients, followed by adjuvant chemoradiotherapy. Tissue sections were evaluated immunohistochemically with a monoclonal anti-CD9 antibody. Of the 49 patients with gastric adenocarcinoma, 11 (22.4%) were CD9-positive, and 38 (77.6%) were CD9-negative. A significant prognostic value in disease-free survival and overall survival was observed in T classification and CD9 positivity. In conclusion, CD9 expression in gastric cancer appears to be associated with poor prognosis.

Protective effects of caffeic acid phenethyl ester on radiation induced lung injury in rats.

PURPOSE: The prevention of radiation-induced pulmonary toxicity may help to improve radiation therapy in the cancer patient. The aim of this study was to investigate the pulmonary protective effects of caffeic acid phenethyl ester (CAPE), an antioxidant, on radiation-induced lung injury in rats. METHODS: 30 Wistar albino rats were divided into three groups and treated with saline, Radiation (RT) and RT + CAPE respectively. All rats were treated with CAPE (50 ?mol/kg i.p.) or saline. The first dose of CAPE was injected 24 h before radiation and application continued daily, with radiation in second day and 2 days more after the radiation treatment. Radiation dose was 800 cGy for total body. At 72 hr after the last radiation application, under general anesthesia using ip ketamine, the lungs were removed immediately after decapitation. After sacrification, antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) activities and malondiadehyde (MDA) levels were evaluated in lung tissue. RESULTS: The level of malondialdehyde (MDA) was higher in the RT group (233.4+/-1.5 nmol/g protein) than in both the control (131.8+/-0.92) and the RT + CAPE (151.4+/-1.8) groups (P < 0.001). However, CAT activity was decreased in the RT group (7.26+/-0.27 U mg protein) compared with control (8.49+/-0.51) and increased again in the RT + CAPE group (8.31+/-0.56; P < 0.001). In accord with CAT activity, SOD activity in the RT group (0.42+/-0.07 nmol MDA/g wet tissue) was different from the control (0.78+/-0.02) and RT + CAPE (0.86+/-0.06) groups (P < 0.001). CONCLUSION: CAPE application with radiation therapy attenuated radiation induced pulmonary injury in vivo, possibly by its antioxidant effect.

Aminoguanidine ameliorates radiation-induced oxidative lung damage in rats.

PURPOSE: To investigate the possible protective effects of aminoguanidine (AG ) on lung damage in whole body irradiated rats. METHODS: To evaluate the biological damage of radiation on rat lung tissue, lipid peroxidation products were measured using biochemical parameters. Thirty Wistar albino rats were divided into three subgroups: control (C) , irradiation alone (RT), and RT + AG combined. After sacrificing the rats, antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities and malondiadehyde (MDA), nitric oxide (NO) levels were evaluated in lung tissue. RESULTS: Administration of AG resulted in an increase in the activities of CAT, SOD and GSHPx in the lungs. All were reduced after radiation. In addition, AG administration resulted in a decrease in both NO and MDA levels in lung compared with the irradiated group. CONCLUSION: Amnoguanidine increased the endogenous antioxidant defence mechanism in rats and protected the animals from radiation-induced lung toxicity. Moreover, AG may protect against ionizing radiation-induced lung damage because of its antioxidant effect.