Search

This current study was designed to determine the effects of in vitro exposure to radioactive cesium-137 on human blood components. Whole blood samples were given a radiation dose of 0.02, 0.05, 0.1, 0.2, and 0.3 mGy of gamma radiation using a 137 Cs radioactive standard source. The whole blood samples that were exposed to 0 mGy served as sham-controls. The spectrofluoroscopic technique was used to determine the autofluorescence spectrum of protein in plasma or red blood cells by using excitation wavelength and range of emission wavelengths at 280 nm and 300-550 nm, respectively. The hemolysis of red blood cells was evaluated by determination of the release of hemoglobin from the red blood cells to the supernatant. Complete blood counts were also determined in whole blood. The results showed that there was no change in the ratio of fluorescence emission intensity at 340 nm of wavelength of protein extract from irradiated whole blood or red blood cells compared to the corresponding non-irradiated control. The hemolysis value did not change in irradiated whole blood when compared to the corresponding non-irradiated group. In addition, complete blood count values in irradiated groups did not differ from non-irradiated group. These current results suggested that there were no harmful effects of the low-dose gamma radiation from radioactive 137 Cs on blood components when human whole blood was exposed to gamma radiation in an in vitro condition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The aim of this study was to determine the effects of pre-low-dose irradiation followed by gallic acid (GA) on cell viability and cellular energetic state of leukemic K562 and K562/Dox cells. The cells were irradiated with 0.02, 0.05, and 0.1 Gy of X-rays. For determining cell viability, pre-low-dose irradiation was followed by 10 or 100 µM GA at 24 h post-irradiation, and the cell viability was then determined at 48 h post-irradiation. For cellular energetic state, pre-low-dose irradiation was followed by 10 or 100 µM GA at 1.5 h post-irradiation and the mitochondrial activity, mitochondrial membrane potential (ΔΨm), and ATP level were determined at 3 h post-irradiation. The % cell viability was significantly decreased in both cells that were irradiated with X-rays followed by treatment with 10 or 100 µM GA at 24 h post-irradiation, when compared with control group. However, this did not happen when compared with GA alone without any pre-low-dose irradiation. The mitochondrial activity had significantly decreased in 10 µM GA-treated K562 cells and the mitochondrial activity, ΔΨm, and ATP levels had significantly decreased in 10 µM GA-treated K562/Dox cells after irradiation to X-rays when compared with GA alone group. In addition, the ΔΨm and ATP levels was significantly decreased in only 100 µM GA-treated K562/Dox cells, but was not decreased in 100 µM GA-treated K562 cells after exposure to X-rays. These findings suggest that pre-low-dose irradiation followed by GA could not kill K562 and K562/Dox cells, but could improve cellular energetic damage of GA effects possibly through mitochondrial impairment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Curcuma comosa has been used in traditional Thai medicine to treat menstrual cycle-related symptoms in women. This study aims to evaluate the diarylheptanoid drug modulator, t rans -1,7-diphenyl-5-hydroxy-1-heptene (DHH), in drug-resistant K562/ADR human leukemic cells. This compound was studied due to its effects on cell cytotoxicity, multidrug resistance (MDR) phenotype, P-glycoprotein (P-gp) expression, and P-gp function. We show that DHH itself is cytotoxic towards K562/ADR cells. However, DHH did not impact P-gp expression. The impact of DHH on the MDR phenotype in the K562/ADR cells was determined by co-treatment of cells with doxorubicin (Dox) and DHH using an MTT assay. The results showed that the DHH changed the MDR phenotype in the K562/ADR cells by decreasing the IC 50 of Dox from 51.6 to 18.2 µM. Treating the cells with a nontoxic dose of DHH increased their sensitivity to Dox in P-gp expressing drug-resistant cells. The kinetics of P-gp mediated efflux of pirarubicin (THP) was used to monitor the P-gp function. DHH was shown to suppress THP efflux and resulted in enhanced apoptosis in the K562/ADR cells. These results demonstrate that DHH is a novel drug modulator of P-gp function and induces drug accumulation in the Dox-resistant K562 leukemic cell line.

(1) Background: Ectopic fat deposition and its effects, metabolic syndrome, have been significantly correlated to lifestyle and caloric consumption. There is no specific noninvasive evaluation tool being used in order to establish clinical markers for tracing the metabolic pathway implicated in obesity-related abnormalities that occur in the body as a result of a high-fat diet (HFD). The purpose of this work is to investigate in vivo ectopic fat distribution and in vitro metabolite profiles given by HFDs, as well as how they are inter-related, in order to find surrogate metabolic biomarkers in the development of metabolic syndrome utilizing noninvasive approaches. (2) Methods: Male Wistar rats were divided into a standard normal chow diet, ND group, and HFD group. After 16 weeks of different diet administration, blood samples were collected for proton nuclear magnetic resonance ( 1 H NMR) and biochemical analysis. Magnetic resonance imaging/proton magnetic resonance spectroscopy (MRI/ 1 H MRS) was performed on the abdomen, liver, and psoas muscle of the rats. (3) Results: Visceral fat showed the strongest relationship with blood cholesterol. Although liver fat content (LFC) was not associated with any biophysical profiles, it had the highest correlation with metabolites such as (-CH 2 ) n very-low-density lipoprotein/low-density lipoprotein (VLDL/LDL), lactate, and N-acetyl glycoprotein of serum 1 H NMR. HFD showed no obvious influence on muscle fat accumulation. Acetoacetate, N-acetyl glycoprotein, lactate, (-CH 2 ) n VLDL/LDL, and valine were the five possible metabolic biomarkers used to differentiate HFD from ND in the present study. (4) Conclusions: Our study has validated the influence of long-term HFD-induced ectopic fat on body metabolism as well as the metabolic profile deterioration both in vivo and in vitro.

Radioimmunoassay (RIA) is one of the most routine laboratory tests for diagnosing thyroid disease. Patients might receive iodine in the form of intravenous iodinated radiographic contrast media (IRCM) before testing of serum thyroxin (T4) or triiodothyronine (T3) concentration by RIA. The objective was to determine the effect of IRCM on T4 and T3 hormone tests in normal, hypothyroid, and hyperthyroid hormone conditions by RIA. IRCMs (0, 2.5, 5 and 10 mgI/mL) used in this study were iopromide and iodixanol. RIA was determined by commercial T4 RIA kit and T3 RIA kits. The method suggested by the manufacturer was followed. Normal, hypothyroid, and hyperthyroid hormones condition were 1.2 ng/mL, 0.2 ng/mL and 2.2 ng/mL for T3 hormone concentration and 70 ng/mL, 30 ng/mL and 140 ng/mL for T4 hormone concentration, respectively. %Bound values were compared between IRCM-incubated groups and non-incubated group. The data showed that iopromide-incubated groups did not statistically significant change %bound values of T3 and T4 hormone tests in normal, hypothyroid, and hyperthyroid conditions, compared to the non-incubated group. In the same way, %bound values of T3 and T4 hormone tests in iodixanol-incubated groups did not change at all conditions when compared to the non-incubated group. This finding suggested that iodinated radiographic contrast media was unlikely to result in significant problems with radioimmunoassay for measuring T3 and T4 thyroid hormones., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The objective was to investigate the effect of 4-hydroxybenzoic acid (4-HBA) and 4-hydroxy-3-methoxybenzoic acid (Vanillic acid, VA) on p-glycoprotein (P-gp) activity in multidrug-resistant K562/Dox cancer cells. The cytotoxic and co-treatment with pirarubicin (Pira) were analyzed using a resazurin assay. A noninvasive functional spectrofluorometric technique was used to determine the kinetics of Pira uptake in living multidrug-resistant K562/Dox cancer cells. The three biological endpoints for determination of cellular energetic state included the activity of mitochondria, mitochondrial membrane potential (ΔΨm), and ATP levels. The results revealed that 4-HBA (10 mM) and VA (5 and 10 mM) statistically decreased cell viability in K562 and multidrug-resistant K562/Dox cancer cells. In ways consistent with that result, 4-HBA and VA (0.01, 0.1, 1, and 10 mM) could statistically decrease the IC 50 of Pira in K562 and multidrug-resistant K562/Dox cancer cells at 48 and 72 h. The overall intracellular Pira concentration increased in 4-HBA- and VA-treated multidrug-resistant K562/Dox cancer cells when compared to control. The ratio of k a i /k a 0 in 4-HBA- and VA-treated multidrug-resistant K562/Dox cancer cells was significantly decreased when 4-HBA and VA concentration increased. The activity of mitochondria, ΔΨm, and ATP levels significantly reduced in multidrug-resistant K562/Dox cancer cells incubated with 0.01, 0.1, 1, and 10 mM 4-HBA and VA at all harvest time points. In conclusion, 4-HBA and VA were able to bring about cell death in multidrug-resistant K562/Dox cancer cell at high concentrations. The 4-HBA and VA could modify P-gp function via an impaired cellular energetic state, resulting in increased in intracellular drug concentration in multidrug-resistant K562/Dox cancer cells., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Leukemia is a common malignancy affecting humans worldwide. Pirarubicin (Pira) is one of the anticancer agents used for the treatment of leukemia. Although Pira is effective, drug resistance may develop in cancer cells exposed to this drug, whereas the combination of natural products with Pira may help to overcome this problem. The aim of the present study was to focus on the effect of gallic acid (GA) on the anticancer activity of Pira in K562 leukemia cells and K562/doxorubicin (Dox)‑resistant leukemia cells in order to investigate the possible underlying mechanisms. The cell viability, mitochondrial activity, mitochondrial membrane potential (ΔΨm) and ATP levels were assessed in living K562 and K562/Dox cancer cells following treatment with GA/Pira combination, GA alone or Pira alone. P‑glycoprotein‑mediated efflux of Pira was determined in GA‑treated K562/Dox cancer cells. The results demonstrated that GA/Pira combination decreased cell viability, mitochondrial activity, ΔΨm and ATP levels in K562 and K562/Dox cancer cells in a GA concentration‑dependent manner compared with non‑treated or Pira‑treated cells. GA inhibited P‑glycoprotein‑mediated efflux of Pira in GA‑treated K562/Dox cancer cells. Therefore, GA enhanced the anticancer effect of Pira on K562 and K562/Dox cancer cells through cellular energy status impairment, and was able to reverse drug resistance in living K562/Dox cancer cells by inhibiting the function of P‑glycoprotein.

Background: Obesity or being overweight is a medical condition of abnormal body fat accumulation which is associated with a higher risk of developing metabolic syndrome. The distinct body fat depots on specific parts of the anatomy have unique metabolic properties and different types of regional excessive fat distribution can be a disease hazard. The aim of this study was to identify the metabolome and molecular imaging phenotypes among a young adult population., Methods: The amount and distribution of fat and lipid metabolites profile in the abdomen, liver, and calf muscles of 46 normal weight, 17 overweight, and 13 obese participants were acquired using MRI and MR spectroscopy (MRS), respectively. The serum metabolic profile was obtained using proton NMR spectroscopy. NMR spectra were integrated into seven integration regions, which reflect relative metabolites., Results: A significant metabolic disorder symptom appeared in the overweight and obese group, and increased lipid deposition occurred in the abdomen, hepatocytes, and muscles that were statistically significant. Overall, the visceral fat depots had a marked influence on dyslipidemia biomarkers, blood triglyceride (r = 0.592, p < 0.001), and high-density lipoprotein cholesterol (r = -0.484, p < 0.001). Intrahepatocellular lipid was associated with diabetes predictors for hemoglobin (HbA1c%; r = 0.379, p < 0.001) and for fasting blood sugar (r = 0.333, p < 0.05). The lipid signals in serum triglyceride and glucose signals gave similar correspondence to biochemical lipid profiles., Conclusions: This study proves the association between alteration in metabolome in young adults, which is the key population for early prevention of obesity and metabolic syndrome. This study suggests that dyslipidemia prevalence is influenced mainly by the visceral fat depot, and liver fat depot is a key determinant for glucose metabolism and hyperglycemia. Moreover, noninvasive advanced molecular imaging completely elucidated the impact of fat distribution on the anthropometric and laboratory parameters, especially indices of the metabolic syndrome biomarkers in young adults.

4-Hydroxybenzoic acids (4-HBA) and 4-hydroxy-3-methoxybenzoic acid (Vanillic acid, VA) have exhibited several pharmacological activities. Generally, the biological activities of compounds are highly involved in the interaction between protein and compounds in blood plasma. The objective was to investigate the interaction of 4-HBA or VA with human serum albumin (HSA) and their anti-proliferation properties on doxorubicin-sensitive K562 and doxorubicin-resistant K562/Dox leukemia cells. The protein binding of 4-HBA or VA to HSA was investigated using fluorescence quenching at temperatures of 298 and 310 Kelvin (K) under the pH of 6.0, 7.4, and 8.0 conditions. The effect of 4-HBA and VA on anti-proliferation was also studied on doxorubicin-sensitive K562 and doxorubicin-resistant K562/Dox leukemia cells using resazurin assay. The results showed that 4-HBA and VA could interact with HSA. The fluorescence quenching process in HSA-4-HBA system might be attributed to static quenching mechanism. In contrast, a dynamic quenching mechanism might be mainly involved in the fluorescence quenching process in the HSA-VA system. Thermodynamic data suggested that the spontaneous interaction between HSA and 4-HBA or VA had occurred in the system and it also indicated that hydrogen bonds and Van der Waals forces contributed to the binding of HSA to 4-HBA or VA. In addition, 4-HBA and VA decreased K562 and K562/Dox cells viability in a dose- and time-dependence manner. In conclusions, the 4-HBA and VA could interact with HSA. In addition, the 4-HBA and VA decreased in cell viability for both doxorubicin-sensitive K562 and doxorubicin-resistant K562/Dox leukemia cells in a dose- and time-dependence manner. Therefore, these current studies could provide useful information about the nature of 4-HBA or VA binding to protein HSA and their anticancer activities in both of these types of leukemia cells. The cell death mechanisms should be investigated through future study., Competing Interests: The authors report no declarations of interest., (© 2021 The Author(s).)

Young adulthood is increasingly considered as a vulnerable age group for significant weight gain, and it is apparent that there is an increasing number of new cases of metabolic syndrome developing among this population. This study included 60 young adult volunteers (18-26 years old). All participants obtained a calculated total abdominal fat percentage, subcutaneous fat percentage, and visceral fat percentage using a semiautomatic segmentation technique from T1-weighted magnetic resonance imaging (MRI) images of the abdomen. The results show strongest correlation between abdominal fat and BMI (r = 0.824) followed by subcutaneous fat (r = 0.768), and visceral fat (r = 0.633) respectively, ( p < 0.001 for all, after having been adjusted for age and gender). Among anthropometric measurements, waist circumference showed strong correlation with all fat compartments (r = 0.737 for abdominal, r = 0.707 for subcutaneous fat, and r = 0.512 for visceral fat; p < 0.001 for all). The results obtained from examining the blood revealed that there was a moderate positive correlation relationship between all fat compartments with triglyceride, high-density lipoprotein, and fasting glucose levels ( p < 0.05 for all). This study suggests that both BMI and waist circumference could be used to assess the fat compartments and treatment targets to reduce the risk of metabolic disorders and health risks in the young adult population.

(1) Since the obesity prevalence rate has been consistently increasing, it is necessary to find an effective way to prevent and treat it. Although progress is being made to reduce obesity in the young adult population, a better understanding of obesity-related metabolomics and related biochemical mechanisms is urgently needed for developing appropriate screening strategies. Therefore, the aim of this study is to identify the serum metabolic profile associated with young adult obesity and its metabolic phenotypes. (2) Methods: The serum metabolic profile of 30 obese and 30 normal-weight young adults was obtained using proton nuclear magnetic resonance spectroscopy ( 1 H NMR). 1 H NMR spectra were integrated into 24 integration regions, which reflect relative metabolites, and were used as statistical variables. (3) Results: The obese group showed increased levels of lipids, glucose, glutamate, N-acetyl glycoprotein, alanine, lactate, 3 hydroxybutyrate and branch chain amino acid (BCAA), and decreased levels of choline as compared with the normal-weight group. Non-hyperlipidemia obese adults showed lower levels of lipids and lactate, glutamate, acetoacetate, N-acetyl glycoprotein, isoleucine, and higher levels of choline and glutamine, as compared with hyperlipidemic obese adults. (4) Conclusions: This study reveals valuable findings in the field of metabolomics and young adult obesity. We propose several serum biomarkers that distinguish between normal weight and obese adults, i.e., glutamine (higher in the normal group, p < 0.05), and lactate, BCAAs, acetoacetate and 3-hydroxybutyrate (higher in the obese group, p < 0.05). In addition, visceral fat and serum TG, glutamate, acetoacetate, N-acetyl glycoprotein, unsaturated lipid, isoleucine, and VLDL/LDL are higher ( p < 0.05) in the obese with hyperlipidemia. Therefore, they can be used as biomarkers to identify these two types of obesity.

The number of individuals suffering from fatty liver is increasing worldwide, leading to interest in the noninvasive study of liver fat. Magnetic resonance spectroscopy (MRS) is a powerful tool that allows direct quantification of metabolites in tissue or areas of interest. MRS has been applied in both research and clinical studies to assess liver fat noninvasively in vivo. MRS has also demonstrated excellent performance in liver fat assessment with high sensitivity and specificity compared to biopsy and other imaging modalities. Because of these qualities, MRS has been generally accepted as the reference standard for the noninvasive measurement of liver steatosis. MRS is an evolving technique with high potential as a diagnostic tool in the clinical setting. This review aims to provide a brief overview of the MRS principle for liver fat assessment and its application, and to summarize the current state of MRS study in comparison to other techniques.

Oral cancer disease is among the most common cancers in the world and are associated with mortality and morbidity. The characterization of saliva samples may help to distinguish patients with oral cancer disease from normal subjects. To characterize spectra of saliva samples from normal subjects and oral cancer patients by use of fluorescence, absorption, and 1 H-NMR spectroscopy. Whole unstimulated saliva samples were collected from patients with oral cancer disease and normal subjects. The saliva samples were analyzed by absorption, fluorescence and 1 H-NMR spectroscopic techniques. The characteristic spectra of saliva samples from patients with oral cancer disease and normal subjects were compared. For fluorescence spectroscopic studies, six fluorophores were found in saliva samples. Autofluorescence emission spectra and synchronous spectra of saliva were different between normal subjects and oral cancer patients. For absorption spectroscopic studies, the typical absorption spectra of saliva samples from normal subjects and oral cancer patients were also different in absorption intensity, 1st and 2nd derivative of absorption spectra values. For 1 H-NMR studies, nine metabolites and four metabolites were found in saliva samples taken from normal subjects and oral cancer patients, respectively. The metabolic profiles of saliva samples from normal subjects and oral cancer patients were not similar. The characteristic spectra of saliva samples from normal subjects and oral cancer patients were found. These results showed differences in the spectra of saliva samples between both that groups. The spectra from each spectroscopic techniques could determine a candidate saliva biomarkers for distinguishing patients with oral cancer disease from normal subjects.

High-dose radiation is deleterious to cells or tissues. However, the health risks of exposure to low-dose radiation remain unclear. The present study aimed to investigate the biological responses of low-dose gamma-ray in vitro exposure to normal red blood cells (RBCs) and erythroleukemia (K562 and K562/Dox) cancer cells. Cells were given a low dose of 0.03, 0.05 and 0.1 mGy of 137 Cs gamma-rays (at a dose rate of 0.001 Gy/min) under in vitro conditions. Cells exposed to 0 Gy served as controls. Hemolysis and reactive oxygen species (ROS) were measured in exposed RBCs following exposure to low-dose gamma-rays. In addition, complete blood count (CBC) parameters were determined in irradiated whole blood. For irradiated K562 and K562/Dox cancer cells, ROS and mitochondrial activity were measured at 0, 30, 60 and 120 post-irradiation times. The results showed no change in the percentage of ROS and hemolysis in irradiated RBCs. The data indicated no perturbation in the CBC parameters in irradiated whole blood. By contrast, statistically significant dose-dependent increases in the percentage of ROS and decreases in the mitochondrial activity in the K562 and K562/Dox cancer cells were observed from 0 min up to 120 min post-irradiation. These findings concluded that there were differences in biological responses in normal cells (RBCs) and cancer cells (K562 and K562/Dox) to low-dose gamma-rays when cells were irradiated under in vitro conditions., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Purpose: To determine the early- and late-occurring damage in the bone marrow (BM) and peripheral blood cells of male CBA/Ca mice after exposure to 0, 0.1, 0.25, or 0.5 Gy of 1 GeV/n titanium ( 48 Ti) ions (one type of space radiation)., Method: We used the mouse in vivo blood-erythrocyte micronucleus (MN) assay for evaluating the cytogenetic effects of various doses of 1 GeV/n 48 Ti ions. The MN assay was coupled with the characterization of epigenetic alterations (the levels of global 5-methylcytosine and 5-hydroxymethylcytosine) in DNA samples isolated from BM cells. These analyses were performed in samples collected at an early time-point (1 week) and a late time-point (6 months) post-irradiation., Results: Our results showed that 48 Ti ions induced genomic instability in exposed mice. Significant dose-dependent loss of global 5-hydroxymethylcytosine was found but there were no changes in global 5-methylcytosine levels., Conclusion: Since persistent genomic instability and loss of global 5-hydroxymethylcytosine are linked to cancer, our findings suggest that exposure to 48 Ti ions may pose health risks.

Background: Gadolinium-based contrast media (GBCM) are commonly used in diagnostic magnetic resonance imaging (MRI) in clinical applications. The objective of this study is to evaluate the antioxidant properties and effects on red blood cells (RBCs) and K562 cancer cells of three GBCMs (i.e.; gadoterate meglumine, gadopentetate dimeglumine, and gadobenate dimeglumine) inin vitro levels., Methods: For determiningin vitro antioxidant properties, the di (phenyl)-(2,4,6-trinitrophenyl) iminoazanium (DPPH) and ferric reducing ability of plasma (FRAP) assay were used. For determining effect on red blood cells, hemolysis, morphology and reactive oxygen species (ROS) were used. For determining effect on K562 cancer cells, cytotoxicity and ROS were used. The GBCM -exposed cells were compared to corresponding non-exposed control groups at various harvest times., Results: The results show no changes occurring in the DPPH data. However, there were significant increases based on FRAP data in three GBCMs compared to the corresponding control at all concentrations. The ROS, morphology, and percentage of hemolysis in red blood cells indicated that no change had occurred in three GBCMs-exposed red blood cells compared to the corresponding non-exposed control groups at all harvest times. The percentage of cell viability in K562 cancer cells showed decreases in gadoterate meglumine- and gadobenate dimeglumine- in a concentration dependent manner, but did not show same in gadopentetate dimeglumine-exposed K562 cancer cells. The percentage of ROS in K562 cancer cells indicated that no change in three GBCMs-exposed cells had occurred when compared to the corresponding non-exposed control groups at all harvest times., Conclusion: These findings suggests thatin vitro antioxidant properties exhibited by those three GBCMs depends on their concentration and species of radical in testing assay. There were no toxic effects from those GBCMs when red blood cells were exposed in an in vitro condition. In addition, some of those GBCMs could induce cell death in cancer cells., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

In this study, the Maprang ( Bouea macrophylla Griffith) seeds of 3 Thai varieties of this plant were studied in terms of nutrition, phytochemicals, chemical antioxidants and the bioactivity of their extracts. Maprang seeds revealed high levels of carbohydrates, dietary fiber, energy, potassium, phosphorus, magnesium, and calcium. The Maprang seed extracts possessed a high polyphenolic content and exhibited antioxidant properties against DPPH˙, ABTS˙ + , and ferric reduction. Additionally, 18-compounds were charaterized by RP-HPLC-DAD with two being recognized as gallic acid and ellagic acid and 16-unknown gallotannins. The HPLC fingerprint was composed of 4 major compounds. The extract showed active growth inhibition against leukemia, lung cancer cell lines and for 15 strains of bacteria. It is known to be particularly effective in drug resistant cells. Our results indicated that maprang seeds are a new natural source of nutrition, minerals and phytochemicals that may be applicable for use as a food supplement and as an effective drug in the treatment of certain diseases.

Background: Overweight (OW) is considered a risk for various metabolic diseases. However, its effects as a mechanism that alters the metabolite profiles remain unclear. The purpose of this study is to investigate the effects that OW has on the lipid and metabolite profiles in young adults., Methods: The serum metabolite profiles of 46 young adults of normal weight and those considered OW were studied by Proton nuclear magnetic resonance spectroscopy ( 1 H NMR) technique., Results: 1 H NMR metabolite analysis shows the alteration of metabolic levels and increased levels of CH 2 lipids and CH 3 lipids, which are used as unique biomarkers to identify OW subjects from the normal weight groups., Conclusion: This present study reveals that OW contributes to the systemic metabolism and the metabolite alteration among young adults. The alteration in serum lipids level could shed the light on metabolic syndrome pathogenesis in young adults and needs further elucidation., Competing Interests: The authors declare that they have no competing interests.

Iodinated radiographic contrast media is used in cancer radiography for cancer diagnosis. The aim of this present study was to examine five iodinated radiographic contrast media (IRCM) (i.e., iohexol, iopamidol, iobitridol, ioxaglate, and iodixanol) in terms of their cytotoxicity, mitochondria membrane potential (ΔΨm), and P-glycoprotein function in multidrug resistant K562/Dox cancer cells and corresponding sensitive cancer cells. The cytotoxicity was determined by colorimetric resazurin reduction assay. The ΔΨm and P-glycoprotein function was measured using a noninvasive functional spectrofluorometry. Rhodamine B, fluorescence probe, was used to estimate ΔΨm. The kinetic of P-glycoprotein-mediated efflux pirarubicin was used to monitor P-glycoprotein function in multidrug resistant (MDR) cancer cells. The results showed that ioxaglate and iodixanol show similar efficacy in MDR cancer cells and for their corresponding sensitive cancer cells. Iopamidol, iohexol, and iobitridol showed higher efficacy in MDR cancer cells than for the corresponding sensitive cancer cells by approximately 2 fold. The results also showed no significant change in the |ΔΨm| values in treated K562 and K562/Dox cancer cells when compared to the non-treated K562 and K562/Dox cancer cells. However, there were notable changes detected for iobitridol and iodixanol at 50 mgI/mL. Similarly, the results showed significant differences in P-glycoprotein function of K562/Dox cancer cells after treatment with IRCM when compared to the non-treated K562/Dox cancer cells, with iohexol and iodixanol being the notable exceptions once again. In this present study, IRCM exhibited cytotoxicity on MDR cancer cells and their corresponding sensitive cancer cells. IRCM also showed potential as an anticancer agent in the future.

Aim: To assess the association between liver fat content (LFC) and weight status in young adults using proton magnetic resonance spectroscopy ( 1 H MRS) technique., Methods: Seventy-eight healthy young adults, between 19-30 years of age participated in this study. This group was then separated into a control of 39 subjects and an overweight/obese group (OW/OB group) consisting of 39 subjects. Blood biochemical quantity and 1 H MRS was performed for LFC assessment., Results: LFC was found to be almost three times higher in OW/OB group when compared to the control group. A 48.7% incidence of non-alcoholic fatty liver disease in the OW/OB group was found. Blood biochemical measurements showed statistically higher low-density lipoproteins and triglyceride, lower high-density lipoproteins, and increased glycosylated hemoglobin and fasting glucose in the OW/OB group. Body mass index was a significant independent predictor for LFC after adjusting for age and sex (multiple linear regression; β = 0.459, P < 0.001)., Conclusion: Due to the prevalence of high LFC in the OW/OB group, it can be proposed that weight gain and obesity are sensitive indicators of high hepatic fat content., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest.

We used 3 biological metrics highly relevant to health risks, that is, cell death, inflammation, and global DNA methylation, to determine the late effects of low doses (0.05 or 0.1 Gy) of 137 Cs γ rays on the bone marrow, lung, and testis collected at 6 months post-irradiation from the same exposed BALB/cJ mouse. This integrative approach has not been used for such a purpose. Mice exposed to 0 or 1 Gy of radiation served as a sham or positive control group, respectively. The results could deliver information for better health risk assessment across tissues, including better scientific basis for radiation protection and clinical application. We found no changes in the levels of all studied biological metrics (except a significant increase in the levels of an anti-inflammatory cytokine, ie, interleukin 10) in tissues of 0.05-Gy exposed mice, when compared to those in sham controls. In contrast, significantly increased levels of cell death and inflammation, including a significant loss of global 5-hydroxymethylcytosine, were found in all tissues of the same mice exposed to 0.1 or 1.0 Gy. Our data demonstrated not only no harm but also hormesis in the 0.05-Gy exposed mice. However, the hormetic effect appears to be dependent on biological metrics and tissue., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To study proton magnetic resonance spectra ( 1 H-MRS) of the muscle metabolite of a leg muscle in neutral (NEU), internal rotation (INT), and external rotation (EXT) leg positioning., Material and Methods: The volunteers were selected for this study. The tibialis anterior (TA), soleus (SOL), and gastrocnemius (GAS) muscles of a non-dominate leg were determined by using single-voxel spectroscopy 8 × 8 × 20 mm 3 in size. 1 H-MRS measurements were performed on a 1.5-Tesla magnetic resonance imaging (MRI) scanner., Results: The results showed that metabolite spectrum of muscle in each NEU, INT, and EXT of leg positioning were not similar. Additionally, the quantification of IMCL (CH 3 ) and EMCL (CH 3 ) is significantly different in SOL., Conclusions: Our study showed that leg positioning influences the appearance and quantification of 1 H-MRS in the calf muscle. Hence, it is necessary to pay close attention to positioning because it interferes with spectral fitting and quantification., Competing Interests: The authors report no conflict of interest.

This study reveals the antioxidant properties of iodinated radiographic contrast media to be used in diagnostic radiology. Di(phenyl)-(2,4,6-trinitrophenyl) iminoazanium (DPPH), ferric reducing ability of plasma (FRAP), and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) assays were used for determining in vitro the antioxidant properties of five iodinated radiographic contrast media such as iobitridol (xenetix), iodixanol (visipaque), iohexol (omnipaque), ioxaglate (hexabrix), and isovue (iopamiro). An ascorbic acid and Trolox solution served as a positive control. The absorbance intensity of the colored product was recorded using a spectrophotometer. For DPPH and ABTS assay, the absorbance intensity at 533 and 752 nm, respectively was decreased when compared to control; it indicated an increase in antioxidant activity. For FRAP assay, the absorbance intensity at 593 nm was increased when compared to control; it indicated an increase in antioxidant activity. The results showed that five iodinated radiographic contrast media did not differ in DPPH • radical-scavenging activity when compared to a corresponding control. The ferric reducing ability of all of these iodinated radiographic contrast media also did not differ when compared to a corresponding control, except for iobitridol at 200 mgI/mL and ioxaglate at 50-200 mgI/mL. All iodinated radiographic contrast media showed ABTS •+ radical-scavenging activity. This finding suggested that iobitridol, iodixanol, iohexol, ioxaglate, and isovue exhibited weak in vitro antioxidant properties. The antioxidant ability depended on the type of free radical production and the concentration of iodinated radiographic contrast media.

Little is known about plasma proteins that can be used as biomarkers for early and late responses to radiation. The purpose of this study was to determine a link between depletion of plasma gelsolin (pGSN) and cell-death as well as inflammatory responses in the lung (one of the tissues known to be radiosensitive) of the same exposed CBA/CaJ mice after exposure to heavy silicon ( 28 Si) ions. To prevent the development of multiple organ dysfunctions, pGSN (an important component of the extracellular actin-scavenging system) is responsible for the removal of actin that is released into the circulation during inflammation and from dying cells. We evaluated the levels of pGSN in plasma collected from groups of mice (5 mice in each) at 1 week (wk) and 1 month (1 mo) after exposure whole body to different doses of 28 Si ions, i.e. 0, 0.1, 0.25, or 0.5 Gy (2 fractionated exposures, 15 days apart that totaled each selected dose). In the same mouse, the measurements of pGSN levels were coupled with the quantitation of injuries in the lung, determined by (a) the levels of cleaved poly (ADP-ribose) polymerase (cleaved-PARP), a marker of apoptotic cell-death, (b) the levels of activated nuclear factor-kappa B (NF-κB) and selected cytokines, i.e. tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6, from tissue-lysates of the lung. Further, the ratio of neutrophils and lymphocytes (N/L) was determined in the same mouse. Our data indicated: (i) the magnitude of pGSN depletion was dependent to radiation dose at both harvest times, (ii) a persistent depletion of pGSN up to 1 mo post-exposure to 0.25 or 0.5 Gy of 28 Si ions, (iii) an inverse-correlation between pGSN depletion and increased levels of cleaved-PARP, including activated NF-κB/pro-inflammatory cytokines in the lung, and (iv) at both harvest times, statistically significant increases in the N/L ratio in groups of mice exposed to 0.5 Gy only. Our findings suggested that depletion in pGSN levels reflects not only the responses to 28 Si-ion exposure at both harvest times but also early and late-occurring damage., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To study the prevalence of bone mineral density (BMD) and osteoporosis in the distal forearm among Thai men over 40 years of age in Mae Chaem District, Chiang Mai Province, Thailand., Methods: The subjects in this study were 194 Thai men, aged between 40 and 87 years who resided in Mae Chaem District, Chiang Mai Province, Thailand. Self-administered questionnaires were used for receiving the demographic characteristics information. BMD was measured by peripheral dual energy X-ray absorptiometry at the nondominant distal forearm in all men., Results: The BMD was highest in the age-group 40-49 years and lowest in the age-group 70-87 years. The average T-score at the distal forearm was also highest in the age-group 40-49 years and lowest in the age-group 70-87 years. The BMD decreased as a function of age-group (p < .05). In contrast, the BMD increased as a function of weight (p < .05). Height had weak impact on the BMD in the distal forearm (p > .05). The percentage of osteopenia and osteoporosis are increased as a function of age-group in, while decreased in that of normal bone density., Conclusions: We found the prevalence of osteoporosis in men who resided in Mae Chaem District, Chiang Mai Province, Thailand.

Low-dose radiation is widely used across the world for the diagnosis of many diseases by means of a variety of imaging technologies. However, the harmful effects of exposure to low-dose radiation during medical examination remain controversial. The authors studied the effects of medical diagnostic low-dose x rays (i.e., 0.03, 0.05, or 0.1 mGy) after an in vitro exposure of human lymphocytes. Cells with no irradiation served as the non-irradiated control group. Three biological indicators were used to determine the effects of medical diagnostic low-dose x rays at 4, 8, 24, 48, and 72 h post-irradiation. These biological endpoints were mitochondrial membrane potential (ΔΨm), cell cycle, and apoptosis. Results indicated no changes in the ΔΨm, number of apoptotic cells, and cell cycle in lymphocytes exposed to these low doses of radiation, as compared to the corresponding non-irradiated lymphocytes at all harvest time-points. These results suggested that there were no harmful effects of the diagnostic low-dose x rays when human lymphocytes were exposed in an in vitro condition.

Although the lung is one of the target organs at risk for cancer induction from exposure to heavy ions found in space, information is insufficient on cellular/molecular responses linked to increased cancer risk. Knowledge of such events may aid in the development of new preventive measures. Furthermore, although it is known that germinal cells are sensitive to X- or γ-rays, there is little information on the effects of heavy ions on germinal cells. Our goal was to investigate in vivo effects of 1 GeV/n (48)Ti ions (one of the important heavy ions found in the space environment) on somatic (lung) and germinal (testis) tissues collected at various times after a whole body irradiation of CBA/CaJ mice (0, 0.1, 0.25, or 0.5 Gy, delivered at 1 cGy/min). We hypothesized that (48)Ti-ion-exposure induced damage in both tissues. Lung tissue was collected from each mouse from each treatment group at 1 week, 1 month, and 6 months postirradiation. For the testis, we collected samples at 6 months postirradiation. Hence, only late-occurring effects of (48)Ti ions in the testis were studied. There were five mice per treatment group at each harvest time. We investigated inflammatory responses after exposure to (48)Ti ions by measuring the levels of activated nuclear factor kappa B and selected pro-inflammatory cytokines in both tissues of the same mouse. These measurements were coupled with the quantitation of the levels of global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Our data clearly showed the induction of chronic inflammation in both tissues of exposed mice. A dose-dependent reduction in global 5hmC was found in the lung at all time-points and in testes collected at 6 months postirradiation. In contrast, significant increases in global 5mC were found only in lung and testes collected at 6 months postirradiation from mice exposed to 0.5 Gy of 1 GeV/n (48)Ti ions. Overall, our data showed that (48)Ti ions may create health risks in both lung and testicular tissues.

Although myeloid leukemia (ML) is one of the major health concerns from exposure to space radiation, the risk prediction for developing ML is unsatisfactory. To increase the reliability of predicting ML risk, a much improved understanding of space radiation-induced changes in the target cells, i.e. hematopoietic stem/progenitor cells (HSPCs), is important. We focused on the in vivo induction of late-occurring damage in HSPCs of mice exposed to (28)Si ions since such damage is associated with radiation-induced genomic instability (a key event of carcinogenesis). We gave adult male CBA/CaJ mice, known to be sensitive to radiation-induced ML, a whole-body exposure (2 fractionated exposures, 15 days apart, that totaled each selected dose, delivered at the dose-rate of 1 cGy/min) to various doses of 300 MeV/n (28)Si ions, i.e. 0 (sham controls), 0.1, 0.25, or 0.5 Gy. At 6 months post-irradiation, we collected bone marrow cells from each mouse (five mice per treatment-group) for obtaining the myeloid-lineage of HSPC-derived clones for analyses. We measured the frequencies of late-occurring chromosome aberrations (CAs), using the genome-wide multicolor fluorescence in situ hybridization method. The measurement of CAs was coupled with the characterization of the global DNA methylation patterns, i.e. 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5 hmC). A dose-dependent increase in the frequencies of CAs was detected (Analysis of Variance or ANOVA, p<0.01), indicating the induction of genomic instability after exposure of mice to 300 MeV/n (28)Si ions. Slight increases in the levels of 5 mC were observed in all treatment groups, as compared to the sham-control level. In contrast, there was a significant reduction in levels of 5 hmC (ANOVA, p<0.01). Since these endpoints were evaluated in the same mouse, our data suggested for the first time a link between a reduction in 5 hmC and genomic instability in HSPC-derived myeloid colonies of CBA/CaJ mice exposed to 300 MeV/n (28)Si ions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Myeloid leukemia (ML) is one of the major health concerns from exposure to radiation. However, the risk assessment for developing ML after exposure to space radiation remains uncertain. To reduce the uncertainty in risk prediction for ML, a much increased understanding of space radiation-induced changes in the target cells, i.e. , hematopoietic stem/progenitor cells (HSPCs), is critically important. We used the label-free quantitative mass spectrometry (LFQMS) proteomic approach to determine the expression of protein in HSPC-derived myeloid colonies obtained at an early time-point (one week) and a late time-point (six months) after an acute whole body exposure of CBA/CaJ mice to a total dose of 0, 0.1, 0.25, or 0.5 Gy of heavy-ion titanium ( 48 Ti ions), which are the important component of radiation found in the space environment. Mice exposed to 0 Gy of 48 Ti ions served as non-irradiated sham controls. There were five mice per treatment groups at each harvest time. The Trans-Proteomic Pipeline (TPP) was used to assign a probability of a particular protein being in the sample. A proof-of-concept based Ingenuity Pathway Analysis (IPA) was used to characterize the functions, pathways, and networks of the identified proteins. Alterations of expression levels of proteins detected in samples collected at one week (wk) post-irradiation reflects acute effects of exposure to 48 Ti ions, while those detected in samples collected at six months (mos) post-irradiation represent protein expression profiles involved in the induction of late-occurring damage (normally referred to as genomic instability). Our results obtained by using the IPA analyses indicate a wide array of signaling pathways involved in response to 1 GeV/n 48 Ti ions at both harvest times. Our data also demonstrate that the patterns of protein expression profiles are dose and time dependent. The majority of proteins with altered expression levels are involved in cell cycle control, cellular growth and proliferation, cell death and survival, cell-to-cell signaling and interaction. The IPA analyses indicate several important processes involved in responses to exposure to 48 Ti ions. These include the proteosme/ubiquination, protein synthesis, post-translation modification, and lipid metabolism. The IPA analyses also indicate that exposure to 1 GeV/n 48 Ti ions affects the development and function of hematological system, immune cell trafficking, including the cytoskeleton. Further, the IPA analyses strongly demonstrate that the NF-κB and MAPKs (ERKs, JNKs, and p38MAPK) pathways play an essential role in signal transduction after exposure to 1 GeV/n 48 Ti ions. At an early time-point (1 week), the top networks identified by the IPA analyses are related to metabolic disease, lipid metabolism, small molecule biochemistry, and development disorder. In contrast, the top networks identified in samples collected at a late time-point (6 mos post-irradiation) by the IPA analyses are related to cancer, hematological disorders, and immunological diseases. In summary, the proteomic findings from our study provide a foundation to uncover compounds potentially be highly effective in radiation countermeasures.

Purpose: To investigate the biological effects of titanium ((48)Ti, one of the important heavy ions found in space) in the liver of exposed-mice., Materials and Methods: We gave adult male CBA/CaJ mice a whole-body exposure to a total dose of 0, 0.1, 0.25 or 0.5 Gy of (48)Ti ions. The liver was collected at 1 week, 1 month, and 6 months post-irradiation (five mice per treatment-group at each harvest-time). Three biological endpoints were used for evaluating the effects of (48)Ti ions: Oxidative-stress, inflammatory responses, and DNA-methylation (5-methylcytosine and 5-hydroxymethylcytosine)., Results: Our data clearly demonstrated dose-dependent increases in oxidative stress and inflammatory responses in the liver of exposed mice at all time-points (Analysis of Variance or ANOVA, p < 0.05). Significant dose-dependent increases in the levels of 5-methylcytosine were detected at 1 week and 1 month (ANOVA, p < 0.05). At 6 months post-irradiation, a significant increase in the level of 5-methylcytosine was found only in 0.5-Gy-(48)Ti-ion-exposed mice. In contrast, dose-dependent decreases in 5-hydroxymethylcytosine levels were found in the liver of exposed mice (ANOVA, p < 0.05) at all time-points., Conclusions: Chronic oxidative-stress, chronic inflammation, and persistent aberrant DNA-methylation occurred in the liver of (48)Ti-exposed mice. Hence, exposure to (48)Ti ions in space may pose health risks.

Little is known about in vivo cytogenetic effects of protons delivered at the dose and dose rates encountered in space. We determined the effects of 100MeV protons, one of the most abundant type of protons produced during solar particle events (SPE), on the induction of chromosome aberrations (CAs) in bone marrow (BM) cells collected at early (3 and 24h) and late (6 months) time-points from groups of BALB/cJ mice (a known radiosensitive strain) exposed whole-body to 0 (sham-controls), 0.5, or 1.0Gy of 100MeV protons, delivered at 0.5 or 1.0cGy/min. These doses and dose-rates are comparable to those produced during SPE events. Additionally, groups of mice were exposed to 0 or 1Gy of (137)Cs γ rays (delivered at 1cGy/min) as a reference radiation. The kinetics of formation/reduction of gamma-histone 2-AX (γH2AX) were determined in BM cells collected at 1.5, 3, and 24h post-irradiation to assess the early-response. There were five mice per treatment-group per harvest-time. Our data indicated that the kinetics of γH2AX formation/reduction differed, depending on the dose and dose rate of protons. Highly significant numbers of abnormal cells and chromatid breaks (p<0.01), related to those in sham-control groups, were detected in BM cells collected at each time-point, regardless of dose or dose-rate. The finding of significant increases in the frequencies of delayed non-clonal and clonal CAs in BM cells collected at a late time-point from exposed mice suggested that 0.5 or 1Gy of 100MeV protons is capable of inducing genomic instability in BM cells. However, the extent of effects induced by these two low dose rates was comparable. Further, the results showed that the in vivo cytogenetic effects induced by 1Gy of 100MeV protons or (137)Cs γ rays (delivered at 1cGy/min) were similar., (Copyright © 2013 Elsevier B.V. All rights reserved.)

It has been well established that the bone marrow (BM) is a radiosensitive tissue, but the radiosensitivity of the heart is poorly understood. In this study, we investigated the comparative effects of ²⁸Silicon (²⁸Si) ions (one type of heavy ion found in space) on tissue from the heart and the BM of exposed mice. We gave adult male CBA/CaJ mice a whole-body exposure to a total dose of 0, 0.1, 0.25, or 0.5 Gy of 300 MeV/nucleon (n) ²⁸Si ions, using a fractionated schedule (two exposures, 15 days apart that totaled each selected dose). The heart and BM were collected from 5 mice per treatment group at various times up to 6 months post-irradiation. In each mouse, we obtained tissue lysates from the heart and from the total population of BM cells for measuring the levels of cleaved poly (ADP-ribose) polymerase (cleaved PARP, a marker of apoptotic cell death) and the levels of activated nuclear factor-kappa B (NF-κB) and selected NF-κB-regulated cytokines known to be involved in inflammatory responses. Our data showed that, up to 6 months post-irradiation, the levels of apoptotic cell death and inflammatory responses in tissues from the heart and BM collected from exposed mice were statistically higher than those in sham controls. Hence, these findings are suggestive of chronic apoptotic cell death and inflammation in both tissues after exposure to ²⁸Si ions. In summary, our data are indicative of a possible association between exposure to ²⁸Si ions during space flight and long-term health risk.

We determined the in vivo efficacy of apigenin, as an anti-oxidant and anti-inflammatory agent, given to mice after irradiation. Various concentrations of apigenin (0, 10, 20, and 40mg/kg body weight) were administered to mice by a single intraperitoneal injection 3hr after receiving 0 or 3Gy of (137)Cs gamma rays. Mice receiving vehicle only (no radiation and no apigenin) served as sham controls. We assessed the anti-oxidative activity of apigenin in vivo by measuring levels of 8-hydroxy-2-deoxy guanosine (8-OH-dG) in bone marrow (BM) cells, collected at days 3 and 10 after irradiation, from groups of mice (5 mice per treatment group) with or without apigenin treatment. Simultaneously, we evaluated the ability of apigenin to diminish radiation-induced inflammatory responses in bone-marrow-derived macrophages (BMDMs) from the same individual mice used for measuring the level of 8-OH-dG. To do this, the levels of activated nuclear factor-kappa B (NF-kappa B) and NF-kappa B-regulated pro-inflammatory cytokines [i.e. interleukin 1-beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha)] were measured in BMDMs. Our results indicated significant reductions (p<0.01 or <0.05) in the levels of 8-OH-dG in BM cells collected at both harvest times from irradiated mice receiving apigenin treatment, at all apigenin concentrations tested. Likewise, activation of NF-kappa B in BMDMs collected from gamma-irradiated mice that received apigenin was suppressed at both harvest times. Further, the levels of pro-inflammatory cytokines in gamma-irradiated mice treated with 20 or 40mg/kg body weight apigenin were significantly lower than those in mice receiving radiation only (p<0.01 or <0.05) even at day 10 post-irradiation. Additionally, the ratio of neutrophils to lymphocytes indicated that apigenin ameliorated radiation-induced hematological toxicity. Our study is the first to demonstrate the mitigative/therapeutic effects of apigenin given to mice after irradiation., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We measured levels of NF-kappaB activation in bone marrow (BM) cells collected at 1 and 4 h from male BALB/cJ mice (10-12 weeks old) given a whole body dose of 0, 0.05, 0.1 and 1 Gy of (137)Cs gamma-rays (at the dose rate of 0.75 Gy/min). At each harvest time-point, BM cells were collected from five mice per dose of radiation. We used two methods for detecting NF-kappaB activation (1) the NF-kappaB/p65 transcription factor enzyme-linked immunosorbance assay (ELISA) and (2) immunofluorescence staining with NF-kappaB/p65 antibody. Results from ELISA indicated 2.0 and 2.8-fold increases in NF-kappaB activation in BM cells isolated at 1 h post-exposure of mice to 0.1 or 1.0 Gy. The immunofluorescence staining method showed similar results. In samples isolated 4 h post-irradiation, however, no activated NF-kappaB signal was found, regardless of the method of detection. The data also demonstrated that NF-kappaB was not activated in bone marrow cells collected either at 1 or 4 h from BALB/cJ mice exposed to a single dose of 0.05 Gy (137)Cs gamma-rays. Taken together, the results from our in vivo study indicate the involvement of NF-kappaB activation in early response to 0.1 and 1.0 Gy (but not 0.05 Gy) of (137)Cs gamma-rays.

The potential use of flavonoids as a radioprotector is of increasing interest because of their high antioxidant activity and abundance in the diet. The aim of this study is to examine genotoxic and radioprotective effects of one of the most common flavonoids, apigenin, on radiation-induced chromosome aberrations in human lymphocytes. The cytokinesis-block micronucleus (CBMN) assay was used to evaluate such effects of apigenin. Blood samples were collected from two non-smoking healthy male volunteers who had no history of previous exposure to other clastogenic agents. Isolated lymphocytes were cultured. There were two tubes per concentration for all treatments. To evaluate the genotoxicity of apigenin, cells were first treated with different concentrations of apigenin (0, 2.5, 5, 10 and 25 microg/mL) at 24 h after culture initiation, followed by cytochalasin-B (Cyt-B) treatment (3 microg/mL) and cell harvest at 44 and 72 h, respectively. Secondly, to investigate the radioprotective effect, cell cultures were exposed to different concentrations of apigenin as described above for 30 min before being irradiated to 2 Gy of 137Cs gamma rays (at a dose rate of 0.75 Gy/min). In all instances, the frequency of MN was scored in binucleated (BN) cells. The nuclear proliferation index also was calculated. We did not detect an increase in the frequency of MN in non-irradiated human lymphocyte cultures treated with 2.5, 5.0 or 10 microg/mL apigenin; although, we did observe an increase in cultures treated with 25 microg/mL apigenin (the highest concentration of apigenin used in our study). We also observed a significant increase in the frequency of MN in irradiated cells overall; however, the frequency was decreased as the concentration of apigenin increased, suggesting a radioprotective effect. These findings provide a basis for additional studies to help clarify the potential use and benefit of apigenin as a radioprotector.