A Narrative Review of the Herbal Preparation of Ayurvedic, Traditional Chinese, and Kampo Medicines Applied as Radioprotectors.

In recent years, there has been growing scientific interest in the search for natural radioprotectors that can be used to mitigate the effects of radiation on patients, healthcare personnel, and even for space travel. This narrative review covers the past fifty years and focuses on herbal preparations of Ayurvedic, Traditional Chinese, and Kampo Medicines that have the potential to reduce or eliminate the harmful effects of radiation. Our findings highlight ten herbal preparations, namely Abana, Amalakyadi Churna, Amritaprasham, Brahma, Bu-zhong-yi-qi-tang (BZYQT), Chyavanaprasha, Cystone, Geriforte, Mentat, and Triphala, which have demonstrated potential radioprotective effects. This review examines their composition, properties, and possible mechanisms of action in relation to their radioprotective properties. Exploring the ethnobotany of traditional Asian medicine is particularly interesting as it may lead to the discovery of new active compounds with radioprotective properties.

Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators.

Ionizing radiation (IR) is the energy released by atoms in the form of electromagnetic waves (e [...].

Combination of natural polyphenols with a precursor of NAD+ and a TLR2/6 ligand lipopeptide protects mice against lethal γ radiation.

INTRODUCTION: Effective agents that could confer long-term protection against ionizing radiation in vivo would have applications in medicine, biotechnology, and in air and space travel. However, at present, drugs that can effectively protect against lethal ionizing radiations are still an unmet need. OBJECTIVE: To investigate if combinations of natural polyphenols, known for their antioxidant potential, could protect against ionizing radiations. METHODS: Plant-derived polyphenols were screened for their potential ability to confer radioprotection to mice given a lethal whole-body γ radiation (137Cs) dose expected to kill 50% of the animals in 30 days. Telomere and centromere staining, Q-FISH and comet assays were used to investigate chromosomal aberration, micronuclei formation and DNA breaks. Molecular oxidations were investigated by enzyme immunoassays and UPLC-MS/MS. RT-PCR, western blotting and siRNA-induced gene silencing were used to study signaling mechanisms and molecular interactions. RESULTS: The combination of pterostilbene (PT) and silibinin (SIL) was the most effective against γ-irradiation, resulting in 100% of the mice surviving at 30 days and 20% survival at one year. Treatment post γ-irradiation with two potential radiomitigators nicotinamide riboside (NR, a vitamin B3 derivative), and/or fibroblast-stimulating lipoprotein 1 (FSL1, a toll-like receptor 2/6 agonist), did not extend survival. However, the combination of PT, SIL, NR and FSL1 achieved a 90% survival one year post γ-irradiation. The mechanism involves induction of the Nrf2-dependent cellular antioxidant defense, reduction of NF-kB signaling, upregulation of the PGC-1α/sirtuins 1 and 3 axis, PARP1-dependent DNA repair, and stimulation of hematopoietic cell recovery. The pathway linking Nrf2, sirtuin 3 and SOD2 is key to radioprotection. Importantly, this combination did not interfere with X-ray mediated killing of different tumor cells in vivo. CONCLUSION: The combination of the radioprotectors PT and SIL with the radiomitigators NR and FSL1 confer effective, long-term protection against γ radiation in vivo. This strategy is potentially capable of protecting mammals against ionizing radiations.

Redox Status, Dose and Antioxidant Intake in Healthcare Workers Occupationally Exposed to Ionizing Radiation.

The purpose of this study was to evaluate the relationship between blood redox status, dose and antioxidant dietary intake of different hospital staff groups exposed to low doses of ionizing radiation (LDIR) (Interventional Radiology and Cardiology, Radiation Oncology, and Nuclear Medicine) and non-exposed. Personal dose equivalent (from last year and cumulative), plasma antioxidant markers (total antioxidant capacity, extracellular superoxide dismutase activity, and glutathione/oxidized glutathione ratio), oxidative stress markers (nitrites and nitrates, and lipid peroxidation) and dietary intake (antioxidant capacity using ORAC values) were collected and analyzed from 28 non-exposed healthcare workers and 42 healthcare workers exposed to LDIR. Hospital staff exposed to LDIR presented a redox imbalance in blood that seems to correlate with dose. Workers from the Nuclear Medicine Unit were the most affected group with the lowest value of plasma antioxidant response and the highest value of plasma thiobarbituric acid reactive substances, TBARS (indicator of lipid peroxidation) of all four groups. Cumulative personal dose equivalent positively correlated with nitrites and negatively correlated with total antioxidant capacity in blood. The diet of healthcare workers from Nuclear Medicine Unit had higher ORAC values than the diet of non-exposed. Therefore, occupational exposure to LDIR, especially for the Nuclear Medicine Unit, seems to produce an imbalanced redox status in blood that would correlate with cumulative personal dose equivalent.

Use of Ganoderma lucidum (Ganodermataceae, Basidiomycota) as Radioprotector.

For millennia, naturopaths and physicians have used Ganoderma lucidum (reishi mushroom) for its diverse therapeutic properties, as recorded in the oldest Chinese herbal encyclopedia. Indeed, a radioprotective effect has been reported in the isolated components of its extracts. A systematic review and meta-analyses (PRISMA) was conducted in March 2020, searching databases including PubMed, Scopus, Embase, and Google Scholar, along with Clinical Trials. The inclusion criteria were ex vivo, in vitro, and in vivo studies, with full texts in English, conducted to determine the radioprotective benefits of G. lucidum, or reports in which ionizing radiation was used. From a total number of 1109 records identified, 15 full text articles were eligible, none of them were clinical trials. In vivo studies reveal the efficiency of G. lucidum aqueous extracts of polysaccharides and triterpenes in mice exposed to γ-rays. In plasmid, they can reduce radiation damage as an increment of the open circular form, as well as increase the DNA extension, as shown in vitro studies. Ex vivo studies conducted in human blood cells show the radioprotective effect of ß-glucan of aqueous extract of G. lucidum, nevertheless, its implementation as radioprotector to humans is in need of further clinical research studies.

Measurement of body composition in cancer patients using CT planning scan at the third lumbar vertebra.

INTRODUCTION: Objective: the main objective was to assess body composition in terms of skeletal muscle index (SMI), myosteatosis, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) as an adjunct of information provided by radiotherapy CT planning scan. Material and methods: a sample of 49 patients with lung and digestive cancers underwent a CT scan for radiotherapy treatment, which included measurements at the L3 region. Images were analyzed with a radiotherapy contouring software, using different Hounsfield Unit (HU) settings. Cross-sectional areas (cm2) were automatically computed by summing tissue pixels and multiplying by pixel surface area. Low SMI (cm2/m2) and muscle density (HU) were determined according to the recently established cut-off points. Results: the prevalence of low SMI was detected in 46.94% of patients, being present in 8 women, 4 men with BMI < 25 kg/m2, and 11 men with BMI ≥ 25 kg/m2. The average mean skeletal attenuation of total skeletal muscle area was 29.02 (± 8.66) HU, and myosteatosis was present in 13 women (81.25%) and 31 men (93.94%). Mean SAT was 131.92 (± 76.80) cm2, mean VAT was 133.19 (± 85.28) cm2, and mean IMAT was 11.29 (± 12.86) cm2. Conclusion: skeletal muscle abnormalities are frequently present in cancer patients and a low SMI may also exist even in the presence of overweight. As CT scans are an important tool at any radiation oncology department, they could also be used to offer highly sensitive and specific information about body composition, as well as to detect early malnutrition before starting radiotherapy treatment.

INTRODUCCIÓN: Objetivo: evaluar la composición corporal mediante el índice de músculo esquelético (IME), el tejido adiposo visceral (TAV), el tejido adiposo subcutáneo (TAS) y el tejido adiposo intermuscular (TAIM) o la densidad muscular (DM) en pacientes oncológicos antes de iniciar el tratamiento con radioterapia mediante cortes de TAC. Materiales y métodos: se estudiaron 49 pacientes con cáncer de pulmón y del aparato digestivo sometidos a tomografía computarizada con cortes en L3 para la determinación del tratamiento con radioterapia. El tejido adiposo y muscular se cuantificó mediante distintas Unidades Hounsfield (UH) (-29 a +150 para masa muscular, -190 a -30 para TAIM/TAS y -150 a -50 para TAV). Resultados: la prevalencia de un IME bajo se detectó en el 46,94% de los pacientes, estando presente en 8 mujeres, 6 de ellas con un IMC ≥ 25 kg/m². Según la distribución masculina, se identificaron 4 hombres con IMC < 25 kg/m² y 11 hombres con ≥ 25 kg/m². La DM media fue de 29,02 (± 8,66) UH y la mioesteatosis estuvo presente en 13 mujeres (81,25%) y 31 hombres (93,94%). La media del TAS fue de 131,92 (± 76,80) cm², la del TAV de 133,19 (± 85,28) cm² y la del TAIM de 11,29 (± 12,86) cm². Conclusión: las anormalidades del músculo esquelético y la masa grasa son muy frecuentes en los pacientes con cáncer, pudiendo existir un bajo IME incluso en presencia de sobrepeso u obesidad. Teniendo en cuenta que la TAC es una herramienta importante en cualquier departamento de radioterapia, también podría utilizarse para ofrecer información sensible y específica sobre la composición corporal, así como para detectar la malnutrición precoz.

Diagnosis of pre-sarcopenia from a single selectional crosscut at C3 region, using CT scans before radiotherapy.

INTRODUCTION: Purpose: the main purpose of this study was to diagnose pre-sarcopenia in cancer patients who had lack of computed tomography (CT) abdominal images, with a newly discovered method based on cervical images. Material and methods: a sample of 37 patients with either lung cancer or a cancer that affected the upper digestive system underwent radiotherapy computed simulation which included measurements at C3 and L3 regions. Skeletal muscle mass (SMM) and skeletal muscle index (SMI) were determined by Hounsfield units and compared in both regions. Pre-sarcopenia was identified according to the cut-points currently established: ≤ 41 cm2/m2 in females, ≤ 43 cm2/m2 in males with a BMI ≤ 25 kg/m2, and ≤ 53 cm2/m2 in males with a BMI > 25 kg/m2. Results: the correlation of SMM and SMI between the C3 and L3 regions was R2 = 0.876 and R2 = 0.805, respectively. Moreover, there was a positive association (86.49%) in terms of the diagnosis of pre-sarcopenia according to both regions. In total, eleven pre-sarcopenic patients (29.37%) were identified; three of them being overweight (27.27%) and two of them being obese (18.18%). Conclusion: a single sectional cross at the level of C3 can be used for the diagnosis of pre-sarcopenia. This new method avoids unnecessary irradiation, saves hospital costs and detects malnutrition before starting radiotherapy treatment in cancer patients who have lack of CT abdominal imaging.

INTRODUCCIÓN: Propósito: el propósito de este estudio fue diagnosticar la presarcopenia en pacientes con cáncer que no disponen de imágenes por tomografía computarizada (TC) a nivel abdominal mediante un método novedoso basado en cortes a nivel cervical. Material y métodos: se analizaron y se compararon mediante unidades la masa muscular y la masa muscular esquelética en 37 pacientes con cáncer de pulmón y neoplasias del aparato digestivo superior que incluían cortes en la TC de planificación a nivel de C3 y L3. La presarcopenia se identificó de acuerdo con los puntos de corte establecidos actualmente: ≤ 41 cm2/m2 para mujeres, ≤ 43 cm2/m2 en hombres con un IMC ≤ 25 kg/m2 y ≤ 53 cm2/m2 en hombres con IMC > 25 kg/m2. Resultados: la correlación de la masa muscular y el índice musculoesquelético entre las regiones C3 y L3 fue R2 = 0.876 y R2 = 0.805, respectivamente. Además, hubo una asociación positiva (86,49%) en términos del diagnóstico de presarcopenia según ambas regiones. En total, se identificaron once pacientes con presarcopenia (29,37%); tres de ellos con sobrepeso (27,27%) y dos con obesidad (18,18%). Conclusión: un solo corte transversal a nivel de la vértebra C3 puede diagnosticar la presarcopenia. Este nuevo método evita la irradiación innecesaria, ahorra costos hospitalarios y detecta la desnutrición antes de iniciar el tratamiento de radioterapia en pacientes con cáncer que no disponen de imágenes a nivel abdominal.

Assessment of the dicentric chromosome assay as a biodosimetry tool for more personalized medicine in a case of a high risk neuroblastoma 131I-mIBG treatment.

PURPOSE: The aims of this study were to estimate the whole - body absorbed - dose with the Dicentric Chromosome Assay (DCA) (biodosimetry) for 131I - metaiodobenzylguanidine (131I - mIBG) therapy for high - risk neuroblastoma, and to obtain an initial correlation with the physical dosimetry calculated as described by the Medical Internal Radiation Dosimetry formalism (MIRD). Together both objectives will aid the optimization of personalized targeted radionuclide therapies. MATERIAL AND METHODS: A 12 year-old child with relapsed high-risk neuroblastoma was treated with 131I-mIBG: a first administration with activity <444 MBq/kg was used as a tracer in order to calculate the activity needed in a second administration to achieve a whole body prescribed dose of ∼4 Gy. Blood samples were obtained before and seven days after each administration to analyze the frequency of dicentrics. Moreover, consequent estimations of retained activity were done every few hours from equivalent dose rate measurements at a fixed position, two meters away from the patient, in order to apply the MIRD procedure. Blood samples were also drawn every 2- to -3 days to assess bone marrow toxicity. RESULTS: For a total activity of 22,867 MBq administered over two phases, both biological and physical dosimetries were performed. The former estimated a whole-body cumulated dose of 3.53 (2.58-4.41) Gy and the latter a total whole-body absorbed dose of 2.32 ± 0.48 Gy. The patient developed thrombocytopenia grade 3 after both infusions and neutropenia grade 3 and grade 4 (based on CTCAE 4.0) during respective phases. CONCLUSION: The results indicate a possible correlation between biodosimetry and standard physical dosimetry in 131I-mIBG treatment for high-risk neuroblastoma. A larger cohort and refinement of the DCA for internal irradiation are needed to define the role of biodosimetry in clinical situations.

Searching trans-resveratrol in fruits and vegetables: a preliminary screening.

Resveratrol is a phytoalexin with potent anti-inflammatory, anti-oxidant and anti-carcinogenic effects. The object of this work was to determine whether this promising compound was present in the typical fruits and vegetables used in the Mediterranean diet. Our results indicated the presence of trans-resveratrol in concentrations ranging from 0.2 µg/g in tomatoes and 3 lg/g. in strawberries.

RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry.

PURPOSE: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. RESULTS: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. CONCLUSIONS: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.

Analysis of the Possible Persistent Genotoxic Damage in Workers Linked to the Ardystil Syndrome.

BACKGROUND: A combination of several factors including a change in the paint application system; a lack of proper hygiene; and inadequate safety measures caused a severe health impact in the workers of some textile painting factories. This outbreak, mainly characterized by respiratory disorders, caused the death of six people and it has been classified as Ardystil syndrome. MATERIALS AND METHODS: Fifty-two workers involved in the outbreak and 48 healthy subjects not known to have exposed to the potentially mutagenic agents participated in the study. The program evaluated possible genotoxic damage through the sister chromatid exchange (SCE) cytogenetic biomarker assay. We determined the frequency of SCE, high-frequency cells (HFCs), and a ratio, which can be considered as a new parameter, allowing for the study of the SCE distribution pattern among the chromosomes. RESULTS: There was no statistically significant difference in the SCE frequency and in the mean number of HFCs between the control and the Ardystil-affected groups. However, smoking increased the incidence of all parameters studied in both the case and control groups. CONCLUSIONS: This study shows that workers involved in the Ardystil syndrome did not suffer genotoxic damage as measured by SCE and HFCs when compared with the control group.

Sister chromatid exchange, (SCE), High-Frequency Cells (HFCs) and SCE distribution patterns in peripheral blood lymphocytes of Spanish adult smokers compared to non-smokers.

According to the International Agency for Research on Cancer, smoking tobacco is a major cause of cancer in humans. It causes about half of all male cancer deaths and an ever increasing number of cancer deaths in females. The aim of this study was to establish whether cigarette smoking increases sister chromatid exchanges (SCEs) in peripheral blood lymphocytes in two Spanish population groups; light and heavy smokers. The mean number of High-Frequency Cells (HFCs) was determined and, the SCE distribution pattern among the chromosomes was analysed represented by a ratio described below. A local sample of 101 adult smokers (n=48) and non-smokers (n=53), aged from 18 to 49 years, was studied using SCE levels in peripheral lymphocytes. Heavy smoking (≥ 10 cigarettes per day) increased significantly the SCE frequency and the HFC parameters. Neither age nor sex significantly influenced the frequencies in the groups studied.

Current knowledge on tumour induction by computed tomography should be carefully used.

Risks associated to ionising radiation from medical imaging techniques have focused the attention of the medical society and general population. This risk is aimed to determine the probability that a tumour is induced as a result of a computed tomography (CT) examination since it makes nowadays the biggest contribution to the collective dose. Several models of cancer induction have been reported in the literature, with diametrically different implications. This article reviews those models, focusing on the ones used by the scientific community to estimate CT detriments. Current estimates of the probability that a CT examination induces cancer are reported, highlighting its low magnitude (near the background level) and large sources of uncertainty. From this objective review, it is concluded that epidemiological data with more accurate dosimetric estimates are needed. Prediction of the number of tumours that will be induced in population exposed to ionising radiation should be avoided or, if given, it should be accompanied by a realistic evaluation of its uncertainty and of the advantages of CTs. Otherwise they may have a negative impact in both the medical community and the patients. Reducing doses even more is not justified if that compromises clinical image quality in a necessary investigation. Key Points • Predictions of radiation-induced cancer should be discussed alongside benefits of imaging. • Estimates of induced cancers have noticeable uncertainties that should always be highlighted. • There is controversy about the acceptance of the linear no-threshold model. • Estimated extra risks of cancer are close to the background level. • Patients should not be alarmed by potential cancer induction by CT examinations.

Radioprotective activity and cytogenetic effect of resveratrol in human lymphocytes: an in vitro evaluation.

Trans-resveratrol is a natural occurring polyphenol, obtained from grapes and other berries. This compound has shown antioxidant, anti-inflammatory, immunostimulant or anti-carcinogenic properties. Our aim was to evaluate the radioprotective efficacy, in vitro, of trans-resveratrol against radiation-induced chromosomal damage and to study the genotoxicity and cytotoxicity of this polyphenol in cell cultures without irradiation. The study was carried out by the pre-treatment of human lymphocytes at concentrations from 0 to 219µM of trans-resveratrol. The results showed that all concentrations tested reduced radiation-induced chromosomal damage compared with cells with any treatment. Maximum damage protection was observed at the concentration of 2.19µM. Concerning genotoxic results, all tested trans-resveratrol concentrations increased the sister chromatid exchange (SCE) index compared with no trans-resveratrol treatment. Cytotoxic indexes (Mitotic and Proliferation Index) showed that the lowest concentrations could enhance the cell proliferation rates and the highest ones could negatively affect to human peripheral lymphocytes growth.

A preliminary study of presence of resveratrol in skins and pulps of European and Japanese plum cultivars.

BACKGROUND: Resveratrol is a polyphenol with health properties being mainly present in the skins of several foods. However, any study has been carried out to analyze the presence of this stilbene in the plum fruit from the genus Prunus in European and Japanese cultivars. RESULTS: The analysis of resveratrol from the skin in different cultivars of plums from Spanish markets with liquid chromatography coupled to ultraviolet (LC-UV) detector with subsequent confirmation by LC-MS/MS has been demonstrated that contents of this compound in plums ranged from 0.1 to 6.2 µg/g. CONCLUSIONS: Values of resveratrol in European plum cultivars is higher than in Japanese cultivars.

In vitro cytogenetic and genotoxic effects of curcumin on human peripheral blood lymphocytes.

Curcumin has shown a wide range of properties such as anti-inflammatory and anti-carcinogenic properties. Many of these effects, mainly the anti-carcinogenic effect, could be linked to its anti-oxidant effects. Nevertheless, some studies suggest that this natural compound possesses both pro- and anti-oxidative effects and that curcumin could be a genotoxic agent for some cell lines. We evaluated the genetic damage induced by curcumin to human lymphocytes exposed to increasing concentrations (0-50 µg/ml) of curcumin. Biomarkers such as chromosome aberrations (CAs) and sister chromatid exchange (SCE) were analyzed. In addition to the cytogenetic analysis, the effect of curcumin in the cell proliferation kinetics (CPK) by the proliferation index (PI) was also analyzed. The results indicated that high concentrations of curcumin induced CAs, mainly acentric fragments. SCEs rate was not statistically different from the control group in any curcumin treated cell group. The PI of cells treated with 2 and 5 µg/ml of curcumin were statistically significant from the control group and finally, the MI showed a tendency to increase in all the concentrations of curcumin tested. In conclusion, it can be assumed that the higher concentrations of curcumin evaluated have a cyto and genotoxic effect, in vitro, for human peripheral lymphocytes.

Germline mutations in CDKN2A are infrequent in female patients with melanoma and breast cancer.

Carriers of mutations in the melanoma susceptibility gene, CDKN2A, exhibit a higher than expected risk of breast cancer. In this study, we aimed to determine mutations in the CDKN2A gene in patients with melanoma and additional breast cancer. Thirty-one women with histologically confirmed melanoma and breast cancer were studied for CDKN2A/ARF gene mutations by direct sequencing analysis. We identified four CDKN2A germline mutations. Two patients harbored the A148T polymorphism, one of them with family history of breast cancer. Another patient, with a melanoma diagnosed at 77 years, a breast cancer diagnosed at 66 and a family history of melanoma, had the V59G mutation. The fourth patient had a melanoma diagnosed at 54 years, a breast cancer at 46, and a strong family history of breast cancer (mother and grandmother), and presented the A85T mutation. The epidemiologic link between cutaneous melanoma and breast cancer is not mainly related to CDKN2A mutations. However, some mutations might have a role in this association or even in familial breast cancer, as it could be inferred from the patient with the A85T mutation.

Radiation effects in interventional radiology using biological and physical dosimetry methods: a case-control study.

Interventional radiologists and staff members are frequently exposed to protracted and fractionated low doses of ionizing radiation, which extend during all their professional activities. These exposures can derive, due to the irradiation of skin tissues and peripheral blood, in deterministic effects (radiodermitis, aged skin, hands depilation) or stochastic ones (skin and non-solid cancers incidence). Epidemiological studies of population exposed to ionizing radiation provide information of radio-induced effects. The radiation risk or radiological detriment has been estimated from a group of six exposed interventionist radiologists of the Hospital La Fe (Valencia, Spain). Dosimetry has been periodically registered from TLDs and wrist dosimeters (physical methods) and estimated through translocations in lymphocytes of peripheral blood (biological methods), by extrapolating the yield of translocations to their respective dose-effect curves. The probability of non-melanoma skin cancer and leukaemia (acute myelogenous, acute lymphocytic and chronic myelogenous leukaemia) incidence has been estimated through the software RADRISK. This software is based on a transport model from epidemiological studies of population exposed to external low-LET ionizing radiation [1]. Other non-solid carcinomas have not been considered due to their low statistical power, such as myeloid and non-Hodgkin lymphomas. The discrepancies observed between the physically recorded doses and biological estimated doses could indicate that exposed workers did not always wear their dosimeters or these dosimeters were not always exposed to the radiation field.