Scientific Publications


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Antioxidants Prevent DNA Double-Strand Breaks From X-Ray Based Cardiac Examinations: A Randomized, Double-Blinded, Placebo-Controlled Trial

Results: In the high–radiation exposure group (C), antioxidant pre-treatment yielded a significant reduction (−66%) in excess foci compared with placebo (0.1 vs. 0.3, p < 0.05) (Fig. 1), whereby the effect of vitamin C (−87%) was more pronounced than the effect of NAC (−43%) (p = 0.005 vs. vitamin C). Pre-treatment with antioxidants before exposure to high radiation dose reduced the amount of excess foci by two-thirds, ranging well within the values of 50% to 87% observed for protective effects of NAC and vitamin C in experimental animal and cell culture studies. 

View full publication - Journal of the American College of Cardiology 2014 

Antioxidant N-acetylcysteine attenuate the acute liver injury caused by X-ray in mice

Abstract: The aim of this study was to evaluate the protective effects of different doses and administration modes of N-acetylcysteine (NAC) against X-ray -induced liver damage in mice. Kun-Ming mice were divided into four groups, each composed of six animals: two control groups and two NAC-treated groups. An acute study was carried out to determine alterations in lipid peroxidation (determined by measuring malondiadehyde (MDA) level), glutathione (GSH) content and superoxide dismutase (SOD) activity (assayed by colorimetric method), and DNA damage (characterized by DNA-single strand break using with comet assay) as well as cell apoptosis (measured by flow cytometry) at 12 h after irradiation. The results showed that there were dose-related decreases in MDA level, DNA damage and cell apoptosis, and dose-dependent increases in GSH content and SOD activity in all NAC-treated groups compared to control groups, indicating that pre-treatment or post-treatment with NAC significantly attenuates the acute liver damage caused by X-ray. In addition, significant positive correlations were observed between MDA level and DNA damage or cell apoptosis, implying that lipid peroxidation plays a major role in X-ray-induced liver injury. The data suggest that NAC exerts its radioprotective effect by counteracting accumulated reactive oxygen species in the liver through its properties as a direct antioxidant and a GSH precursor, when administered before or after X-ray irradiation.

Influence of Different Antioxidants on X-Ray Induced DNA Double-Strand Breaks (DSBs) Using y-H2AX Immunofluorescence Microscopy in a Preliminary Study  

Results: For zinc, trolox and lipoic acid regardless of concentration or pre-incubation time, no significant decrease of γ-H2AX-foci was found. However, ß-carotene (15%), selenium (14%), vitamin E (12%), vitamin C (25%), NAC (43%) and Q 10 (18%) led to a significant reduction of γ-H2AX-foci at a pre-incubation time of 1 hour. The combination of different antioxidants did not have an additive effect.     

Effects of Dietary Supplements on Space Radiation-Induced Oxidative Stress in Sprague-Dawley Rats  

Abstract: Of particular concern for the health of astronauts during space travel is radiation from protons and high-mass, high-atomic-number (Z), and high-energy particles (HZE particles). Space radiation is known to induce oxidative stress in astronauts after extended space flight. In the present study, the total antioxidant status was used as a biomarker to evaluate oxidative stress induced by γ rays, protons and HZE-particle radiation. The results demonstrate that the plasma level of total antioxidants in Sprague-Dawley rats was significantly decreased (P < 0.01) in a dose-dependent manner within 4 h after exposure to γ rays. Exposure to protons and HZE-particle radiation also significantly decreased the serum or plasma level of total antioxidants in the irradiated animals. Diet supplementation with L-selenomethionine alone or a combination of selected antioxidant agents was shown to partially or completely prevent the decrease in the serum or plasma levels of total antioxidants in animals exposed to γ rays, protons or HZE particles. These findings suggest that exposure to space radiation may compromise the capacity of the host antioxidant defense and that this adverse biological effect can be prevented at least partially by dietary supplementation with L-selenomethionine and antioxidants.

View full publication - Radiation Research 2004

Prevention and mitigation of acute death of mice after abdominal irradiation by the antioxidant N-acetyl-cycsteine (NAC)

Abstract: Gastrointestinal (GI) injury is a major cause of acute death after total-body exposure to large doses of ionizing radiation, but the cellular and molecular explanations for GI death remain dubious. To address this issue, we developed a murine abdominal irradiation model. Mice were irradiated with a single dose of X rays to the abdomen, treated with daily s.c. injection of N-acetyl-l-cysteine (NAC) or vehicle for 7 days starting either 4 h before or 2 h after irradiation, and monitored for up to 30 days. Separately, mice from each group were assayed 6 days after irradiation for bone marrow reactive oxygen species (ROS), ex vivo colony formation of bone marrow stromal cells, and histological changes in the duodenum. Irradiation of the abdomen caused dose-dependent weight loss and mortality. Radiation-induced acute death was preceded not only by a massive loss of duodenal villi but also, surprisingly, abscopal suppression of stromal cells and elevation of ROS in the nonirradiated bone marrow. NAC diminished these radiation-induced changes and improved 10- and 30-day survival rates to >50% compared with <5% in vehicle-treated controls. Our data establish a central role for abscopal stimulation of bone marrow ROS in acute death in mice after abdominal irradiation.

View full publication - Radiation Research 2010

Memory impairment, oxidative damage and apoptosis induced by space radiation: ameliorative potential of alpha-lipoid acid. 

Abstract: Exposure to high-energy particle radiation (HZE) may cause oxidative stress and cognitive impairment in the same manner that seen in aged mice. This phenomenon has raised the concerns about the safety of an extended manned mission into deep space where a significant portion of the radiation burden would come from HZE particle radiation. The present study aimed at investigating the role of alpha-lipoic acid against space radiation-induced oxidative stress and antioxidant status in cerebellum and its correlation with cognitive dysfunction. We observed spontaneous motor activities and spatial memory task of mice using pyroelectric infrared sensor and programmed video tracking system, respectively. Whole body irradiation of mice with high-LET (56)Fe beams (500 MeV/nucleon, 1.5 Gy) substantially impaired the reference memory at 30 day post-irradiation; however, no significant effect was observed on motor activities of mice. Acute intraperitoneal treatment of mice with alpha-lipoic acid prior to irradiation significantly attenuated such memory dysfunction. Radiation-induced apoptotic damage in cerebellum was examined using a neuronal-specific terminal deoxynucleotidyl transferase-mediated nick end-labeling method (NeuroTACS). Radiation-induced apoptotic and necrotic cell death of granule cells and Purkinje cells were inhibited significantly by alpha-lipoic acid pretreatment. Alpha-lipoic acid pretreatment exerted a very high magnitude of protection against radiation-induced augmentation of DNA damage (comet tail movement and serum 8-OHdG), lipid proxidation products (MDA+HAE) and protein carbonyls in mice cerebellum. Further, radiation-induced decline of non-protein sulfhydryl (NP-SH) contents of cerebellum and plasma ferric reducing power (FRAP) was also inhibited by alpha-lipoic acid pre-treatment. Results clearly indicate that alpha-lipoic acid is a potent neuroprotective antioxidant. Moreover, present finding also support the idea suggesting the cerebellar involvement in cognition.

View publication - Behavioral Brain Research 2008

Effects of dietary supplements on the space radiation-induced reduction in total antioxidant status in CBA mice.

Abstract: In the present study, the total antioxidant status was used as a biomarker to evaluate oxidative stress induced by proton, HZE-particle and gamma radiation in CBA mice. The results demonstrated that the plasma level of TAS was significantly decreased (P < 0.05) in CBA mice after exposure to a 50-cGy dose of radiation from HZE particles or a 3-Gy dose of radiation from protons or gamma rays. Diet supplementation with Bowman-Birk Inhibitor Concentrate (BBIC), L-selenomethionine (L-SeM), or a combination of N-acetyl cysteine, sodium ascorbate, co-enzyme Q10 (CoQ10), alpha-lipoic acid, L-SeM and vitamin E succinate could partially or completely prevent the reduction in the plasma level of TAS in CBA mice exposed to proton or HZE-particle radiation. The selected antioxidant combination with or without CoQ10 has a comparable protective effect on the gamma-radiation-induced drop in TAS in CBA mice. These results indicate that BBIC, L-SeM and the selected antioxidant combinations may serve as countermeasures for space radiation-induced adverse biological effects.

View publication - Radiation Research 2006

Trends in the development of radioprotective agents.

Abstract: People may be exposed to ionizing radiation during radiotherapy or following exposure to radionuclides in nuclear medicine. Radioprotective agents have been used to reduce morbidity or mortality produced by ionizing irradiation. Early developments of such agents focused on thiol synthetic compounds, such as amifostine. This compound reduced mortality; however, there were difficulties in administering aminothiols that led to adverse effects. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted much attention. Natural compounds have been evaluated as radioprotectants and they seem to exert their effect through antioxidant and immunostimulant activities. Although recent agents have lower efficacy, they have lower toxicity, more favourable administration routes and improved pharmacokinetics compared to the older thiol compounds.

View publication - Drug Discovery Today 2007

Antioxidant dietary supplementation in mice exposed to proton radiation attenuates expression of programmed cell death-associated genes. 

Abstract: Dietary antioxidants have radioprotective effects after ionizing radiation exposure that limit hematopoietic cell depletion. We sought to determine the mechanism of proton-induced hematopoietic cell death in animals receiving a moderate dose of whole-body proton radiation. In addition, animals were maintained on diets supplemented with or without dietary antioxidants. In the presence of the dietary antioxidants, total bone marrow mRNA and protein expression of apoptosis-related genes were decreased compared to the expression profiles in the irradiated mice not receiving the antioxidant formulation. These data confirm high-energy proton-induced gene expression of classical apoptosis markers including BAX, caspase-3 and PARP-1. Antioxidant supplementation resulted in decreased expression of these genes in addition to increased protein expression of the anti-apoptosis markers Bcl2 and Bcl-xL. In conclusion, oral supplementation with antioxidants appears to be an effective approach for radioprotection against hematopoietic cell death.

View publication - Radiation Research 2011

Dietary antioxidants protect hematopoietic cells and improve animal survival after total-body irradiation. 

Abstract: The purpose of this study was to determine whether a dietary supplement consisting of L-selenomethionine, vitamin C, vitamin E succinate, alpha-lipoic acid and N-acetyl cysteine could improve the survival of mice after total-body irradiation. Antioxidants significantly increased the 30-day survival of mice after exposure to a potentially lethal dose of X rays when given prior to or after animal irradiation. Pretreatment of animals with antioxidants resulted in significantly higher total white blood cell and neutrophil counts in peripheral blood at 4 and 24 h after 1 Gy and 8 Gy. Antioxidants were effective in preventing peripheral lymphopenia only after low-dose irradiation. Antioxidant supplementation was also associated with increased bone marrow cell counts after irradiation. Supplementation with antioxidants was associated with increased Bcl2 and decreased Bax, caspase 9 and TGF-beta1 mRNA expression in the bone marrow after irradiation. Maintenance of the antioxidant diet was associated with improved recovery of the bone marrow after sublethal or potentially lethal irradiation. Taken together, oral supplementation with antioxidants appears to be an effective approach for radioprotection of hematopoietic cells and improvement of animal survival, and modulation of apoptosis is implicated as a mechanism for the radioprotection of the hematopoietic system by antioxidants.

View publication - Radiation Research 2008

Effect of Antioxidants on X-Ray-induced y-h2aX Foci in Human Blood Lymphocyes

Results: In the in vitro experiments, 15-minute preincubation with antioxidants significantly reduced mean y-H2AX foci levels by 23% (P < .0001), whereas addition of antioxidants immediately after irradiation did not lead to a reduction of x-ray–induced foci (P = .6905). Mean 53BP1 foci were also reduced by preincubation with the radioprotectant. In the in vivo/in vitro tests, oral pretreatment with anti- oxidants also led to a significant reduction of y-H2AX foci formation; administration 60 minutes before irradiation resulted in a mean foci reduction of 58% (P < .0001).

Pilot Study - Unpublished Results from Nasa at Houston

Book Excerpt: In a pilot study we observed that this formulation of multiple antioxidants, when administered orally before radiation exposure, increased the survival rate of lethally irradiated mice from 0 to 40 percent. The same formulation of antioxidants, when administered orally before and after irradiation in sheep exposed to a very high dose of radiation (causing 100 percent death within seven days), increased the animals' survival time from seven days to thirty-eight days. 

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