Ionizing radiation causes the massive apoptosis of human tissue cells,leading to dysfunction of the gastrointestinal tract and hematopoietic system.Thus,high-efficiency,low-toxicity radiation protection drugs are urgently needed.Toll-like receptor agonists have been developed based on the anti-apoptotic mechanism of tumor cells in recent years,which exert their radioprotective effects by activating downstream pathways,mainly nuclear factor-κB.Here we elucidate several agonists of Toll-like receptors involved in radiation protection,with an attempt to inform the research and development of new radiation protection agents.
Apoptosis ; Humans ; NF-kappa B ; Radiation Protection ; Radiation, Ionizing ; Radiation-Protective Agents/pharmacology* ; Toll-Like Receptors/agonists*

Caesalpinia sappan L., belonging to the family Leguminosae, is a medicinal plant that is distributed in Southeast Asia. The dried heartwood of this plant is used as a traditional ingredient of food, red dyes, and folk medicines in the treatment of diarrhea, dysentery, tuberculosis, skin infections, and inflammation. Brazilin is the major active compound, which has exhibited various pharmacological effects, including anti-platelet activity, anti-hepatotoxicity, induction of immunological tolerance, and anti-inflammatory and antioxidant activities. The present study aimed to evaluate the antioxidant activity and expression of antioxidant enzymes of C. sappan L. extract and its major compound, brazilin, in human epidermal keratinocytes exposed to UVA irradiation. Our results indicated that C. sappan L. extract reduced UVA-induced HO production via GPX7 activation. Moreover, brazilin exhibited antioxidant effects that were similar to those of C. sappan L. via glutathione peroxidase 7 (GPX7), suggesting that C. sappan L. extract and its natural compound represent potential treatments for oxidative stress-induced photoaging of skin.
Antioxidants ; pharmacology ; Benzopyrans ; pharmacology ; Caesalpinia ; chemistry ; Humans ; Hydrogen Peroxide ; toxicity ; Keratinocytes ; cytology ; drug effects ; enzymology ; radiation effects ; Oxidative Stress ; drug effects ; radiation effects ; Peroxidases ; genetics ; metabolism ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Ultraviolet Rays

Depleted uranium (DU) has been widely applied in industrial and military activities, and is often obtained from producing fuel for nuclear reactors. DU may be released into the environment, polluting air, soil, and water, and is considered to exert both radiological and chemical toxicity. In humans and animals, DU can induce multiple health effects, such as renal tubular necrosis and bone malignancies. This review summarizes the known information on DU's routes of entry, mechanisms of toxicity, and health effects. In addition, we survey the chelating agents used in ameliorating DU toxicity.
Animals ; Chelating Agents ; pharmacology ; Humans ; Inactivation, Metabolic ; Radiation-Protective Agents ; pharmacology ; Uranium ; metabolism ; toxicity

Objective: To investigate the improving effect of astaxanthin (AST) on the sperm quality of rats with ornidazole (ORN)-induced oligoasthenozoospermiaand its action mechanism. METHODS: Forty adult male SD rats were equally randomized into groups A (solvent control), B (low-dose ORN ［400 mg/（kg·d）］), C (high-dose ORN ［800 mg/（kg·d）］), D (low-dose ORN ［400 mg/（kg·d）］ + AST ［20 mg/（kg·d）］), and E (high-dose ORN ［800 mg/（kg·d）］ + AST ［20 mg/（kg·d）］), all treated intragastrically for3 weeks.After treatment, the epididymal tails ononeside was taken for determination of sperm concentration and activity, and the epididymideson the other side harvested for measurement of the activities of GSH-Px, GR, CAT and SOD and the MDA contentin the homogenate. RESULTS: Compared with group A, sperm motilityin the epididymal tail andGSH-Px and SOD activities in theepididymiswere markedly decreased while the MDAcontent significantlyincreased in group B (P<0.05), spermmotility and concentrationin the epididymal tail, testisindex, and the activities of GSH-Px, GR, CAT and SOD in the epididymis were remarkably reduced while theMDA contentsignificantly increased in group C(P<0.05). In comparison with group B, group D showed markedly increased sperm motility (［45.3±8.7］% vs ［66.3±8.9］%, P<0.05) in the epididymal tail and SOD activity in the epididymis (［116.7±25.3］ U/mg prot vs ［146.1±23.8］ U/mg prot, P<0.05), decreased MDA content(［1.68±0.45］ nmol/mg prot vs ［1.19±0.42］ nmol/mg prot, P<0.05).Compared with group C, group Eexhibited significant increases in the weight gained (［89.0±9.5］ vs ［99.9±4.1］ %, P<0.05) and sperm motility (［17.9±3.5］% vs ［27.3±5.3］ %, P<0.05) but a decrease in the content of MDA (［2.03±0.30］ nmol/mg prot vs ［1.52±0.41］ nmol/mg prot, P<0.05). CONCLUSIONS AST can improve spermquality in rats with ORN-inducedoligoasthenozoospermia, which may be associated with its enhancing effect on the antioxidant capacity of the epididymis.
Animals ; Antioxidants ; pharmacology ; Asthenozoospermia ; prevention & control ; Epididymis ; drug effects ; metabolism ; Male ; Oligospermia ; prevention & control ; Ornidazole ; Oxidative Stress ; Protective Agents ; pharmacology ; Radiation-Sensitizing Agents ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Sperm Motility ; Spermatozoa ; drug effects ; metabolism ; Xanthophylls ; pharmacology

Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group (P<0.01), while obviously reduced the MDA and PCO contents and the ROS levels derived from of the brain mitochondria. The shikonin also noticeably improved the spatial memory deficits caused by carbon ion beam irradiation. All results demonstrated that shikonin could improve the irradiated brain injury which might resulted from its modulation effects on the oxidative stress induced by the 12C6+ ion beam.
Animals ; Antioxidants ; pharmacology ; Brain Injuries ; prevention & control ; Catalase ; metabolism ; Heavy Ion Radiotherapy ; Male ; Malondialdehyde ; metabolism ; Mice ; Naphthoquinones ; pharmacology ; Protein Carbonylation ; Radiation Injuries, Experimental ; prevention & control ; Radiation-Protective Agents ; pharmacology ; Random Allocation ; Specific Pathogen-Free Organisms ; Superoxide Dismutase ; metabolism

OBJECTIVETo observe the effect of Liuweidihuang Pills in relieving cellphone electromagnetic radiation-induced histomorphological abnormality, oxidative injury, and cell apoptosis in the rat testis.

METHODSThirty adult male SD rats were equally randomized into a normal, a radiated, and a Liuweidihuang group, the animals in the latter two groups exposed to electromagnetic radiation of 900 MHz cellphone frequency 4 hours a day for 18 days. Meanwhile, the rats in the Liuweidihuang group were treated with the suspension of Liuweidihuang Pills at 1 ml/100 g body weight and the other rats intragastrically with the equal volume of purified water. Then all the rats were killed for observation of testicular histomorphology by routine HE staining, measurement of testicular malondialdehyde (MDA) and glutathione (GSH) levels by colorimetry, and determination of the expressions of bax and bcl-2 proteins in the testis tissue by immunohistochemistry.

RESULTSCompared with the normal controls, the radiated rats showed obviously loose structure, reduced layers of spermatocytes, and cavitation in the seminiferous tubules. Significant increases were observed in the MDA level (P < 0.01) and bax expression (P < 0.01) but decreases in the GSH level (P < 0.01) and bcl-2 expression (P < 0.01) in the testis issue of the radiated rats. In comparison with the radiated rats, those of the Liuweidihuang group exhibited nearly normal testicular structure, significantly lower MDA level (P < 0.05), bax expression (P < 0.01), and bcl-2 expression (P < 0.01).

CONCLUSIONLiuweidihuang Pills can improve cellphone electromagnetic radiation-induced histomorphological abnormality of the testis tissue and reduce its oxidative damage and cell apoptosis.

Animals ; Apoptosis ; drug effects ; radiation effects ; Body Weight ; drug effects ; radiation effects ; Cell Phone ; Drugs, Chinese Herbal ; pharmacology ; Electromagnetic Radiation ; Glutathione ; metabolism ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; Radiation-Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Seminiferous Tubules ; drug effects ; radiation effects ; Spermatocytes ; drug effects ; metabolism ; radiation effects ; Staining and Labeling ; Testis ; drug effects ; metabolism ; pathology ; radiation effects

PURPOSE: Acute side effects of radiation such as oral mucositis are observed in most patients. Although several potential radioprotective agents have been proposed, no effective agent has yet been identified. In this study, we investigated the effectiveness of synthetic compound 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) as a radioprotective agent. MATERIALS AND METHODS: Cell viability, apoptosis, the generation of reactive oxygen species (ROS), mitochondrial membrane potential changes, and changes in apoptosis-related signaling were examined in human keratinocyte (HaCaT). RESULTS: KR22332 inhibited irradiation-induced apoptosis and intracellular ROS generation, and it markedly attenuated the changes in mitochondrial membrane potential in primary human keratinocytes. Moreover, KR22332 significantly reduced the protein expression levels of ataxia telangiectasia mutated protein, p53, and tumor necrosis factor (TNF)-alpha compared to significant increases observed after radiation treatment. CONCLUSION: KR22332 significantly inhibited radiation-induced apoptosis in human keratinocytes in vitro, indicating that it might be a safe and effective treatment for the prevention of radiation-induced mucositis.
Apoptosis/drug effects/physiology ; Cell Line, Tumor ; Cell Survival/drug effects/physiology ; Humans ; Keratinocytes/metabolism ; Membrane Potential, Mitochondrial/drug effects/physiology ; Radiation-Protective Agents/chemistry/*pharmacology ; Reactive Oxygen Species/metabolism

PURPOSE: Acute side effects of radiation such as oral mucositis are observed in most patients. Although several potential radioprotective agents have been proposed, no effective agent has yet been identified. In this study, we investigated the effectiveness of synthetic compound 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) as a radioprotective agent. MATERIALS AND METHODS: Cell viability, apoptosis, the generation of reactive oxygen species (ROS), mitochondrial membrane potential changes, and changes in apoptosis-related signaling were examined in human keratinocyte (HaCaT). RESULTS: KR22332 inhibited irradiation-induced apoptosis and intracellular ROS generation, and it markedly attenuated the changes in mitochondrial membrane potential in primary human keratinocytes. Moreover, KR22332 significantly reduced the protein expression levels of ataxia telangiectasia mutated protein, p53, and tumor necrosis factor (TNF)-alpha compared to significant increases observed after radiation treatment. CONCLUSION: KR22332 significantly inhibited radiation-induced apoptosis in human keratinocytes in vitro, indicating that it might be a safe and effective treatment for the prevention of radiation-induced mucositis.
Apoptosis/drug effects/physiology ; Cell Line, Tumor ; Cell Survival/drug effects/physiology ; Humans ; Keratinocytes/metabolism ; Membrane Potential, Mitochondrial/drug effects/physiology ; Radiation-Protective Agents/chemistry/*pharmacology ; Reactive Oxygen Species/metabolism

The aim of this study was to investigate the effect of WR2721(amifostine) against bone marrow hematopoietic damage of mice exposed to 6.5 Gy of (60)Co-γ ray. A total of 60 C57/BL6J mice was divided into 3 groups:normal group (mice were injected with physiological salt solution), irradiation group (mice were injected with physiologic salt solution before irradiation) and WR2721 group (mice were injected with WR2721 before irradiation). The WBC, neutrophil (Neut), Plt and RBC levels in peripheral blood of 3 group mice were counted within 60 days after irradiation; the bone marrow nuclear cells (BMNC) were counted at 2 and 24 hours after irradiation; the hematopoietic stem/progenitor cell (LK/LSK) level and colony formation capability were detected by flow cytometry at 2 and 24 hours after irradiation. The results indicated that the counts of WBC and neut at 4 and 18 days, Plt at 7-18 days and RBC at 10-30 day after irradiation in WR2721 group were higher than those in irradiation group (P < 0.05); the BMNC, LSK and LK levels obviously increased at 24 hours after irradiation (P < 0.05), the CFU-GEMM, CFU-GM, CFU-MK BFU-E and CFU-E all significantly increased at 2 and 24 hours after irradiation (P < 0.01), as compared with irradiation group. It is concluded that WR2721 can effectively alleviate early hematopoietic damage and promote the fast recovery of peripheral blood cells in mice exposed to γ-ray, suggesting that the WR2721 has significant radioprotective effect on hematopoietic system.
Amifostine ; pharmacology ; Animals ; Blood Cell Count ; Bone Marrow Cells ; cytology ; drug effects ; radiation effects ; Gamma Rays ; Hematopoietic Stem Cells ; cytology ; drug effects ; radiation effects ; Male ; Mice ; Mice, Inbred C57BL ; Radiation-Protective Agents ; pharmacology ; Whole-Body Irradiation

OBJECTIVETo investigate the effect of Inonotus obliquus polysaccharides on testicular injury induced by exposure to high power microwave (HPM) in rats.

METHODSA total of 30 male Wistar rats were randomly divided into 5 groups, i.e., the normal control group, the microwave radiation model group, the treatment group, the new microwave radiation model group, and the prevention group, 6 in each group. All rats, except those in the normal control group, were exposed to microwave at an average power density of 200 mW/cm2 for 6 min. Rats in the control group and the model group were administered with normal saline by gastrogavage, once a day. Rats in the treatment group and the prevention group were given with Inonotus obliquus polysaccharides by gastrogavage, 2 mL each time (400 mg/kg body weight), once a day. All rats were sacrificed on the 11th day.The sperm density and the rate of sperm deformity were determined. Pathological changes of testis were observed by light microscope and transmission electron microscope.

RESULTSShort-term HPM irradiation could significantly reduce the sperm density and increase the sperm deformity rate (P < 0.05). Meanwhile, obvious pathological changes of testes occurred. Compared with the two model groups, the sperm density increased and the sperm deformity rate decreased in the treatment group and the prevention group (P < 0.05). Under the light microscope, injuries of spermatogenic cells and stromal cells, as well as vascular dilatation and congestion were obviously alleviated in the treatment group and the prevention group. Mitochondrial swelling and endoplasmic reticulum expansion shown by ultrastructural observation were also significantly alleviated. Of them, injuries of spermatogenic cells and inflammation response were milder in the treatment group than in the prevention group.

CONCLUSIONSInonotus obliquus polysaccharides had significant protective effect on microwave radiation induced testicular injury. Better effect was obtained by therapeutic medication than preventive medication.

Animals ; Basidiomycota ; chemistry ; Male ; Microwaves ; adverse effects ; Polysaccharides ; pharmacology ; Radiation Injuries, Experimental ; prevention & control ; Radiation-Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Testis ; drug effects ; pathology ; radiation effects