Increasing the radiation-induced cytotoxicity by silver nanoparticles and docetaxel in prostate cancer cells.

BACKGROUND: Radiation therapy is utilized for treatment of localized prostate cancer. Nevertheless, cancerous cells frequently develop radiation resistance. While higher radiation doses have not always been effective, radiosensitizers have been extensively studied for their ability to enhance the cytotoxic effects of radiation. So, this study aims to evaluate the possible radiosensitization effects of docetaxel (DTX) and silver nanoparticles (SNP) in LNCaP cells. METHODS: The cytotoxic effects of DTX, SNP and 2 Gy of X-Ray radiation treatments were assessed in human LNCaP cell line using the MTT test after 24 h. Moreover, the effects of DTX, SNP and radiation on Epidermal growth factor (EGF), Caspase 3, inducible nitric oxide synthase and E-cadherin gene expression were analyzed using the Real-time PCR method. The level of Hydrogen peroxide (H2O2), an oxidative stress marker, was also detected 24 h after various single and combined treatments. RESULTS: The combinations of SNP (in low toxic concentration) and/or DTX (0.25× IC50 and 0.5 × IC50 concentrations for triple and double combinations respectively) with radiation induced significant cytotoxicity in LNCaP cells in comparison to monotherapies. These cytotoxic effects were associated with the downregulation of EGF mRNA. Additionally, H2O2 levels increased after Radiation + SNP + DTX triple combination and double combinations including Radiation + SNP and Radiation + DTX versus single treatments. The triple combination treatment also increased Caspase 3 and and E-cadherin mRNA levels in compared to single treatments in LNCaP cells. CONCLUSION: Our results indicate that the combination of SNP and DTX with radiation induces significant anti-cancer effects. Upregulation of Caspase 3 and E-cadherin gene expression, and decreased mRNA expression level of EGF may be exerted specifically by use of this combination versus single treatments.

Ferulic acid in synergy with retinol alleviates oxidative injury of HaCaT cells during UVB-induced photoaging.

Application of retinol (Vitamin A, VA) in skincare is limited for instability, poor water solubility, and skin intolerance that combats skin aging. We employed computer-aided virtual screening and cell experiments with transcriptomics, thereby unveiling the comprehensive gene expression and regulation pathway of photoaging HaCaT cell treated with ferulic acid (FA) in synergizing with VA. Through network pharmacology analysis, the combined use of VA and FA exhibited highly correlated cross-targets with skin aging acting on EGFR, PTPN1, ESR2, GSK3B, BACE1, PYGL, PTGS2 and APP. The indicators of oxidative stress, such as SOD, GSH, MDA, CAT and ROS in HaCaT cells after co-administration, were significantly improved from those in photoaging group (p<0.0001). 155 differential expressed genes (DEGs) were specific between groups, while reducing the expression of PTGS2 was identified as an important regulatory factor in photoaging HaCaT cells by VA and FA. Those DEGs of co-administration group focused on oxidative-reduction enzyme activity, skin growth, keratinization, and steroid biosynthesis. Apparently, the co-administration of VA and FA effectively mitigated the process of UVB-induced photoaging by reducing oxidative stress injury, inflammation responses, and regulating cell growth. This synergistic approach significantly slowed down the photoaging progression and improved the applied performance of VA in HaCaT cells.

Water-soluble intracellular extract of Desmodesmus sp. YT enhanced the antioxidant capacity of human skin fibroblast to protect the skin from UV damage.

BACKGROUND: The oxidative stress induced by ultraviolet (UV) radiation is a pivotal factor in skin aging and can even contribute to the development of skin cancer. AIM: This study explored the antioxidant effect and mechanism of water-soluble intracellular extract (WIE) of Desmodesmus sp.YT (YT), aiming to develop a natural antioxidant suitable for incorporation into cosmetics. METHODS: The study evaluated the scavenging capacity of YT-WIE against free radicals and assessed its impact on human skin fibroblasts (HSF) cell viability and UV resistance using Cell Counting Kit-8 (CCK-8). Transcriptome sequencing was employed to elucidate the mechanism of action, while RT-qPCR and western blot were used to validate the expression of key genes. RESULTS: YT-WIE displayed robust antioxidant activity, demonstrating potent scavenging abilities against 2,2-diphenyl-1-picrylhydrazyl (DPPH; IC50 = 0.55 mg mL-1), 2,2'-Azino-bis (3 ethylbenzothiazoline-6-sulfonic acid; ABTS; IC50 = 3.11 mg mL-1), Hydroxyl (·OH; IC50 = 2.21 mg mL-1), and Superoxide anion (O2 •-; IC50 = 0.98 mg mL-1). Furthermore, compared to the control group, the YT-WIE group exhibited an 89.30% enhancement in HSF viability and a 44.63% increase in survival rate post-UV irradiation. Significant upregulation of antioxidant genes (GCLC, GCLM, TXNRD1, HMOX1, NQO1) was observed with YT-WIE treatment at 400 µg mL-1, with fold increases ranging from 1.13 to 5.85 times. CONCLUSION: YT-WIE demonstrated considerable potential as an antioxidant, shielding human cells from undue oxidative stress triggered by external stimuli such as UV radiation. This suggests its promising application in cosmetics antioxidants.

Melatonin injection and red light irradiation affect the antioxidant response and cell damage in disk abalone (Haliotis discus hannai) exposed to high water temperatures.

The effects of red light-emitting diode (LED) light irradiation (630 nm, 0.5 W/m2) and melatonin (10-8 and 10-7 M) on oxidative stress and physiological responses in abalones exposed to high temperatures (28°C) were investigated. Changes in messenger RNA (mRNA) expressions of melatonin receptor (MT-R), heat shock protein 70 (HSP70), and antioxidant enzymes, as well as alterations in H2O2 levels in the hemolymph, were examined. The results revealed that high-temperature-stressed abalones treated with melatonin injections or exposed to red LED light showed a significant increase in MT-R mRNA expression, while HSP70 mRNA expression decreased. Notably, HSP70 mRNA expression levels in the red LED light-irradiated group were similar to those in the group injected with 10-8 M melatonin after 24 h exposure. Abalones treated with melatonin at 20°C or irradiated with red LED light exhibited decreased H2O2 levels and reduced antioxidant enzyme mRNA expression compared with those of the control group. However, the high-temperature environment induced oxidative stress in abalones, leading to increased antioxidant enzyme mRNA expression compared with that under 20°C conditions. Moreover, abalones exposed to high-temperature stress exhibited hepatopancreatic DNA damage, which was attenuated by melatonin treatment or red LED light irradiation. Hence, red LED light reduces oxidative stress, boosts antioxidant enzymes, and alleviates DNA damage in high-temperature-stressed abalones, akin to 10-8 M melatonin treatment. Therefore, considering the practical challenges of continuous melatonin administration to abalones, utilizing red LED light emerges as a practical, effective alternative to protect abalones from oxidative stress compared to 10-8 M melatonin treatment.

Anti-radiation effect of MRN-100: a hydro-ferrate fluid, in vivo.

Ionizing radiation (IR) severely harms many organs, especially the hematopoietic tissue, mandating the development of protective nutraceuticals. MRN-100, a hydro-ferrate fluid, has been shown to protect γ-radiated fish against hematopoietic tissue damage and lethality. The current study aimed to examine MRN-100's protective effect against irradiated mice and explore the mechanisms underlying its effect. Mice received a single acute, sub-lethal, 5 Gy, whole body dose of X-ray IR. MRN-100 treatment was administered daily for 2-weeks pre-irradiation until 1-week post-irradiation. Spleen and blood were analysed for oxidative stress, hematological, histological and biochemical parameters. Radiation exposure markedly decreased complete blood count (CBC) parameters including hemoglobin, hematocrit, red blood cells, platelets, white blood cells and lymphocytes, and significantly increased neutrophils. In contrast, MRN-100 supplementation to irradiated mice ameliorated all CBC parameters and protected against DNA damage in both splenic cells and serum. It also had an antioxidant effect, increasing the levels of glutathione, superoxide dismutase, catalase and total antioxidant capacity, which were otherwise decreased by irradiation. MRN-100 intake reduced the oxidative stress biomarker levels of nitric oxide, protein carbonyl, malondialdehyde, reactive oxygen species and 8-hydroxydeoxyguanosine, a marker specific to DNA damage. Furthermore, MRN-100 enhanced serum iron and reversed the radiation-induced elevations of liver enzymes. Finally, MRN-100 protected splenic tissue from irradiation as observed by histology. We conclude that MRN-100 consumption may protect against oxidative stress generated by radiation exposure, suggesting that it may be employed as an adjuvant treatment to prevent radiation's severe damage to important organs.

Effects of 4G mobile phone radiation exposure on reproductive, hepatic, renal, and hematological parameters of male Wistar rat.

BACKGROUND AND OBJECTIVE: Mobile phones have become a vital part of human life. Due to drastic increase in the number of mobile phone subscribers, exposure to radiofrequency radiation (RFR) emitted from these phones has increased dramatically. Hence, the effect of RFR on humans is an area of concern. This study was performed to determine the impact of 4G mobile phone radiation on the male reproductive system, liver, kidney, and hematological parameters. METHODS: Seventy-day-old Wistar rats were exposed to 4G radiation (2350 MHz for 2 h/day for 56 days). Sperm parameters such as sperm count, viability, sperm head morphology, mitochondrial activity, total antioxidant activity, and lipid peroxidation of sperm were evaluated. Histopathology of the testis, prostate, epididymis, seminal vesicle, liver, and kidney was carried out. Complete blood count, liver and kidney function tests, and testosterone hormone analysis were done. RESULTS: At the end of the experiment, results showed a significant (p < 0.05) decrease in sperm viability with alterations in the histology of the liver, kidney, testis, and other reproductive organs in the exposed group of rats. A reduced level of testosterone, total antioxidant capacity, and decreased sperm mitochondrial function were also observed in the exposed rats. Moreover, the exposed rats showed an increase in sperm lipid peroxidation and sperm abnormality. Hematological parameters like hemoglobin, red blood cells (RBC), and packed cell volume (PCV) showed a significant (p < 0.05) increase in the exposed rats. CONCLUSION: The results indicate that chronic exposure to 4G radiation may affect the male reproductive system, hematological system, liver, and kidney of rats.

Effects of HZE-Particle Exposure Location and Energy on Brain Inflammation and Oxidative Stress in Rats.

Astronauts on exploratory missions will be exposed to particle radiation of high energy and charge (HZE particles), which have been shown to produce neurochemical and performance deficits in animal models. Exposure to HZE particles can produce both targeted effects, resulting from direct ionization of atoms along the particle track, and non-targeted effects (NTEs) in cells that are distant from the track, extending the range of potential damage beyond the site of irradiation. While recent work suggests that NTEs are primarily responsible for changes in cognitive function after HZE exposures, the relative contributions of targeted and non-targeted effects to neurochemical changes after HZE exposures are unclear. The present experiment was designed to further explore the role of targeted and non-targeted effects on HZE-induced neurochemical changes (inflammation and oxidative stress) by evaluating the effects of exposure location and particle energy/linear energy transfer (LET). Forty-six male Sprague-Dawley rats received head-only or body-only exposures to 56Fe particles [600 MeV/n (75 cGy) or 1,000 MeV/n (100 cGy)] or 48Ti particles [500 MeV/n (50 cGy) or 1,100 MeV/n (75 cGy)] or no irradiation (0 cGy). Twenty-four h after irradiation, rats were euthanized, and the brain was dissected for analysis of HZE-particle-induced neurochemical changes in the hippocampus and frontal cortex. Results showed that exposure to 56Fe and 48Ti ions produced changes in measurements of brain inflammation [glial fibrillary astrocyte protein (GFAP)], oxidative stress [NADPH-oxidoreductase-2 (NOX2)] and antioxidant enzymes [superoxide dismutase (SOD), glutathione S-transferase (GST), nuclear factor erythroid 2-related factor 2 (Nrf2)]. However, radiation effects varied depending upon the specific measurement, brain region, and exposure location. Although overall exposures of the head produced more detrimental changes in neuroinflammation and oxidative stress than exposures of the body, body-only exposures also produced changes relative to no irradiation, and the effect of particle energy/LET on neurochemical changes was minimal. Results indicate that both targeted and non-targeted effects are important contributors to neurochemical changes after head-only exposure. However, because there were no consistent neurochemical changes as a function of changes in track structure after head-only exposures, the role of direct effects on neuronal function is uncertain. Therefore, these findings, although in an animal model, suggest that NTEs should be considered in the estimation of risk to the central nervous system (CNS) and development of countermeasures.

Effect of postharvest nicotinamide treatment on NAD+ metabolism and redox status in strawberry fruit during storage.

The increased activity of PARP enzymes is associated with a deficiency of NAD+, as well as with a loss of NADPH and ATP, and consequent deterioration of the redox state in fruits. In this study, we checked whether treatment with nicotinamide (NAM) would affect PARP-1 expression and NAD+ metabolism in strawberry fruit during storage. For this purpose, strawberry fruits were treated with 10 mM NAM and co-treated with NAM and UV-C, and then stored for 5 days at 4 °C. Research showed that nicotinamide contributes to reducing oxidative stress level by reducing PARP-1 mRNA gene expression and the protein level resulting in higher NAD+ availability, as well as improving energy metabolism and NADPH levels in fruits, regardless of whether they are exposed to UV-C. The above effects cause fruits treated with nicotinamide to be characterised by higher anti-radical activity, and a lower level of reactive oxygen species in the tissue.

Nanotechnology enabled radioprotectants to reduce space radiation-induced reactive oxidative species.

Interest in space exploration has seen substantial growth following recent launch and operation of modern space technologies. In particular, the possibility of travel beyond low earth orbit is seeing sustained support. However, future deep space travel requires addressing health concerns for crews under continuous, longer-term exposure to adverse environmental conditions. Among these challenges, radiation-induced health issues are a major concern. Their potential to induce chronic illness is further potentiated by the microgravity environment. While investigations into the physiological effects of space radiation are still under investigation, studies on model ionizing radiation conditions, in earth and micro-gravity conditions, can provide needed insight into relevant processes. Substantial formation of high, sustained reactive oxygen species (ROS) evolution during radiation exposure is a clear threat to physiological health of space travelers, producing indirect damage to various cell structures and requiring therapeutic address. Radioprotection toward the skeletal system components is essential to astronaut health, due to the high radio-absorption cross-section of bone mineral and local hematopoiesis. Nanotechnology can potentially function as radioprotectant and radiomitigating agents toward ROS and direct radiation damage. Nanoparticle compositions such as gold, silver, platinum, carbon-based materials, silica, transition metal dichalcogenides, and ceria have all shown potential as viable radioprotectants to mitigate space radiation effects with nanoceria further showing the ability to protect genetic material from oxidative damage in several studies. As research into space radiation-induced health problems develops, this review intends to provide insights into the nanomaterial design to ameliorate pathological effects from ionizing radiation exposure. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Effects of low-dose/high-dose-rate X-irradiation on oxidative stress in organs following forced swim test and its combined effects on alcohol-induced liver damage in mice.

The liver's susceptibility to oxidative stress after a combination of forced swim test (FST) and low-dose-rate γ-irradiation has been observed. Therefore, this study aims to clarify the effects of low-dose (0.1 and 0.5 Gy)/high-dose-rate (1.2 Gy/min) irradiation on combined oxidative stressors-liver damage associated with FST and alcohol administration. In addition, the effects of similar irradiation on FST-induced immobility, which induces psychomotor retardation, and antioxidative effects on the brain, lungs, liver and kidneys were investigated, and the results were compared with those of a similar previous study that utilized low-dose-rate irradiation. Low-dose/high-dose-rate (especially 0.5 Gy) irradiation temporarily worsened liver antioxidant function and hepatic function with FST- and alcohol administration-related oxidative damage; however, the damages improved soon after. In addition, the increase in total glutathione content in the liver contributed to the early improvement of hepatic functions. However, pre-irradiation did not suppress immobility during the FST. The results also suggested that the effects of low-dose/high-dose-rate irradiation on the antioxidant functions of each organ after the FST were different from those of low-dose/low-dose-rate irradiation. Overall, this study provides further insights into the effects of low-dose irradiation on exposure to a combination of different oxidative stressors. It will also contribute to the elucidation of dose rate effects on oxidative stress in the low-dose irradiation range.

Antioxidative and Mitochondrial Protection in Retinal Pigment Epithelium: New Light Source in Action.

Low-color-temperature light-emitting diodes (LEDs) (called 1900 K LEDs for short) have the potential to become a healthy light source due to their blue-free property. Our previous research demonstrated that these LEDs posed no harm to retinal cells and even protected the ocular surface. Treatment targeting the retinal pigment epithelium (RPE) is a promising direction for age-related macular degeneration (AMD). Nevertheless, no study has evaluated the protective effects of these LEDs on RPE. Therefore, we used the ARPE-19 cell line and zebrafish to explore the protective effects of 1900 K LEDs. Our results showed that the 1900 K LEDs could increase the cell vitality of ARPE-19 cells at different irradiances, with the most pronounced effect at 10 W/m2. Moreover, the protective effect increased with time. Pretreatment with 1900 K LEDs could protect the RPE from death after hydrogen peroxide (H2O2) damage by reducing reactive oxygen species (ROS) generation and mitochondrial damage caused by H2O2. In addition, we preliminarily demonstrated that irradiation with 1900 K LEDs in zebrafish did not cause retinal damage. To sum up, we provide evidence for the protective effects of 1900 K LEDs on the RPE, laying the foundation for future light therapy using these LEDs.

Invitro impact of a combination of red and infrared LEDs, infrared laser and magnetic field on biomarkers of oxidative stress and hemolysis of erythrocytes sampled from healthy individuals and diabetes patients.

AIMS: Low-intensity infrared laser irradiation with output emissions of the laser and LED for in vitro irradiation of plasma and erythrocyte samples collected from healthy individuals and diabetes mellitus (DM) patients was used in the current study. METHODS: The generated emission was in the range 0.85-0.89 nm with pulse duration near 130 ns and repetition rates of pulses 50, 150, 600, and 1500 Hz, average power 0, 50, or 100 mW, in the range of 1-9 min for different 30 variants of irradiation. The levels of 2-thiobarbituric-acid reactive substances (TBARS), aldehydic and ketonic derivatives of oxidatively modified proteins (OMP), total antioxidant capacity (TAC), acid-induced resistance of erythrocytes, and activities of the main antioxidant enzymes were assessed in erythrocyte and plasma samples after irradiation. RESULTS: The low-intensity infrared laser irradiation and low-intensity light emitted by a red LED decreased the lipid peroxidation levels in the erythrocytes of both healthy individuals and DM patients. A statistically significant decrease in TBARS and OMP levels and an increase in the TAC level were observed at the irradiation energy of 34.39 and 68.79 J/cm2 for samples collected from both healthy individuals and DM patients. The effects of the irradiation were accompanied by a statistically significant decrease in catalase activity of both healthy individuals and DM patients. CONCLUSIONS: In many variants of the laser irradiation and low-intensity light emitted by a red LED used in our study, a decrease in the percent of hemolyzed erythrocytes was observed, suggesting that laser therapy protocols should take into account fluencies, frequencies, and wavelengths of the laser before the beginning of treatment, especially in DM patients.

Adverse effects of 900, 1800 and 2100 MHz radiofrequency radiation emitted from mobile phones on bone and skeletal muscle.

The goal of this study was to biomechanically and morphologically research both the impact of mobile phone like radiofrequency radiations (RFR) on the tibia and the effects on skeletal muscle through oxidative stress parameters. Fifty-six rats (200-250 g) were put into groups: healthy sham (n = 7), healthy RFR (900, 1800, 2100 MHz) (n = 21), diabetic sham (n = 7) and diabetic RFR (900, 1800, 2100 MHz) (n = 21). Over a month, each group spent two hours/day in a Plexiglas carousel. The rats in the experimental group were exposed to RFR, but the sham groups were not. At the end of the experiment, the right tibia bones and skeletal muscle tissue were removed. The three-point bending test and radiological evaluations were performed on the bones, and CAT, GSH, MDA, and IMA in muscles were measured. There were differences in biomechanics properties and radiological evaluations between the groups (p < .05). In the measurements in the muscle tissues, significant differences were statistically found (p < .05). The average whole-body SAR values for GSM 900, 1800 and 2100 MHz were 0.026, 0.164, and 0.173 W/kg. RFRs emitted from mobile phone may cause adverse effects on tibia and skeletal muscle health, though further studies are needed.

Long-term blue light exposure impairs mitochondrial dynamics in the retina in light-induced retinal degeneration in vivo and in vitro.

Long-term light exposure, especially in the spectrum of blue light, frequently causes excessive oxidative stress in dry age-related macular degeneration (AMD). Here, to gain insight into the underlying mechanism, we focused on mitochondrial dynamics alterations under long-term exposure to blue light in mouse and retinal cells. Six-month-old C57BL/6 mice were exposed to blue light (450 nm, 800 lx) for 2 weeks. The phenotypic changes in the retina were assayed using haematoxylin-eosin staining and transmission electron microscopy. Long-term blue light exposure significantly thinned each retinal layer in mice, induced retinal apoptosis and impaired retinal mitochondria. A retinal pigment epithelial cell line (ARPE-19) was used to verify the phototoxicity of blue light. Flow cytometry, immunofluorescence and MitoSox Red probe experiments confirmed that more total and mitochondria-specific ROS were generated in the blue light group than in the control group. Mito-Tracker Green probe showed fragmented mitochondrial morphology. The western blotting results indicated a significant increase in DRP1, OMA1, and BAX and a decrease in OPA1 and Bcl-2. In conclusion, long-term exposure to blue light damaged the retinas of mice, especially the ONL and RPE cells. There was destruction and dysfunction of mitochondria in RPE cells in vivo and in vitro. Mitochondrial dynamics were disrupted with characteristics of fusion-related obstruction after blue-light irradiation.

Pyruvate and lactate based hydrogel film inhibits UV radiation-induced skin inflammation and oxidative stress.

Solar skin damage is one of the most common diseases among outdoor workers. An important cause for the damage is the ultraviolet and infrared rays in sunlight, which are absorbed by the skin in large amounts, leading to severe skin inflammation and oxidative stress. Therefore, physical prevention by shielding the light from harmful wavelengths can be an effective method of skin protection from radiation. However, for existing skin lesions, prompt treatment is essential to avoid the aggravation of the injury and promote repair. Therefore, to improve the therapeutic effect on sun-damaged skin, we attempted to design a system with a dual purpose of eliminating toxic free radicals and modulating tissue inflammatory response. Here, we designed and synthesized a poly-acryloyl lysine (P-Ac-Lys) and polyvinyl alcohol-dihydroxyphenylalanine (PVA-DOPA) composite hydrogel (PAL@PVA-DOPA Hydrogel) loaded with lactate and pyruvate, that exhibites a good free radical scavenging activity and an excellent ability to modulate the inflammatory response. Experimental results showe that this hydrogel film could effectively reduce the UV-induced skin inflammation response, alleviate pathological damage and promote the recovery of the damaged skin.

Low dose radiation upregulates Ras/p38 and NADPH oxidase in mouse colon two months after exposure.

BACKGROUND: Exposure to ionizing is known to cause persistent cellular oxidative stress and NADPH oxidase (Nox) is a major source of cellular oxidant production. Chronic oxidative stress is associated with a myriad of human diseases including gastrointestinal cancer. However, the roles of NADPH oxidase in relation of long-term oxidative stress in colonic epithelial cells after radiation exposure are yet to be clearly established. METHODS AND RESULTS: Mice were exposed either to sham or to 0.5 Gy γ radiation, and NADPH oxidase, oxidative stress, and related signaling pathways were assessed in colon samples 60 days after exposure. Radiation exposure led to increased expression of colon-specific NADPH oxidase isoform, Nox1, as well as upregulation of its modifiers such as Noxa1 and Noxo1 at the mRNA and protein level. Co-immunoprecipitation experiments showed enhanced binding of Rac1, an activator of NADPH oxidase, to Nox1. Increased 4-hydroxynonenal, 8-oxo-dG, and γH2AX along with higher protein carbonylation levels suggest increased oxidative stress after radiation exposure. Immunoblot analysis demonstrates upregulation of Ras/p38 pathway, and Gata6 and Hif1α after irradiation. Increased staining of ß-catenin, cyclinD1, and Ki67 after radiation was also observed. CONCLUSIONS: In summary, data show that exposure to a low dose of radiation was associated with upregulation of NADPH oxidase and its modifiers along with increased Ras/p38/Gata6 signaling in colon. When considered along with oxidative damage and proliferative markers, our observations suggest that the NADPH oxidase pathway could be playing a critical role in propagating long-term oxidative stress after radiation with implications for colon carcinogenesis.

Protective effects of L-carnitine on X irradiation-induced uterus injury via antioxidant and anti-inflammatory pathways.

PURPOSE: Ionizing radiation causes oxidative stress induced tissue damage as well as a decline in reproduction incidence. The purpose of our study was to evaluate the effects of L-carnitine on radiation-induced uterine injury. MATERIALS AND METHODS: Thirty Wistar albino rats were classified into five groups. Physiological saline was administered intraperitoneally to the control group. A single dose of 8.3 Gy whole body X-irradiation was applied to the radiation-1 and radiation-2 groups. These groups were sacrificed on the 6th hour and 4th day, respectively, after irradiation. Radiation-1 + L-carnitine and radiation-2 + L-carnitine groups received a daily dose of 200 mg/kg L-carnitine in addition to the same dose of irradiation. L-carnitine was also applied one day before and four days after irradiation. RESULTS: L-carnitine therapy partially blocks the depletion of the deep glands and radiation-induced flattening of the glandular epithelium and endometrial surface. Proinflammatory cytokines such as IL-1ß, IL-6 and TNF-α were found to be significantly expressed in the uterus tissue of irradiated mice. In the radiation groups, NFκB and PARP-1 expressions in uterine tissue was significantly increased compared to L-carnitine treated and the control groups. It was observed that the oxidative stress index increased in the radiation groups, but decreased in the L-carnitine applied groups. CONCLUSIONS: Our findings showed that L-carnitine has a positive effect on radiation-induced uterine damage. L-carnitine may be a potential safe radio protective agent during radiotherapy for pelvic cancer provided the tumor is not protected from radiation damage to the same extent as the normal tissue is. However, prospective clinical trial studies are necessary to understand its efficacy.

Impact of the redox environment on propagation of radiation bystander effects: The modulating effect of oxidative metabolism and oxygen partial pressure.

Redox modulated pathways play important roles in out-of-field effects of ionizing radiation. We investigated how the redox environment impacts the magnitude of propagation of stressful effects from irradiated to bystander cells. Normal human fibroblasts that have incorporated [3H]-thymidine were intimately co-cultured with bystander cells in a strategy that allowed isolation of bystander cells with high purity. The antioxidant glutathione peroxidase (GPX) was maintained either at wild-type conditions or overexpressed in the bystanders. Following 24 h of coculture, levels of stress-responsive p21Waf1, p-Hdm2, and connexin43 proteins were increased in bystander cells expressing wild-type GPX relative to respective controls. These levels were significantly attenuated when GPX was ectopically overexpressed, demonstrating by direct approach the involvement of a regulator of intracellular redox homeostasis. Evidence of participation of pro-oxidant compounds was generated by exposing confluent cell cultures to low fluences of 3.7 MeV α particles in presence or absence of t-butyl hydroperoxide. By 3 h post-exposure to fluences wherein only ∼2% of cells are traversed through the nucleus by a particle track, increases in chromosomal damage were greater than expected in absence of the drug (p < 0.001) and further enhanced in its presence (p < 0.05). While maintenance and irradiation of cell cultures at low oxygen pressure (pO2 3.8 mm Hg) to mimic in vivo still supported the participation of bystander cells in responses assessed by chromosomal damage and stress-responsive protein levels (p < 0.001), the effects were attenuated compared to ambient pO2 (155 mm Hg) (p < 0.05). Together, the results show that bystander effects are attenuated at below ambient pO2 and when metabolic oxidative stress is reduced but increased when the basal redox environment tilts towards oxidizing conditions. They are consistent with bystander effects being independent of radiation dose rate.

Ultraviolet B modulates gamma radiation-induced stress responses in Lemna minor at multiple levels of biological organisation.

Elevated levels of ionizing and non-ionizing radiation may co-occur and pose cumulative hazards to biota. However, the combined effects and underlying toxicity mechanisms of different types of radiation in aquatic plants remain poorly understood. The present study aims to demonstrate how different combined toxicity prediction approaches can collectively characterise how chronic (7 days) exposure to ultraviolet B (UVB) radiation (0.5 W m-2) modulates gamma (γ) radiation (14.9, 19.5, 43.6 mGy h-1) induced stress responses in the macrophyte Lemna minor. A suite of bioassays was applied to quantify stress responses at multiple levels of biological organisation. The combined effects (no-enhancement, additivity, synergism, antagonism) were determined by two-way analysis of variance (2 W-ANOVA) and a modified Independent Action (IA) model. The toxicological responses and the potential causality between stressors were further visualised by a network of toxicity pathways. The results showed that γ-radiation or UVB alone induced oxidative stress and programmed cell death (PCD) as well as impaired oxidative phosphorylation (OXPHOS) and photosystem II (PSII) activity in L. minor. γ-radiation also activated antioxidant responses, DNA damage repair and chlorophyll metabolism, and inhibited growth at higher dose rates (≥20 mGy h-1). When co-exposed, UVB predominantly caused non-interaction (no-enhancement or additive) effects on γ-radiation-induced antioxidant gene expression, energy quenching in PSII and growth for all dose rates, whereas antagonistic effects were observed for lipid peroxidation, OXPHOS, PCD, oxidative stress, chlorophyll metabolism and genes involved in DNA damage responses. Synergistic effects were observed for changes in photochemical quenching and non-photochemical quenching, and up-regulation of antioxidant enzyme genes (GST) at one or more dose rates, while synergistic reproductive inhibition occurred at all three γ-radiation dose rates. The present study provides mechanistic knowledge, quantitative understanding and novel analytical strategies to decipher combined effects across levels of biological organisation, which should facilitate future cumulative hazard assessments of multiple stressors.

Alleviation of the Genotoxic Effect of Experimental Circulatory Brain Hypoxia in Rat Cornea under the Effect of Infrared Low-Level Laser Radiation.

Experimental modeling of oxidative stress was conducted by creating circulatory brain hypoxia, accompanied by development of free radical processes leading to genome instability through an example of anterior epithelial layer of rat cornea. We studied the influence of infrared low-level laser radiation (ILLLR) in the therapeutic dose and mode (pulse power 8 W, λ=0.89 µm). Exposure of animals with circulatory brain hypoxia (ischemia) to ILLLR reduced the level of chromosome aberrations in corneal epitheliocytes and led to change in the mitotic index. Correction of the damaging effects of ischemia in the experiment in the absence of mutagenic effect of ILLLR in therapeutic dose and mode of exposure indicates the possibility of applying this physical method for correcting after-effects of oxidative stress during progression of degenerative eye diseases in ophthalmic practice.