Science.gov

Sample records for accident damage protection

  1. 49 CFR 178.345-8 - Accident damage protection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PACKAGINGS Specifications for Containers for Motor Vehicle Transportation § 178.345-8 Accident damage protection. (a) General. Each cargo tank motor vehicle must be designed and constructed in accordance with... 49 Transportation 2 2010-10-01 2010-10-01 false Accident damage protection. 178.345-8 Section...

  2. 49 CFR 178.345-8 - Accident damage protection.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... retention integrity of the cargo tank. Accident induced stresses resulting from the appropriate accident damage protection device requirements in combination with the stresses from the cargo tank operating at the MAWP may not result in a cargo tank wall stress greater than the ultimate strength of the...

  3. 49 CFR 178.345-8 - Accident damage protection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... retention integrity of the cargo tank. Accident induced stresses resulting from the appropriate accident damage protection device requirements in combination with the stresses from the cargo tank operating at the MAWP may not result in a cargo tank wall stress greater than the ultimate strength of the...

  4. 49 CFR 178.337-10 - Accident damage protection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... self-closing stop valve, excess flow valve, and check valve must be protected by a shear section or... protection. (a) All valves, fittings, pressure relief devices, and other accessories to the tank proper shall... relief valves shall be so protected that in the event of overturn of the vehicle onto a hard...

  5. 49 CFR 178.337-10 - Accident damage protection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... flow valve, and check valve must be protected by a shear section or other sacrificial device. The... valves, fittings, pressure relief devices, and other accessories to the tank proper shall be protected in... vehicles or objects, jack-knifing and overturning. In addition, pressure relief valves shall be...

  6. 49 CFR 178.338-10 - Accident damage protection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... tensile strength of the material, shall be used. The protective device or the housing must be made of steel at least 3/16-inch thick, or other material of equivalent strength. (c) Rear-end tank protection... strength of the materials used, with such load being applied horizontally and parallel to the major axis...

  7. 49 CFR 178.338-10 - Accident damage protection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... strength of the material, shall be used. The protective device or the housing must be made of steel at least 3/16-inch thick, or other material of equivalent strength. (c) Rear-end tank protection. Rear-end... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR...

  8. 49 CFR 178.345-8 - Accident damage protection.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... of construction using a safety factor of 1.3. Deformation of the protection device is acceptable... not to exceed 6 feet. Suspension components and structural mounting members may be used to provide all... safe point of discharge away from any structural component of the cargo tank motor vehicle. (d)...

  9. 49 CFR 178.337-10 - Accident damage protection.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume and... requirements of § 393.86 of this title; or (2) Conform to the requirements of § 178.345-8(d). (d) Chlorine tanks. A chlorine tank must be equipped with a protective housing and a manway cover to permit the...

  10. 49 CFR 178.337-10 - Accident damage protection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume and... requirements of § 393.86 of this title; or (2) Conform to the requirements of § 178.345-8(d). (d) Chlorine tanks. A chlorine tank must be equipped with a protective housing and a manway cover to permit the...

  11. Cardiac damage presenting late after road accidents.

    PubMed Central

    Mackintosh, A F; Fleming, H A

    1981-01-01

    Six examples of cardiac damage secondary to non-penetrating trauma in road accidents are described. In all six cases the lesion was not recognised at the time of the accident but became clinically important two days to 17 years later. As the patients were young or had unusual lesions, the damage could be attributed to the accident. In older patients with common cardiac problems the trauma might not be recognised as the underlying cause. PMID:7330802

  12. Chemical Protection Against Radiation Damage

    ERIC Educational Resources Information Center

    Campaigne, Ernest

    1969-01-01

    Discusses potential war time and medical uses for chemical compounds giving protection against radiation damage. Describes compounds known to protect, research aimed at discovering such compounds, and problems of toxicity. (EB)

  13. Radiation damage aspects of the chernobyl accident

    NASA Astrophysics Data System (ADS)

    Parmentier, N.; Nenot, J. C.

    During the night of 25 to 26 April 1986, the most severe nuclear accident occurred at the Chernobyl power station, about 150km north of Kiev, in the Ukraine. It resulted in the irradiation of 237 workers at dose levels justifying medical care. The most severe cases (115) were hospitalized in Moscow, with 20 patients with doses higher than 6 Gy. In most cases, the treatment was classical, based on transfusion of red cells and platelets, and heavy supportive therapy. For 19 patients with severe aplasia, transplantations of bone marrow (13) or foetal liver (6) were decided. Of these patients only one survived, which justifies the statement from U.S.S.R. physicians: after an accident the indications of grafting are limited and its risks may not justify its use. Most of the complications were related to radiation burns which involved 56 victims and resulted in fatal outcomes in at least 19 patients. The population was evacuated from a 30 km zone around the site; based on direct measurements and calculations, the collective dose was evaluated at 1.6 × 10 4 man Sv, with an individual average lower than 250 mSv. The European part of U.S.S.R. with 75 million persons is supposed to have received a collective dose likely to increase the natural mortality by less than 0.1%. The numbers with cancer in the Northern Hemisphere might increase by 0.004% over the next 50 years.

  14. [Medical protection during radiation accidents: some results and lessons of the Chernobyl accident].

    PubMed

    Legeza, V I; Grebeniuk, A N; Zatsepin, V V

    2011-01-01

    Actions of medical radiation protection of liquidators of consequences of on Chernobyl atomic power station accident are analysed. It is shown, that during the early period of the accident medical protection of liquidators was provided by administration of radioprotectors, means of prophylaxis: of radioactive iodine incorporation and agent for preventing psychological and emotional stress. When carrying out decontamination and regenerative works, preparations which action is caused by increase of nonspecific resistance of an organism were applied. The lessons taken from the results of the Chernobyl accident, have allowed one to improve the system of medical protection and to introduce in practice new highly effective radioprotective agents.

  15. Collider and detector protection at beam accidents

    SciTech Connect

    I. L. Rakhno; N. V. Mokhov; A. I. Drozhdin

    2003-12-10

    Dealing with beam loss due to abort kicker prefire is considered for hadron colliders. The prefires occurred at Tevatron (Fermilab) during Run I and Run II are analyzed and a protection system implemented is described. The effect of accidental beam loss in the Large Hadron Collider (LHC) at CERN on machine and detector components is studied via realistic Monte Carlo calculations. The simulations show that beam loss at an unsynchronized beam abort would result in severe heating of conventional and superconducting magnets and possible damage to the collider detector elements. A proposed set of collimators would reduce energy deposition effects to acceptable levels. Special attention is paid to reducing peak temperature rise within the septum magnet and minimizing quench region length downstream of the LHC beam abort straight section.

  16. Child protection. Accident prevention: a community approach.

    PubMed

    Roberts, H

    1991-07-01

    Child accidents are the main cause of death and a considerable cause of morbidity in children, as well as anxiety to adults. Attempts to tackle this major health problem have tended to rely on campaigns of education and exhortation; public health strategies remain underdeveloped. Health visitors are well placed to pursue child safety strategies which build on parents' own knowledge and experience. Helen Roberts describes an initiative based not on the question, why did that accident happen? but the more intriguing question of how is it that most parents manage to keep their children safe most of the time and what can we learn from them?

  17. Accident response group (ARG) containers for recovery of damaged warheads

    SciTech Connect

    York, A.R. II; Hoffman, J.P.

    1993-09-01

    This report provides an overview of the containers that are currently stored at Pantex and available for use in response to an accident or for use in any other application where a sealed containment vessel and accident resistant overpack may be needed.

  18. Radiation protection issues on preparedness and response for a severe nuclear accident: experiences of the Fukushima accident.

    PubMed

    Homma, T; Takahara, S; Kimura, M; Kinase, S

    2015-06-01

    Radiation protection issues on preparedness and response for a severe nuclear accident are discussed in this paper based on the experiences following the accident at Fukushima Daiichi nuclear power plant. The criteria for use in nuclear emergencies in the Japanese emergency preparedness guide were based on the recommendations of International Commission of Radiological Protection (ICRP) Publications 60 and 63. Although the decision-making process for implementing protective actions relied heavily on computer-based predictive models prior to the accident, urgent protective actions, such as evacuation and sheltering, were implemented effectively based on the plant conditions. As there were no recommendations and criteria for long-term protective actions in the emergency preparedness guide, the recommendations of ICRP Publications 103, 109, and 111 were taken into consideration in determining the temporary relocation of inhabitants of heavily contaminated areas. These recommendations were very useful in deciding the emergency protective actions to take in the early stages of the Fukushima accident. However, some suggestions have been made for improving emergency preparedness and response in the early stages of a severe nuclear accident.

  19. Radiation protection issues on preparedness and response for a severe nuclear accident: experiences of the Fukushima accident.

    PubMed

    Homma, T; Takahara, S; Kimura, M; Kinase, S

    2015-06-01

    Radiation protection issues on preparedness and response for a severe nuclear accident are discussed in this paper based on the experiences following the accident at Fukushima Daiichi nuclear power plant. The criteria for use in nuclear emergencies in the Japanese emergency preparedness guide were based on the recommendations of International Commission of Radiological Protection (ICRP) Publications 60 and 63. Although the decision-making process for implementing protective actions relied heavily on computer-based predictive models prior to the accident, urgent protective actions, such as evacuation and sheltering, were implemented effectively based on the plant conditions. As there were no recommendations and criteria for long-term protective actions in the emergency preparedness guide, the recommendations of ICRP Publications 103, 109, and 111 were taken into consideration in determining the temporary relocation of inhabitants of heavily contaminated areas. These recommendations were very useful in deciding the emergency protective actions to take in the early stages of the Fukushima accident. However, some suggestions have been made for improving emergency preparedness and response in the early stages of a severe nuclear accident. PMID:25915551

  20. Aging, Loss-of-Coolant Accident (LOCA), and high potential testing of damaged cables

    SciTech Connect

    Vigil, R.A.; Jacobus, M.J.

    1994-04-01

    Experiments were conducted to assess the effects of high potential testing of cables and to assess the survivability of aged and damaged cables under Loss-of-Coolant Accident (LOCA) conditions. High potential testing at 240 Vdc/mil on undamaged cables suggested that no damage was incurred on the selected virgin cables. During aging and LOCA testing, Okonite ethylene propylene rubber (EPR) cables with a bonded jacket experienced unexpected failures. The failures appear to be primarily related to the level of thermal aging and the presence of a bonded jacket that ages more rapidly than the insulation. For Brand Rex crosslinked polyolefin (XLPO) cables, the results suggest that 7 mils of insulation remaining should give the cables a high probability of surviving accident exposure following aging. The voltage necessary to detect when 7 mils of insulation remain on unaged Brand Rex cables is approximately 35 kVdc. This voltage level would almost certainly be unacceptable to a utility for use as a damage assessment tool. However, additional tests indicated that a 35 kvdc voltage application would not damage virgin Brand Rex cables when tested in water. Although two damaged Rockbestos silicone rubber cables also failed during the accident test, no correlation between failures and level of damage was apparent.

  1. 49 CFR 178.345-8 - Accident damage protection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... distribution of loads to the cargo tank wall and to minimize the possibility of adversely affecting the lading... impact must be considered as being uniformly applied in the horizontal plane at an angle of 10 degrees...

  2. 49 CFR 178.338-10 - Accident damage protection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... equal twice the loaded weight of the tank and attachments. A safety factor of four, based on the tensile... of the loaded cargo tank and attachments, using a safety factor of four based on the tensile...

  3. Assessment of light water reactor fuel damage during a reactivity initiated accident

    SciTech Connect

    MacDonald, P.E.; Seiffert, S.L.; Martinson, Z.R.; McCardell, R.K.; Owen, D.E.; Fukuda, S.K.

    1980-01-01

    This paper presents an assessment of LWR fuel damage during a reactivity initiated accident and comments on the adequacy of the present USNRC design requirements. Results from early SPERT tests are reviewed and compared with results from recent computer simulations and PBF tests. A progression of fuel rod and cladding damage events is presented. High strain rate deformation of relatively cool irradiated cladding early in the transient may result in fracture at a radial average peak fuel enthalpy of approximately 140 cal/g UO/sub 2/. Volume expansion of previously irradiated fuel upon melting may cause deformation and rupture of the cladding, and coolant channel blockage at higher peak enthalpies.

  4. Damage Detection/Locating System Providing Thermal Protection

    NASA Technical Reports Server (NTRS)

    Woodard, Stanley E. (Inventor); Jones, Thomas W. (Inventor); Taylor, Bryant D. (Inventor); Qamar, A. Shams (Inventor)

    2010-01-01

    A damage locating system also provides thermal protection. An array of sensors substantially tiles an area of interest. Each sensor is a reflective-surface conductor having operatively coupled inductance and capacitance. A magnetic field response recorder is provided to interrogate each sensor before and after a damage condition. Changes in response are indicative of damage and a corresponding location thereof.

  5. Description of particle induced damage on protected silver coatings.

    PubMed

    Schwinde, Stefan; Schürmann, Mark; Jobst, Paul Johannes; Kaiser, Norbert; Tünnermann, Andreas

    2015-06-01

    In the visible to infrared spectral range, highly-reflective silver mirrors are applied in the manufacture of optical instruments such as telescopes. However, it is still difficult to combine high reflectivity and long-term stability of the protected silver coating. We show that the deposition of impervious protective layers is necessary but often not sufficient for long-term environmental stability. Hygroscopic air borne particles absorbed by the protections surface attract water molecules and form a solution. This solution first damages the protection, subsequently permeates the protection and finally damages the silver whereby the reflectivity is reduced. We demonstrate this particular damage mechanism with different experiments and describe this mechanism in detail. PMID:26192652

  6. Extracellular ATP protects endothelial cells against DNA damage.

    PubMed

    Aho, Joonas; Helenius, Mikko; Vattulainen-Collanus, Sanna; Alastalo, Tero-Pekka; Koskenvuo, Juha

    2016-09-01

    Cell damage can lead to rapid release of ATP to extracellular space resulting in dramatic change in local ATP concentration. Evolutionary, this has been considered as a danger signal leading to adaptive responses in adjacent cells. Our aim was to demonstrate that elevated extracellular ATP or inhibition of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1/CD39) activity could be used to increase tolerance against DNA-damaging conditions. Human endothelial cells, with increased extracellular ATP concentration in cell proximity, were more resistant to irradiation or chemically induced DNA damage evaluated with the DNA damage markers γH2AX and phosphorylated p53. In our rat models of DNA damage, inhibiting CD39-driven ATP hydrolysis with POM-1 protected the heart and lung tissues against chemically induced DNA damage. Interestingly, the phenomenon could not be replicated in cancer cells. Our results show that transient increase in extracellular ATP can promote resistance to DNA damage.

  7. Follow-up studies on genome damage in children after Chernobyl nuclear power plant accident.

    PubMed

    Fucic, Aleksandra; Aghajanyan, Anna; Druzhinin, Vladimir; Minina, Varvara; Neronova, Elizaveta

    2016-09-01

    As children are more susceptible to ionizing radiation than adults, each nuclear accident demands special attention and care of this vulnerable population. The Chernobyl nuclear disaster occurred in a region populated with a large number of children, but despite all efforts and expertise of nuclear specialists, it was not possible to avoid casualties. As vast regions of Ukraine, Belarus and Russia were exposed to doses of ionizing radiation, which are known to be related with different diseases, shortly after the accident medical surveillance was launched, which also included analysis of genome damage. Child population affected by internal and external radiation consisted of subjects exposed prenatally, postnatally (both evacuated and non-evacuated), born by irradiated fathers who worked as liquidators, and parents exposed environmentally. In all groups of children during the last 30 years who were exposed to doses which were significantly higher than that recommended for general population of 1 mSv per year, increased genome damage was detected. Increased genome damage includes statistically higher frequency of dicentric and ring chromosomes, chromated and chromosome breaks, acentric fragments, translocations, and micronuclei. The presence of rogue cells confirmed internal contamination. Genome instability and radiosensitivity in children was detected both in evacuated and continuously exposed children. Today the population exposed to ionizing radiation in 1986 is in reproductive period of life and follow-up of this population and their offspring is of great importance. This review aims to give insight in results of studies, which reported genome damage in children in journals without language restrictions. PMID:27329326

  8. Follow-up studies on genome damage in children after Chernobyl nuclear power plant accident.

    PubMed

    Fucic, Aleksandra; Aghajanyan, Anna; Druzhinin, Vladimir; Minina, Varvara; Neronova, Elizaveta

    2016-09-01

    As children are more susceptible to ionizing radiation than adults, each nuclear accident demands special attention and care of this vulnerable population. The Chernobyl nuclear disaster occurred in a region populated with a large number of children, but despite all efforts and expertise of nuclear specialists, it was not possible to avoid casualties. As vast regions of Ukraine, Belarus and Russia were exposed to doses of ionizing radiation, which are known to be related with different diseases, shortly after the accident medical surveillance was launched, which also included analysis of genome damage. Child population affected by internal and external radiation consisted of subjects exposed prenatally, postnatally (both evacuated and non-evacuated), born by irradiated fathers who worked as liquidators, and parents exposed environmentally. In all groups of children during the last 30 years who were exposed to doses which were significantly higher than that recommended for general population of 1 mSv per year, increased genome damage was detected. Increased genome damage includes statistically higher frequency of dicentric and ring chromosomes, chromated and chromosome breaks, acentric fragments, translocations, and micronuclei. The presence of rogue cells confirmed internal contamination. Genome instability and radiosensitivity in children was detected both in evacuated and continuously exposed children. Today the population exposed to ionizing radiation in 1986 is in reproductive period of life and follow-up of this population and their offspring is of great importance. This review aims to give insight in results of studies, which reported genome damage in children in journals without language restrictions.

  9. Radiological protection issues arising during and after the Fukushima nuclear reactor accident.

    PubMed

    González, Abel J; Akashi, Makoto; Boice, John D; Chino, Masamichi; Homma, Toshimitsu; Ishigure, Nobuhito; Kai, Michiaki; Kusumi, Shizuyo; Lee, Jai-Ki; Menzel, Hans-Georg; Niwa, Ohtsura; Sakai, Kazuo; Weiss, Wolfgang; Yamashita, Shunichi; Yonekura, Yoshiharu

    2013-09-01

    Following the Fukushima accident, the International Commission on Radiological Protection (ICRP) convened a task group to compile lessons learned from the nuclear reactor accident at the Fukushima Daiichi nuclear power plant in Japan, with respect to the ICRP system of radiological protection. In this memorandum the members of the task group express their personal views on issues arising during and after the accident, without explicit endorsement of or approval by the ICRP. While the affected people were largely protected against radiation exposure and no one incurred a lethal dose of radiation (or a dose sufficiently large to cause radiation sickness), many radiological protection questions were raised. The following issues were identified: inferring radiation risks (and the misunderstanding of nominal risk coefficients); attributing radiation effects from low dose exposures; quantifying radiation exposure; assessing the importance of internal exposures; managing emergency crises; protecting rescuers and volunteers; responding with medical aid; justifying necessary but disruptive protective actions; transiting from an emergency to an existing situation; rehabilitating evacuated areas; restricting individual doses of members of the public; caring for infants and children; categorising public exposures due to an accident; considering pregnant women and their foetuses and embryos; monitoring public protection; dealing with 'contamination' of territories, rubble and residues and consumer products; recognising the importance of psychological consequences; and fostering the sharing of information. Relevant ICRP Recommendations were scrutinised, lessons were collected and suggestions were compiled. It was concluded that the radiological protection community has an ethical duty to learn from the lessons of Fukushima and resolve any identified challenges. Before another large accident occurs, it should be ensured that inter alia: radiation risk coefficients of potential

  10. Computational Aerodynamics of Shuttle Orbiter Damage Scenarios in Support of the Columbia Accident Investigation

    NASA Technical Reports Server (NTRS)

    Bibb, Karen L.; Prabhu, Ramadas K.

    2004-01-01

    In support of the Columbia Accident Investigation, inviscid computations of the aerodynamic characteristics for various Shuttle Orbiter damage scenarios were performed using the FELISA unstructured CFD solver. Computed delta aerodynamics were compared with the reconstructed delta aerodynamics in order to postulate a progression of damage through the flight trajectory. By performing computations at hypervelocity flight and CF4 tunnel conditions, a bridge was provided between wind tunnel testing in Langley's 20-Inch CF4 facility and the flight environment experienced by Columbia during re-entry. The rapid modeling capability of the unstructured methodology allowed the computational effort to keep pace with the wind tunnel and, at times, guide the wind tunnel efforts. These computations provided a detailed view of the flowfield characteristics and the contribution of orbiter components (such as the vertical tail and wing) to aerodynamic forces and moments that were unavailable from wind tunnel testing. The damage scenarios are grouped into three categories. Initially, single and multiple missing full RCC panels were analyzed to determine the effect of damage location and magnitude on the aerodynamics. Next is a series of cases with progressive damage, increasing in severity, in the region of RCC panel 9. The final group is a set of wing leading edge and windward surface deformations that model possible structural deformation of the wing skin due to internal heating of the wing structure. By matching the aerodynamics from selected damage scenarios to the reconstructed flight aerodynamics, a progression of damage that is consistent with the flight data, debris forensics, and wind tunnel data is postulated.

  11. Optical power control filters: from laser dazzling to damage protection

    NASA Astrophysics Data System (ADS)

    Donval, Ariela; Golding, Karin; Nevo, Doron; Fisher, Tali; Lipman, Ofir; Oron, Moshe

    2012-02-01

    With the development of more powerful lasers for applications, optical limiters and blockers are required for providing human eye and optical sensors protection. In some scenarios, laser radiation may seriously interrupt the signal, from transient saturation and can lead to permanent damage. We present a variety of non-linear, solid-state dynamic filter solutions protecting from dazzling and damage in a passive way. Our filters either limit or block the transmission, only if the power exceeds a certain threshold as opposed to spectral filters that block a certain wavelength permanently. We propose a dynamic protection for cameras, sensors and the human eye from laser threats.

  12. Insulin Protects against Hepatic Damage Postburn

    PubMed Central

    Jeschke, Marc G; Kraft, Robert; Song, Juquan; Gauglitz, Gerd G; Cox, Robert A; Brooks, Natasha C; Finnerty, Celeste C; Kulp, Gabriela A; Herndon, David N; Boehning, Darren

    2011-01-01

    Burn injury causes hepatic dysfunction associated with endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR). ER stress/UPR leads to hepatic apoptosis and activation of the Jun-N-terminal kinase (JNK) signaling pathway, leading to vast metabolic alterations. Insulin has been shown to attenuate hepatic damage and to improve liver function. We therefore hypothesized that insulin administration exerts its effects by attenuating postburn hepatic ER stress and subsequent apoptosis. Male Sprague Dawley rats received a 60% total body surface area (TBSA) burn injury. Animals were randomized to receive saline (controls) or insulin (2.5 IU/kg q. 24 h) and euthanized at 24 and 48 h postburn. Burn injury induced dramatic changes in liver structure and function, including induction of the ER stress response, mitochondrial dysfunction, hepatocyte apoptosis, and up-regulation of inflammatory mediators. Insulin decreased hepatocyte caspase-3 activation and apoptosis significantly at 24 and 48 h postburn. Furthermore, insulin administration decreased ER stress significantly and reversed structural and functional changes in hepatocyte mitochondria. Finally, insulin attenuated the expression of inflammatory mediators IL-6, MCP-1, and CINC-1. Insulin alleviates burn-induced ER stress, hepatocyte apoptosis, mitochondrial abnormalities, and inflammation leading to improved hepatic structure and function significantly. These results support the use of insulin therapy after traumatic injury to improve patient outcomes. PMID:21267509

  13. Free radical tissue damage: Protective role of antioxidant nutrients

    SciTech Connect

    Machling, L.J.; Bendich, A. )

    1987-12-01

    Highly reactive molecules called free radicals can cause tissue damage by reacting with polyunsaturated fatty acids in cellular membranes, nucleotides in DNA, and critical sulfhydryl bonds in proteins. Free radicals can originate endogenously from normal metabolic reactions or exogenously as components of tobacco smoke and air pollutants and indirectly through the metabolism of certain solvents, drugs, and pesticides as well as through exposure to radiation. There is some evidence that free radical damage contributes to the etiology of many chronic health problems such as emphysema, cardiovascular and inflammatory diseases, cataracts, and cancer. The extent of tissue damage is the result of the balance between the free radicals generated and the antioxidant protective defense system. Several dietary micronutrients contribute greatly to the protective system. Based on the growing interest in free radical biology and the lack of effective therapies for many of the chronic diseases, the usefulness of essential, safe nutrients in protecting against the adverse effects of oxidative injury warrants further study.

  14. Gate oxide damage reduction using a protective dielectric layer

    NASA Astrophysics Data System (ADS)

    Gabriel, Calvin T.; Weling, Milind G.

    1994-08-01

    Gate oxide damage from charge entering through the top surface of the gate electrode during plasma ashing, ion implantation, and LDD spacer oxide etching was measured using antenna structures. Significant charge damage to the 9.0 nm-thick gate oxide was detected for each of these processes. The damage was reduced by using a protective dielectric layer, in this case a thermally deposited TEOS oxide, over the polycide gate electrode before gate definition. The dielectric appears to block charge penetration into the antenna. Damage can be reduced further by increasing the thickness of the dielectric layer; for a sufficiently thick layer (about 150 nm), charge entering through the top surface of the antenna was effectively eliminated.

  15. Evaluation of warning and protective action implementation times for chemical weapons accidents. [None

    SciTech Connect

    Sorensen, J.H.

    1988-04-01

    This is a preliminary evaluation of warning systems and protective action options for off-site emergency planning for chemical weapons accidents. The analysis concentrates on the timing of warning and protective action implementation which is defined as the length of time it will take to protect off-site populations given different warning systems and protective action configurations. The evaluation concludes: (1) A specialized warning system using tone alert radios, automatic telephone dialing systems, sirens, or some combination thereof is desirable within 10 km of the fixed sites. (2) A rapid means of respiratory protection and expedient protective sheltering are the protective actions that could be most rapidly implemented within 10 km of a fixed-site release point. (3) Populations at distances greater than 10 km should have time to evacuate without the installation of specialized warning systems except in institutional facilities such as schools and nursing homes. (4) The detection and warning decision times are critical elements in determining the feasibility of population protection. A 5-to-15-minute organizational response is needed to provide warning to potentially threatened populations. Even an expedient organizational response, however, will not provide 100% assurance that everyone will have time to learn of the accident and take action. 9 refs., 4 tabs.

  16. Curculigo orchioides protects cisplatin-induced cell damage.

    PubMed

    Kang, Tong Ho; Hong, Bin Na; Jung, Su-Young; Lee, Jeong-Han; So, Hong-Seob; Park, Raekil; You, Yong-Ouk

    2013-01-01

    Cisplatin is commonly used as a chemotherapeutic agent against many human cancers. However, it generates reactive oxygen species (ROS) and has serious dose-limiting side effects, including ototoxicity. The roots of Curculigo orchioides (C. orchioides) have been used to treat auditory diseases such as tinnitus and hearing loss in Chinese traditional medicine. In the present study, we investigated the protective effects of an ethanol extract obtained from C. orchioides rhizome (COR) on cisplatin-induced cell damage in auditory cells (HEI-OC1). COR (2.5-25 μg/ml) inhibited cisplatin-induced HEI-OC1 cell damage in a dose-dependent manner. To investigate the protective mechanism of COR on cisplatin cytotoxicity in HEI-OC1 cells, we measured the effects of COR on ROS generation and lipid peroxidation in cisplatin-treated cells as well as its scavenging activities against superoxide radicals, hydroxyl radicals, hydrogen peroxide, and DPPH radicals. COR (1-25 μg/ml) had scavenging activities against superoxide radicals, hydroxyl radicals, hydrogen peroxide, and DPPH radicals, as well as reduced lipid peroxidation. In in vivo experiments, COR was shown to reduce cochlear and peripheral auditory function impairments through cisplatin-induced auditory damage in mice. These results indicate that COR protects from cisplatin-induced auditory damage by inhibiting lipid peroxidation and scavenging activities against free radicals.

  17. Glimepiride protects neurons against amyloid-β-induced synapse damage.

    PubMed

    Osborne, Craig; West, Ewan; Nolan, William; McHale-Owen, Harriet; Williams, Alun; Bate, Clive

    2016-02-01

    Alzheimer's disease is associated with the accumulation within the brain of amyloid-β (Aβ) peptides that damage synapses and affect memory acquisition. This process can be modelled by observing the effects of Aβ on synapses in cultured neurons. The addition of picomolar concentrations of soluble Aβ derived from brain extracts triggered the loss of synaptic proteins including synaptophysin, synapsin-1 and cysteine string protein from cultured neurons. Glimepiride, a sulphonylurea used for the treatment of diabetes, protected neurons against synapse damage induced by Aβ. The protective effects of glimepiride were multi-faceted. Glimepiride treatment was associated with altered synaptic membranes including the loss of specific glycosylphosphatidylinositol (GPI)-anchored proteins including the cellular prion protein (PrP(C)) that acts as a receptor for Aβ42, increased synaptic gangliosides and altered cell signalling. More specifically, glimepiride reduced the Aβ-induced increase in cholesterol and the Aβ-induced activation of cytoplasmic phospholipase A2 (cPLA2) in synapses that occurred within cholesterol-dense membrane rafts. Aβ42 binding to glimepiride-treated neurons was not targeted to membrane rafts and less Aβ42 accumulated within synapses. These studies indicate that glimepiride modified the membrane micro-environments in which Aβ-induced signalling leads to synapse damage. In addition, soluble PrP(C), released from neurons by glimepiride, neutralised Aβ-induced synapse damage. Such observations raise the possibility that glimepiride may reduce synapse damage and hence delay the progression of cognitive decline in Alzheimer's disease. PMID:26432105

  18. Glimepiride protects neurons against amyloid-β-induced synapse damage.

    PubMed

    Osborne, Craig; West, Ewan; Nolan, William; McHale-Owen, Harriet; Williams, Alun; Bate, Clive

    2016-02-01

    Alzheimer's disease is associated with the accumulation within the brain of amyloid-β (Aβ) peptides that damage synapses and affect memory acquisition. This process can be modelled by observing the effects of Aβ on synapses in cultured neurons. The addition of picomolar concentrations of soluble Aβ derived from brain extracts triggered the loss of synaptic proteins including synaptophysin, synapsin-1 and cysteine string protein from cultured neurons. Glimepiride, a sulphonylurea used for the treatment of diabetes, protected neurons against synapse damage induced by Aβ. The protective effects of glimepiride were multi-faceted. Glimepiride treatment was associated with altered synaptic membranes including the loss of specific glycosylphosphatidylinositol (GPI)-anchored proteins including the cellular prion protein (PrP(C)) that acts as a receptor for Aβ42, increased synaptic gangliosides and altered cell signalling. More specifically, glimepiride reduced the Aβ-induced increase in cholesterol and the Aβ-induced activation of cytoplasmic phospholipase A2 (cPLA2) in synapses that occurred within cholesterol-dense membrane rafts. Aβ42 binding to glimepiride-treated neurons was not targeted to membrane rafts and less Aβ42 accumulated within synapses. These studies indicate that glimepiride modified the membrane micro-environments in which Aβ-induced signalling leads to synapse damage. In addition, soluble PrP(C), released from neurons by glimepiride, neutralised Aβ-induced synapse damage. Such observations raise the possibility that glimepiride may reduce synapse damage and hence delay the progression of cognitive decline in Alzheimer's disease.

  19. Nitroxides block DNA scission and protect cells from oxidative damage

    SciTech Connect

    Samuni, A.; Godinger, D.; Aronovitch, J. ); Russo, A.; Mitchell, J. )

    1991-01-01

    The protective effect of cyclic stable nitroxide free radicals, having SOD-like activity, against oxidative damage was studied by using Escherichia coli xthA DNA repair-deficient mutant hypersensitive to H{sub 2}O{sub 2}. Oxidative damage induced by H{sub 2}O{sub 2} was assayed by monitoring cell survival. The metal chelator 1,10-phenanthroline (OP), which readily intercalates into DNA, potentiated with H{sub 2}O{sub 2}-induced damage. The extent of in vivo DNA scission and degradation was studied and compared with the loss of cell viability. The extent of DNA breakage correlated with cell killing, supporting previous suggestions that DNA is the crucial cellular target of H{sub 2}O{sub 2} cytotoxicity. The xthA cells were protected by catalase but not by superoxide dismutase (SOD). Both five- and six-membered ring nitroxides, having SOD-like activity, protected growing and resting cells from H{sub 2}O{sub 2} toxicity, without lowering H{sub 2}O{sub 2} concentration. To check whether nitroxides protect against O{sub 2}{sup {center dot}{minus}}-independent injury also, experiments were repeated under hypoxia. These nitroxides also protected hypoxic cells against H{sub 2}O{sub 2}, suggesting alternative modes of protection. Since nitroxides were found to reoxidize DNA-bound iron(II), the present results suggest that nitroxides protect by oxidizing reduced transition metals, thus interfering with the Fenton reaction.

  20. Protective effect of Pterostilbene against free radical mediated oxidative damage

    PubMed Central

    2013-01-01

    Background Pterostilbene, a methoxylated analog of Resveratrol, is gradually gaining more importance as a therapeutic drug owing to its higher lipophilicity, bioavailability and biological activity than Resveratrol. This study was undertaken to characterize its ability to scavenge free radicals such as superoxide, hydroxyl and hydrogen peroxide and to protect bio-molecules within a cell against oxidative insult. Methods Anti-oxidant activity of Pterostilbene was evaluated extensively by employing several in vitro radical scavenging/inhibiting assays and pulse radiolysis study. In addition, its ability to protect rat liver mitochondria against tertiary-butyl hydroperoxide (TBHP) and hydroxyl radical generated oxidative damage was determined by measuring the damage markers such as protein carbonyls, protein sulphydryls, lipid hydroperoxides, lipid peroxides and 8-hydroxy-2'-deoxyguanosine. Pterostilbene was also evaluated for its ability to inhibit •OH radical induced single strand breaks in pBR322 DNA. Result Pterostilbene exhibited strong anti-oxidant activity against various free radicals such as DPPH, ABTS, hydroxyl, superoxide and hydrogen peroxide in a concentration dependent manner. Pterostilbene conferred protection to proteins, lipids and DNA in isolated mitochondrial fractions against TBHP and hydroxyl radical induced oxidative damage. It also protected pBR322 DNA against oxidative assault. Conclusions Thus, present study provides an evidence for the strong anti-oxidant property of Pterostilbene, methoxylated analog of Resveratrol, thereby potentiating its role as an anti-oxidant. PMID:24070177

  1. Precursors to potential severe core damage accidents, 1986: A status report: Main report and Appendixes A,B, and C

    SciTech Connect

    Minarick, J W; Harris, J D; Austin, P N; Cletcher, J W; Hagen, E W

    1988-05-01

    The Accident Sequence Precursor Program reviews licensee event reports of operational events that have occurred at LWRs to identify and categorize precursors to potential severe core-damage accidents. Accident sequences considered in the study are those associated with inadequate core cooling. Accident sequence precursors are events that are important elements in such sequences. Such precursors could be infrequent initiating events or equipment failures that, when coupled with one or more postulated events, could result in a plant condition with inadequate core cooling. Originally proposed in the Risk Assessment Review Group Report (Lewis Committee report) in 1978, the study - subsequently named the Accident Sequence Precursor Program - was initiated at the Nuclear Operations Analysis Center in 1979. Earlier reports by the program involved assessment of events that occurred in 1969-1981 and 1984-1985. The present report involves the assessment of events that occurred during 1986. A nuclear plant has safety systems for mitigating the consequences of accidents or off-normal initiating events that may occur during the course of plant operation. These systems are built to high-quality standards and are redundant; nonetheless, they have a nonzero probability of failing or being in a failed state when required to operate. This report uses LERs and other plant data, estimated system unavailabilities, the expected average frequency of initiating events (LOFWs, LOOPs, LOCAs), and event details to evaluate the potential impact of the following two situations.

  2. Quercitrin protects skin from UVB-induced oxidative damage

    SciTech Connect

    Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J.; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

    2013-06-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.

  3. Salicylic acid protects the skin from UV damage.

    PubMed

    Mammone, Thomas; Gan, David; Goyarts, Earl; Maes, Daniel

    2006-01-01

    Aspirin(acetyl salicylate) has long been used as an analgesic. Salicylic acid has been reported to have anti-inflammatory properties. These activities include inhibiting activity of cox-1, cox-2, and NF-kb. In addition, salicylic acid has also been shown in some systems to induce Hsp70. We have demonstrated that salicylic acid inhibits UVB-induced sunburn cell formation, as well as increase the removal of UVB induced TT dimer formation in living skin equivalents. Given these protective properties of salicylic acid, we propose the use of salicylic acid as a topical therapeutic to protect the skin from sun damage.

  4. Lifting and protecting residential structures from subsidence damage using airbags

    SciTech Connect

    Triplett, T.L.; Bennett, R.M.

    1998-12-31

    Conventional practice in protecting residential structures from subsidence damage concentrates on saving the superstructure. The foundation is sacrificed, even though it represents the structural component with the greatest replacement cost. In this study, airbags were used to lift a 20 ft x 30 ft structure to test their ability to protect both the foundation and superstructure from ground settlement. Two contiguous sides of the test foundation were unreinforced, and the other two contiguous sides incorporated footing and wall reinforcement. The airbags successfully lifted the structure without causing damage, even on the unreinforced sides. This paper gives a procedure for determining airbag spacing, and describes installation and operation techniques of the airbags. The paper then focuses on the performance of the airbags in lifting the structure, and shows that airbags can preserve existing foundations during subsidence movements.

  5. Quercitrin protects skin from UVB-induced oxidative damage.

    PubMed

    Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

    2013-06-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin.

  6. Plasmalogen phospholipids protect internodal myelin from oxidative damage.

    PubMed

    Luoma, Adrienne M; Kuo, Fonghsu; Cakici, Ozgur; Crowther, Michelle N; Denninger, Andrew R; Avila, Robin L; Brites, Pedro; Kirschner, Daniel A

    2015-07-01

    Reactive oxygen species (ROS) are implicated in a range of degenerative conditions, including aging, neurodegenerative diseases, and neurological disorders. Myelin is a lipid-rich multilamellar sheath that facilitates rapid nerve conduction in vertebrates. Given the high energetic demands and low antioxidant capacity of the cells that elaborate the sheaths, myelin is considered intrinsically vulnerable to oxidative damage, raising the question whether additional mechanisms prevent structural damage. We characterized the structural and biochemical basis of ROS-mediated myelin damage in murine tissues from both central nervous system (CNS) and peripheral nervous system (PNS). To determine whether ROS can cause structural damage to the internodal myelin, whole sciatic and optic nerves were incubated ex vivo with a hydroxyl radical-generating system consisting of copper (Cu), hydrogen peroxide (HP), and ortho-phenanthroline (OP). Quantitative assessment of unfixed tissue by X-ray diffraction revealed irreversible compaction of myelin membrane stacking in both sciatic and optic nerves. Incubation in the presence of the hydroxyl radical scavenger sodium formate prevented this damage, implicating hydroxyl radical species. Myelin membranes are particularly enriched in plasmalogens, a class of ether-linked phospholipids proposed to have antioxidant properties. Myelin in sciatic nerve from plasmalogen-deficient (Pex7 knockout) mice was significantly more vulnerable to Cu/OP/HP-mediated ROS-induced compaction than myelin from WT mice. Our results directly support the role of plasmalogens as endogenous antioxidants providing a defense that protects ROS-vulnerable myelin.

  7. RNA protects a nucleoprotein complex against radiation damage

    PubMed Central

    Bury, Charles S.; McGeehan, John E.; Antson, Alfred A.; Carmichael, Ian; Gerstel, Markus; Shevtsov, Mikhail B.; Garman, Elspeth F.

    2016-01-01

    Radiation damage during macromolecular X-ray crystallographic data collection is still the main impediment for many macromolecular structure determinations. Even when an eventual model results from the crystallographic pipeline, the manifestations of radiation-induced structural and conformation changes, the so-called specific damage, within crystalline macromolecules can lead to false interpretations of biological mechanisms. Although this has been well characterized within protein crystals, far less is known about specific damage effects within the larger class of nucleoprotein complexes. Here, a methodology has been developed whereby per-atom density changes could be quantified with increasing dose over a wide (1.3–25.0 MGy) range and at higher resolution (1.98 Å) than the previous systematic specific damage study on a protein–DNA complex. Specific damage manifestations were determined within the large trp RNA-binding attenuation protein (TRAP) bound to a single-stranded RNA that forms a belt around the protein. Over a large dose range, the RNA was found to be far less susceptible to radiation-induced chemical changes than the protein. The availability of two TRAP molecules in the asymmetric unit, of which only one contained bound RNA, allowed a controlled investigation into the exact role of RNA binding in protein specific damage susceptibility. The 11-fold symmetry within each TRAP ring permitted statistically significant analysis of the Glu and Asp damage patterns, with RNA binding unexpectedly being observed to protect these otherwise highly sensitive residues within the 11 RNA-binding pockets distributed around the outside of the protein molecule. Additionally, the method enabled a quantification of the reduction in radiation-induced Lys and Phe disordering upon RNA binding directly from the electron density. PMID:27139628

  8. Protective Behaviour of Citizens to Transport Accidents Involving Hazardous Materials: A Discrete Choice Experiment Applied to Populated Areas nearby Waterways

    PubMed Central

    de Bekker-Grob, Esther W.; Bergstra, Arnold D.; Bliemer, Michiel C. J.; Trijssenaar-Buhre, Inge J. M.; Burdorf, Alex

    2015-01-01

    Background To improve the information for and preparation of citizens at risk to hazardous material transport accidents, a first important step is to determine how different characteristics of hazardous material transport accidents will influence citizens’ protective behaviour. However, quantitative studies investigating citizens’ protective behaviour in case of hazardous material transport accidents are scarce. Methods A discrete choice experiment was conducted among subjects (19–64 years) living in the direct vicinity of a large waterway. Scenarios were described by three transport accident characteristics: odour perception, smoke/vapour perception, and the proportion of people in the environment that were leaving at their own discretion. Subjects were asked to consider each scenario as realistic and to choose the alternative that was most appealing to them: staying, seeking shelter, or escaping. A panel error component model was used to quantify how different transport accident characteristics influenced subjects’ protective behaviour. Results The response was 44% (881/1,994). The predicted probability that a subject would stay ranged from 1% in case of a severe looking accident till 62% in case of a mild looking accident. All three transport accident characteristics proved to influence protective behaviour. Particularly a perception of strong ammonia or mercaptan odours and visible smoke/vapour close to citizens had the strongest positive influence on escaping. In general, ‘escaping’ was more preferred than ‘seeking shelter’, although stated preference heterogeneity among subjects for these protective behaviour options was substantial. Males were less willing to seek shelter than females, whereas elderly people were more willing to escape than younger people. Conclusion Various characteristics of transport accident involving hazardous materials influence subjects’ protective behaviour. The preference heterogeneity shows that information needs

  9. Bimatoprost protects retinal neuronal damage via Akt pathway.

    PubMed

    Takano, Norihito; Tsuruma, Kazuhiro; Ohno, Yuta; Shimazawa, Masamitsu; Hara, Hideaki

    2013-02-28

    Worldwide, prostaglandin analogs, such as bimatoprost, have become the major therapeutic class for medical treatment of glaucoma because of their efficacy and generally well tolerated systemic safety profile. However, the detailed mechanism of the direct action of bimatoprost on retinal ganglion cells (RGC) has rarely been understood. Thus, in this study, we elucidated the mechanism of the protective effects of bimatoprost on RGC against oxidative stress. To examine the protective effects of bimatoprost, cultured RGC with various concentrations of bimatoprost (in both free acid and amide form) were exposed to l-buthionin-(S,R)-sulfoximine (BSO) plus glutamate or serum depletion in vitro and intravitreal injection of N-methyl-D-aspartate (NMDA) was used to induce retinal damage in vivo. To elucidate the protective mechanism of bimatoprost, we used western blot analysis to investigate the phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Bimatoprost significantly reduced BSO plus glutamate- and serum deprivation-induced death in concentration-dependent manners. Bimatoprost induced activation of Akt and ERK, and a phosphatidylinositol 3-kinase inhibitor, LY294002, attenuated the protective effect of bimatoprost. On the other hand, a mitogen-activated protein kinase kinase inhibitor, U0126, exhibited protective effect unexpectedly. Moreover, ERK was more phosphorylated by attenuation of Akt activity in cultured RGC. In an in vivo study, bimatoprost reduced NMDA-induced RGC death. Taken together, these findings indicate that bimatoprost has protective effects on in vitro and in vivo retinal damage, suggesting that the mechanism underlying may be via the Akt pathway, which may modulate the ERK pathway.

  10. Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism

    PubMed Central

    Wang, Tingting; Lin, Huajuan; Tu, Qian; Liu, Jingjing; Li, Xican

    2016-01-01

    Purpose: The paper tries to assess the protective effect of fisetin against •OH-induced DNA damage, then to investigate the possible mechanism. Methods: The protective effect was evaluated based on the content of malondialdehyde (MDA). The possible mechanism was analyzed using various antioxidant methods in vitro, including •OH scavenging (deoxyribose degradation), •O2- scavenging (pyrogallol autoxidation), DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays. Results: Fisetin increased dose-dependently its protective percentages against •OH-induced DNA damage (IC50 value =1535.00±29.60 µM). It also increased its radical-scavenging percentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in •OH scavenging, •O2- scavenging, DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays, were 47.41±4.50 µM, 34.05±0.87 µM, 9.69±0.53 µM, 2.43±0.14 µM, and 1.49±0.16 µM, respectively. Conclusion: Fisetin can effectively protect DNA against •OH-induced oxidative damage possibly via reactive oxygen species (ROS) scavenging approach, which is assumed to be hydrogen atom (H•) and/or single electron (e) donation (HAT/SET) pathways. In the HAT pathway, the 3’,4’-dihydroxyl moiety in B ring of fisetin is thought to play an important role, because it can be ultimately oxidized to a stable ortho-benzoquinone form. PMID:27478791

  11. Radiological protection from radioactive waste management in existing exposure situations resulting from a nuclear accident

    PubMed Central

    Sugiyama, Daisuke; Hattori, Takatoshi

    2013-01-01

    In environmental remediation after nuclear accidents, radioactive wastes have to be appropriately managed in existing exposure situations with contamination resulting from the emission of radionuclides by such accidents. In this paper, a framework of radiation protection from radioactive waste management in existing exposure situations for application to the practical and reasonable waste management in contaminated areas, referring to related ICRP recommendations was proposed. In the proposed concept, intermediate reference levels for waste management are adopted gradually according to the progress of the reduction in the existing ambient dose in the environment on the basis of the principles of justification and optimisation by taking into account the practicability of the management of radioactive waste and environmental remediation. It is essential to include the participation of relevant stakeholders living in existing exposure situations in the selection of reference levels for the existing ambient dose and waste management. PMID:22719047

  12. Radiological protection from radioactive waste management in existing exposure situations resulting from a nuclear accident.

    PubMed

    Sugiyama, Daisuke; Hattori, Takatoshi

    2013-01-01

    In environmental remediation after nuclear accidents, radioactive wastes have to be appropriately managed in existing exposure situations with contamination resulting from the emission of radionuclides by such accidents. In this paper, a framework of radiation protection from radioactive waste management in existing exposure situations for application to the practical and reasonable waste management in contaminated areas, referring to related ICRP recommendations was proposed. In the proposed concept, intermediate reference levels for waste management are adopted gradually according to the progress of the reduction in the existing ambient dose in the environment on the basis of the principles of justification and optimisation by taking into account the practicability of the management of radioactive waste and environmental remediation. It is essential to include the participation of relevant stakeholders living in existing exposure situations in the selection of reference levels for the existing ambient dose and waste management.

  13. Radiological protection from radioactive waste management in existing exposure situations resulting from a nuclear accident.

    PubMed

    Sugiyama, Daisuke; Hattori, Takatoshi

    2013-01-01

    In environmental remediation after nuclear accidents, radioactive wastes have to be appropriately managed in existing exposure situations with contamination resulting from the emission of radionuclides by such accidents. In this paper, a framework of radiation protection from radioactive waste management in existing exposure situations for application to the practical and reasonable waste management in contaminated areas, referring to related ICRP recommendations was proposed. In the proposed concept, intermediate reference levels for waste management are adopted gradually according to the progress of the reduction in the existing ambient dose in the environment on the basis of the principles of justification and optimisation by taking into account the practicability of the management of radioactive waste and environmental remediation. It is essential to include the participation of relevant stakeholders living in existing exposure situations in the selection of reference levels for the existing ambient dose and waste management. PMID:22719047

  14. Legal considerations on the liability of damage compensation in medical accidents in China.

    PubMed

    Shen, Xiuqin; Chen, Xiaoyang

    2008-12-01

    In the past years, there has been an increasing number of medical accidents in various places around the country. Some of them often led to medical litigations. The responsibility of medical accident compensation is the key factor, which involves either the harmony between physician-patient relationship, or the realization of patients' rights. Though relevant legal provisions on the responsibility of medical accidents have been made in national law, regulation and some judicial interpretation, there exist so many problems in reality, such as the uniformity of law application, compensational rate and the deficiency of compensational scope and method. Therefore, in this article, the author tries to analysis the attribute of medical accident compensation, relevant laws and regulations and the problems in practical life, and to put forward advice on how to perfect medical accident legislation.

  15. Radiation protection: an analysis of thyroid blocking. [Effectiveness of KI in reducing radioactive uptake following potential reactor accident

    SciTech Connect

    Aldrich, D C; Blond, R M

    1980-01-01

    An analysis was performed to provide guidance to policymakers concerning the effectiveness of potassium iodide (KI) as a thyroid blocking agent in potential reactor accident situations, the distance to which (or area within which) it should be distributed, and its relative effectiveness compared to other available protective measures. The analysis was performed using the Reactor Safety Study (WASH-1400) consequence model. Four categories of accidents were addressed: gap activity release accident (GAP), GAP without containment isolation, core melt with a melt-through release, and core melt with an atmospheric release. Cost-benefit ratios (US $/thyroid nodule prevented) are given assuming that no other protective measures are taken. Uncertainties due to health effects parameters, accident probabilities, and costs are assessed. The effects of other potential protective measures, such as evacuation and sheltering, and the impact on children (critical population) are evaluated. Finally, risk-benefit considerations are briefly discussed.

  16. Medicinal protection with Chinese herb-compound against radiation damage

    SciTech Connect

    Zhang, R.J.; Qian, J.K.; Yang, G.H.; Wang, B.Z.; Wen, X.L. )

    1990-08-01

    Experiments were carried out on mice and the subjects irradiated for cancer therapy to evaluate the protective efficacy of a Chinese medicinal herb-compound (CMHC). The lethality and the degree of leucopenia caused by radiation in mice medicated with CMHC were significantly less in comparison with control mice (p less than 0.01 and p less than 0.001, respectively). CMHC significantly improved the WBC and the thrombocytes in irradiated workers (p less than 0.01 and p less than 0.001, respectively). The WBC count of 40 patients under radiotherapy while treated with CMHC recovered from 3450 +/- 77/c.mm to 5425 +/- 264/c.mm (p less than 0.001); whereas, in the control group, without any medication, the WBC count dropped significantly (p less than 0.001). Our results revealed the applicabilities of CMHC in protection against radiation damage in spaceflight and in other fields.

  17. The protective effect of a helmet in three bicycle accidents--A finite element study.

    PubMed

    Fahlstedt, Madelen; Halldin, Peter; Kleiven, Svein

    2016-06-01

    There is some controversy regarding the effectiveness of helmets in preventing head injuries among cyclists. Epidemiological, experimental and computer simulation studies have suggested that helmets do indeed have a protective effect, whereas other studies based on epidemiological data have argued that there is no evidence that the helmet protects the brain. The objective of this study was to evaluate the protective effect of a helmet in single bicycle accident reconstructions using detailed finite element simulations. Strain in the brain tissue, which is associated with brain injuries, was reduced by up to 43% for the accident cases studied when a helmet was included. This resulted in a reduction of the risk of concussion of up to 54%. The stress to the skull bone went from fracture level of 80 MPa down to 13-16 MPa when a helmet was included and the skull fracture risk was reduced by up to 98% based on linear acceleration. Even with a 10% increased riding velocity for the helmeted impacts, to take into account possible increased risk taking, the risk of concussion was still reduced by up to 46% when compared with the unhelmeted impacts with original velocity. The results of this study show that the brain injury risk and risk of skull fracture could have been reduced in these three cases if a helmet had been worn. PMID:26974030

  18. Sirtuin 6 protects the heart from hypoxic damage

    SciTech Connect

    Maksin-Matveev, Anna; Kanfi, Yariv; Hochhauser, Edith; Isak, Ahuva; Cohen, Haim Y.; Shainberg, Asher

    2015-01-01

    Sirtuin 6 (SIRT6) is a protein associated with prolonged life expectancy. We investigated whether life extension is associated with cardioprotection against hypoxia. The proposed study is to develop approaches to reduce hypoxic damage through the use of the sirtuin pathway and to elucidate the mechanism involved. For that purpose we subjected cardiomyocytes from transgenic mice (TG) with over-expression of SIRT6, to hypoxic stress in cell cultures. We hypothesized that cardiomyocytes from transgenic mice subjected to prolonged hypoxia may release survival factors or fewer damage markers to protect them from hypoxic stress compared with wild type (WT) mice. Lactate dehydrogenase (LDH) and creatine kinase (CK) released to the medium and propidium iodide (PI) binding, were markedly decreased following hypoxia in TG cardiomyocytes. The protective mechanism of SIRT6 over-expression includes the activation of pAMPKα pathway, the increased protein level of B-cell lymphoma 2 (Bcl2), the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), the decrease of reactive oxygen species (ROS) and the reduction in the protein level of phospho-protein kinase B (pAkt) during hypoxia. Together, all these processes impede the necrosis/apoptosis pathways leading to the improved survival of cardiomyocytes following hypoxia, which might explain life extension. - Highlights: • Sirtuin 6 is a protein associated with prolonged life expectancy. • Over-expression of sirtuin 6 protects cardiocytes from hypoxia and oxidative stress. • Over-expression of sirtuin 6 activates the pAMPKα pathway and the Bcl2 expression. • Over-expression of sirtuin 6 decreases ROS formation and pAkt level during hypoxia. • These pathways protect cardiocytes from hypoxia and might explain lifespan extension.

  19. Nitroxide stable radicals protect beating cardiomyocytes against oxidative damage

    SciTech Connect

    Samuni, A.; Winkelsberg, D.; Pinson, A.; Hahn, S.M.; Mitchell, J.B.; Russo, A. )

    1991-05-01

    The protective effect of stable nitroxide radicals against oxidative damage was studied using cardiomyocyte cultures obtained from newborn rats. Monolayered cardiomyocytes were exposed to H{sub 2}O{sub 2} and the effect on spontaneous beating and leakage of LDH was determined. Hydrogen peroxide irreversibly blocked rhythmic beating and resulted in a significant membrane injury as shown by release of LDH. The injury was prevented by catalase which removes H{sub 2}O{sub 2} and by cell-permeable, metal-chelating agents such as desferrioxamine or bipyridine. In contrast, reagents which are excluded from the cell such as superoxide dismutase or DTPA did not protect the cells against H{sub 2}O{sub 2}. Five- and six-membered ring, stable nitroxide radicals which have previously been shown to chemically act as low-molecular weight, membrane-permeable, SOD-mimetic compounds provided full protection. The nitroxides prevented leakage of LDH and preserved normal cardiomyocyte contractility, presumably by intercepting intracellular O{sub 2}-radicals. Alternatively, protection may result through nitroxides reacting with reduced transition metal ions or by detoxifying secondary organic radicals.

  20. Antioxidant and DNA damage protection potentials of selected phenolic acids.

    PubMed

    Sevgi, Kemal; Tepe, Bektas; Sarikurkcu, Cengiz

    2015-03-01

    In this study, ten different phenolic acids (caffeic, chlorogenic, cinnamic, ferulic, gallic, p-hydroxybenzoic, protocatechuic, rosmarinic, syringic, and vanillic acids) were evaluated for their antioxidant and DNA damage protection potentials. Antioxidant activity was evaluated by using four different test systems named as β-carotene bleaching, DPPH free radical scavenging, reducing power and chelating effect. In all test systems, rosmarinic acid showed the maximum activity potential, while protocatechuic acid was determined as the weakest antioxidant in β-carotene bleaching, DPPH free radical scavenging, and chelating effect assays. Phenolic acids were also screened for their protective effects on pBR322 plasmid DNA against the mutagenic and toxic effects of UV and H2O2. Ferulic acid was found as the most active phytochemical among the others. Even at the lowest concentration value (0.002 mg/ml), ferulic acid protected all of the bands in the presence of H2O2 and UV. It is followed by caffeic, rosmarinic, and vanillic acids. On the other hand, cinnamic acid (at 0.002 mg/ml), gallic acid (at 0.002 mg/ml), p-hydroxybenzoic acid (at 0.002 and 0.004 mg/ml), and protocatechuic acid (at 0.002 and 0.004 mg/ml) could not protect plasmid DNA. PMID:25542528

  1. Electrochemically reduced water protects neural cells from oxidative damage.

    PubMed

    Kashiwagi, Taichi; Yan, Hanxu; Hamasaki, Takeki; Kinjo, Tomoya; Nakamichi, Noboru; Teruya, Kiichiro; Kabayama, Shigeru; Shirahata, Sanetaka

    2014-01-01

    Aging-related neurodegenerative disorders are closely associated with mitochondrial dysfunction and oxidative stresses and their incidence tends to increase with aging. Brain is the most vulnerable to reactive species generated by a higher rate of oxygen consumption and glucose utilization compared to other organs. Electrochemically reduced water (ERW) was demonstrated to scavenge reactive oxygen species (ROS) in several cell types. In the present study, the protective effect of ERW against hydrogen peroxide (H2O2) and nitric oxide (NO) was investigated in several rodent neuronal cell lines and primary cells. ERW was found to significantly suppress H2O2 (50-200 μM) induced PC12 and SFME cell deaths. ERW scavenged intracellular ROS and exhibited a protective effect against neuronal network damage caused by 200 μM H2O2 in N1E-115 cells. ERW significantly suppressed NO-induced cytotoxicity in PC12 cells despite the fact that it did not have the ability to scavenge intracellular NO. ERW significantly suppressed both glutamate induced Ca(2+) influx and the resulting cytotoxicity in primary cells. These results collectively demonstrated for the first time that ERW protects several types of neuronal cells by scavenging ROS because of the presence of hydrogen and platinum nanoparticles dissolved in ERW. PMID:25383141

  2. Sleep protects excitatory cortical circuits against oxidative damage.

    PubMed

    Schulze, Georg

    2004-01-01

    Activity in excitatory cortical pathways increases the oxidative metabolism of the brain and the risk of oxidative damage. Oxyradicals formed during periods of activity are mopped up by neural pools of nuclear factor kappa-B resulting in their activation and translocation to cell nuclei. During waking hours, glucocorticoids inhibit transactivation by nuclear factor kappa-B, increase central norepinephrine release, and elevate expression of prostaglandin D2. The build-up of nuclear factor kappa-B and prostaglandin D2 produces sleep pressures leading to sleep onset, normally gated by circadian melatonin release. During slow wave sleep nuclear factor kappa-B induces transcription of synaptogenic and antioxidant products and synaptic remodeling follows. Synaptically remodeled neural circuits have modified conductivity patterns and timescales and need to be resynchronized with existing unmodified neural circuits. The resynchronization process, mediated by theta rhythm, occurs during rapid eye movement sleep and is orchestrated from pontine centers. Resynchronization of remodeled neural circuits produces dreams. The waking state results upon successful resynchronization. Rapid eye movement sleep deprivation results in a lack of resynchronization and leads to cognitive inefficiencies. The model presented here proposes that the primary purpose of sleep is to protect cortical circuits against oxidative damage by reducing cortical activity and by remodeling and resynchronizing cortical circuits during this period of reduced activity to sustain new patterns of activation more effectively.

  3. Fullerene derivatives protect endothelial cells against NO-induced damage

    NASA Astrophysics Data System (ADS)

    Lao, Fang; Li, Wei; Han, Dong; Qu, Ying; Liu, Ying; Zhao, Yuliang; Chen, Chunying

    2009-06-01

    Functional fullerene derivatives have been demonstrated with potent antioxidation properties. Nitric oxide (NO) is a free radical that plays a part in leading to brain damage when it is accumulated to a high concentration. The possible scavenging activity of NO by the hydroxylated fullerene derivative C60(OH)22 and malonic acid derivative C60(C(COOH)2)2 was investigated using primary rat brain cerebral microvessel endothelial cells (CMECs). Results demonstrate that sodium nitroprusside (SNP), used as an NO donor, caused a marked decrease in cell viability and an increase in apoptosis. However, fullerene derivatives can remarkably protect against the apoptosis induced by NO assault. In addition, fullerene derivatives can also prevent NO-induced depolymerization of cytoskeleton and damage of the nucleus and accelerate endothelial cell repair. Further investigation shows that the sudden increase of the intercellular reactive oxygen species (ROS) induced by NO was significantly attenuated by post-treatment with fullerene derivatives. Our results suggest that functional fullerene derivatives are potential applications for NO-related disorders.

  4. Liposomal Antioxidants for Protection against Oxidant-Induced Damage

    PubMed Central

    Suntres, Zacharias E.

    2011-01-01

    Reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress. PMID:21876690

  5. Ascorbic acid (AA) metabolism in protection against radiation damage

    SciTech Connect

    Rose, R.C.; Koch, M.J.

    1986-03-05

    The possibility is considered that AA protects tissues against radiation damage by scavenging free radicals that result from radiolysis of water. A physiologic buffer (pH 6.7) was incubated with /sup 14/C-AA and 1 mM thiourea (to slow spontaneous oxidation of AA). Aliquots were assayed by HPLC and scintillation spectrometry to identify the /sup 14/C-label. Samples exposed to Cobalt-60 radiation had a half time of AA decay of < 3 minutes compared with nonirradiated samples (t/sub 1/2/ > 30 minutes) indicating that AA scavenges radiation-induced free radicals and forms the ascorbate free radical (AFR). Pairs of /sup 14/C-AFR disproportionate, with the net effect of /sup 14/C-dehydroascorbic acid formation from /sup 14/C-AA. Having established that AFR result from ionizing radiation in an aqueous solution, the possibility was evaluated that a tissue factor reduces AFR. Cortical tissue from the kidneys of male rats was minced, homogenized in buffer and centrifuged at 8000 xg. The supernatant was found to slow the rate of radiation-induced AA degradation by > 90% when incubated at 23/sup 0/C in the presence of 15 ..mu..M /sup 14/C-AA. Samples of supernatant maintained at 100/sup 0/C for 10 minutes or precipitated with 5% PCA did not prevent radiation-induced AA degradation. AA may have a specific role in scavenging free radicals generated by ionizing radiation and thereby protect body tissues.

  6. Carbonic Anhydrase Protects Fatty Liver Grafts against Ischemic Reperfusion Damage

    PubMed Central

    Bejaoui, Mohamed; Pantazi, Eirini; De Luca, Viviana; Panisello, Arnau; Folch-Puy, Emma; Hotter, Georgina; Capasso, Clemente; T. Supuran, Claudiu; Rosselló-Catafau, Joan

    2015-01-01

    Carbonic anhydrases (CAs) are ubiquitous metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton. CAs are involved in numerous physiological and pathological processes, including acid-base homeostasis, electrolyte balance, oxygen delivery to tissues and nitric oxide generation. Given that these processes are found to be dysregulated during ischemia reperfusion injury (IRI), and taking into account the high vulnerability of steatotic livers to preservation injury, we hypothesized a new role for CA as a pharmacological agent able to protect against ischemic damage. Two different aspects of the role of CA II in fatty liver grafts preservation were evaluated: 1) the effect of its addition to Institut Georges Lopez (IGL-1) storage solution after cold ischemia; 2) and after 24h of cold storage followed by two hours of normothermic ex-vivo perfusion. In all cases, liver injury, CA II protein concentration, CA II mRNA levels and CA II activity were determined. In case of the ex-vivo perfusion, we further assessed liver function (bile production, bromosulfophthalein clearance) and Western blot analysis of phosphorylated adenosine monophosphate activated protein kinase (AMPK), mitogen activated protein kinases family (MAPKs) and endoplasmic reticulum stress (ERS) parameters (GRP78, PERK, IRE, eIF2α and ATF6). We found that CA II was downregulated after cold ischemia. The addition of bovine CA II to IGL-1 preservation solution efficiently protected steatotic liver against cold IRI. In the case of reperfusion, CA II protection was associated with better function, AMPK activation and the prevention of ERS and MAPKs activation. Interestingly, CA II supplementation was not associated with enhanced CO2 hydration. The results suggest that CA II modulation may be a promising target for fatty liver graft preservation. PMID:26225852

  7. Characterization of Space Shuttle External Tank Thermal Protection System (TPS) Materials in Support of the Columbia Accident Investigation

    NASA Technical Reports Server (NTRS)

    Wingard, Charles D.

    2004-01-01

    NASA suffered the loss of the seven-member crew of the Space Shuttle Columbia on February 1, 2003 when the vehicle broke apart upon re-entry to the Earth's atmosphere. The final report of the Columbia Accident Investigation Board (CAIB) determined that the accident was caused by a launch ascent incident-a suitcase-sized chunk of insulating foam on the Shuttle's External Tank (ET) broke off, and moving at almost 500 mph, struck an area of the leading edge of the Shuttle s left wing. As a result, one or more of the protective Reinforced Carbon-Carbon (RCC) panels on the wing leading edge were damaged. Upon re-entry, superheated air approaching 3,000 F breached the wing damage and caused the vehicle breakup and loss of crew. The large chunk of insulating foam that broke off during the Columbia launch was determined to come from the so-called bipod ramp area where the Shuttle s orbiter (containing crew) is attached to the ET. Underneath the foam in the bipod ramp area is a layer of TPS that is a cork-filled silicone rubber composite. In March 2003, the NASA Marshall Space Flight Center (MSFC) in Huntsville, Alabama received cured samples of the foam and composite for testing from the Michoud Assembly Facility (MAF) in New Orleans, Louisiana. The MAF is where the Shuttle's ET is manufactured. The foam and composite TPS materials for the ET have been well characterized for mechanical property data at the super-cold temperatures of the liquid oxygen and hydrogen fuels used in the ET. However, modulus data on these materials is not as well characterized. The TA Instruments 2980 Dynamic Mechanical Analyzer (DMA) was used to determine the modulus of the two TPS materials over a range of -145 to 95 C in the dual cantilever bending mode. Multi-strain, fixed frequency DMA tests were followed by multi-frequency, fixed strain tests to determine the approximate bounds of linear viscoelastic behavior for the two materials. Additional information is included in the original extended

  8. [Health protection after the Chernobyl accident. The relation of costs and reduction of radioactive dosage level].

    PubMed

    Strand, P; Reitan, J B; Harbitz, O; Brynildsen, L

    1990-01-30

    This article describes the nutritional measures introduced to protect health after the Chernobyl accident, and the associated costs. The total value of the reindeer meat, mutton, lamb and goat meat saved as a result of such measures in 1987 amounted to approx. NOK 250 million. The measures cost approx. NOK 60 million. The resulting reduction in the radiation dose level to which the population was exposed was 450 manSv. In 1988, mutton/lamb and goat meat valued at approx. NOK 310 million was saved from condemnation by similar measures, which cost approx. NOK 50 million. The resulting dose level reduction was approx. 200 manSv. The relationship (cost/benefit ratio) between the overall cost of the measures taken to reduce radioactivity levels in food and the dose level reduction achieved was acceptable.

  9. Protective Effect of Folic Acid on Oxidative DNA Damage

    PubMed Central

    Guo, Xiaojuan; Cui, Huan; Zhang, Haiyang; Guan, Xiaoju; Zhang, Zheng; Jia, Chaonan; Wu, Jia; Yang, Hui; Qiu, Wenting; Zhang, Chuanwu; Yang, Zuopeng; Chen, Zhu; Mao, Guangyun

    2015-01-01

    < 0.001). Test of interaction between hypercholesterolemia and FA supplementation on urinary 8-OHdG reduction was significant (P = 0.001). The present study demonstrates that FA fortification is independently linked to the reduction of urinary 8-OHdG/Cr in a dose-related pattern, which suggests that FA is beneficial to protect against oxidative damage to DNA. This effect is apparently stronger in those with hypercholesterolemia. The authors provide a new insight into the prevention and reversal of oxidative DNA damage. PMID:26559255

  10. Determination of possible damage/degradation of the Sandia National Laboratories Personal Nuclear Accident Dosimeter (PNAD).

    SciTech Connect

    Potter, Charles Augustus; Ward, Dann C.

    2008-05-01

    This report describes the results of an inspection performed on the existing stock of SNL Personal Nuclear Accident Dosimeters (PNADs). The current stock is approximately 20 years old, and has not been examined since their initial acceptance. A small random sample of PNADs were opened (a destructive process) and the contents visually examined. Sample contents were not degraded and indicate that the existing stock of SNL PNADs is acceptable for continued use.

  11. Protection against radiation induced damage to spermatogenesis by Podophyllum hexandrum.

    PubMed

    Samanta, Namita; Goel, H C

    2002-07-01

    Aqueous extract of rhizome of Podophyllum hexandrum (RP-1) has been found to render protection against lethal whole body irradiation (10 Gy), damage to haemopoietic and gastrointestinal tissue etc. in mice. In order to assess its suitability from clinical point of view its effects were investigated on male germinal tissue in mice. Swiss albino strain 'A' male mice (10-12 weeks) were exposed to varied radiation doses (0.5, 2.0, 5.0 and 10 Gy) with and without 200 mg/kg b.w. of RP-1 and sacrificed at different time periods (10, 35 and 70 days) to collect the tissue. Administration of RP-1, 2 h before irradiation rendered a significant increase in the testis weight, repopulating tubules, resting primary spermatocytes, stem cell survival index, sperm counts and reduction in abnormalities of sperm morphology, at all the time periods studied here. RP-1 treatment alone did not generate any adverse effects. These results reveal that RP-1, if put to clinical application, will not be harmful to the testicular system.

  12. Modified hydroxyethyl starch protects cells from oxidative damage.

    PubMed

    Filippov, Sergey K; Sergeeva, Olga Yu; Vlasov, Petr S; Zavyalova, Margarita S; Belostotskaya, Galina B; Garamus, Vasil M; Khrustaleva, Raisa S; Stepanek, Petr; Domnina, Nina S

    2015-12-10

    This article describes the synthesis of novel starch-antioxidant conjugates, which show great potential for biomedical applications to protect cells from oxidative damage. These conjugates were synthesized by the modification of a hydroxyethyl starch (molecular weight=200,000g/mol) with various sterically hindered phenols that differ in radical scavenging activity. They possess substantial radical scavenging activity toward a model free radical. It was found that the polymer conjugate conformation depends on the antioxidant structure and degree of substitution. We constructed the complete conformational phase behavior for the polymers with increasing degrees of substitution from small-angle neutron scattering data. It was observed that the conjugate conformation changes are the result of water shifting from a thermodynamically favorable solvent to an unfavorable one, a process that then leads to compaction of the conjugate. We selected the conjugates that possess high substitution degree but still exhibit coil conformation for biological studies. The high efficiency of the conjugates was confirmed by different in vitro (hypotonic hemolysis of erythrocytes/osmotic resistance of erythrocytes and the change of [Ca(2+)]i inside freshly isolated cardiomyocytes) and in vivo (acute hemorrhage/massive blood loss) methods. PMID:26428130

  13. 49 CFR 192.355 - Customer meters and regulators: Protection from damage.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... damage. (a) Protection from vacuum or back pressure. If the customer's equipment might create either a vacuum or a back pressure, a device must be installed to protect the system. (b) Service regulator...

  14. 49 CFR 192.355 - Customer meters and regulators: Protection from damage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... damage. (a) Protection from vacuum or back pressure. If the customer's equipment might create either a vacuum or a back pressure, a device must be installed to protect the system. (b) Service regulator...

  15. Precursors to potential severe core damage accidents. A status report, 1982--1983

    SciTech Connect

    Forester, J.A.; Mitchell, D.B.; Whitehead, D.W.

    1997-04-01

    This study is a continuation of earlier work that evaluated 1969-1981 and 1984-1994 events affecting commercial light-water reactors. One-hundred nine operational events that affected 51 reactors during 1982 and 1983 and that are considered to be precursors to potential severe core damage are described. All these events had conditional probabilities of subsequent severe core damage greater than or equal to 1.0 x 10{sup {minus}6}. These events were identified by first computer screening the 1982-83 licensee event reports from commercial light-water reactors to select events that could be precursors to core damage. Candidates underwent engineering evaluation that identified, analyzed, and documented the precursors. This report discusses the general rationale for the study, the selection and documentation of events as precursors, and the estimation of conditional probabilities of subsequent severe core damage for the events.

  16. Radiological Protection Issues Arising During and After the Fukushima Nuclear Reactor Accident-Memorandum of TG 84 of ICRP.

    PubMed

    Weiss, Wolfgang

    2016-09-01

    Observations and lessons identified after the Fukushima accident have been collected and assessed by ICRP Task Group 84. Together with the observations of other expert organizations, they are being used to further develop the current system of protection. While many of the established protection criteria remain valid, improvements are needed in three areas. Key issues related to the need of planning for long-term protective actions (criteria for returning home, dealing with waste) have to be implemented as important elements of the national protection strategies during the preparedness stage. The justification of disruptive protective actions and the protection of vulnerably groups of the population need to be reconsidered to avoid unpleasant imbalances and outcomes. The coexistence of radiation-induced health effects and health effects with social determinants requires consideration of both aspects in decision-making and response.

  17. Radiological Protection Issues Arising During and After the Fukushima Nuclear Reactor Accident-Memorandum of TG 84 of ICRP.

    PubMed

    Weiss, Wolfgang

    2016-09-01

    Observations and lessons identified after the Fukushima accident have been collected and assessed by ICRP Task Group 84. Together with the observations of other expert organizations, they are being used to further develop the current system of protection. While many of the established protection criteria remain valid, improvements are needed in three areas. Key issues related to the need of planning for long-term protective actions (criteria for returning home, dealing with waste) have to be implemented as important elements of the national protection strategies during the preparedness stage. The justification of disruptive protective actions and the protection of vulnerably groups of the population need to be reconsidered to avoid unpleasant imbalances and outcomes. The coexistence of radiation-induced health effects and health effects with social determinants requires consideration of both aspects in decision-making and response. PMID:27451427

  18. Precursors to potential severe core damage accidents: 1995 A status report

    SciTech Connect

    Belles, R.J.; Cletcher, J.W.; Copinger, D.A.

    1997-04-01

    Ten operational events that affected 10 commercial light-water reactors during 1995 and that are considered to be precursors to potential severe core damage are described. All these events had conditional probabilities of subsequent severe core damage greater than or equal to 1.0 x 10{sup {minus}6}. These events were identified by first computer-screening the 1995 licensee event reports from commercial light-water reactors to identify those events that could potentially be precursors. Candidate precursors were selected and evaluated in a process similar to that used in previous assessments. Selected events underwent engineering evaluation that identified, analyzed, and documented the precursors. Other events designated by the Nuclear Regulatory Commission (NRC) also underwent a similar evaluation. Finally, documented precursors were submitted for review by licensees and NRC headquarters and regional offices to ensure the plant design and its response to the precursor were correctly characterized. This study is a continuation of earlier work, which evaluated 1969-1981 and 1984-1994 events. The report discusses the general rationale for this study, the selection and documentation of events as precursors, and the estimation of conditional probabilities of subsequent severe core damage for the events.

  19. Precursors to potential severe core damage accidents: 1994, a status report. Volume 22: Appendix I

    SciTech Connect

    Belles, R.J.; Cletcher, J.W.; Copinger, D.A.; Vanden Heuvel, L.N.; Dolan, B.W.; Minarick, J.W. |

    1995-12-01

    Nine operational events that affected eleven commercial light-water reactors (LWRs) during 1994 and that are considered to be precursors to potential severe core damage are described. All these events had conditional probabilities of subsequent severe core damage greater than or equal to 1.0 {times} 10{sup {minus}6}. These events were identified by computer-screening the 1994 licensee event reports from commercial LWRs to identify those that could be potential precursors. Candidate precursors were then selected and evaluated in a process similar to that used in previous assessments. Selected events underwent engineering evaluation that identified, analyzed, and documented the precursors. Other events designated by the Nuclear Regulatory Commission (NRC) also underwent a similar evaluation. Finally, documented precursors were submitted for review by licensees and NRC headquarters and regional offices to ensure that the plant design and its response to the precursor were correctly characterized. This study is a continuation of earlier work, which evaluated 1969--1981 and 1984--1993 events. The report discusses the general rationale for this study, the selection and documentation of events as precursors, and the estimation of conditional probabilities of subsequent severe core damage for events. This document is bound in two volumes: Vol. 21 contains the main report and Appendices A--H; Vol. 22 contains Appendix 1.

  20. DNA damage by smoke: Protection by turmeric and other inhibitors of ROS

    SciTech Connect

    Srinivas, L.; Shalini, V.K. )

    1991-01-01

    Twigs-dry leaves smoke condensate (TDS), as a source of clastogenic ROS and carcinogenic PAH, was investigated for its in vitro DNA-damaging effect in calf thymus DNA and human peripheral lymphocytes. An aqueous turmeric component--Aq.T--with an established antioxidant activity, was tested as a DNA protectant. TDS induced 13-fold damage to calf thymus DNA as judged by the emergence of a DNA damage specific, fluorescent product (em: 405 nm). Aq.T at 800 ng/microL extended 69% protection to calf thymus DNA and was comparable to the other protectants such as curcumin, BHA, vitamin E, SOD, and CAT. In human peripheral lymphocytes, TDS induced extensive DNA damage in comparison with the tumor promoter TPA, as judged by FADU. Aq.T at 300 ng/microL extended 90% protection to human lymphocyte DNA against TDS-induced damage, and was more effective than the other protectants--DABCO, D-mannitol, sodium benzoate, vitamin E (ROS quenchers), SOD, CAT (antioxidant enzymes), tannic acid, flufenamic acid, BHA, BHT, n-PG, curcumin and quercetin (antioxidants). Aq.T offered 65% protection to human lymphocyte DNA against TPA-induced damage and was comparable to SOD. The above results indicate that TDS induces substantial DNA damage in calf thymus DNA and human lymphocytes and Aq.T is an efficient protectant.

  1. Assessment of Spatial Unevenness of Road Accidents Severity as Instrument of Preventive Protection from Emergency Situations in Road Complex

    NASA Astrophysics Data System (ADS)

    Petrov, A.; Petrova, D.

    2016-08-01

    Emergency situations in road complex are road traffic accidents (RA) with severe consequences. These are incidents connected with the death and injury of large number of people. The most common reasons for this are the collision of three or more cars, the collision of buses with trains at railroad crossings, the fall of the buses in the mountain gorge, and other similar cases. Is it possible to predict such events? How to build a preventive protection against such emergencies? We have to understand that emergencies in a road complex are qualitative expression of the quantitative processes that characterize the general state of road safety in the region. In this regard, at the level of state monitoring of emergency situations it is important to understand in general - in which region the situation is more complicated and in which is more favorable. This knowledge helps to more efficiently reallocate resources intended to solve the problems of road safety provision. The consequence of this is improvement of the quality of preventive protection from the emergencies in the road complex. The article presents quantitative values of severity of accidents in the Russian Federation regions and the Pareto chart distribution of cumulates of the accident severity for the Russian Federation. On the basis of the complex assessment of the spatial non-uniformity of the accident severity results it offers two important recommendations, implementation of which will alleviate the issue of formation of emergency situations in the road of the Russian Federation on the basis of the complex assessment of the spatial nonuniformity of the accident severity results.

  2. [Medico-criminal examination of damages to clothes in flight accidents].

    PubMed

    Zviagin, V N; Alpatov, I M

    2005-01-01

    Examination of cloths is a permanent sphere in the practice of forensic-medical expert and an indispensable expertise stage providing for decision-making on the key issues set before the expert. Although, the examination of cloth in forensic-medical expertise has been productive, research in this field slowed down during the recent decades; definition of new sets of evident informative signs has been also suspended. The methodological potentialities of examination of cloths items were demonstrated by examples of aviation incidents because such incidents reflect the principle variations of impacts, i.e. blow, explosion, fire, compression and chemical factors etc., which are subject to examination in the forensic-medical practice. Identification of mechanism causing damage and other signs on cloths helps a lot the forensic-medical expert in solving quite a number of issues related with circumstances of an incident and with a nature of an impact encountered by a person.

  3. [Orofacial injuries in skateboard accidents].

    PubMed

    Frohberg, U; Bonsmann, M

    1992-04-01

    In a clinical study, 25 accidents involving injuries by a fall with a skateboard were investigated and classified in respect of epidemiology, accident mechanism and injury patterns in the facial region. Accident victims are predominantly boys between 7 and 9 years of age. A multiple trauma involving the teeth and the dental system in general and the soft parts of the face is defined as a characteristic orofacial injury pattern in skateboard accidents. The high proportion of damage to the front teeth poses problems of functional and aesthetic rehabilitation necessitating long-term treatment courses in children and adolescents. Effective prevention of facial injuries may be possible by evolving better facial protection systems and by creating areas of playgrounds where skateboarders can practise safely.

  4. Present concept on current water protection and remediation activities for the areas contaminated by the 1986 Chernobyl accident.

    PubMed

    Voitsekhovitch, O; Prister, B; Nasvit, O; Los, I; Berkovski, V

    1996-07-01

    The results of radiation monitoring data and migration pathway analysis of water bodies within areas affected by the 1986 Chernobyl accident provide a unique opportunity for decision-makers working in other extensively contaminated regions to optimize their approaches to surface and groundwater protection. Most engineering measures within the Chernobyl 30-km exclusion zone were focused on preventing secondary contamination of surface and groundwater from entering the Pripyat River and the Kiev Reservoir. However, implementation of these measures required huge financial and human resources. Therefore, lessons about post-accidental water protection activities can be learned from the Chernobyl example. PMID:8655324

  5. Present concept on current water protection and remediation activities for the areas contaminated by the 1986 Chernobyl accident

    SciTech Connect

    Voitsekhovitch, O.; Prister, B.; Nasvit, O.; Los, I.; Berkovski, V.

    1996-07-01

    The results of radiation monitoring data and migration pathway analysis of water bodies within areas affected by the 1986 Chernobyl accident provide a unique opportunity for decision-makers working in other extensively contaminated regions to optimize their approaches to surface and groundwater protection. Most engineering measures within the Chernobyl 30-km exclusion zone were focused on preventing secondary contamination of surface and groundwater from entering the Pripyat River and the Kiev Reservoir. However, implementation of these measures required huge financial and human resources. Therefore, lessons about post-accidental water protection activities can be learned form the Chernobyl example. 9 refs., 9 figs.

  6. Present concept on current water protection and remediation activities for the areas contaminated by the 1986 Chernobyl accident.

    PubMed

    Voitsekhovitch, O; Prister, B; Nasvit, O; Los, I; Berkovski, V

    1996-07-01

    The results of radiation monitoring data and migration pathway analysis of water bodies within areas affected by the 1986 Chernobyl accident provide a unique opportunity for decision-makers working in other extensively contaminated regions to optimize their approaches to surface and groundwater protection. Most engineering measures within the Chernobyl 30-km exclusion zone were focused on preventing secondary contamination of surface and groundwater from entering the Pripyat River and the Kiev Reservoir. However, implementation of these measures required huge financial and human resources. Therefore, lessons about post-accidental water protection activities can be learned from the Chernobyl example.

  7. Metal Oxide Silicon /MOS/ transistors protected from destructive damage by wire

    NASA Technical Reports Server (NTRS)

    Deboo, G. J.; Devine, E. J.

    1966-01-01

    Loop of flexible, small diameter, nickel wire protects metal oxide silicon /MOS/ transistors from a damaging electrostatic potential. The wire is attached to a music-wire spring, slipped over the MOS transistor case, and released so the spring tensions the wire loop around all the transistor leads, shorting them together. This allows handling without danger of damage.

  8. Cytogenetic damage in lymphocytes for the purpose of dose reconstruction: a review of three recent radiation accidents.

    PubMed

    Wojcik, A; Gregoire, E; Hayata, I; Roy, L; Sommer, S; Stephan, G; Voisin, P

    2004-01-01

    The analysis of chromosomal aberrations in peripheral blood of radiation accident victims is an established method of biological dosimetry. The dose estimate on the basis of an in vitro calibration curve is straightforward when the radiation exposure is homogeneous and the analysis not delayed. In recent years three radiation accidents occurred, where the irradiation or sampling conditions precluded a simple estimation of the dose. During the Georgian accident soldiers carried in their pockets small sources of 137Cs leading to partial and protracted body exposures. During the Tokai-mura accident, three employees involved in the process of 235U enrichment were exposed to very high doses of gamma rays and neutrons. During the Bialystok accident, five patients with breast cancer undergoing radiotherapy were exposed to a single dose of electrons which reached about 100 Gy. In the present paper the approaches chosen to estimate, by cytogenetic methods, the doses absorbed by the people involved in the accidents are described. PMID:15162038

  9. Cytogenetic damage in lymphocytes for the purpose of dose reconstruction: a review of three recent radiation accidents.

    PubMed

    Wojcik, A; Gregoire, E; Hayata, I; Roy, L; Sommer, S; Stephan, G; Voisin, P

    2004-01-01

    The analysis of chromosomal aberrations in peripheral blood of radiation accident victims is an established method of biological dosimetry. The dose estimate on the basis of an in vitro calibration curve is straightforward when the radiation exposure is homogeneous and the analysis not delayed. In recent years three radiation accidents occurred, where the irradiation or sampling conditions precluded a simple estimation of the dose. During the Georgian accident soldiers carried in their pockets small sources of 137Cs leading to partial and protracted body exposures. During the Tokai-mura accident, three employees involved in the process of 235U enrichment were exposed to very high doses of gamma rays and neutrons. During the Bialystok accident, five patients with breast cancer undergoing radiotherapy were exposed to a single dose of electrons which reached about 100 Gy. In the present paper the approaches chosen to estimate, by cytogenetic methods, the doses absorbed by the people involved in the accidents are described.

  10. Characterization of Space Shuttle Thermal Protection System (TPS) Materials for Return-to-Flight following the Shuttle Columbia Accident Investigation

    NASA Technical Reports Server (NTRS)

    Wingard, Doug

    2006-01-01

    During the Space Shuttle Columbia Accident Investigation, it was determined that a large chunk of polyurethane insulating foam (= 1.67 lbs) on the External Tank (ET) came loose during Columbia's ascent on 2-1-03. The foam piece struck some of the protective Reinforced Carbon-Carbon (RCC) panels on the leading edge of Columbia's left wing in the mid-wing area. This impact damaged Columbia to the extent that upon re-entry to Earth, superheGed air approaching 3,000 F caused the vehicle to break up, killing all seven astronauts on board. A paper after the Columbia Accident Investigation highlighted thermal analysis testing performed on External Tank TPS materials (1). These materials included BX-250 (now BX-265) rigid polyurethane foam and SLA-561 Super Lightweight Ablator (highly-filled silicone rubber). The large chunk of foam from Columbia originated fiom the left bipod ramp of the ET. The foam in this ramp area was hand-sprayed over the SLA material and various fittings, allowed to dry, and manually shaved into a ramp shape. In Return-to-Flight (RTF) efforts following Columbia, the decision was made to remove the foam in the bipod ramp areas. During RTF efforts, further thermal analysis testing was performed on BX-265 foam by DSC and DMA. Flat panels of foam about 2-in. thick were sprayed on ET tank material (aluminum alloys). The DSC testing showed that foam material very close to the metal substrate cured more slowly than bulk foam material. All of the foam used on the ET is considered fully cured about 21 days after it is sprayed. The RTF culminated in the successful launch of Space Shuttle Discovery on 7-26-05. Although the flight was a success, there was another serious incident of foam loss fiom the ET during Shuttle ascent. This time, a rather large chunk of BX-265 foam (= 0.9 lbs) came loose from the liquid hydrogen (LH2) PAL ramp, although the foam did not strike the Shuttle Orbiter containing the crew. DMA testing was performed on foam samples taken fiom

  11. Genomic profiles of damage and protection in human intracerebral hemorrhage

    PubMed Central

    Carmichael, S Thomas; Vespa, Paul M; Saver, Jeffery L; Coppola, Giovanni; Geschwind, Daniel H; Starkman, Sidney; Miller, Chad M; Kidwell, Chelsea S; Liebeskind, David S; Martin, Neil A

    2009-01-01

    Intracerebral hemorrhage (ICH) produces a high rate of death and disability. The molecular mechanisms of damage in perihematomal tissue in humans have not been systematically characterized. This study determines the gene expression profile and molecular networks that are induced in human perihematomal tissue through molecular analysis of tissue obtained from endoscopic clot evacuation. Differentially expressed genes and their cellular origin were confirmed in a mouse model of ICH. A total of 624 genes showed altered regulation in human ICH. Bioinformatic analysis shows that these genes form interconnected networks of proinflammatory, anti-inflammatory, and neuronal signaling cascades. Intracerebral hemorrhage evokes coordinated upregulation of proinflammatory signaling through specific cytokines and chemokines and their downstream molecular pathways. Anti-inflammatory networks are also induced by ICH, including annexins A1 and A2 and transforming growth factor beta (TGF β) and their intracellular cascades. Intracerebral hemorrhage downregulates many neuronal signaling systems, including the N-methyl-d-aspartic acid (NMDA) receptor complex and membrane ion channels. Select portions of these molecular networks were confirmed in the mouse, and the proteins in a subset of these networks localized to subsets of neurons, oligodendrocytes, or leukocytes. These inflammatory and anti-inflammatory networks interact at several key points in neutrophil signaling, apoptotic cell death, and protease responses, and indicate that secondary damage in ICH activates opposing molecular systems. PMID:18628781

  12. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

    PubMed Central

    Colombo, N.B.R.; Rangel, M.P.; Martins, V.; Hage, M.; Gelain, D.P.; Barbeiro, D.F.; Grisolia, C.K.; Parra, E.R.; Capelozzi, V.L.

    2015-01-01

    The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days) significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress. PMID:26200231

  13. Oxidant conditioning protects cartilage from mechanically induced damage.

    PubMed

    Ramakrishnan, Prem; Hecht, Benjamin A; Pedersen, Douglas R; Lavery, Matthew R; Maynard, Jerry; Buckwalter, Joseph A; Martin, James A

    2010-07-01

    Articular cartilage degeneration in osteoarthritis has been linked to abnormal mechanical stresses that are known to cause chondrocyte apoptosis and metabolic derangement in in vitro models. Evidence implicating oxidative damage as the immediate cause of these harmful effects suggests that the antioxidant defenses of chondrocytes might influence their tolerance for mechanical injury. Based on evidence that antioxidant defenses in many cell types are stimulated by moderate oxidant exposure, we hypothesized that oxidant preconditioning would reduce acute chondrocyte death and proteoglycan depletion in cartilage explants after exposure to abnormal mechanical stresses. Porcine cartilage explants were treated every 48 h with tert-butyl hydrogen peroxide (tBHP) at nonlethal concentrations (25, 100, 250, and 500 microM) for a varying number of times (one, two, or four) prior to a bout of unconfined axial compression (5 MPa, 1 Hz, 1800 cycles). When compared with untreated controls, tBHP had significant positive effects on post-compression viability, lactate production, and proteoglycan losses. Overall, the most effective regime was 100 microM tBHP applied four times. RNA analysis revealed significant effects of 100 microM tBHP on gene expression. Catalase, hypoxia-inducible factor-1alpha (HIF-1alpha), and glyceraldehyde 6-phosphate dehydrogenase (GAPDH) were significantly increased relative to untreated controls in explants treated four times with 100 microM tBHP, a regime that also resulted in a significant decrease in matrix metalloproteinase-3 (MMP-3) expression. These findings demonstrate that repeated exposure of cartilage to sublethal concentrations of peroxide can moderate the acute effects of mechanical stress, a conclusion supported by evidence of peroxide-induced changes in gene expression that could render chondrocytes more resistant to oxidative damage. PMID:20058262

  14. Establishment of new regulations for radiological protection for decontamination work involving radioactive fallout emitted by the Fukushima Daiichi APP accident.

    PubMed

    Yasui, Shojiro

    2013-01-01

    In response to the accident at the Fukushima Daiichi Atomic Power Plant (APP) on March 11, 2011, the Japanese government decided to carry out decontamination projects around the plant. For the radiological protection of the decontamination workers, the Japanese government needed to establish new regulations because the existing regulation did not fit into "existing exposure situations" in which radioactive sources were scattered and spread in a wide area around the plant. The new regulations aim to set the appropriate protection standards in accordance with the risk of the ambient dose rate, radioactivity concentration, and type of radio nucleolus resulting from the APP accident, which is equivalent to or more than the typical protection required in planned situations. To maintain practicability, the Japanese government employed a validated and simplified measurement methodology for the internal exposure, ambient dose rate, and radioactivity concentration, considering restrictions in human resources and shortages of supplies in the affected areas. The article also identifies key challenges which require further research. PMID:23915240

  15. Resveratrol Protects the Brain of Obese Mice from Oxidative Damage

    PubMed Central

    Rege, Shraddha D.; Kumar, Sruthi; Wilson, David N.; Tamura, Leslie; Geetha, Thangiah; Mathews, Suresh T.; Huggins, Kevin W.; Broderick, Tom L.; Babu, Jeganathan Ramesh

    2013-01-01

    Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a polyphenolic phytoalexin that exerts cardioprotective, neuroprotective, and antioxidant effects. Recently it has been shown that obesity is associated with an increase in cerebral oxidative stress levels, which may enhance neurodegeneration. The present study evaluates the neuroprotective action of resveratrol in brain of obese (ob/ob) mice. Resveratrol was administered orally at the dose of 25 mg kg−1 body weight daily for three weeks to lean and obese mice. Resveratrol had no effect on body weight or blood glucose levels in obese mice. Lipid peroxides were significantly increased in brain of obese mice. The enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and nonenzymatic antioxidants tocopherol, ascorbic acid, and glutathione were decreased in obese mice brain. Administration of resveratrol decreased lipid peroxide levels and upregulated the antioxidant activities in obese mice brain. Our findings indicate a neuroprotective effect of resveratrol by preventing oxidative damage in brain tissue of obese mice. PMID:24163719

  16. Treatment with spermidine protects chrysanthemum seedlings against salinity stress damage.

    PubMed

    Zhang, Naiyuan; Shi, Xiaomeng; Guan, Zhiyong; Zhao, Shuang; Zhang, Fei; Chen, Sumei; Fang, Weiming; Chen, Fadi

    2016-08-01

    Salinity-stressed plants of salinity sensitive ('Qx096') and tolerant ('Qx097') chrysanthemum cultivar were treated with a range of concentrations of spermidine (Spd). Plant performance, as indicated by various parameters associated with growth, was improved by the treatment, as was the tissue content of soluble protein and proline. The extent of both Na(+) accumulation and K(+) loss was reduced. Activity levels of the stress-related enzymes SOD, POD, APX and CAT were significantly increased and the production of malondialdehyde (MDA) decreased. The suggestion was that treatment with 1.5 mM Spd would be an effective means alleviating salinity-stress induced injury through its positive effect on photosynthetic efficiency, reactive oxygen species scavenging ability and the control of ionic balance and osmotic potential. Its protective capacity was more apparent in 'Qx096' than in 'Qx097'. PMID:27173095

  17. G6PD protects from oxidative damage and improves healthspan in mice

    PubMed Central

    Nóbrega-Pereira, Sandrina; Fernandez-Marcos, Pablo J.; Brioche, Thomas; Gomez-Cabrera, Mari Carmen; Salvador-Pascual, Andrea; Flores, Juana M.; Viña, Jose; Serrano, Manuel

    2016-01-01

    Reactive oxygen species (ROS) are constantly generated by cells and ROS-derived damage contributes to ageing. Protection against oxidative damage largely relies on the reductive power of NAPDH, whose levels are mostly determined by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Here, we report a transgenic mouse model with moderate overexpression of human G6PD under its endogenous promoter. Importantly, G6PD-Tg mice have higher levels of NADPH, lower levels of ROS-derived damage, and better protection from ageing-associated functional decline, including extended median lifespan in females. The G6PD transgene has no effect on tumour development, even after combining with various tumour-prone genetic alterations. We conclude that a modest increase in G6PD activity is beneficial for healthspan through increased NADPH levels and protection from the deleterious effects of ROS. PMID:26976705

  18. Polymyxin E Induces Rapid Paenibacillus polymyxa Death by Damaging Cell Membrane while Ca2+ Can Protect Cells from Damage

    PubMed Central

    Cai, Yuanning; Qin, Wangrong; Lin, Jianxun

    2015-01-01

    Polymyxin E, produced by Paenibacillus polymyxa, is an important antibiotic normally against Gram-negative pathogens. In this study, we found that polymyxin E can kill its producer P. polymyxa, a Gram-positive bacterium, by disrupting its cell membrane. Membrane damage was clearly revealed by detecting the leakage of intracellular molecules. The observation using scanning electron microscopy also supported that polymyxin E can destroy the cell membrane and cause an extensive cell surface alteration. On the other hand, divalent cations can give protection against polymyxin E. Compared with Mg2+, Ca2+ can more effectively alleviate polymyxin E-induced damage to the cell membrane, thus remarkably increasing the P. polymyxa survival. Our findings would shed light on a not yet described bactericidal mechanism of polymyxin E against Gram-positive bacteria and more importantly the nature of limited fermentation output of polymyxin E from P. polymyxa. PMID:26252512

  19. The protection of RIVERLIFE by mitigation of flood damages RIVERLIFE

    NASA Astrophysics Data System (ADS)

    Adler, M. J.

    2003-04-01

    The long-term development objective of the RIVERLIFE project is to contribute to sustainable human end economic development in the Timis-Bega river basin area as part of the Danube River Basin (DRB), through reinforcing the capacities of Romanian central and local authorities to develop effective mechanisms and tools for integrated river basin management in the Timis-Bega basin. The overall objective of the project is to assist the country in the EU enlargement and accession process to meet the EU requirements of water related Directives with emphasis on the EU Water Framework Directive (WFD). The specific objective of the project is to support the WFD implementation process at the level of a sub-unit within the limits of the DRB, through the development of a River Basin Management Plan (RBMP). The project will also facilitate the implementation of the Danube River Protection Convention (DRPC) as an essential element in the implementation of the Directive in the transboundary river basins. Expected outcomes in the recipient country consist of (i) responding to a real hazard problem, which affects the quality of life of many citizens, and (ii) improvement in the environmental conditions in the targeted areas. Flooding is one of the major natural hazards to human society and an important influence on social and economic development for Romania causing financially greater losses per annum on average than any other natural hazard. One key concept of the WFD is the coordination, organization and regulation of water management at the level of river basins. Therefore, river basin districts are shaped in such a way as to include not only the surface run-off through streams and rivers to the sea, but the total area of land and sea together with the associated groundwater and coastal waters. The concept allows even for the small river basins directly discharging into the sea to be combined into one river basin district. As a principle, the complex decisions on the use or

  20. Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

    SciTech Connect

    Zheng, Juanjuan; Zhang, Yu; Xu, Wentao; Luo, YunBo; Hao, Junran; Shen, Xiao Li; Yang, Xuan; Li, Xiaohong; Huang, Kunlun

    2013-04-15

    Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by

  1. Investigation of Stinson Beach Park storm damage and evaluation of alternative shore protection measures

    SciTech Connect

    Ecker, R.M.; Whelan, G.

    1984-07-01

    An investigation was made of storm damage during the winter of 1982-83 to the National Park Service's Stinson Beach Park. The investigation included an assessment of the storm damage, evaluation of physical processes contributing to the damage, subsequent beach recovery, and the feasibility of implementing shoreline protection measure to reduce future risk. During the winter of 1982-83, the beach was almost completely denuded of sand, wave overwash damaged the foredune, vegetation on the foredune was destroyed, and backshore flooding occurred. Two structures and a parking lot were endangered as the shoreline receded. Subsequent recovery of the park beach was rapid. By January 1982 sand had moved back onshore and a beach berm was beginning to reform. The foredune and dune vegetation received the only permanent damage. Four shoreline protection alternatives were evaluated. These include no action, dune development/enhancement, construction of a rock riprap revetment, and offshore installation of artificial seaweed. The first costs (estimated costs, excluding maintenance) range from about $90,000 to $475,000. The least-cost protection measure is riprap revetment, which protects the two structures and parking lot endangered during the 1982-83 winter storms. Construction of a foredune along the entire park beach is the highest cost protection measure. If no shore protection action measures are implemented, wave overwash of the foredune can be expected to occur on the average of every 2 to 3 years, and beach degradation, similar to that during the 1982-83 winter, can be expected to occur on the average of every 10 to 12 years. 12 references, 19 figures, 18 tables.

  2. Accident progression event tree analysis for postulated severe accidents at N Reactor

    SciTech Connect

    Wyss, G.D.; Camp, A.L.; Miller, L.A.; Dingman, S.E.; Kunsman, D.M. ); Medford, G.T. )

    1990-06-01

    A Level II/III probabilistic risk assessment (PRA) has been performed for N Reactor, a Department of Energy (DOE) production reactor located on the Hanford reservation in Washington. The accident progression analysis documented in this report determines how core damage accidents identified in the Level I PRA progress from fuel damage to confinement response and potential releases the environment. The objectives of the study are to generate accident progression data for the Level II/III PRA source term model and to identify changes that could improve plant response under accident conditions. The scope of the analysis is comprehensive, excluding only sabotage and operator errors of commission. State-of-the-art methodology is employed based largely on the methods developed by Sandia for the US Nuclear Regulatory Commission in support of the NUREG-1150 study. The accident progression model allows complex interactions and dependencies between systems to be explicitly considered. Latin Hypecube sampling was used to assess the phenomenological and systemic uncertainties associated with the primary and confinement system responses to the core damage accident. The results of the analysis show that the N Reactor confinement concept provides significant radiological protection for most of the accident progression pathways studied.

  3. Protective Effects of Extracts from Fructus rhodomyrti against Oxidative DNA Damage In Vitro and In Vivo

    PubMed Central

    Ke, Yuebin; Xu, Xinyun; Wu, Shuang; Huang, Juan; Misra, Hara; Li, Yunbo

    2013-01-01

    Objective. To evaluate the potential protective effects of extracts from Fructus rhodomyrti (FR) against oxidative DNA damage using a cellular system and the antioxidant ability on potassium bromate- (KBrO3-) mediated oxidative stress in rats. Methods. The effects of FR on DNA damage induced by hydrogen peroxide (H2O2) were evaluated by comet assay in primary spleen lymphocytes cultures. The effects of FR on the activities of SOD, CAT, and GPx and the levels of GSH, hydroperoxides, and 8-OHdG were determined in the plasma and tissues of rats treated with KBrO3. Results. FR was shown to effectively protect against DNA damage induced by H2O2  in vitro, and the maximum protective effect was observed when FR was diluted 20 times. Endogenous antioxidant status, namely, the activities of SOD, CAT, and GPx and the levels of GSH were significantly decreased in the plasma, the liver, and the kidney of the KBrO3-treated rats, while the pretreatment of FR prevented the decreases of these parameters. In addition, the pretreatment of FR was also able to prevent KBrO3-induced increases in the levels of hydroperoxides and 8-OHdG in the plasma, the liver, and the kidney in rats. Conclusions. Our findings suggested that FR might act as a chemopreventive agent with antioxidant properties offering effective protection against oxidative DNA damage in a concentration-dependent manner in vitro and in vivo. PMID:24089629

  4. Juglans mandshurica leaf extract protects skin fibroblasts from damage by regulating the oxidative defense system.

    PubMed

    Park, Gunhyuk; Jang, Dae Sik; Oh, Myung Sook

    2012-05-01

    Skin is mainly damaged by genetic and environmental factors such as ultraviolet light, xenobiotics, hormonal changes, heat, and smoking. ROS production is commonly involved in the pathogenesis of skin damage induced by these factors, causing skin aging, including wrinkling, by activating the metalloproteinases (MMP-1) that break down type I collagen (COL1A1). The walnut tree Juglans mandshurica MAX. (JM) is found in China, Siberia and Korea. JM has been reported to have various pharmacological activities, such as anti-tumor, anti-oxidative, and anti-bacterial effects. In the present study, we investigated the protective effect of JM leaf extract (JME) against oxidative stress in HS68 human skin fibroblasts. JME significantly and dose-dependently protected HS68 cells against H₂O₂-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Other assays demonstrated that JME protected HS68 cells by regulating ROS production and increasing levels of glutathione, heme oxygenase-1, and activated NF-E2-related factor 2. JME additionally prevented the elevation of MMP-1 and reduction of COL1A1 induced by H₂O₂. It also inhibited H₂O₂-induced phosphorylation of ERK, p38, and JNK. These results indicate that JME protects human skin fibroblasts from H₂O₂-induced damage by regulating the oxidative defense system.

  5. Derinat Protects Skin against Ultraviolet-B (UVB)-Induced Cellular Damage.

    PubMed

    Hsu, Wen-Li; Lu, Jian-He; Noda, Mami; Wu, Ching-Ying; Liu, Jia-Dai; Sakakibara, Manabu; Tsai, Ming-Hsien; Yu, Hsin-Su; Lin, Ming-Wei; Huang, Yaw-Bin; Yan, Shian-Jang; Yoshioka, Tohru

    2015-01-01

    Ultraviolet-B (UVB) is one of the most cytotoxic and mutagenic stresses that contribute to skin damage and aging through increasing intracellular Ca(2+) and reactive oxygen species (ROS). Derinat (sodium deoxyribonucleate) has been utilized as an immunomodulator for the treatment of ROS-associated diseases in clinics. However, the molecular mechanism by which Derinat protects skin cells from UVB-induced damage is poorly understood. Here, we show that Derinat significantly attenuated UVB-induced intracellular ROS production and decreased DNA damage in primary skin cells. Furthermore, Derinat reduced intracellular ROS, cyclooxygenase-2 (COX-2) expression and DNA damage in the skin of the BALB/c-nu mice exposed to UVB for seven days in vivo. Importantly, Derinat blocked the transient receptor potential canonical (TRPC) channels (TRPCs), as demonstrated by calcium imaging. Together, our results indicate that Derinat acts as a TRPCs blocker to reduce intracellular ROS production and DNA damage upon UVB irradiation. This mechanism provides a potential new application of Derinat for the protection against UVB-induced skin damage and aging. PMID:26569211

  6. Distinguishing neglect from abuse and accident: analysis of the case files of a hospital child protection team in Israel.

    PubMed

    Davidson-Arad, Bilha; Benbenishty, Rami; Chen, Wendy; Glasser, Saralee; Zur, Shmuel; Lerner-Geva, Liat

    2010-11-01

    The study compares the characteristics of children assessed as neglected, physically abused, or accident victims by a hospital child protection team (CPT) and identifies the information on which the CPT based its assessments. The comparison is based on content analysis of records of 414 children examined by the CPT in a major hospital in Israel between 1991 and 2006, of whom 130 (31.4%) were neglected, 54 (13.0%) were physically abused, and 230 (55.6%) were accident victims. Findings of three hierarchical logistic regressions show that the children classified as neglected had the most early development problems, but were the least likely to have received psychological treatment, and that that their families were the most likely to be receiving state financial support and to have had prior contact with the social services. They also show that the CPT had received the least information indicative of maltreatment about these children from the community and that their medical and physical examinations aroused the least suspicion. Finally, they show that the impressions the hospital staff and CPT had of the parents during the hospital visit had greater power to distinguish between the groups than the children's characteristics or the parents' socio-demographic background. The findings attest to the ability of the CPT to differentiate between neglect victims and physical abuse or accident victims. With this, they also point to ambiguities in the classification process that should be addressed by further research and training and to the need for detailed and thorough documentation of the information and observations on which the CPT's assessments are based.

  7. Antioxidant Protective Effect of Honey in Cigarette Smoke-Induced Testicular Damage in Rats

    PubMed Central

    Mohamed, Mahaneem; Sulaiman, Siti Amrah; Jaafar, Hasnan; Sirajudeen, Kuttulebbai Nainamohamed Salam

    2011-01-01

    Cigarette smoke (CS) can cause testicular damage and we investigated the possible protective effect of honey against CS-induced testicular damage and oxidative stress in rats. CS exposure (8 min, 3 times daily) and honey supplementation (1.2 g/kg daily) were given for 13 weeks. Rats exposed to CS significantly had smaller seminiferous tubules diameter and epithelial height, lower Leydig cell count and increased percentage of tubules with germ cell loss. CS also produced increased lipid peroxidation (TBARS) and glutathione peroxidase (GPx) activity, as well as reduced total antioxidant status (TAS) and activities of superoxide dismutase (SOD) and catalase (CAT). However, supplementation of honey significantly reduced histological changes and TBARS level, increased TAS level, as well as significantly restored activities of GPx, SOD and CAT in rat testis. These findings may suggest that honey has a protective effect against damage and oxidative stress induced by CS in rat testis. PMID:22016605

  8. Fuel containment, lightning protection and damage tolerance in large composite primary aircraft structures

    NASA Technical Reports Server (NTRS)

    Griffin, Charles F.; James, Arthur M.

    1985-01-01

    The damage-tolerance characteristics of high strain-to-failure graphite fibers and toughened resins were evaluated. Test results show that conventional fuel tank sealing techniques are applicable to composite structures. Techniques were developed to prevent fuel leaks due to low-energy impact damage. For wing panels subjected to swept stroke lightning strikes, a surface protection of graphite/aluminum wire fabric and a fastener treatment proved effective in eliminating internal sparking and reducing structural damage. The technology features developed were incorporated and demonstrated in a test panel designed to meet the strength, stiffness, and damage tolerance requirements of a large commercial transport aircraft. The panel test results exceeded design requirements for all test conditions. Wing surfaces constructed with composites offer large weight savings if design allowable strains for compression can be increased from current levels.

  9. A new potent natural antioxidant mixture provides global protection against oxidative skin cell damage.

    PubMed

    Jorge, A T S; Arroteia, K F; Lago, J C; de Sá-Rocha, V M; Gesztesi, J; Moreira, P L

    2011-04-01

    Oxidative stress occurs when there is an over production of free radicals and cells are not able to neutralize them by their own antioxidant mechanisms. These excess of free radicals will attack cellular macromolecules leading to cell damage, function impairment or death. Because of that, antioxidant substances have been largely used in products to offer complementary protection. In this study a new mixture of three known antioxidants (cocoa, green tea and alpha-tocopherol) was evaluated and its antioxidant protection was assessed focusing on its capacity to protect main cell macromolecules. Results have shown that it has a high antioxidant capacity by protecting lipids, DNA and proteins against oxidative damage. The antioxidant effect of the mixture on cells was also investigated and it was able to reduce oxidative stress generated by lipopolisacharide in human fibroblasts. Finally, as the mixture has proved to be highly antioxidant, its effect on cell senescence was evaluated, and it was demonstrated that fibroblasts in culture had delayed senescence when treated with these actives on a mixture. All results together provide important data about a new antioxidant mixture that uses a small amount of actives and is able to protect cell against oxidative damages in a global way.

  10. A new potent natural antioxidant mixture provides global protection against oxidative skin cell damage.

    PubMed

    Jorge, A T S; Arroteia, K F; Lago, J C; de Sá-Rocha, V M; Gesztesi, J; Moreira, P L

    2011-04-01

    Oxidative stress occurs when there is an over production of free radicals and cells are not able to neutralize them by their own antioxidant mechanisms. These excess of free radicals will attack cellular macromolecules leading to cell damage, function impairment or death. Because of that, antioxidant substances have been largely used in products to offer complementary protection. In this study a new mixture of three known antioxidants (cocoa, green tea and alpha-tocopherol) was evaluated and its antioxidant protection was assessed focusing on its capacity to protect main cell macromolecules. Results have shown that it has a high antioxidant capacity by protecting lipids, DNA and proteins against oxidative damage. The antioxidant effect of the mixture on cells was also investigated and it was able to reduce oxidative stress generated by lipopolisacharide in human fibroblasts. Finally, as the mixture has proved to be highly antioxidant, its effect on cell senescence was evaluated, and it was demonstrated that fibroblasts in culture had delayed senescence when treated with these actives on a mixture. All results together provide important data about a new antioxidant mixture that uses a small amount of actives and is able to protect cell against oxidative damages in a global way. PMID:20646086

  11. Anthracyclines Induce DNA Damage Response-Mediated Protection against Severe Sepsis

    PubMed Central

    Figueiredo, Nuno; Chora, Angelo; Raquel, Helena; Pejanovic, Nadja; Pereira, Pedro; Hartleben, Björn; Neves-Costa, Ana; Moita, Catarina; Pedroso, Dora; Pinto, Andreia; Marques, Sofia; Faridi, Hafeez; Costa, Paulo; Gozzelino, Raffaella; Zhao, Jimmy L.; Soares, Miguel P.; Gama-Carvalho, Margarida; Martinez, Jennifer; Zhang, Qingshuo; Döring, Gerd; Grompe, Markus; Simas, J. Pedro; Huber, Tobias B.; Baltimore, David; Gupta, Vineet; Green, Douglas R.; Ferreira, João A.; Moita, Luis F.

    2014-01-01

    Summary Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options in addition to organ support measures. Here we show that the clinically approved group of anthracyclines acts therapeutically at a low dose regimen to confer robust protection against severe sepsis in mice. This salutary effect is strictly dependent on the activation of DNA damage response and autophagy pathways in the lung, as demonstrated by deletion of the ataxia telangiectasia mutated (Atm) or the autophagy-related protein 7 (Atg7) specifically in this organ. The protective effect of anthracyclines occurs irrespectively of pathogen burden, conferring disease tolerance to severe sepsis. These findings demonstrate that DNA damage responses, including the ATM and Fancony Anemia pathways, are important modulators of immune responses and might be exploited to confer protection to inflammation-driven conditions, including severe sepsis. PMID:24184056

  12. Mcl-1 protects prostate cancer cells from cell death mediated by chemotherapy-induced DNA damage

    PubMed Central

    Reiner, Teresita; de las Pozas, Alicia; Parrondo, Ricardo; Palenzuela, Deanna; Cayuso, William; Rai, Priyamvada; Perez-Stable, Carlos

    2015-01-01

    The anti-apoptotic protein Mcl-1 is highly expressed in castration-resistant prostate cancer (CRPC), resulting in resistance to apoptosis and association with poor prognosis. Although predominantly localized in the cytoplasm, there is evidence that Mcl-1 exhibits nuclear localization where it is thought to protect against DNA damage-induced cell death. The role of Mcl-1 in mediating resistance to chemotherapy-induced DNA damage in prostate cancer (PCa) is not known. We show in human PCa cell lines and in TRAMP, a transgenic mouse model of PCa, that the combination of the antimitotic agent ENMD-1198 (analog of 2-methoxyestradiol) with betulinic acid (BA, increases proteotoxic stress) targets Mcl-1 by increasing its proteasomal degradation, resulting in increased γH2AX (DNA damage) and apoptotic/necrotic cell death. Knockdown of Mcl-1 in CRPC cells leads to elevated γH2AX, DNA strand breaks, and cell death after treatment with 1198 + BA- or doxorubicin. Additional knockdowns in PC3 cells suggests that cytoplasmic Mcl-1 protects against DNA damage by blocking the mitochondrial release of apoptosis-inducing factor and thereby preventing its nuclear translocation and subsequent interaction with the cyclophilin A endonuclease. Overall, our results suggest that chemotherapeutic agents that target Mcl-1 will promote cell death in response to DNA damage, particularly in CRPC. PMID:26425662

  13. Neisseria gonorrhoeae DNA recombination and repair enzymes protect against oxidative damage caused by hydrogen peroxide.

    PubMed

    Stohl, Elizabeth A; Seifert, H Steven

    2006-11-01

    The strict human pathogen Neisseria gonorrhoeae is exposed to oxidative damage during infection. N. gonorrhoeae has many defenses that have been demonstrated to counteract oxidative damage. However, recN is the only DNA repair and recombination gene upregulated in response to hydrogen peroxide (H(2)O(2)) by microarray analysis and subsequently shown to be important for oxidative damage protection. We therefore tested the importance of RecA and DNA recombination and repair enzymes in conferring resistance to H(2)O(2) damage. recA mutants, as well as RecBCD (recB, recC, and recD) and RecF-like pathway mutants (recJ, recO, and recQ), all showed decreased resistance to H(2)O(2). Holliday junction processing mutants (ruvA, ruvC, and recG) showed decreased resistance to H(2)O(2) resistance as well. Finally, we show that RecA protein levels did not increase as a result of H(2)O(2) treatment. We propose that RecA, recombinational DNA repair, and branch migration are all important for H(2)O(2) resistance in N. gonorrhoeae but that constitutive levels of these enzymes are sufficient for providing protection against oxidative damage by H(2)O(2). PMID:16936020

  14. Some lessons on radiological protection learnt from the accident at the Fukushima Dai-ichi nuclear power plant.

    PubMed

    Kai, M

    2012-03-01

    The accident at the Fukushima Dai-ichi nuclear power plant released a large quantity of radioactive iodine and caesium into the environment. In terms of radiological protection, the evacuation and food restrictions that were adopted in a timely manner by the authorities effectively reduced the dose received by people living in the affected area. Since late March, the transition from an emergency to an existing exposure situation has been in progress. In selecting the reference exposure levels in some areas under an existing exposure situation, the authorities tried to follow the situation-based approach recommended by the ICRP. However, a mixture of emergency and post-emergency approaches confused the people living in the contaminated areas because the reactor conditions continued to be not completely stable. In deriving the criteria in an existing exposure situation, the regulatory authority selected 20 mSv y(-1). The mothers in the affected area believed that a dose of 20 mSv y(-1) was unacceptably high for children since 1 mSv y(-1) is the dose limit for the public under normal conditions. Internet information accelerated concern about the internal exposure to children and the related health effects. From some experiences after the accident the following lessons could be learned. The selection of reference doses in existing exposure situations after an accident must be openly communicated with the public using a risk-informed approach. The detriment-adjusted nominal risk coefficient was misused for calculating the hypothetical number of cancer deaths by some non-radiation experts. It would not be possible to resolve this problem unless the ICRP addressed an alternative risk assessment to convey the meaning and associated uncertainty of the risk to an exposed population. A situation-based approach in addition to a risk-informed approach needs to be disseminated properly in order to select the level of protection that would be the best possible under the

  15. Performance of collision damage mitigation braking systems and their effects on human injury in the event of car-to-pedestrian accidents.

    PubMed

    Matsui, Yasuhiro; Han, Yong; Mizuno, Koji

    2011-11-01

    The number of traffic deaths in Japan was 4,863 in 2010. Pedestrians account for the highest number (1,714, 35%), and vehicle occupants the second highest (1,602, 33%). Pedestrian protection is a key countermeasure to reduce casualties in traffic accidents. A striking vehicle's impact velocity could be considered a parameter influencing the severity of injury and possibility of death in pedestrian crashes. A collision damage mitigation braking system (CDMBS) using a sensor to detect pedestrians could be effective for reducing the vehicle/pedestrian impact velocity. Currently in Japan, cars equipped with the CDMBS also have vision sensors such as a stereo camera for pedestrian detection. However, the ability of vision sensors in production cars to properly detect pedestrians has not yet been established. The effect of reducing impact velocity on the pedestrian injury risk has also not been determined. The first objective of this study is to evaluate the performance of the CDMBS in detecting pedestrians when it is installed in production cars. The second objective of this study is to evaluate the effect of reducing impact velocity on mitigating pedestrian injury. Firstly, impact experiments were performed using a car with the CDMBS in which the car collided with a pedestrian surrogate. In these tests, the velocity was chosen for the various test runs to be 20, 40 and 60 km/h, respectively, which were based on the velocity distribution in real-world pedestrian crashes. The results indicated that the impact velocity reduction ranged approximately from 10 to 15 km/h at the standing location of a pedestrian surrogate at both daytime and nighttime lighting conditions. These results show that the system has the potential to reduce pedestrian casualties from car-to-pedestrian contacts. Secondly, finite-element analyses were performed simulating vehicle-to- pedestrian impacts with the THUMS pedestrian models. The vehicle models selected for the study included a medium sedan

  16. Performance of collision damage mitigation braking systems and their effects on human injury in the event of car-to-pedestrian accidents.

    PubMed

    Matsui, Yasuhiro; Han, Yong; Mizuno, Koji

    2011-11-01

    The number of traffic deaths in Japan was 4,863 in 2010. Pedestrians account for the highest number (1,714, 35%), and vehicle occupants the second highest (1,602, 33%). Pedestrian protection is a key countermeasure to reduce casualties in traffic accidents. A striking vehicle's impact velocity could be considered a parameter influencing the severity of injury and possibility of death in pedestrian crashes. A collision damage mitigation braking system (CDMBS) using a sensor to detect pedestrians could be effective for reducing the vehicle/pedestrian impact velocity. Currently in Japan, cars equipped with the CDMBS also have vision sensors such as a stereo camera for pedestrian detection. However, the ability of vision sensors in production cars to properly detect pedestrians has not yet been established. The effect of reducing impact velocity on the pedestrian injury risk has also not been determined. The first objective of this study is to evaluate the performance of the CDMBS in detecting pedestrians when it is installed in production cars. The second objective of this study is to evaluate the effect of reducing impact velocity on mitigating pedestrian injury. Firstly, impact experiments were performed using a car with the CDMBS in which the car collided with a pedestrian surrogate. In these tests, the velocity was chosen for the various test runs to be 20, 40 and 60 km/h, respectively, which were based on the velocity distribution in real-world pedestrian crashes. The results indicated that the impact velocity reduction ranged approximately from 10 to 15 km/h at the standing location of a pedestrian surrogate at both daytime and nighttime lighting conditions. These results show that the system has the potential to reduce pedestrian casualties from car-to-pedestrian contacts. Secondly, finite-element analyses were performed simulating vehicle-to- pedestrian impacts with the THUMS pedestrian models. The vehicle models selected for the study included a medium sedan

  17. Protection from radiation-induced mitochondrial and genomic DNA damage by an extract of Hippophae rhamnoides.

    PubMed

    Shukla, Sandeep Kumar; Chaudhary, Pankaj; Kumar, Indracanti Prem; Samanta, Namita; Afrin, Farhat; Gupta, Manju Lata; Sharma, Upendra Kumar; Sinha, Arun Kumar; Sharma, Yogendra Kumar; Sharma, Rakesh Kumar

    2006-12-01

    Hippophae rhamnoides or seabuckthorn is used extensively in Indian and Tibetan traditional medicine for the treatment of circulatory disorders, ischemic heart disease, hepatic injury, and neoplasia. In the present study, we have evaluated the radioprotective potential of REC-1001, a fraction isolated from the berries of H. rhamnoides. Chemical analysis of the extract indicated that REC-1001 was approximately 68% by weight polyphenols, and contained kaempferol, isorhamnetin, and quercetin. The effect of REC-1001 on modulating radiation-induced DNA damage was determined in murine thymocytes by measuring nonspecific nuclear DNA damage at the whole genome level using the alkaline halo assay and by measuring sequence/gene-specific DNA damage both in nuclear DNA (beta-globin gene) and in mitochondrial DNA using a quantitative polymerase chain reaction. Treatment with 10 Gy resulted in a significant amount of DNA damage in the halo assay and reductions in the amplification of both the beta-globin gene and mitochondrial DNA. REC-1001 dose-dependently reduced the amount of damage detected in each assay, with the maximum protective effects observed at the highest REC-1001 dose evaluated (250 micro g/ml). Studies measuring the nicking of naked plasmid DNA further established the radioprotective effect of REC-1001. To elucidate possible mechanisms of action, the antioxidant properties and the free-radical scavenging activities of REC-1001 were evaluated. REC-1001 dose-dependently scavenged radiation-induced hydroxyl radicals, chemically-generated superoxide anions, stabilized DPPH radicals, and reduced Fe(3+) to Fe(2+). The results of the study indicate that the REC-1001 extract of H. rhamnoides protects mitochondrial and genomic DNA from radiation-induced damage. The polyphenols/flavonoids present in the extract might be responsible for the free radical scavenging and DNA protection afforded by REC-1001. PMID:16948057

  18. Protecting the radiation-damaged skin from friction: a mini review.

    PubMed

    Herst, Patries M

    2014-06-01

    Radiation-induced skin reactions are an unavoidable side effect of external beam radiation therapy, particularly in areas prone to friction and excess moisture such as the axilla, head and neck region, perineum and skin folds. Clinical studies investigating interventions for preventing or managing these reactions have largely focussed on formulations with moisturising, anti-inflammatory, anti-microbial and wound healing properties. However, none of these interventions has emerged as a consistent candidate for best practice. Much less emphasis has been placed on evaluating ways to protect the radiation-damaged skin from friction and excess moisture. This mini review analyses the clinical evidence for barrier products that form a protective layer by adhering very closely to the skin folds and do not cause further trauma to the radiation-damaged skin upon removal. A database search identified only two types of barrier products that fitted these criteria and these were tested in two case series and six controlled clinical trials. Friction protection was most effective when the interventions were used from the start of treatment and continued for several weeks after completion of treatment. Soft silicone dressings (Mepilex Lite and Mepitel Film) and Cavilon No Sting Barrier Film, but not Cavilon Moisturizing Barrier Cream, decreased skin reaction severity, most likely due to differences in formulation and skin build-up properties. It seems that prophylactic use of friction protection of areas at risk could be a worthwhile addition to routine care of radiation-damaged skin.

  19. Protecting the radiation-damaged skin from friction: a mini review

    PubMed Central

    Herst, Patries M

    2014-01-01

    Radiation-induced skin reactions are an unavoidable side effect of external beam radiation therapy, particularly in areas prone to friction and excess moisture such as the axilla, head and neck region, perineum and skin folds. Clinical studies investigating interventions for preventing or managing these reactions have largely focussed on formulations with moisturising, anti-inflammatory, anti-microbial and wound healing properties. However, none of these interventions has emerged as a consistent candidate for best practice. Much less emphasis has been placed on evaluating ways to protect the radiation-damaged skin from friction and excess moisture. This mini review analyses the clinical evidence for barrier products that form a protective layer by adhering very closely to the skin folds and do not cause further trauma to the radiation-damaged skin upon removal. A database search identified only two types of barrier products that fitted these criteria and these were tested in two case series and six controlled clinical trials. Friction protection was most effective when the interventions were used from the start of treatment and continued for several weeks after completion of treatment. Soft silicone dressings (Mepilex Lite and Mepitel Film) and Cavilon No Sting Barrier Film, but not Cavilon Moisturizing Barrier Cream, decreased skin reaction severity, most likely due to differences in formulation and skin build-up properties. It seems that prophylactic use of friction protection of areas at risk could be a worthwhile addition to routine care of radiation-damaged skin. PMID:26229646

  20. Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage.

    PubMed

    Wei, Na; Shi, Yi; Truong, Lan N; Fisch, Kathleen M; Xu, Tao; Gardiner, Elisabeth; Fu, Guangsen; Hsu, Yun-Shiuan Olivia; Kishi, Shuji; Su, Andrew I; Wu, Xiaohua; Yang, Xiang-Lei

    2014-10-23

    Tyrosyl-tRNA synthetase (TyrRS) is known for its essential aminoacylation function in protein synthesis. Here we report a function for TyrRS in DNA damage protection. We found that oxidative stress, which often downregulates protein synthesis, induces TyrRS to rapidly translocate from the cytosol to the nucleus. We also found that angiogenin mediates or potentiates this stress-induced translocalization. The nuclear-localized TyrRS activates transcription factor E2F1 to upregulate the expression of DNA damage repair genes such as BRCA1 and RAD51. The activation is achieved through direct interaction of TyrRS with TRIM28 to sequester this vertebrate-specific epigenetic repressor and its associated HDAC1 from deacetylating and suppressing E2F1. Remarkably, overexpression of TyrRS strongly protects against UV-induced DNA double-strand breaks in zebrafish, whereas restricting TyrRS nuclear entry completely abolishes the protection. Therefore, oxidative stress triggers an essential cytoplasmic enzyme used for protein synthesis to translocate to the nucleus to protect against DNA damage.

  1. Evaluation of protective effects of fish oil against oxidative damage in rats exposed to methylmercury.

    PubMed

    Grotto, Denise; Vicentini, Juliana; Angeli, José Pedro Friedmann; Latorraca, Elder Francisco; Monteiro, Patrícia Alves Pontes; Barcelos, Gustavo Rafael Mazzaron; Somacal, Sabrina; Emanuelli, Tatiana; Barbosa, Fernando

    2011-03-01

    The present study evaluates a possible protective effect of fish oil against oxidative damage promoted by methylmercury (MeHg) in sub-chronically exposed rats. Reduced glutathione peroxidase and catalase enzyme activity and reduced glutathione levels were observed in MeHg-exposed animals compared to controls. Methylmercury exposure was also associated with DNA damage. Administration of fish oil to the methylmercury-exposed animals did not ameliorate enzyme activity or glutathione levels. On the other hand, a significant DNA protective effect (about 30%) was observed with fish oil treatment. There were no differences in the total mercury concentration in rat liver, kidney, heart or brain after MeHg administration with or without fish oil co-administration. Histopathological analyses showed a significant leukocyte infiltration in rat tissues after MeHg exposure, but this effect was significantly reduced after co-administration of fish oil. Taken together, our findings demonstrate oxidative damage even after low-level MeHg exposure and the protective effect of fish oil. This protection seems not to be related to antioxidant defenses or mercury re-distribution in rat tissues. It is probably due to the anti-inflammatory effects of fish oil. PMID:20970192

  2. Protecting the radiation-damaged skin from friction: a mini review

    SciTech Connect

    Herst, Patries M

    2014-06-15

    Radiation-induced skin reactions are an unavoidable side effect of external beam radiation therapy, particularly in areas prone to friction and excess moisture such as the axilla, head and neck region, perineum and skin folds. Clinical studies investigating interventions for preventing or managing these reactions have largely focussed on formulations with moisturising, anti-inflammatory, anti-microbial and wound healing properties. However, none of these interventions has emerged as a consistent candidate for best practice. Much less emphasis has been placed on evaluating ways to protect the radiation-damaged skin from friction and excess moisture. This mini review analyses the clinical evidence for barrier products that form a protective layer by adhering very closely to the skin folds and do not cause further trauma to the radiation-damaged skin upon removal. A database search identified only two types of barrier products that fitted these criteria and these were tested in two case series and six controlled clinical trials. Friction protection was most effective when the interventions were used from the start of treatment and continued for several weeks after completion of treatment. Soft silicone dressings (Mepilex Lite and Mepitel Film) and Cavilon No Sting Barrier Film, but not Cavilon Moisturizing Barrier Cream, decreased skin reaction severity, most likely due to differences in formulation and skin build-up properties. It seems that prophylactic use of friction protection of areas at risk could be a worthwhile addition to routine care of radiation-damaged skin.

  3. Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage

    PubMed Central

    Bhattacharya, Anannya; Hegazy, Ahmed N.; Deigendesch, Nikolaus; Kosack, Lindsay; Cupovic, Jovana; Kandasamy, Richard K.; Hildebrandt, Andrea; Merkler, Doron; Kühl, Anja A.; Vilagos, Bojan; Schliehe, Christopher; Panse, Isabel; Khamina, Kseniya; Baazim, Hatoon; Arnold, Isabelle; Flatz, Lukas; Xu, Haifeng C.; Lang, Philipp A.; Aderem, Alan; Takaoka, Akinori; Superti-Furga, Giulio; Colinge, Jacques; Ludewig, Burkhard; Löhning, Max; Bergthaler, Andreas

    2015-01-01

    Summary Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1−/− mice exhibited increased inflammation and aggravated liver damage upon viral infection, which was independent of T and NK cells and could be ameliorated by antioxidant treatment. Type I interferon (IFN-I) led to a downregulation of Sod1 and caused oxidative liver damage in Sod1−/− and wild-type mice. Genetic and pharmacological ablation of the IFN-I signaling pathway protected against virus-induced liver damage. These results delineate IFN-I mediated oxidative stress as a key mediator of virus-induced liver damage and describe a mechanism of innate-immunity-driven pathology, linking IFN-I signaling with antioxidant host defense and infection-associated tissue damage. Video Abstract PMID:26588782

  4. World commercial aircraft accidents

    SciTech Connect

    Kimura, C.Y.

    1993-01-01

    This report is a compilation of all accidents world-wide involving aircraft in commercial service which resulted in the loss of the airframe or one or more fatality, or both. This information has been gathered in order to present a complete inventory of commercial aircraft accidents. Events involving military action, sabotage, terrorist bombings, hijackings, suicides, and industrial ground accidents are included within this list. Included are: accidents involving world commercial jet aircraft, world commercial turboprop aircraft, world commercial pistonprop aircraft with four or more engines and world commercial pistonprop aircraft with two or three engines from 1946 to 1992. Each accident is presented with information in the following categories: date of the accident, airline and its flight numbers, type of flight, type of aircraft, aircraft registration number, construction number/manufacturers serial number, aircraft damage, accident flight phase, accident location, number of fatalities, number of occupants, cause, remarks, or description (brief) of the accident, and finally references used. The sixth chapter presents a summary of the world commercial aircraft accidents by major aircraft class (e.g. jet, turboprop, and pistonprop) and by flight phase. The seventh chapter presents several special studies including a list of world commercial aircraft accidents for all aircraft types with 100 or more fatalities in order of decreasing number of fatalities, a list of collision accidents involving commercial aircrafts, and a list of world commercial aircraft accidents for all aircraft types involving military action, sabotage, terrorist bombings, and hijackings.

  5. A damage assessment model of oil spill accident combining historical data and satellite remote sensing information: a case study in Penglai 19-3 oil spill accident of China.

    PubMed

    Wei, Lai; Hu, Zhuowei; Dong, Lin; Zhao, Wenji

    2015-02-15

    Oil spills are one of the major sources of marine pollution; it is important to conduct comprehensive assessment of losses that occur as a result of these events. Traditional methods are required to assess the three parts of losses including cleanup, socioeconomic losses, and environmental costs. It is relatively slow because assessment is complex and time consuming. A relatively quick method was developed to improve the efficiency of assessment, and then applied to the Penglai 19-3 accident. This paper uses an SAR image to calculate the oil spill area through Neural Network Classification, and uses historical oil-spill data to build the relationship between loss and other factors including sea-surface wind speed, and distance to the coast. A multiple regression equation was used to assess oil spill damage as a function of the independent variables. Results of this study can be used for regulating and quickly dealing with oil spill assessment.

  6. Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells.

    PubMed

    Wang, Yichong; Dacosta, Christopher; Wang, Wei; Zhou, Zhigang; Liu, Ming; Bao, Yongping

    2015-07-01

    Dietary isothiocyanates are potent inducers of the NF-E2-related factor 2 (Nrf2) pathway. Sulforaphane (SFN), a representative dietary isothiocyanate, has previously been shown to up-regulate antioxidant enzymes such as selenium (Se)-dependent thioredoxin reductase-1 (TrxR-1) in many tumor cell lines. In the present study, we hypothesized that a combination of SFN and Se would have a synergistic effect on the up-regulation of TrxR-1 and the protection against oxidative damage in the normal colonic cell line CCD841. Treatment of cells with SFN and Se significantly induced TrxR-1 expression. Pretreatment of cells with SFN protects against H2O2-induced cell death; this protection was enhanced by cotreatment with Se. The small interfering RNA knockdown of either TrxR-1 or Nrf2 reduced the protection afforded by SFN and Se cotreatment; TrxR-1 and Nrf2 knockdown reduced cell viabilities to 66.5% and 51.1%, respectively, down from 82.4% in transfection-negative controls. This suggests that both TrxR-1 and Nrf2 are important in SFN-mediated protection against free radical-induced cell death. Moreover, flow cytometric analysis showed that TrxR-1 and Nrf2 were involved in SFN-mediated protection against H2O2-induced apoptosis. In summary, SFN activates the Nrf2 signaling pathway and protects against H2O2-mediated oxidative damage in normal colonic cells. Combined SFN and Se treatment resulted in a synergistic up-regulation of TrxR-1 that in part contributed to the enhanced protection against free radical-mediated cell death provided by the cotreatment.

  7. DNA binding, antioxidant activity, and DNA damage protection of chiral macrocyclic Mn(III) salen complexes.

    PubMed

    Pandya, Nirali; Khan, Noor-ul H; Prathap, K Jeya; Kureshy, Rukhsana I; Abdi, Sayed H R; Mishra, Sandhya; Bajaj, Hari C

    2012-12-01

    We are reporting the synthesis, characterization, and calf thymus DNA binding studies of novel chiral macrocyclic Mn(III) salen complexes S-1, R-1, S-2, and R-2. These chiral complexes showed ability to bind with DNA, where complex S-1 exhibits the highest DNA binding constant 1.20 × 10(6) M(-1). All the compounds were screened for superoxide and hydroxyl radical scavenging activities; among them, complex S-1 exhibited significant activity with IC(50) 1.36 and 2.37 μM, respectively. Further, comet assay was used to evaluate the DNA damage protection in white blood cells against the reactive oxygen species wherein complex S-1 was found effective in protecting the hydroxyl radicals mediated plasmid and white blood cells DNA damage.

  8. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage

    SciTech Connect

    Frei, B. )

    1991-12-01

    The authors exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

  9. Phenolic compounds protect HepG2 cells from oxidative damage: relevance of glutathione levels.

    PubMed

    Lima, Cristovao F; Fernandes-Ferreira, Manuel; Pereira-Wilson, Cristina

    2006-10-19

    In the present work, the potential hepatoprotective effects of five phenolic compounds against oxidative damages induced by tert-butyl hydroperoxide (t-BHP) were evaluated in HepG2 cells in order to relate in vitro antioxidant activity with cytoprotective effects. t-BHP induced considerable cell damage in HepG2 cells as shown by significant LDH leakage, increased lipid peroxidation, DNA damage as well as decreased levels of reduced glutathione (GSH). All tested phenolic compounds significantly decreased cell death induced by t-BHP (when in co-incubation). If the effects of quercetin are given the reference value 1, the compounds rank in the following order according to inhibition of cell death: luteolin (4.0) > quercetin (1.0) > rosmarinic acid (0.34) > luteolin-7-glucoside (0.30) > caffeic acid (0.21). The results underscore the importance of the compound's lipophilicity in addition to its antioxidant potential for its biological activity. All tested phenolic compounds were found to significantly decrease lipid peroxidation and prevent GSH depletion induced by t-BHP, but only luteolin and quercetin significantly decreased DNA damage. Therefore, the lipophilicity of the natural antioxidants tested appeared to be of even greater importance for DNA protection than for cell survival. The protective potential against cell death was probably achieved mainly by preventing intracellular GSH depletion. The phenolic compounds studied here showed protective potential against oxidative damage induced in HepG2 cells. This could be beneficial against liver diseases where it is known that oxidative stress plays a crucial role. PMID:16857214

  10. Epigallocatechin gallate eye drops protect against ultraviolet B–induced corneal oxidative damage in mice

    PubMed Central

    Chen, Mu-Hsin; Tsai, Chia-Fang; Lu, Fung-Jou

    2014-01-01

    Purpose Ultraviolet B (UVB) radiation from sunlight is a known risk factor for human corneal injury. The aim of the present study was to investigate the protective effects of green tea polyphenol epigallocatechin gallate (EGCG) on UVB radiation–induced corneal oxidative damage in male imprinting control region (ICR) mice. Methods Corneal oxidative damage was induced by exposure to UVB radiation at 560 μW/cm2. The animals received 0%, 0.1%, and 0.01% EGCG eye drops at a 5 mg/ml dose, twice daily for 8 days. Corneal surface damage was graded according to smoothness and the extent of lissamine green staining. Corneal glutathione (GSH), thiobarbituric acid-reactive substances (TBARS), and protein carbonyl levels, as well as superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rd) activity in the cornea, were measured to monitor corneal injury. Results UVB radiation caused significant damage to the corneas, including apparent corneal ulceration and severe epithelial exfoliation, leading to a decrease in SOD, catalase, GSH-Px, GSH-Rd, and GSH activity in the cornea. However, the corneal TBARS and protein carbonyls increased compared with the control group. Treatment with EGCG eye drops significantly (p<0.05) ameliorated corneal damage, increased SOD, catalase, GSH-Px, GSH-Rd, and GSH activity, and decreased the TBARS and protein carbonyls in the corneas compared with the UVB-treated group. Conclusions EGCG eye drops exhibit potent protective effects on UVB radiation–induced corneal oxidative damage in mice, likely due to the increase in antioxidant defense system activity and the inhibition of lipid peroxidation and protein oxidation. PMID:24520184

  11. Chromosome 11 protects against DNA damage by reactive oxygen species (ROS)

    SciTech Connect

    Hofseth, L.J.; Rosin, M.P.

    1994-12-31

    Recent evidence suggests that chromosome 11 plays an important role in determining a cell`s sensitivity to DNA damage by ROS. The induction of micronuclei (MN) by treatment with ROS was found to be reduced in a bladder carcinoma cell line ({open_quotes}parent{close_quotes}) when a normal chromosome 11 was inserted ({open_quotes}hybrid{close_quotes}). These studies have been extended to include a third cell line ({open_quotes}revertant{close_quotes}) derived from the {open_quotes}hybrid{close_quotes} by spontaneous loss of the chromosome (11) insert. In this study, MN induction and nuclear division indices (NDI) were determined in all 3 lines after exposure to either hydrogen peroxide (H{sub 2}O{sub 2}) (0-32.3 {mu}M) or to {gamma}-radiation (0-3 Gy). For both agents, there was a significant protection against induction of MN in the hybrid cell line (p<0.0001). This protection was lost in the revertant line. There was significantly more protection against H{sub 2}O{sub 2}-induced damage than against damage by irradiation. At the highest dose for H{sub 2}O{sub 2} (32.3{mu}M), induced MN frequencies for hybrid cells (3.7%) were approximately 5-fold lower than frequencies in the parent (17.1%) or revertant (18.6%) cells. In contrast, after 1 Gy of irradiation, induced MN frequencies in hybrid cells (18.7%) were 1.4-fold less than either the parent (26.2%) or revertant (27.6%) cells (ratio at 3 Gy was 1.4-fold also). The 2 treatments also had a different effect on the NDI (an index of toxicity and/or growth inhibition). Both treatments induced a decrease in NDI. The chromosome 11 insert protected hybrid cells from this effect but only after exposure to H{sub 2}O{sub 2} and not to irradiation. These data suggest a protective effect against ROS. Since only a portion of DNA damage from {gamma}-ray treatment is due to ROS, this may account for the reduced ability of the chromosome 11 to provide a protective effect against DNA damage due to {gamma}-ray exposure.

  12. Mitochondrial aldehyde dehydrogenase 2 protects gastric mucosa cells against DNA damage caused by oxidative stress.

    PubMed

    Duan, Yantao; Gao, Yaohui; Zhang, Jun; Chen, Yinan; Jiang, Yannan; Ji, Jun; Zhang, Jianian; Chen, Xuehua; Yang, Qiumeng; Su, Liping; Zhang, Jun; Liu, Bingya; Zhu, Zhenggang; Wang, Lishun; Yu, Yingyan

    2016-04-01

    Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a member of the aldehyde dehydrogenase superfamily and is involved with the metabolic processing of aldehydes. ALDH2 plays a cytoprotective role by removing aldehydes produced during normal metabolism. We examined the cytoprotective role of ALDH2 specifically in gastric mucosa cells. Overexpression of ALDH2 increased the viability of gastric mucosa cells treated with H2O2, while knockdown of ALDH2 had an opposite effect. Moreover, overexpression of ALDH2 protected gastric mucosa cells against oxidative stress-induced apoptosis as determined by flow cytometry, Hoechst 33342, and TUNEL assays. Consistently, ALDH2 knockdown had an opposite effect. Additionally, DNA damage was ameliorated in ALDH2-overexpressing gastric mucosa cells treated with H2O2. We further identified that this cytoprotective role of ALDH2 was mediated by metabolism of 4-hydroxynonenal (4-HNE). Consistently, 4-HNE mimicked the oxidative stress induced by H2O2 in gastric mucosa cells. Treatment with 4-HNE increased levels of DNA damage in ALDH2-knockdown GES-1 cells, while overexpression of ALDH2 decreased 4-HNE-induced DNA damage. These findings suggest that ALDH2 can protect gastric mucosa cells against DNA damage caused by oxidative stress by reducing levels of 4-HNE.

  13. MiR-25 protects cardiomyocytes against oxidative damage by targeting the mitochondrial calcium uniporter.

    PubMed

    Pan, Lei; Huang, Bi-Jun; Ma, Xiu-E; Wang, Shi-Yi; Feng, Jing; Lv, Fei; Liu, Yuan; Liu, Yi; Li, Chang-Ming; Liang, Dan-Dan; Li, Jun; Xu, Liang; Chen, Yi-Han

    2015-03-10

    MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been documented to be abundant in cardiomyocytes, but its function in the heart remains unknown. Here, we report that miR-25 can protect cardiomyocytes against oxidative damage by down-regulating mitochondrial calcium uniporter (MCU). MiR-25 was markedly elevated in response to oxidative stimulation in cardiomyocytes. Further overexpression of miR-25 protected cardiomyocytes against oxidative damage by inactivating the mitochondrial apoptosis pathway. MCU was identified as a potential target of miR-25 by bioinformatical analysis. MCU mRNA level was reversely correlated with miR-25 under the exposure of H2O2, and MCU protein level was largely decreased by miR-25 overexpression. The luciferase reporter assay confirmed that miR-25 bound directly to the 3' untranslated region (UTR) of MCU mRNA. MiR-25 significantly decreased H2O2-induced elevation of mitochondrial Ca2+ concentration, which is likely to be the result of decreased activity of MCU. We conclude that miR-25 targets MCU to protect cardiomyocytes against oxidative damages. This finding provides novel insights into the involvement of miRNAs in oxidative stress in cardiomyocytes.

  14. Chronic administration of troxerutin protects mouse kidney against D-galactose-induced oxidative DNA damage.

    PubMed

    Liu, Chan-Min; Ma, Jie-Qiong; Lou, Yao

    2010-10-01

    Troxerutin, a natural bioflavonoid, has been reported to have many benefits and medicinal properties. In this study, we evaluated the protective effect of troxerutin against D-gal-induced oxidative DNA damage in mouse kidney, and explored the potential mechanism of its action. Our data showed that troxerutin significantly decreased levels of urea, uric acid and creatinine in serum and the renal histological injury in D-gal-treated mice. Troxerutin markedly restored Cu/Zn-SOD, CAT and GPx activities in the kidney of D-gal-treated mouse. Furthermore, the increase of 8-hydroxydeoxyguanosine (a marker of oxidative DNA damage) induced by d-gal was effectively suppressed by troxerutin. Internucleosomal DNA ladder fragmentation and the number of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling (TUNEL)-positive cells in D-gal-treated mice were inhibited by troxerutin, which might be attributed to its antioxidant property by decreasing activities of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) and levels of reactive oxygen species (ROS). In conclusion, these results suggested that troxerutin could protect the mouse kidney against D-gal-induced injury by improving renal function, attenuating histopathologic changes, reducing ROS production, renewing the activities of antioxidant enzymes and decreasing DNA oxidative damage. This study provided novel insights into the protective mechanisms of troxerutin in D-gal-induced kidney injury.

  15. Eugenol protects nicotine-induced superoxide mediated oxidative damage in murine peritoneal macrophages in vitro.

    PubMed

    Kar Mahapatra, Santanu; Chakraborty, Subhankari Prasad; Majumdar, Subrata; Bag, Braja Gopal; Roy, Somenath

    2009-11-25

    The present work is aimed at evaluating the protective effect of eugenol against in vitro nicotine-induced toxicity in murine peritoneal macrophages, compared with N-acetylcysteine. Eugenol was isolated from Ocimum gratissimum and characterized by HPLC, FTIR, (1)H NMR. To establish most effective protective support, we used five different concentrations of eugenol (1, 5, 10, 15, and 20microg/ml) and N-acetylcysteine (0.25, 0.5, 1.0, 2.0, and 5.0microg/ml) against 10mM nicotine in mice peritoneal macrophages. A dose-dependent protective effect was observed with all doses of eugenol and N-acetylcysteine, as evidenced by decreased level of superoxide anion generation and malondialdehyde, and also increased level of reduced glutathione, and superoxide dismutase activity. Moreover, maximum protection was observed at the concentration of 15.0microg/ml eugenol (0.09nM) and 1.0microg/ml N-acetylcysteine (0.006nM). Further, eugenol (15.0microg/ml) and N-acetylcysteine (1.0microg/ml) were tested against nicotine (10mM) toxicity by analyzing the radical generation, lipid, protein, DNA damage, and endogenous antioxidant status. There was a significant increase in the level of radical generation, NADPH oxidase and myeloperoxidase activity, lipid, protein, DNA damage and oxidized glutathione level in nicotine-treated group, which were significantly reduced by eugenol and N-acetylcysteine supplementation. Antioxidant status was significantly depleted in the nicotine-treated group, which was effectively restored by eugenol and N-acetylcysteine supplementation. The protection by eugenol against nicotine toxicity was merely equal effective to that of N-acetylcysteine. These findings suggest the potential use and benefit of eugenol isolated from O. gratissimum as a modulator of nicotine-induced cellular damage and it may be used as an immunomodulatory drug against nicotine toxicity.

  16. Eugenol protects nicotine-induced superoxide mediated oxidative damage in murine peritoneal macrophages in vitro.

    PubMed

    Kar Mahapatra, Santanu; Chakraborty, Subhankari Prasad; Majumdar, Subrata; Bag, Braja Gopal; Roy, Somenath

    2009-11-25

    The present work is aimed at evaluating the protective effect of eugenol against in vitro nicotine-induced toxicity in murine peritoneal macrophages, compared with N-acetylcysteine. Eugenol was isolated from Ocimum gratissimum and characterized by HPLC, FTIR, (1)H NMR. To establish most effective protective support, we used five different concentrations of eugenol (1, 5, 10, 15, and 20microg/ml) and N-acetylcysteine (0.25, 0.5, 1.0, 2.0, and 5.0microg/ml) against 10mM nicotine in mice peritoneal macrophages. A dose-dependent protective effect was observed with all doses of eugenol and N-acetylcysteine, as evidenced by decreased level of superoxide anion generation and malondialdehyde, and also increased level of reduced glutathione, and superoxide dismutase activity. Moreover, maximum protection was observed at the concentration of 15.0microg/ml eugenol (0.09nM) and 1.0microg/ml N-acetylcysteine (0.006nM). Further, eugenol (15.0microg/ml) and N-acetylcysteine (1.0microg/ml) were tested against nicotine (10mM) toxicity by analyzing the radical generation, lipid, protein, DNA damage, and endogenous antioxidant status. There was a significant increase in the level of radical generation, NADPH oxidase and myeloperoxidase activity, lipid, protein, DNA damage and oxidized glutathione level in nicotine-treated group, which were significantly reduced by eugenol and N-acetylcysteine supplementation. Antioxidant status was significantly depleted in the nicotine-treated group, which was effectively restored by eugenol and N-acetylcysteine supplementation. The protection by eugenol against nicotine toxicity was merely equal effective to that of N-acetylcysteine. These findings suggest the potential use and benefit of eugenol isolated from O. gratissimum as a modulator of nicotine-induced cellular damage and it may be used as an immunomodulatory drug against nicotine toxicity. PMID:19769960

  17. Curcumin protects DNA damage in a chronically arsenic-exposed population of West Bengal.

    PubMed

    Biswas, Jaydip; Sinha, Dona; Mukherjee, Sutapa; Roy, Soumi; Siddiqi, Maqsood; Roy, Madhumita

    2010-06-01

    Groundwater arsenic contamination has been a health hazard for West Bengal, India. Oxidative stress to DNA is recognized as an underlying mechanism of arsenic carcinogenicity. A phytochemical, curcumin, from turmeric appears to be potent antioxidant and antimutagenic agent. DNA damage prevention with curcumin could be an effective strategy to combat arsenic toxicity. This field trial in Chakdah block of West Bengal evaluated the role of curcumin against the genotoxic effects of arsenic. DNA damage in human lymphocytes was assessed by comet assay and fluorescence-activated DNA unwinding assay. Curcumin was analyzed in blood by high performance liquid chromatography (HPLC). Arsenic induced oxidative stress and elucidation of the antagonistic role of curcumin was done by observation on reactive oxygen species (ROS) generation, lipid peroxidation and protein carbonyl. Antioxidant enzymes like catalase, superoxide dismutase, glutathione reductase, glutathioneS-transferase, glutathione peroxidase and non-enzymatic glutathione were also analyzed. The blood samples of the endemic regions showed severe DNA damage with increased levels of ROS and lipid peroxidation. The antioxidants were found with depleted activity. Three months curcumin intervention reduced the DNA damage, retarded ROS generation and lipid peroxidation and raised the level of antioxidant activity. Thus curcumin may have some protective role against the DNA damage caused by arsenic.

  18. Autophagy confers DNA damage repair pathways to protect the hematopoietic system from nuclear radiation injury

    PubMed Central

    Lin, Weiwei; Yuan, Na; Wang, Zhen; Cao, Yan; Fang, Yixuan; Li, Xin; Xu, Fei; Song, Lin; Wang, Jian; Zhang, Han; Yan, Lili; Xu, Li; Zhang, Xiaoying; Zhang, Suping; Wang, Jianrong

    2015-01-01

    Autophagy is essentially a metabolic process, but its in vivo role in nuclear radioprotection remains unexplored. We observed that ex vivo autophagy activation reversed the proliferation inhibition, apoptosis, and DNA damage in irradiated hematopoietic cells. In vivo autophagy activation improved bone marrow cellularity following nuclear radiation exposure. In contrast, defective autophagy in the hematopoietic conditional mouse model worsened the hematopoietic injury, reactive oxygen species (ROS) accumulation and DNA damage caused by nuclear radiation exposure. Strikingly, in vivo defective autophagy caused an absence or reduction in regulatory proteins critical to both homologous recombination (HR) and non-homologous end joining (NHEJ) DNA damage repair pathways, as well as a failure to induce these proteins in response to nuclear radiation. In contrast, in vivo autophagy activation increased most of these proteins in hematopoietic cells. DNA damage assays confirmed the role of in vivo autophagy in the resolution of double-stranded DNA breaks in total bone marrow cells as well as bone marrow stem and progenitor cells upon whole body irradiation. Hence, autophagy protects the hematopoietic system against nuclear radiation injury by conferring and intensifying the HR and NHEJ DNA damage repair pathways and by removing ROS and inhibiting apoptosis. PMID:26197097

  19. Curcumin protects DNA damage in a chronically arsenic-exposed population of West Bengal.

    PubMed

    Biswas, Jaydip; Sinha, Dona; Mukherjee, Sutapa; Roy, Soumi; Siddiqi, Maqsood; Roy, Madhumita

    2010-06-01

    Groundwater arsenic contamination has been a health hazard for West Bengal, India. Oxidative stress to DNA is recognized as an underlying mechanism of arsenic carcinogenicity. A phytochemical, curcumin, from turmeric appears to be potent antioxidant and antimutagenic agent. DNA damage prevention with curcumin could be an effective strategy to combat arsenic toxicity. This field trial in Chakdah block of West Bengal evaluated the role of curcumin against the genotoxic effects of arsenic. DNA damage in human lymphocytes was assessed by comet assay and fluorescence-activated DNA unwinding assay. Curcumin was analyzed in blood by high performance liquid chromatography (HPLC). Arsenic induced oxidative stress and elucidation of the antagonistic role of curcumin was done by observation on reactive oxygen species (ROS) generation, lipid peroxidation and protein carbonyl. Antioxidant enzymes like catalase, superoxide dismutase, glutathione reductase, glutathioneS-transferase, glutathione peroxidase and non-enzymatic glutathione were also analyzed. The blood samples of the endemic regions showed severe DNA damage with increased levels of ROS and lipid peroxidation. The antioxidants were found with depleted activity. Three months curcumin intervention reduced the DNA damage, retarded ROS generation and lipid peroxidation and raised the level of antioxidant activity. Thus curcumin may have some protective role against the DNA damage caused by arsenic. PMID:20056736

  20. Dandelion Extracts Protect Human Skin Fibroblasts from UVB Damage and Cellular Senescence.

    PubMed

    Yang, Yafan; Li, Shuangshuang

    2015-01-01

    Ultraviolet (UV) irradiation causes damage in skin by generating excessive reactive oxygen species (ROS) and induction of matrix metalloproteinases (MMPs), leading to skin photoageing. Dandelion extracts have long been used for traditional Chinese medicine and native American medicine to treat cancers, hepatitis, and digestive diseases; however, less is known on the effects of dandelion extracts in skin photoageing. Here we found that dandelion leaf and flower extracts significantly protect UVB irradiation-inhibited cell viability when added before UVB irradiation or promptly after irradiation. Dandelion leaf and flower extracts inhibited UVB irradiation-stimulated MMP activity and ROS generation. Dandelion root extracts showed less action on protecting HDFs from UVB irradiation-induced MMP activity, ROS generation, and cell death. Furthermore, dandelion leaf and flower but not root extracts stimulated glutathione generation and glutathione reductase mRNA expression in the presence or absence of UVB irradiation. We also found that dandelion leaf and flower extracts help absorb UVB irradiation. In addition, dandelion extracts significantly protected HDFs from H2O2-induced cellular senescence. In conclusion, dandelion extracts especially leaf and flower extracts are potent protective agents against UVB damage and H2O2-induced cellular senescence in HDFs by suppressing ROS generation and MMP activities and helping UVB absorption. PMID:26576225

  1. Hole hopping through tyrosine/tryptophan chains protects proteins from oxidative damage

    PubMed Central

    Gray, Harry B.; Winkler, Jay R.

    2015-01-01

    Living organisms have adapted to atmospheric dioxygen by exploiting its oxidizing power while protecting themselves against toxic side effects. Reactive oxygen and nitrogen species formed during oxidative stress, as well as high-potential reactive intermediates formed during enzymatic catalysis, could rapidly and irreversibly damage polypeptides were protective mechanisms not available. Chains of redox-active tyrosine and tryptophan residues can transport potentially damaging oxidizing equivalents (holes) away from fragile active sites and toward protein surfaces where they can be scavenged by cellular reductants. Precise positioning of these chains is required to provide effective protection without inhibiting normal function. A search of the structural database reveals that about one third of all proteins contain Tyr/Trp chains composed of three or more residues. Although these chains are distributed among all enzyme classes, they appear with greatest frequency in the oxidoreductases and hydrolases. Consistent with a redox-protective role, approximately half of the dioxygen-using oxidoreductases have Tyr/Trp chain lengths ≥3 residues. Among the hydrolases, long Tyr/Trp chains appear almost exclusively in the glycoside hydrolases. These chains likely are important for substrate binding and positioning, but a secondary redox role also is a possibility. PMID:26195784

  2. Dandelion Extracts Protect Human Skin Fibroblasts from UVB Damage and Cellular Senescence.

    PubMed

    Yang, Yafan; Li, Shuangshuang

    2015-01-01

    Ultraviolet (UV) irradiation causes damage in skin by generating excessive reactive oxygen species (ROS) and induction of matrix metalloproteinases (MMPs), leading to skin photoageing. Dandelion extracts have long been used for traditional Chinese medicine and native American medicine to treat cancers, hepatitis, and digestive diseases; however, less is known on the effects of dandelion extracts in skin photoageing. Here we found that dandelion leaf and flower extracts significantly protect UVB irradiation-inhibited cell viability when added before UVB irradiation or promptly after irradiation. Dandelion leaf and flower extracts inhibited UVB irradiation-stimulated MMP activity and ROS generation. Dandelion root extracts showed less action on protecting HDFs from UVB irradiation-induced MMP activity, ROS generation, and cell death. Furthermore, dandelion leaf and flower but not root extracts stimulated glutathione generation and glutathione reductase mRNA expression in the presence or absence of UVB irradiation. We also found that dandelion leaf and flower extracts help absorb UVB irradiation. In addition, dandelion extracts significantly protected HDFs from H2O2-induced cellular senescence. In conclusion, dandelion extracts especially leaf and flower extracts are potent protective agents against UVB damage and H2O2-induced cellular senescence in HDFs by suppressing ROS generation and MMP activities and helping UVB absorption.

  3. Dandelion Extracts Protect Human Skin Fibroblasts from UVB Damage and Cellular Senescence

    PubMed Central

    Yang, Yafan; Li, Shuangshuang

    2015-01-01

    Ultraviolet (UV) irradiation causes damage in skin by generating excessive reactive oxygen species (ROS) and induction of matrix metalloproteinases (MMPs), leading to skin photoageing. Dandelion extracts have long been used for traditional Chinese medicine and native American medicine to treat cancers, hepatitis, and digestive diseases; however, less is known on the effects of dandelion extracts in skin photoageing. Here we found that dandelion leaf and flower extracts significantly protect UVB irradiation-inhibited cell viability when added before UVB irradiation or promptly after irradiation. Dandelion leaf and flower extracts inhibited UVB irradiation-stimulated MMP activity and ROS generation. Dandelion root extracts showed less action on protecting HDFs from UVB irradiation-induced MMP activity, ROS generation, and cell death. Furthermore, dandelion leaf and flower but not root extracts stimulated glutathione generation and glutathione reductase mRNA expression in the presence or absence of UVB irradiation. We also found that dandelion leaf and flower extracts help absorb UVB irradiation. In addition, dandelion extracts significantly protected HDFs from H2O2-induced cellular senescence. In conclusion, dandelion extracts especially leaf and flower extracts are potent protective agents against UVB damage and H2O2-induced cellular senescence in HDFs by suppressing ROS generation and MMP activities and helping UVB absorption. PMID:26576225

  4. The effect of various cosmetic pretreatments on protecting hair from thermal damage by hot flat ironing.

    PubMed

    Zhou, Y; Rigoletto, R; Koelmel, D; Zhang, G; Gillece, T W; Foltis, L; Moore, D J; Qu, X; Sun, C

    2011-01-01

    Hot flat irons are used to create straight hair styles. As these devices operate at temperatures over 200 °C they can cause significant damage to hair keratin. In this study, hair thermal damage and the effect of various polymeric pretreatments were investigated using FTIR imaging spectroscopy, DSC, dynamic vapor sorption (DVS), AFM, SEM, and thermal image analysis. FTIR imaging spectroscopy of hair cross sections provides spatially resolved molecular information such as protein distribution and structure. This approach was used to monitor thermally induced modification of hair protein, including the conversion of α-helix to β-sheet and protein degradation. DSC measurements of thermally treated hair also demonstrated degradation of hair keratin. DVS of thermally treated hair shows the reduced water regain and lower water retention, compared to the non-thermally treated hair, which might be attributed to the protein conformation changes due to heat damage. The protection of native protein structure associated with selected polymer pretreatments leads to improved moisture restoration and water retention of hair. This contributes to heat control on repeated hot flat ironing. Thermally stressing hair led to significantly increased hair breakage when subjected to combing. These studies indicate that hair breakage can be reduced significantly when hair is pretreated with selected polymers such as VP/acrylates/lauryl methacrylate copolymer, polyquaternium-55, and a polyelectrolyte complex of PVM/MA copolymer and polyquaternium-28. In addition, polymeric pretreatments provide thermal protection against thermal degradation of keratin in the cortex as well as hair surface damage. The morphological improvement in cuticle integrity and smoothness with the polymer pretreatment plays an important role in their anti-breakage effect. Insights into structure-property relationships necessary to provide thermal protection to hair are presented.

  5. The antioxidant activity of sulphurous thermal water protects against oxidative DNA damage: a comet assay investigation.

    PubMed

    Braga, P C; Ceci, C; Marabini, L; Nappi, G

    2013-04-01

    Various studies have recently shown that sulphurous waters acts against the oxidants released during respiratory bursts of human neutrophils, and free radicals such as HO•, O2¯•, Tempol and Fremy's salt. However, there is still a lack of data concerning their direct protection of DNA. The aim of this study was to investigate the antigenotoxicity effects of sulphurous water, which has never been previously investigated for this purpose, using the alkaline single cell gel electrophoresis (SCGE) approach (comet assay). The comet assay is a sensitive method for assessing DNA fragmentation in individual cells in genotoxicity studies but can also be used to investigate the activity of agents that protect against DNA damage. The extent of migration was measured by means of SCGE, and DNA damage was expressed as tail moment. All of these assays were made using natural sulphurous water, degassed sulphurous water (no detectable HS), and reconstituted sulphurous water (degassed plus NaHS). DNA damages was significantly inhibited by natural water with HS concentrations of 5.0 and 2.5 μg/mL. The use of degassed water did not lead to any significant differences from baseline values, whereas the reconstituted water led to significant results overlapping those obtained using natural water. These findings confirm the importance of the presence of an HS group (reductive activity) and indicate that, in addition to their known mucolytic activity and trophic effects on respiratory mucosa, HS groups in sulphurous water also protect against oxidative DNA damage and contribute to the water's therapeutic effects on upper and lower airway inflammatory diseases.

  6. The effect of various cosmetic pretreatments on protecting hair from thermal damage by hot flat ironing.

    PubMed

    Zhou, Y; Rigoletto, R; Koelmel, D; Zhang, G; Gillece, T W; Foltis, L; Moore, D J; Qu, X; Sun, C

    2011-01-01

    Hot flat irons are used to create straight hair styles. As these devices operate at temperatures over 200 °C they can cause significant damage to hair keratin. In this study, hair thermal damage and the effect of various polymeric pretreatments were investigated using FTIR imaging spectroscopy, DSC, dynamic vapor sorption (DVS), AFM, SEM, and thermal image analysis. FTIR imaging spectroscopy of hair cross sections provides spatially resolved molecular information such as protein distribution and structure. This approach was used to monitor thermally induced modification of hair protein, including the conversion of α-helix to β-sheet and protein degradation. DSC measurements of thermally treated hair also demonstrated degradation of hair keratin. DVS of thermally treated hair shows the reduced water regain and lower water retention, compared to the non-thermally treated hair, which might be attributed to the protein conformation changes due to heat damage. The protection of native protein structure associated with selected polymer pretreatments leads to improved moisture restoration and water retention of hair. This contributes to heat control on repeated hot flat ironing. Thermally stressing hair led to significantly increased hair breakage when subjected to combing. These studies indicate that hair breakage can be reduced significantly when hair is pretreated with selected polymers such as VP/acrylates/lauryl methacrylate copolymer, polyquaternium-55, and a polyelectrolyte complex of PVM/MA copolymer and polyquaternium-28. In addition, polymeric pretreatments provide thermal protection against thermal degradation of keratin in the cortex as well as hair surface damage. The morphological improvement in cuticle integrity and smoothness with the polymer pretreatment plays an important role in their anti-breakage effect. Insights into structure-property relationships necessary to provide thermal protection to hair are presented. PMID:21635854

  7. Investigation of large transit vehicle accidents and establishing appropriate protection for wheelchair riders.

    PubMed

    Shaw, Greg

    2008-01-01

    Securing wheelchairs and restraining wheelchair riders on buses is difficult for many wheelchair riders and transit providers. This study examined injury-producing events aboard large transit buses in general in an attempt to better understand the potential risks and required protection for wheelchair users. The study found that few injuries and fatalities occur on large transit buses. Examination of the relatively few injury-producing events advanced the understanding of these events in terms of acceleration/deceleration magnitude and direction. Low acceleration/deceleration, or low-g, events such as those involving abrupt braking or turning occur frequently and are associated with approximately half of onboard passenger injuries. Unfortunately, the actual frequency of high-g events was not determined. Most of the injurious events involved the bus rapidly decelerating because of frontal impacts with another vehicle or roadside object. Further study is needed to determine the magnitude and frequency of high-g events. This information is necessary to determine the level of protection commensurate with real-world risk necessary for wheelchair riders in the transit bus environment and may ultimately facilitate the development of easier-to-use safety systems that secure and restrain wheelchairs and their riders.

  8. Protected areas mitigate diseases of reef-building corals by reducing damage from fishing.

    PubMed

    Lamb, Joleah B; Williamson, David H; Russ, Garry R; Willis, Bette L

    2015-09-01

    Parks and protected areas have been instrumental in reducing anthropogenic sources of damage in terrestrial and aquatic environments. Pathogen invasion often succeeds physical wounding and injury, yet links between the reduction of damage and the moderation of disease have not been assessed. Here, we examine the utility of no-take marine reserves as tools for mitigating diseases that affect reef-building corals. We found that sites located within reserves had fourfold reductions in coral disease prevalence compared to non-reserve sites (80466 corals surveyed). Of 31 explanatory variables assessed, coral damage and the abundance of derelict fishing line best explained differences in disease assemblages between reserves and non-reserves. Unexpectedly, we recorded significantly higher levels of disease, coral damage, and derelict fishing line in non-reserves with fishing gear restrictions than in those without gear restrictions. Fishers targeting stocks perceived to be less depleted, coupled with enhanced site access from immediately adjacent boat moorings, may explain these unexpected patterns. Significant correlations between the distance from mooring sites and prevalence values for a ciliate disease known to infest wounded tissue (r = -0.65), coral damage (r = -0.64), and the abundance of derelict fishing line (r = -0.85) corroborate this interpretation. This is the first study to link disease with recreational use intensity in a park, emphasizing the need to evaluate the placement of closures and their direct relationship to ecosystem health. Since corals are modular, ecological processes that govern reproductive and competitive fitness are frequently related to colony surface area therefore, even low levels of cumulative tissue loss from progressing diseases pose significant threats to reef coral persistence. Disease mitigation through reductions in physical injury in areas where human activities are concentrated is another mechanism by which protected areas may

  9. Protected areas mitigate diseases of reef-building corals by reducing damage from fishing.

    PubMed

    Lamb, Joleah B; Williamson, David H; Russ, Garry R; Willis, Bette L

    2015-09-01

    Parks and protected areas have been instrumental in reducing anthropogenic sources of damage in terrestrial and aquatic environments. Pathogen invasion often succeeds physical wounding and injury, yet links between the reduction of damage and the moderation of disease have not been assessed. Here, we examine the utility of no-take marine reserves as tools for mitigating diseases that affect reef-building corals. We found that sites located within reserves had fourfold reductions in coral disease prevalence compared to non-reserve sites (80466 corals surveyed). Of 31 explanatory variables assessed, coral damage and the abundance of derelict fishing line best explained differences in disease assemblages between reserves and non-reserves. Unexpectedly, we recorded significantly higher levels of disease, coral damage, and derelict fishing line in non-reserves with fishing gear restrictions than in those without gear restrictions. Fishers targeting stocks perceived to be less depleted, coupled with enhanced site access from immediately adjacent boat moorings, may explain these unexpected patterns. Significant correlations between the distance from mooring sites and prevalence values for a ciliate disease known to infest wounded tissue (r = -0.65), coral damage (r = -0.64), and the abundance of derelict fishing line (r = -0.85) corroborate this interpretation. This is the first study to link disease with recreational use intensity in a park, emphasizing the need to evaluate the placement of closures and their direct relationship to ecosystem health. Since corals are modular, ecological processes that govern reproductive and competitive fitness are frequently related to colony surface area therefore, even low levels of cumulative tissue loss from progressing diseases pose significant threats to reef coral persistence. Disease mitigation through reductions in physical injury in areas where human activities are concentrated is another mechanism by which protected areas may

  10. Anatomy of an Accident.

    ERIC Educational Resources Information Center

    Mobley, Michael

    1984-01-01

    The findings of industrial safety engineers in the areas of accident causation and prevention are wholly applicable to adventure programs. Adventure education instructors can use safety engineering concepts to assess the risk in a particular activity, understand factors that cause accidents, and intervene to minimize injuries and damages if…

  11. Protective Effect of Acacia nilotica (L.) against Acetaminophen-Induced Hepatocellular Damage in Wistar Rats

    PubMed Central

    Kannan, Narayanan; Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

    2013-01-01

    The potential biological functions of A. nilotica have long been described in traditional system of medicine. However, the protective effect of A. nilotica on acetaminophen-induced hepatotoxicity is still unknown. The present study attempted to investigate the protective effect of A. nilotica against acetaminophen-induced hepatic damage in Wistar rats. The biochemical liver functional tests Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin, total protein, oxidative stress test (Lipid peroxidation), antioxidant parameter glutathione (GSH), and histopathological changes were examined. Our results show that the pretreatment with A. nilotica (250 mg/kg·bw) orally revealed attenuation of serum activities of ALT, AST, ALP, liver weight, and total bilirubin levels that were enhanced by administration of acetaminophen. Further, pretreatment with extract elevated the total protein and GSH level and decreased the level of LPO. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by acetaminophen. The present study undoubtedly provides a proof that hepatoprotective action of A. nilotica extract may rely on its effect on reducing the oxidative stress in acetaminophen-induced hepatic damage in rat model. PMID:23864853

  12. YAP activation protects urothelial cell carcinoma from treatment-induced DNA damage

    PubMed Central

    Ciamporcero, Eric; Shen, He; Ramakrishnan, Swathi; Ku, Sheng Yu; Chintala, Sreenivasulu; Shen, Li; Adelaiye, Remi; Miles, Kiersten Marie; Ullio, Chiara; Pizzimenti, Stefania; Daga, Martina; Azabdaftari, Gissou; Attwood, Kris; Johnson, Candace; Zhang, Jianmin; Barrera, Giuseppina; Pili, Roberto

    2015-01-01

    Current standard of care for muscle-invasive urothelial cell carcinoma (UCC) is surgery along with perioperative platinum-based chemotherapy. UCC is sensitive to cisplatin-based regimens, but acquired resistance eventually occurs, and a subset of tumors is intrinsically resistant. Thus, there is an unmet need for new therapeutic approaches to target chemotherapy-resistant UCC. Yes-associated protein (YAP) is a transcriptional co-activator that has been associated with bladder cancer progression and cisplatin resistance in ovarian cancer. In contrast, YAP has been shown to induce DNA damage associated apoptosis in non-small cell lung carcinoma. However, no data have been reported on the YAP role in UCC chemo-resistance. Thus, we have investigated the potential dichotomous role of YAP in UCC response to chemotherapy utilizing two patient-derived xenograft models recently established. Constitutive expression and activation of YAP inversely correlated with in vitro and in vivo cisplatin sensitivity. YAP overexpression protected while YAP knock-down sensitized UCC cells to chemotherapy and radiation effects via increased accumulation of DNA damage and apoptosis. Furthermore, pharmacological YAP inhibition with verteporfin inhibited tumor cell proliferation and restored sensitivity to cisplatin. In addition, nuclear YAP expression was associated with poor outcome in UCC patients who received perioperative chemotherapy. In conclusion, these results suggest that YAP activation exerts a protective role and represents a pharmacological target to enhance the anti-tumor effects of DNA damaging modalities in the treatment of UCC. PMID:26119935

  13. Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage

    NASA Astrophysics Data System (ADS)

    Webb, Andrew; Bond, Richard; McLean, Peter; Uppal, Rakesh; Benjamin, Nigel; Ahluwalia, Amrita

    2004-09-01

    Nitric oxide (NO) is thought to protect against the damaging effects of myocardial ischemia-reperfusion injury, whereas xanthine oxidoreductase (XOR) normally causes damage through the generation of reactive oxygen species. In the heart, inorganic nitrite has the potential to act as an endogenous store of NO, liberated specifically during ischemia. Using a detection method that we developed, we report that under ischemic conditions both rat and human homogenized myocardium and the isolated perfused rat heart (Langendorff preparation) generate NO from in a reaction that depends on XOR activity. Functional studies of rat hearts in the Langendorff apparatus showed that nitrite (10 and 100 µM) reduced infarct size from 47.3 ± 2.8% (mean percent of control ± SEM) to 17.9 ± 4.2% and 17.4 ± 1.0%, respectively (P < 0.001), and was associated with comparable improvements in recovery of left ventricular function. This protective effect was completely blocked by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (carboxy-PTIO). In summary, the generation of NO from •, rather than damaging.

  14. Antioxidative Activity of Platinum Nanocolloid and Its Protective Effect Against Chemical-Induced Hepatic Cellular Damage.

    PubMed

    Choi, Mi-Ran; Do, Le Thanh; Chung, Yong-Hoon; Yoo, Hoon; Yu, Rina

    2015-08-01

    Oxidative stress, a major cause of cellular injuries, is closely associated with a variety of chronic diseases such as cancer, liver diseases, degenerative brain disease and aging. In this study, we investigated antioxidant properties of platinum nanocolloid (PNC) against various oxidative stress conditions in vitro/in vivo by treating PNC on liver cell or tissue. Antioxidant activities of the PNC were determined by measuring quenching capacity on reactive oxygen species and its protective action against hydrogen peroxide or CCl4-induced oxidative cellular damage in HepG2 cell or liver tissue of mice. In vitro study, PNC markedly suppressed the production H2O2, ·OH, α,α-diphenyl-β-picrylhydrazyl radical and nitric oxide in a dose-dependent manner. PNC also inhibited hydrogen peroxide-induced oxidative cellular damage in HepG2 hepatocytes. In vivo study with mice, PNC reduced hepatic lipid peroxidation and CCl4 induced toxicity. Our results support that platinum nanocolloid has antioxidant activities and protects hepatic cellular oxidative damage. Thus platinum nanocolloid may have a potential to be used as an antioxidant supplement.

  15. Ganglioside GT1b protects human spermatozoa from hydrogen peroxide-induced DNA and membrane damage.

    PubMed

    Gavella, Mirjana; Garaj-Vrhovac, Verica; Lipovac, Vaskresenija; Antica, Mariastefania; Gajski, Goran; Car, Nikica

    2010-06-01

    We have reported previously that various gangliosides, the sialic acid containing glycosphingolipids, provide protection against sperm injury caused by reactive oxygen species (ROS). In this study, we investigated the effect of treatment of human spermatozoa with ganglioside GT1b on hydrogen peroxide (H(2)O(2))-induced DNA fragmentation and plasma membrane damage. Single-cell gel electrophoresis (Comet assay) used in the assessment of sperm DNA integrity showed that in vitro supplemented GT1b (100 microm) significantly reduced DNA damage induced by H(2)O(2) (200 microm) (p < 0.05). Measurements of Annexin V binding in combination with the propidium iodide vital dye labelling demonstrated that the spermatozoa pre-treated with GT1b exhibited a significant increase (p < 0.05) in the percentage of live cells with intact membrane and decreased phosphatidylserine translocation after exposure to H(2)O(2). Flow cytometry using the intracellular ROS-sensitive fluorescence dichlorodihydrofluorescein diacetate dye employed to investigate the transport of the extracellularly supplied H(2)O(2) into the cell interior revealed that ganglioside GT1b completely inhibited the passage of H(2)O(2) through the sperm membrane. These results suggest that ganglioside GT1b may protect human spermatozoa from H(2)O(2)-induced damage by rendering sperm membrane more hydrophobic, thus inhibiting the diffusion of H(2)O(2) across the membrane.

  16. Hydroxytyrosol glucuronides protect renal tubular epithelial cells against H(2)O(2) induced oxidative damage.

    PubMed

    Deiana, Monica; Incani, Alessandra; Rosa, Antonella; Atzeri, Angela; Loru, Debora; Cabboi, Barbara; Paola Melis, M; Lucas, Ricardo; Morales, Juan C; Assunta Dessì, M

    2011-09-30

    Hydroxytyrosol (2-(3',4'-dihydroxyphenyl)ethanol; HT), the most active ortho-diphenolic compound, present either in free or esterified form in extravirgin olive oil, is extensively metabolized in vivo mainly to O-methylated, O-sulfated and glucuronide metabolites. We investigated the capacity of three glucuronide metabolites of HT, 3'-O-β-d-glucuronide and 4'-O-β-d-glucuronide derivatives and 2-(3',4'-dihydroxyphenyl)ethanol-1-O-β-d-glucuronide, in comparison with the parent compound, to inhibit H(2)O(2) induced oxidative damage and cell death in LLC-PK1 cells, a porcine kidney epithelial cell line. H(2)O(2) treatment exerted a toxic effect inducing cell death, interacting selectively within the pro-death extracellular-signal relate kinase (ERK 1/2) and the pro-survival Akt/PKB signaling pathways. It also produced direct oxidative damage initiating the membrane lipid peroxidation process. None of the tested glucuronides exhibited any protection against the loss in renal cell viability. They also failed to prevent the changes in the phosphorylation states of ERK and Akt, probably reflecting their inability to enter the cells, while HT was highly effective. Notably, pretreatment with glucuronides exerted a protective effect at the highest concentration tested against membrane oxidative damage, comparable to that of HT: the formation of malondialdehyde, fatty acid hydroperoxides and 7-ketocholesterol was significantly inhibited.

  17. p53-dependent SIRT6 expression protects Aβ42-induced DNA damage

    PubMed Central

    Jung, Eun Sun; Choi, Hyunjung; Song, Hyundong; Hwang, Yu Jin; Kim, Ahbin; Ryu, Hoon; Mook-Jung, Inhee

    2016-01-01

    Alzheimer’s disease (AD) is the most common type of dementia and age-related neurodegenerative disease. Elucidating the cellular changes that occur during ageing is an important step towards understanding the pathogenesis and progression of neurodegenerative disorders. SIRT6 is a member of the mammalian sirtuin family of anti-aging genes. However, the relationship between SIRT6 and AD has not yet been elucidated. Here, we report that SIRT6 protein expression levels are reduced in the brains of both the 5XFAD AD mouse model and AD patients. Aβ42, a major component of senile plaques, decreases SIRT6 expression, and Aβ42-induced DNA damage is prevented by the overexpression of SIRT6 in HT22 mouse hippocampal neurons. Also, there is a strong negative correlation between Aβ42-induced DNA damage and p53 levels, a protein involved in DNA repair and apoptosis. In addition, upregulation of p53 protein by Nutlin-3 prevents SIRT6 reduction and DNA damage induced by Aβ42. Taken together, this study reveals that p53-dependent SIRT6 expression protects cells from Aβ42-induced DNA damage, making SIRT6 a promising new therapeutic target for the treatment of AD. PMID:27156849

  18. Tempol protects blood proteins and lipids against peroxynitrite-mediated oxidative damage

    PubMed Central

    Mustafa, Ayman G; Bani-Ahmad, Mohammad A; Jaradat, Ahmad Q

    2015-01-01

    Oxidative stress is characterized by excessive production of various free radicals and reactive species among which, peroxynitrite is most frequently produced in several pathological conditions. Peroxynitrite is the product of the superoxide anion reaction with nitric oxide, which is reported to take place in the intravascular compartment. Several studies have reported that peroxynitrite targets red blood cells, platelets and plasma proteins, and induces various forms of oxidative damage. This in vitro study was designed to further characterize the types of oxidative damage induced in platelets and plasma proteins by peroxynitrite. This study also determined the ability of tempol to protect blood plasma and platelets against peroxynitrite-induced oxidative damage. The ability of various concentrations of tempol (25, 50, 75, and 100 µM) to antagonize peroxynitrite-induced oxidation was evaluated by measuring the levels of protein carbonyl groups and thiobarbituric-acid-reactive substances in experimental groups. Exposure of platelets and plasma to 100 µM peroxynitrite resulted in an increased levels of carbonyl groups and lipid peroxidation (P < 0.05). Tempol significantly inhibited carbonyl group formation in plasma and platelet proteins (P < 0.05). In addition, tempol significantly reduced the levels of lipid peroxidation in both plasma and platelet samples (P < 0.05). Thus, tempol has antioxidative properties against peroxynitrite-induced oxidative damage in blood plasma and platelets. PMID:25107897

  19. Edaravone protect against retinal damage in streptozotocin-induced diabetic mice.

    PubMed

    Yuan, Dongqing; Xu, Yidan; Hang, Hui; Liu, Xiaoyi; Chen, Xi; Xie, Ping; Yuan, Songtao; Zhang, Weiwei; Lin, Xiaojun; Liu, Qinghuai

    2014-01-01

    Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, is used for the clinical treatment of retinal injury. In this study, we investigated the protective effects of edaravone against diabetic retinal damage in the mouse. Diabetic retinopathy in the mouse was induced by injection of streptozotocin. Edaravone was given once-daily and was intraperitoneally (i.p.) treated at a dose of 3 mg/kg from streptozotocin injection to 4 weeks after onset of diabetes. Retinal ganglion cells (RGCs) damage was evaluated by recording the pattern electroretinogram (ERG). RGCs damage was also detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of reactive oxygen species (ROS) were determined fluorometrically. The expressions of phosporylated-ERK1/2, BDNF, and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expression of BDNF was significantly decreased in the retinas of diabetic mice, compared to nondiabetic mice. Administration of edaravone significantly attenuated diabetes induced RGCs death, upregulation of ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and downregulation of BDNF. These findings suggest that oxidative stress plays a pivotal role in diabetic retinal damage and that systemic administration of edaravone may slow the progression of retinal neuropathy induced by diabetes.

  20. Ginger-derived nanoparticles protect against alcohol-induced liver damage.

    PubMed

    Zhuang, Xiaoying; Deng, Zhong-Bin; Mu, Jingyao; Zhang, Lifeng; Yan, Jun; Miller, Donald; Feng, Wenke; McClain, Craig J; Zhang, Huang-Ge

    2015-01-01

    Daily exposure of humans to nanoparticles from edible plants is inevitable, but significant advances are required to determine whether edible plant nanoparticles are beneficial to our health. Additionally, strategies are needed to elucidate the molecular mechanisms underlying any beneficial effects. Here, as a proof of concept, we used a mouse model to show that orally given nanoparticles isolated from ginger extracts using a sucrose gradient centrifugation procedure resulted in protecting mice against alcohol-induced liver damage. The ginger-derived nanoparticle (GDN)-mediated activation of nuclear factor erythroid 2-related factor 2 (Nrf2) led to the expression of a group of liver detoxifying/antioxidant genes and inhibited the production of reactive oxygen species, which partially contributes to the liver protection. Using lipid knock-out and knock-in strategies, we further identified that shogaol in the GDN plays a role in the induction of Nrf2 in a TLR4/TRIF-dependent manner. Given the critical role of Nrf2 in modulating numerous cellular processes, including hepatocyte homeostasis, drug metabolism, antioxidant defenses, and cell-cycle progression of liver, this finding not only opens up a new avenue for investigating GDN as a means to protect against the development of liver-related diseases such as alcohol-induced liver damage but sheds light on studying the cellular and molecular mechanisms underlying interspecies communication in the liver via edible plant-derived nanoparticles. PMID:26610593

  1. Nrf2 protects against As(III)-induced damage in mouse liver and bladder.

    PubMed

    Jiang, Tao; Huang, Zheping; Chan, Jefferson Y; Zhang, Donna D

    2009-10-01

    Arsenic compounds are classified as toxicants and human carcinogens. Environmental exposure to arsenic imposes a big health issue worldwide. Arsenic elicits its toxic efforts through many mechanisms, including generation of reactive oxygen species (ROS). Nrf2 is the primary transcription factor that controls expression of a main cellular antioxidant response, which is required for neutralizing ROS and thus defending cells from exogenous insults. Previously, we demonstrated a protective role of Nrf2 against arsenic-induced toxicity using a cell culture model. In this report, we present evidence that Nrf2 protects against liver and bladder injury in response to six weeks of arsenic exposure in a mouse model. Nrf2(-/-) mice displayed more severe pathological changes in the liver and bladder, compared to Nrf2(+/+) mice. Furthermore, Nrf2(-/-) mice were more sensitive to arsenic-induced DNA hypomethylation, oxidative DNA damage, and apoptotic cell death. These results indicate a protective role of Nrf2 against arsenic toxicity in vivo. Hence, this work demonstrates the feasibility of using dietary compounds that target activation of the Nrf2 signaling pathway to alleviate arsenic-induced damage. PMID:19538980

  2. Nrf2 protects against As(III)-induced damage in mouse liver and bladder

    SciTech Connect

    Jiang Tao; Huang Zheping; Chan, Jefferson Y.; Zhang, Donna D.

    2009-10-01

    Arsenic compounds are classified as toxicants and human carcinogens. Environmental exposure to arsenic imposes a big health issue worldwide. Arsenic elicits its toxic efforts through many mechanisms, including generation of reactive oxygen species (ROS). Nrf2 is the primary transcription factor that controls expression of a main cellular antioxidant response, which is required for neutralizing ROS and thus defending cells from exogenous insults. Previously, we demonstrated a protective role of Nrf2 against arsenic-induced toxicity using a cell culture model. In this report, we present evidence that Nrf2 protects against liver and bladder injury in response to six weeks of arsenic exposure in a mouse model. Nrf2{sup -/-} mice displayed more severe pathological changes in the liver and bladder, compared to Nrf2{sup +/+} mice. Furthermore, Nrf2{sup -/-} mice were more sensitive to arsenic-induced DNA hypomethylation, oxidative DNA damage, and apoptotic cell death. These results indicate a protective role of Nrf2 against arsenic toxicity in vivo. Hence, this work demonstrates the feasibility of using dietary compounds that target activation of the Nrf2 signaling pathway to alleviate arsenic-induced damage.

  3. Nrf2 protects against As(III)-induced damage in mouse liver and bladder.

    PubMed

    Jiang, Tao; Huang, Zheping; Chan, Jefferson Y; Zhang, Donna D

    2009-10-01

    Arsenic compounds are classified as toxicants and human carcinogens. Environmental exposure to arsenic imposes a big health issue worldwide. Arsenic elicits its toxic efforts through many mechanisms, including generation of reactive oxygen species (ROS). Nrf2 is the primary transcription factor that controls expression of a main cellular antioxidant response, which is required for neutralizing ROS and thus defending cells from exogenous insults. Previously, we demonstrated a protective role of Nrf2 against arsenic-induced toxicity using a cell culture model. In this report, we present evidence that Nrf2 protects against liver and bladder injury in response to six weeks of arsenic exposure in a mouse model. Nrf2(-/-) mice displayed more severe pathological changes in the liver and bladder, compared to Nrf2(+/+) mice. Furthermore, Nrf2(-/-) mice were more sensitive to arsenic-induced DNA hypomethylation, oxidative DNA damage, and apoptotic cell death. These results indicate a protective role of Nrf2 against arsenic toxicity in vivo. Hence, this work demonstrates the feasibility of using dietary compounds that target activation of the Nrf2 signaling pathway to alleviate arsenic-induced damage.

  4. Protective effect of hemin against cadmium-induced testicular damage in rats.

    PubMed

    Fouad, Amr A; Qureshi, Habib A; Al-Sultan, Ali Ibrahim; Yacoubi, Mohamed T; Ali, Abdellah Abusrie

    2009-03-29

    The protective effect of hemin, the heme oxygenase-1 inducer, was investigated in rats with cadmium induced-testicular injury, in which oxidative stress and inflammation play a major role. Testicular damage was induced by a single i.p. injection of cadmium chloride (2mg/kg). Hemin was given for three consecutive days (40 micromol/kg/day, s.c.), starting 1 day before cadmium administration. Hemin treatment significantly increased serum testosterone level that was reduced by cadmium. Hemin compensated deficits in the antioxidant defense mechanisms (reduced glutathione, and catalase and superoxide dismutase activities), and suppressed lipid peroxidation in testicular tissue resulted from cadmium administration. Also, hemin attenuated the cadmium-induced elevations in testicular tumor necrosis factor-alpha and nitric oxide levels, and caspase-3 activity. Additionally, hemin ameliorated cadmium-induced testicular tissue damage observed by light and electron microscopic examinations. The protective effect afforded by hemin was abolished by prior administration of zinc protoporphyrin-IX, the heme oxygenase-1 inhibitor. It was concluded that hemin, through its antioxidant, anti-inflammatory and antiapoptotic effects, represents a potential therapeutic option to protect the testicular tissue from the detrimental effects of cadmium. PMID:19150641

  5. Ultrastructural confirmation of neuronal protection by melatonin against the neurotoxin 6-hydroxydopamine cell damage.

    PubMed

    Mayo, J C; Sainz, R M; Antolín, I; Rodriguez, C

    1999-02-13

    6-Hydroxydopamine (6-OHDA) is a neurotoxin used in the induction of experimental Parkinson's disease in both animals and cultured neuronal cells. Biochemical and molecular approaches showed previously that low doses of 6-OHDA induced apoptosis in PC12 cells, while high doses of this neurotoxin induced necrosis. Melatonin has been shown to protect against the neuronal programmed cell death induced by 6-OHDA, although it was not able to prevent the massive necrotic cellular death occurring after the addition of high doses of the neurotoxin. In the present work, we demonstrate by ultrastructural analysis that although low doses of 6-OHDA induced apoptosis in PC12 cells, it also damaged the non-apoptotic cells, morphologically corresponding this damage to incipient and reversible necrotic lesions. When the doses of the neurotoxin increase, there are still apoptotic cells, although most of the cells show necrotic irreversible lesions. We also found that melatonin partially prevents the incipient necrotic lesions caused by low doses of 6-OHDA. The fact that melatonin was shown in previous work to prevent apoptosis caused by low doses of 6-OHDA, but not necrosis induced by high doses of the neurotoxin, seemed to indicate that this agent is only able to protect against apoptosis. However, our present results, melatonin preventing also the incipient necrotic neuronal lesions, suggest that this hormone may provide a general protection against cell death, suggesting that higher doses should be tried in order to prevent the necrotic cell death induced by high doses of the neurotoxin.

  6. Protection of Erwinia amylovora bacteriophage Y2 from UV-induced damage by natural compounds

    PubMed Central

    Born, Yannick; Bosshard, Lars; Duffy, Brion; Loessner, Martin J.; Fieseler, Lars

    2015-01-01

    Bacteriophages have regained much attention as biocontrol agents against bacterial pathogens. However, with respect to stability, phages are biomolecules and are therefore sensitive to a number of environmental influences. UV-irradiation can readily inactivate phage infectivity, which impedes their potential application in the plant phyllosphere. Therefore, phages for control of Erwinia amylovora, the causative agent of fire blight, need to be protected from UV-damage by adequate measures. We investigated the protective effect of different light-absorbing substances on phage particles exposed to UV-light. For this, natural extracts from carrot, red pepper, and beetroot, casein and soy peptone in solution, and purified substances such as astaxanthin, aromatic amino acids, and Tween 80 were prepared and tested as natural sunscreens for phage. All compounds were found to significantly increase half-life of UV-irradiated phage particles and they did not negatively affect phage viability or infectivity. Altogether, a range of readily available, natural substances are suitable as UV-protectants to prevent phage particles from UV-light damage. PMID:26904378

  7. Crash protectiveness to occupant injury and vehicle damage: An investigation on major car brands.

    PubMed

    Huang, Helai; Li, Chunyang; Zeng, Qiang

    2016-01-01

    This study sets out to investigate vehicles' crash protectiveness on occupant injury and vehicle damage, which can be deemed as an extension of the traditional crash worthiness. A Bayesian bivariate hierarchical ordered logistic (BVHOL) model is developed to estimate the occupant protectiveness (OP) and vehicle protectiveness (VP) of 23 major car brands in Florida, with considering vehicles' crash aggressivity and controlling external factors. The proposed model not only takes over the strength of the existing hierarchical ordered logistic (HOL) model, i.e. specifying the order characteristics of crash outcomes and cross-crash heterogeneities, but also accounts for the correlation between the two crash responses, driver injury and vehicle damage. A total of 7335 two-vehicle-crash records with 14,670 cars involved in Florida are used for the investigation. From the estimation results, it's found that most of the luxury cars such as Cadillac, Volvo and Lexus possess excellent OP and VP while some brands such as KIA and Saturn perform very badly in both aspects. The ranks of the estimated safety performance indices are even compared to the counterparts in Huang et al. study [Huang, H., Hu, S., Abdel-Aty, M., 2014. Indexing crash worthiness and crash aggressivity by major car brands. Safety Science 62, 339-347]. The results show that the rank of occupant protectiveness index (OPI) is relatively coherent with that of crash worthiness index, but the ranks of crash aggressivity index in both studies is more different from each other. Meanwhile, a great discrepancy between the OPI rank and that of vehicle protectiveness index is found. What's more, the results of control variables and hyper-parameters estimation as well as comparison to HOL models with separate or identical threshold errors, demonstrate the validity and advancement of the proposed model and the robustness of the estimated OP and VP.

  8. Crash protectiveness to occupant injury and vehicle damage: An investigation on major car brands.

    PubMed

    Huang, Helai; Li, Chunyang; Zeng, Qiang

    2016-01-01

    This study sets out to investigate vehicles' crash protectiveness on occupant injury and vehicle damage, which can be deemed as an extension of the traditional crash worthiness. A Bayesian bivariate hierarchical ordered logistic (BVHOL) model is developed to estimate the occupant protectiveness (OP) and vehicle protectiveness (VP) of 23 major car brands in Florida, with considering vehicles' crash aggressivity and controlling external factors. The proposed model not only takes over the strength of the existing hierarchical ordered logistic (HOL) model, i.e. specifying the order characteristics of crash outcomes and cross-crash heterogeneities, but also accounts for the correlation between the two crash responses, driver injury and vehicle damage. A total of 7335 two-vehicle-crash records with 14,670 cars involved in Florida are used for the investigation. From the estimation results, it's found that most of the luxury cars such as Cadillac, Volvo and Lexus possess excellent OP and VP while some brands such as KIA and Saturn perform very badly in both aspects. The ranks of the estimated safety performance indices are even compared to the counterparts in Huang et al. study [Huang, H., Hu, S., Abdel-Aty, M., 2014. Indexing crash worthiness and crash aggressivity by major car brands. Safety Science 62, 339-347]. The results show that the rank of occupant protectiveness index (OPI) is relatively coherent with that of crash worthiness index, but the ranks of crash aggressivity index in both studies is more different from each other. Meanwhile, a great discrepancy between the OPI rank and that of vehicle protectiveness index is found. What's more, the results of control variables and hyper-parameters estimation as well as comparison to HOL models with separate or identical threshold errors, demonstrate the validity and advancement of the proposed model and the robustness of the estimated OP and VP. PMID:26551733

  9. Isorhamnetin Protects Human Keratinocytes against Ultraviolet B-Induced Cell Damage

    PubMed Central

    Han, Xia; Piao, Mei Jing; Kim, Ki Cheon; Madduma Hewage, Susara Ruwan Kumara; Yoo, Eun Sook; Koh, Young Sang; Kang, Hee Kyoung; Shin, Jennifer H; Park, Yeunsoo; Yoo, Suk Jae; Chae, Sungwook; Hyun, Jin Won

    2015-01-01

    Isorhamnetin (3-methylquercetin) is a flavonoid derived from the fruits of certain medicinal plants. This study investigated the photoprotective properties of isorhamnetin against cell damage and apoptosis resulting from excessive ultraviolet (UV) B exposure in human HaCaT keratinocytes. Isorhamnetin eliminated UVB-induced intracellular reactive oxygen species (ROS) and attenuated the oxidative modification of DNA, lipids, and proteins in response to UVB radiation. Moreover, isorhamnetin repressed UVB-facilitated programmed cell death in the keratinocytes, as evidenced by a reduction in apoptotic body formation, and nuclear fragmentation. Additionally, isorhamnetin suppressed the ability of UVB light to trigger mitochondrial dysfunction. Taken together, these results indicate that isorhamnetin has the potential to protect human keratinocytes against UVB-induced cell damage and death. PMID:26157553

  10. Hydrolysates of citrus plants stimulate melanogenesis protecting against UV-induced dermal damage.

    PubMed

    Chiang, Hsiu-Mei; Lin, Jen-Wen; Hsiao, Pei-Ling; Tsai, Shang-Yuan; Wen, Kuo-Ching

    2011-04-01

    The sun-tanning process occurs as a spontaneous response to ultraviolet (UV) irradiation. UV will induce tanning and DNA damage, processes that can lead to photoaging and skin disorders such as hyperpigmentation and cancer. The pigment melanin protects skin from UV damage; therefore, an efficient melanin-promoting suntan lotion could be highly beneficial. In this study, a process was developed to increase the content of naringenin in citrus extracts and to determine whether a higher naringenin content of citrus would induce melanogenesis. Melanin content and tyrosinase expression in mouse B16 melanoma cells were assayed after treatment with citrus plant extracts and their hydrolysates. The results indicate that hydrolysis increased the naringenin content in citrus extracts and that citrus preparations stimulated cellular melanogenesis and tyrosinase expression. It is suggested that this method is applicable to the industrial production of melanin-promoting suntan lotions with antiphotocarcinogenic properties derived from citrus rind and citrus products.

  11. Isorhamnetin Protects Human Keratinocytes against Ultraviolet B-Induced Cell Damage.

    PubMed

    Han, Xia; Piao, Mei Jing; Kim, Ki Cheon; Madduma Hewage, Susara Ruwan Kumara; Yoo, Eun Sook; Koh, Young Sang; Kang, Hee Kyoung; Shin, Jennifer H; Park, Yeunsoo; Yoo, Suk Jae; Chae, Sungwook; Hyun, Jin Won

    2015-07-01

    Isorhamnetin (3-methylquercetin) is a flavonoid derived from the fruits of certain medicinal plants. This study investigated the photoprotective properties of isorhamnetin against cell damage and apoptosis resulting from excessive ultraviolet (UV) B exposure in human HaCaT keratinocytes. Isorhamnetin eliminated UVB-induced intracellular reactive oxygen species (ROS) and attenuated the oxidative modification of DNA, lipids, and proteins in response to UVB radiation. Moreover, isorhamnetin repressed UVB-facilitated programmed cell death in the keratinocytes, as evidenced by a reduction in apoptotic body formation, and nuclear fragmentation. Additionally, isorhamnetin suppressed the ability of UVB light to trigger mitochondrial dysfunction. Taken together, these results indicate that isorhamnetin has the potential to protect human keratinocytes against UVB-induced cell damage and death. PMID:26157553

  12. Protective effects of Healon and Occucoat against air bubble endothelial damage during ultrasonic agitation of the anterior chamber.

    PubMed

    Monson, M C; Tamura, M; Mamalis, N; Olson, R J; Olson, R J

    1991-09-01

    An important aspect of any new viscoelastic substance is the corneal endothelial protection. We compared the protective effects of sodium hyaluronate (Healon) and hydroxypropylmethylcellulose (Occucoat) by introducing a controlled volume of air bubbles into the anterior chamber of human eye bank eyes during ultrasonic agitation of the anterior chamber. Eight eyes received Healon and 11 eyes received Occucoat. Damage to endothelial cells in the central cornea was quantified by vital staining. Endothelial damage averaged 4.5% in eyes in which no viscoelastic was used (positive control); damage was 0.4% in eyes in which a viscoelastic was injected but no air bubbles were introduced (negative control). We found that endothelial damage averaged 4.25% in specimens that received air plus Healon and 1.4% in specimens that received air plus Occucoat. Occucoat appeared to have somewhat better protective effects than Healon against air bubble damage to the corneal endothelium during ultrasonic agitation of the anterior chamber.

  13. Protection from radiation-induced damage to spermatogenesis by hormone treatment

    SciTech Connect

    Kurdoglu, B.; Wilson, G.; Parchuri, N.; Ye, W.; Meistrich, M.L.

    1994-07-01

    Infertility caused by killing of the spermatogonial stem cells occurs frequently in men treated for cancer with radiotherapy and chemotherapy. We investigated whether pretreatment of rats with testosterone plus estradiol, which reversibly inhibits the completion of spermatogenesis and protects spermatogonial stem cells from procarbazine-induced damage, would also protect these cells from radiation. Adult male LBNF rats were implanted for 6 weeks with capsules containing testosterone and estradiol and then irradiated with doses from 2.5-7.0 Gy. Controls were irradiated with 1.8-3.5 Gy. Implants were removed 1 day after irradiation, and all animals were killed 10 weeks later for assessment of stem cell survival by counting repopulating tubules in histological sections and by sperm head counts. At doses of 2.5 and 3.5 Gy the repopulation indices and sperm head counts were significantly higher (P < 0.001) in the rats treated with testosterone and estradiol than in the controls. Protection factors calculated from the dose-response curves were in the range of 1.5-2.2. Elucidation of the mechanism of protection is essential to apply it to clinical situations. The fact that the spermatogonia are protected against radiation as well as procarbazine indicates that the mechanism does not involve drug delivery or metabolism. 32 refs., 3 figs.

  14. Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain

    PubMed Central

    Rump, Travis J.; Muneer, P.M. Abdul; Szlachetka, Adam M.; Lamb, Allyson; Haorei, Catherine; Alikunju, Saleena; Xiong, Huangui; Keblesh, James; Liu, Jianuo; Zimmerman, Matthew C.; Jones, Jocelyn; Donohue, Terrence M.; Persidsky, Yuri; Haorah, James

    2011-01-01

    The studies presented here demonstrate the protective effect of acetyl-L-carnitine (ALC) against alcohol-induced oxidative neuroinflammation, neuronal degeneration, and impaired neurotransmission. Our findings reveal the cellular and biochemical mechanisms of alcohol-induced oxidative damage in various types of brain cells. Chronic ethanol administration to mice caused an increase in inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine adduct formation in frontal cortical neurons but not in astrocytes from brains of these animals. Interestingly, alcohol administration caused a rather selective activation of NADPH oxidase (NOX), which, in turn, enhanced levels of reactive oxygen species (ROS) and 4-hydroxynonenal, but these were predominantly localized in astrocytes and microglia. Oxidative damage in glial cells was accompanied by their pronounced activation (astrogliosis) and coincident neuronal loss, suggesting that inflammation in glial cells caused neuronal degeneration. Immunohistochemistry studies indicated that alcohol consumption induced different oxidative mediators in different brain cell types. Thus, nitric oxide was mostly detected in iNOS-expressing neurons, whereas ROS were predominantly generated in NOX-expressing glial cells after alcohol ingestion. Assessment of neuronal activity in ex vivo frontal cortical brain tissue slices from ethanol-fed mice showed a reduction in long-term potentiation synaptic transmission compared with slices from controls. Coadministration of ALC with alcohol showed a significant reduction in oxidative damage and neuronal loss and a restoration of synaptic neurotransmission in this brain region, suggesting that ALC protects brain cells from ethanol-induced oxidative injury. These findings suggest the potential clinical utility of ALC as a neuroprotective agent that prevents alcohol-induced brain damage and development of neurological disorders. PMID:20708681

  15. Protection against UVA-induced photooxidative damage in mammalian cell lines expressing increased levels of metallothionein

    SciTech Connect

    Dudek, E.J. Illinois Inst. of Tech., Chicago, IL . Dept. of Biology); Peak, J.G.; Peak, M.J. ); Roth, R.M. . Dept. of Biology)

    1990-01-01

    Metallothionein (MT) is an endogenous low molecular weight protein that is inducible in a variety of eukaryotic cells and has the ability to selectivity bind heavy metal ions such as zinc and the cadmium. Although the exact physiological role of MT is still not understood, there is strong evidence that MT is involved in providing cellular resistance against the damaging effects of heavy metals and in the regulation of intracellular zinc and copper. Recently, it has been demonstrated that MT can scavenge radiation-induced reactive oxygen intermediates in vitro, specifically hydroxyl and superoxide radicals, and because of these observations it has been suggested that MT may provide protection against radiation-induced oxidative stress in vivo. Cell lines expressing increased levels of MT have demonstrated resistance to ionizing radiation, to ultraviolet radiation, and also to various DNA damaging agents including melphalan and cis-diaminedichloroplatinum. It is therefore important to gain some insight into the relationship between cellular MT content and cellular resistance to radiation and other DNA damaging agents. In this study we investigated the role of MT in providing protection against monochromatic 365-nm UVA radiation, which is known to generate intracellular reactive oxygen species that are involved in both DNA damage and cell killing. For this purpose, we used zinc acetate, a potent inducer of MT, to elevate MT levels in V79 Chinese hamster fibroblasts prior to UVA exposure and determined cell survival for uninduced and induced cultures. In order to eliminate any zinc effects other than MT induction, we also isolated and characterized cadmium chloride-resistant clones of V79 cells that have increased steady-state levels of both MT mRNA and protein, and we examined their survival characteristics against 365-nm radiation in the absence of zinc acetate. 14 refs., 3 figs.

  16. Milk phospholipid's protective effects against UV damage in skin equivalent models

    NASA Astrophysics Data System (ADS)

    Dargitz, Carl; Russell, Ashley; Bingham, Michael; Achay, Zyra; Jimenez-Flores, Rafael; Laiho, Lily H.

    2012-03-01

    Exposure of skin tissue to UV radiation has been shown to cause DNA photodamage. If this damaged DNA is allowed to replicate, carcinogenesis may occur. DNA damage is prevented from being passed on to daughter cells by upregulation of the protein p21. p21 halts the cells cycle allowing the cell to undergo apoptosis, or repair its DNA before replication. Previous work suggested that milk phospholipids may possess protective properties against UV damage. In this study, we observed cell morphology, cell apoptosis, and p21 expression in tissue engineered epidermis through the use of Hematoxylin and Eosin staining, confocal microscopy, and western blot respectively. Tissues were divided into four treatment groups including: a control group with no UV and no milk phospholipid treatment, a group exposed to UV alone, a group incubated with milk phospholipids alone, and a group treated with milk phospholipids and UV. All groups were incubated for twenty-four hours after treatment. Tissues were then fixed, processed, and embedded in paraffin. Performing western blots resulted in visible p21 bands for the UV group only, implying that in every other group, p21 expression was lesser. Numbers of apoptotic cells were determined by observing the tissues treated with Hoechst dye under a confocal microscope, and counting the number of apoptotic and total cells to obtain a percentage of apoptotic cells. We found a decrease in apoptotic cells in tissues treated with milk phospholipids and UV compared to tissues exposed to UV alone. Collectively, these results suggest that milk phospholipids protect cell DNA from damage incurred from UV light.

  17. Protective effect of carboxymethyl-glucan (CM-G) against DNA damage in patients with advanced prostate cancer.

    PubMed

    Magnani, Marciane; Castro-Gomez, Raul Jorge Hernan; Mori, Mateus Prates; Kuasne, Hellen; Gregório, Emerson Pereira; Libos, Farid; de Syllos Cólus, Ilce Mara

    2011-01-01

    Carboxymethyl-glucan (CM-G) is a soluble derivative from Saccharomyces cerevisiae (1 → 3)(1 → 6)-β-D-glucan. The protective efficiency of CM-G against DNA damage in cells from patients with advanced prostate cancer (PCa), and undergoing Androgen Deprivation Therapy (ADT), was evaluated. DNA damage scores were obtained by the comet assay, both before and after treatment with CM-G. The reduction in DNA damage, ranging from 18% to 87%, with an average of 59%, was not related to the increased number of leukocytes in peripheral blood. The results demonstrate for the first time the protective effect of CM-G against DNA damage in patients with advanced PCa. Among smokers, three presented the highest reduction in DNA damage after treatment with CM-G. There was no observable relationship between DNA damage scores before and after treatment, and age, alcoholism and radiotherapy.

  18. Protective effect of carboxymethyl-glucan (CM-G) against DNA damage in patients with advanced prostate cancer

    PubMed Central

    Magnani, Marciane; Castro-Gomez, Raul Jorge Hernan; Mori, Mateus Prates; Kuasne, Hellen; Gregório, Emerson Pereira; Libos, Farid; de Syllos Cólus, Ilce Mara

    2011-01-01

    Carboxymethyl-glucan (CM-G) is a soluble derivative from Saccharomyces cerevisiae (1 → 3)(1 → 6)-β-D-glucan. The protective efficiency of CM-G against DNA damage in cells from patients with advanced prostate cancer (PCa), and undergoing Androgen Deprivation Therapy (ADT), was evaluated. DNA damage scores were obtained by the comet assay, both before and after treatment with CM-G. The reduction in DNA damage, ranging from 18% to 87%, with an average of 59%, was not related to the increased number of leukocytes in peripheral blood. The results demonstrate for the first time the protective effect of CM-G against DNA damage in patients with advanced PCa. Among smokers, three presented the highest reduction in DNA damage after treatment with CM-G. There was no observable relationship between DNA damage scores before and after treatment, and age, alcoholism and radiotherapy. PMID:21637556

  19. Differential protection by nitroxides and hydroxylamines to radiation-induced and metal ion-catalyzed oxidative damage.

    PubMed

    Xavier, Sandhya; Yamada, Ken-ichi; Samuni, Ayelet M; Samuni, Amram; DeGraff, William; Krishna, Murali C; Mitchell, James B

    2002-11-14

    Modulation of radiation- and metal ion-catalyzed oxidative-induced damage using plasmid DNA, genomic DNA, and cell survival, by three nitroxides and their corresponding hydroxylamines, were examined. The antioxidant property of each compound was independently determined by reacting supercoiled DNA with copper II/1,10-phenanthroline complex fueled by the products of hypoxanthine/xanthine oxidase (HX/XO) and noting the protective effect as assessed by agarose gel electrophoresis. The nitroxides and their corresponding hydroxylamines protected approximately to the same degree (33-47% relaxed form) when compared to 76.7% relaxed form in the absence of protectors. Likewise, protection by both the nitroxide and corresponding hydroxylamine were observed for Chinese hamster V79 cells exposed to hydrogen peroxide. In contrast, when plasmid DNA damage was induced by ionizing radiation (100 Gy), only nitroxides (10 mM) provide protection (32.4-38.5% relaxed form) when compared to radiation alone or in the presence of hydroxylamines (10 mM) (79.8% relaxed form). Nitroxide protection was concentration dependent. Radiation cell survival studies and DNA double-strand break (DBS) assessment (pulse field electrophoresis) showed that only the nitroxide protected or prevented damage, respectively. Collectively, the results show that nitroxides and hydroxylamines protect equally against the damage mediated by oxidants generated by the metal ion-catalyzed Haber-Weiss reaction, but only nitroxides protect against radiation damage, suggesting that nitroxides may more readily react with intermediate radical species produced by radiation than hydroxylamines.

  20. Pim1 kinase protects airway epithelial cells from cigarette smoke-induced damage and airway inflammation.

    PubMed

    de Vries, M; Heijink, I H; Gras, R; den Boef, L E; Reinders-Luinge, M; Pouwels, S D; Hylkema, M N; van der Toorn, M; Brouwer, U; van Oosterhout, A J M; Nawijn, M C

    2014-08-01

    Exposure to cigarette smoke (CS) is the main risk factor for developing chronic obstructive pulmonary disease and can induce airway epithelial cell damage, innate immune responses, and airway inflammation. We hypothesized that cell survival factors might decrease the sensitivity of airway epithelial cells to CS-induced damage, thereby protecting the airways against inflammation upon CS exposure. Here, we tested whether Pim survival kinases could protect from CS-induced inflammation. We determined expression of Pim kinases in lung tissue, airway inflammation, and levels of keratinocyte-derived cytokine (KC) and several damage-associated molecular patterns in bronchoalveolar lavage in mice exposed to CS or air. Human bronchial epithelial BEAS-2B cells were treated with CS extract (CSE) in the presence or absence of Pim1 inhibitor and assessed for loss of mitochondrial membrane potential, induction of cell death, and release of heat shock protein 70 (HSP70). We observed increased expression of Pim1, but not of Pim2 and Pim3, in lung tissue after exposure to CS. Pim1-deficient mice displayed a strongly enhanced neutrophilic airway inflammation upon CS exposure compared with wild-type controls. Inhibition of Pim1 activity in BEAS-2B cells increased the loss of mitochondrial membrane potential and reduced cell viability upon CSE treatment, whereas release of HSP70 was enhanced. Interestingly, we observed release of S100A8 but not of double-strand DNA or HSP70 in Pim1-deficient mice compared with wild-type controls upon CS exposure. In conclusion, we show that expression of Pim1 protects against CS-induced cell death in vitro and neutrophilic airway inflammation in vivo. Our data suggest that the underlying mechanism involves CS-induced release of S100A8 and KC. PMID:24816488

  1. Optimization of health protection of the public following a major nuclear accident: Interaction between radiation protection and social and psychological factors

    SciTech Connect

    Allen, P.T.; Archangelskaya, G.V.; Ramsaev, P.V.

    1996-11-01

    National and international guidance on the optimization of countermeasures to reduce doses in the post-release phase of an accident rightly emphasizes the importance and relevance of psychological, social, and economic factors to this process (e.g., NRPB 1990; ICRP 1991: CEC 1993; IAEA 1994). However, whilst economic factors are, at least partially, taken into account in developing the advice, explicit guidance is not provided on how psychological and social factors should be included in the optimization. Instead it is suggested that this is a matter for those with the appropriate competence and those with responsibility for making the final decisions. This approach implicitly assumes that the optimization of psychological and social factors, and that the results of the two procedures can then be combined to arrive at an optimum course of action. We recognize that formal optimization only forms one input to the process of making decisions on countermeasures and that it is important that psychological and social factors, as well as any other factors, are not {open_quotes}double-counted.{close_quotes} i.e., accounted for within international advice and then again at the time of the decision. It is our view that the optimization of radiation protection and economic factors, and certain psychological and social factors, should not be carried out independently. Research conducted by our respective organization indicates a number of areas in which the optimization of radiation protection and economic factors requires an understanding of key psychological and social processes. These areas fall into three groups; the need to ensure that countermeasures are successfully implemented, the need to achieve a net benefit for overall health, and the need to ensure a smooth transition back to normal living. 10 refs.

  2. The protective mechanisms of paracetamol against ethanol-induced gastric mucosal damage in rats.

    PubMed

    Poon, Y K; Cho, C H; Ogle, C W

    1989-08-01

    The protective mechanisms of paracetamol against ethanol-induced gastric mucosal damage have been examined. The antiulcer action of subcutaneously (s.c.)-injected paracetamol, 250 mg kg-1, was attenuated by either subdiaphragmatic vagotomy or s.c. injection of N-ethylmaleimide, 10 mg kg-1. This attenuation was not seen in rats given paracetamol by the oral route (p.o.). Indomethacin pretreatment, 5 mg kg-1, did not influence the lesion-preventing action of paracetamol given s.c. or p.o. The findings suggest that the antiulcer effect of s.c.-administered paracetamol results from an action involving the vagal nerve and tissue sulfhydryls, but not prostaglandins. On the other hand, the protective mechanism of paracetamol p.o. is independent of the vagal system or tissue sulfhydryls and prostaglandins. It seems that paracetamol given p.o. exerts its antiulcer effect by acting directly on the mucosal cell to strengthen mucosal integrity.

  3. Protection by WR-151327 against late-effect damage from fission-spectrum neutrons

    SciTech Connect

    Grdina, D.J. Chicago Univ., IL . Dept. of Radiation and Cellular Oncology); Wright, B.J.; Carnes, B.A. )

    1990-01-01

    Considerable effort has been expended to develop chemical agents capable of modifying radiation-induced damage to biological systems. The authors describe here differences in the radioprotective effect of WR-151327, depending on the sex of the animal and the post-irradiation time interval considered. The greatest effect in female animals is prior to 805 days post irradiation. The greater protection in male animals is seen during the time increment following 850 days after irradiation. While it is difficult at present to ascribe these effects to a particulate model, it is suggestive that hormonal factors may play a role in aminothiol protection against radiation-induced life shortening and concomitant tumor induction in the B6CF{sub 1} hybrid mouse system. With respect to subsequent tumor induction, their preliminary findings to be published elsewhere suggest that tumors of lymphoreticular origin are the class of tumors most affected by the administration of a radioprotector prior to irradiation. 23 refs., 4 figs.

  4. [Radiological estimation of the protective measures used in agricultural complex of Belarus Republic in 2000-2005 (20 years after the accident on the Chernobyl NPP)].

    PubMed

    Podoliak, A G; Bogdevich, I M; Ageets, V Iu; Timofeev, S F

    2007-01-01

    The radiological estimation of the basic agrochemistry measures spent for the agriculture of the Republic of Belarus in 2000-2005 is given. Laws of behavior radionuclides 137Cs and 90Sr in agrosystems are considered depending on used protective a measures (countermeasures) and the primary goals on liquidation of consequences in sphere of agrarian and industrial complex which are necessary for solving during the remote period after accident ChNNP (in 2006-2010) are studied.

  5. Precursors to potential severe core damage accidents: 1994, a status report. Volume 21: Main report and appendices A--H

    SciTech Connect

    Belles, R.J.; Cletcher, J.W.; Copinger, D.A.; Vanden Heuvel, L.N.; Dolan, B.W.; Minarick, J.W. |

    1995-12-01

    Nine operational events that affected eleven commercial light-water reactors (LWRs) during 1994 and that are considered to be precursors to potential severe core damage are described. All these events had conditional probabilities of subsequent severe core damage greater than or equal to 1.0 {times} 10{sup {minus}6}. These events were identified by computer-screening the 1994 licensee event reports from commercial LWRs to identify those that could be potential precursors. Candidate precursors were then selected and evaluated in a process similar to that used in previous assessments. Selected events underwent engineering evaluation that identified, analyzed, and documented the precursors. Other events designated by the Nuclear Regulatory Commission (NRC) also underwent a similar evaluation. Finally, documented precursors were submitted for review by licensees and NRC headquarters and regional offices to ensure that the plant design and its response to the precursor were correctly characterized. This study is a continuation of earlier work, which evaluated 1969--1981 and 1984--1993 events. The report discusses the general rationale for this study, the selection and documentation of events as precursors, and the estimation of conditional probabilities of subsequent severe core damage for events. This document is bound in two volumes: Vol. 21 contains the main report and Appendices A--H; Vol. 22 contains Appendix 1.

  6. H. R. 3124: A bill to require the Secretary of Transportation to take actions to protect against railroad accidents involving hazardous materials, introduced in the US House of Representatives, One Hundred Second Congress, First Session, July 31, 1991

    SciTech Connect

    Not Available

    1991-01-01

    This bill was introduced into the US House of Representatives on July 31, 1991 to require the Secretary of Transportation to take actions to protect against railroad accidents involving hazardous materials. One of the main aspects of this legislation is to identify railroad routes which present the greatest danger of accidents and to find alternative routes.

  7. Essential Metals Zinc, Selenium, and Strontium Protect against Chromosome Damage Caused by Polycyclic Aromatic Hydrocarbons Exposure.

    PubMed

    Bai, Yansen; Feng, Wei; Wang, Suhan; Zhang, Xiao; Zhang, Wangzhen; He, Meian; Zhang, Xiaomin; Wu, Tangchun; Guo, Huan

    2016-01-19

    Essential metals play important roles in maintaining cellular homeostasis, but the effects of their interaction with the environmental pollutants are still not very well-known in human subjects. The aim of this study was to evaluate the roles of essential metals and their interactions with polycyclic aromatic hydrocarbons (PAHs) on chromosome damage, an early carcinogenic event. A total of 1245 male workers were included in this study and the levels of 11 urinary essential metals, 12 urinary PAH metabolites, plasma concentrations of benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, and lymphocyte micronucleus (MN) frequencies were monitored. We found that zinc (Zn), selenium (Se), and strontium (Sr) have significant inverse dose-response relationships with MN frequencies (all P < 0.05). Furthermore, the protective roles of Zn, Se, and Sr were mainly shown among subjects with high levels of BPDE-Alb adducts. Significant effect modification of BPDE-Alb adducts on the associations of Zn, Se, and Sr with MN frequencies was observed (all Pinteraction < 0.05). Our study showed evidence that Zn, Se, and Sr play protective roles in reducing chromosome damage, and these effects can be modified by PAH exposure levels. These findings add potential evidence for the preventive effects of Zn, Se, and Sr against carcinogenesis in human subjects.

  8. Protective Effect of Sundakai (Solanum torvum) Seed Protein (SP) Against Oxidative Membrane Damage in Human Erythrocytes.

    PubMed

    Sivapriya, M; Gowda, S S Thammanna; Srinivas, Leela

    2015-12-01

    Lipid peroxidation by ROS at the membrane level disturbs the inherit integrity of components activating subsequent alterations in the function. In this study, the protective effect of purified Sundakai (Solanum torvum) seed protein (SP) was tested against oxidative membrane damage in erythrocyte membrane. SP prevented oxidative RBC lysis induced by pro-oxidants; Fe:As (2:20 μmol), periodate (0.4 mM), and t-BOOH (1 mM) up to 86, 81, and 86 %, respectively. Further, SP prevented the Fe:As-induced K(+) leakage up to the tune of 95 %. The inhibition offered by SP on K(+) leakage was comparable to inhibition offered by quinine sulfate, a known K(+) channel blocker. SP dose dependently restored Na(+)K(+) ATPase and Ca(2+)Mg(2+) ATPase activities in erythrocyte membrane. The restoration of ATPase activity by SP was two times more than standard antioxidants BHA and α-tocopherol. Besides, SP at 1.6 μmol restored the membrane proteins over Fe:As induction when analyzed by SDS-PAGE, which was comparable to protection offered by BHA. In conclusion, SP is an effective antioxidant in preventing oxidative membrane damage and associated functions mediated by ROS. As SP is non-toxic, it can be used as an effective bioprotective antioxidant agent to cellular components. PMID:26374653

  9. Bright cyclic light rearing-mediated retinal protection against damaging light exposure in adrenalectomized mice.

    PubMed

    Tanito, Masaki; Anderson, Robert E

    2006-09-01

    Previous studies have shown that albino rats and mice raised in bright cyclic light are protected from light-induced retinal damage. We tested if the stress response mediated by the adrenal grand is involved in the initiation of this neuroprotective phenomenon. Balb/c mice that were adrenalectomized (Adrex) or sham operated at 28 days of age were kept under dim (5 lux) or bright (400 lux) cyclic light (12h on/off) for 2 weeks. Thereafter, their electroretinogram (ERG), outer nuclear layer (ONL) thickness and area, and plasma corticosterone levels were measured in animals with (dim+light and bright+light groups) and without (dim and bright groups) damaging light exposure (3000 lux for 24 h). In the dim+light group, a- and b-wave amplitudes and the ONL thicknesses and areas were significantly higher in the Adrex animals than the sham animals, indicating that adrenalectomy itself yielded retinal protection. In the Adrex animals, the ONL areas were significantly larger in the bright+light group than the dim+light group, indicating that bright cyclic light rearing yielded further retinal tolerance, even in the absence of the adrenal gland. In sham animals, the plasma corticosterone concentration did not change between the dim and the light groups. Accordingly, glucocorticoid secreted from the adrenal gland is not likely to be required for the mechanisms of the light-adaptation neuroprotection phenomenon in mice.

  10. DNA Protection against Oxidative Damage Using the Hydroalcoholic Extract of Garcinia mangostana and Alpha-Mangostin.

    PubMed

    Carvalho-Silva, Ronaldo; Pereira, Alanna Cibelle Fernandes; Dos Santos Alves, Rúbens Prince; Guecheva, Temenouga N; Henriques, João A P; Brendel, Martin; Pungartnik, Cristina; Rios-Santos, Fabrício

    2016-01-01

    Garcinia mangostana, popularly known as "mangosteen fruit," originates from Southeast Asia and came to Brazil about 80 years ago where it mainly grows in the states of Pará and Bahia. Although mangosteen or its extracts have been used for ages in Asian folk medicine, data on its potential genotoxicity is missing. We, therefore, evaluated genotoxicity/mutagenicity of hydroethanolic mangosteen extract [HEGM, 10 to 640 μg/mL] in established test assays (Comet assay, micronucleus test, and Salmonella/microsome test). In the Comet assay, HEGM-exposed human leukocytes showed no DNA damage. No significant HEGM-induced mutation in TA98 and TA100 strains of Salmonella typhimurium (with or without metabolic activation) was observed and HEGM-exposed human lymphocytes had no increase of micronuclei. However, HEGM suggested exposure concentration-dependent antigenotoxic potential in leukocytes and antioxidant potential in the yeast Saccharomyces cerevisiae. HEGM preloading effectively protected against H2O2-induced DNA damage in leukocytes (Comet assay). Preloading of yeast with HEGM for up to 4 h significantly protected the cells from lethality of chronic H2O2-exposure, as expressed in better survival. Absence of genotoxicity and demonstration of an antigenotoxic and antioxidant potential suggest that HEGM or some substances contained in it may hold promise for pharmaceutical or nutraceutical application.

  11. DNA Protection against Oxidative Damage Using the Hydroalcoholic Extract of Garcinia mangostana and Alpha-Mangostin

    PubMed Central

    Carvalho-Silva, Ronaldo; Pereira, Alanna Cibelle Fernandes; dos Santos Alves, Rúbens Prince; Guecheva, Temenouga N.; Henriques, João A. P.; Brendel, Martin; Rios-Santos, Fabrício

    2016-01-01

    Garcinia mangostana, popularly known as “mangosteen fruit,” originates from Southeast Asia and came to Brazil about 80 years ago where it mainly grows in the states of Pará and Bahia. Although mangosteen or its extracts have been used for ages in Asian folk medicine, data on its potential genotoxicity is missing. We, therefore, evaluated genotoxicity/mutagenicity of hydroethanolic mangosteen extract [HEGM, 10 to 640 μg/mL] in established test assays (Comet assay, micronucleus test, and Salmonella/microsome test). In the Comet assay, HEGM-exposed human leukocytes showed no DNA damage. No significant HEGM-induced mutation in TA98 and TA100 strains of Salmonella typhimurium (with or without metabolic activation) was observed and HEGM-exposed human lymphocytes had no increase of micronuclei. However, HEGM suggested exposure concentration-dependent antigenotoxic potential in leukocytes and antioxidant potential in the yeast Saccharomyces cerevisiae. HEGM preloading effectively protected against H2O2-induced DNA damage in leukocytes (Comet assay). Preloading of yeast with HEGM for up to 4 h significantly protected the cells from lethality of chronic H2O2-exposure, as expressed in better survival. Absence of genotoxicity and demonstration of an antigenotoxic and antioxidant potential suggest that HEGM or some substances contained in it may hold promise for pharmaceutical or nutraceutical application. PMID:27042187

  12. Phenolic profile, antioxidant potential and DNA damage protecting activity of sugarcane (Saccharum officinarum).

    PubMed

    Abbas, Syed Rizwan; Sabir, Syed Mubashar; Ahmad, Syed Dilnawaz; Boligon, Aline Augusti; Athayde, Margareth Linde

    2014-03-15

    The present study investigated the antioxidant and phenolic composition of sugarcane. The leaves and juices of thirteen varieties of sugarcane were studied for their antioxidant activity and protective effect on DNA damage. 2,2-Diphenyl-1-picrylhydrazyl radical (DPPH) assay was used to determine the radical scavenging activities in leaves and juices. Different varieties of sugarcane showed good antioxidant properties, IC50 values ranged from 20.82 to 27.47 μg/ml for leaves and from 63.95 to higher than 200 μg/ml for juice. The leaves and juice possess strong ability to protect against DNA damage induced by hydroxyl radical generated in Fenton reaction. The major phenolic acids, some flavonoid aglycone and glycosides were identified in leaves by high performance liquid chromatography. Ferulic acid (14.63 ± 0.03 mg/g), cumaric acid (11.65 ± 0.03 mg/g), quercetrin (10.96 ± 0.02 mg/g), caffeic acid (9.16 ± 0.01 mg/g) and ellagic acid (9.03 ± 0.02 mg/g) were prédominant in infusion of sugarcane.

  13. Oenanthe Javanica Extract Protects Against Experimentally Induced Ischemic Neuronal Damage via its Antioxidant Effects

    PubMed Central

    Park, Joon Ha; Cho, Jeong Hwi; Kim, In Hye; Ahn, Ji Hyeon; Lee, Jae-Chul; Chen, Bai Hui; Shin, Bich-Na; Tae, Hyun-Jin; Yoo, Ki-Yeon; Hong, SeongKweon; Kang, Il Jun; Won, Moo-Ho; Kim, Jong-Dai

    2015-01-01

    Background: Water dropwort (Oenanthe javanica) as a popular traditional medicine in Asia shows various biological properties including antioxidant activity. In this study, we firstly examined the neuroprotective effect of Oenanthe javanica extract (OJE) in the hippocampal cornus ammonis 1 region (CA1 region) of the gerbil subjected to transient cerebral ischemia. Methods: Gerbils were established by the occlusion of common carotid arteries for 5 min. The neuroprotective effect of OJE was estimated by cresyl violet staining. In addition, 4 antioxidants (copper, zinc superoxide dismutase [SOD], manganese SOD, catalase, and glutathione peroxidase) immunoreactivities were investigated by immunohistochemistry. Results: Pyramidal neurons in the CA1 region showed neuronal death at 5 days postischemia; at this point in time, all antioxidants immunoreactivities disappeared in CA1 pyramidal neurons and showed in many nonpyramidal cells. Treatment with 200 mg/kg, not 100 mg/kg, OJE protected CA1 pyramidal neurons from ischemic damage. In addition, 200 mg/kg OJE treatment increased or maintained antioxidants immunoreactivities. Especially, among the antioxidants, glutathione peroxidase immunoreactivity was effectively increased in the CA1 pyramidal neurons of the OJE-treated sham-operated and ischemia-operated groups. Conclusion: Our present results indicate that treatment with OJE can protect neurons from transient ischemic damage and that the neuroprotective effect may be closely associated with increased or maintained intracellular antioxidant enzymes by OJE. PMID:26521793

  14. DNA Protection against Oxidative Damage Using the Hydroalcoholic Extract of Garcinia mangostana and Alpha-Mangostin.

    PubMed

    Carvalho-Silva, Ronaldo; Pereira, Alanna Cibelle Fernandes; Dos Santos Alves, Rúbens Prince; Guecheva, Temenouga N; Henriques, João A P; Brendel, Martin; Pungartnik, Cristina; Rios-Santos, Fabrício

    2016-01-01

    Garcinia mangostana, popularly known as "mangosteen fruit," originates from Southeast Asia and came to Brazil about 80 years ago where it mainly grows in the states of Pará and Bahia. Although mangosteen or its extracts have been used for ages in Asian folk medicine, data on its potential genotoxicity is missing. We, therefore, evaluated genotoxicity/mutagenicity of hydroethanolic mangosteen extract [HEGM, 10 to 640 μg/mL] in established test assays (Comet assay, micronucleus test, and Salmonella/microsome test). In the Comet assay, HEGM-exposed human leukocytes showed no DNA damage. No significant HEGM-induced mutation in TA98 and TA100 strains of Salmonella typhimurium (with or without metabolic activation) was observed and HEGM-exposed human lymphocytes had no increase of micronuclei. However, HEGM suggested exposure concentration-dependent antigenotoxic potential in leukocytes and antioxidant potential in the yeast Saccharomyces cerevisiae. HEGM preloading effectively protected against H2O2-induced DNA damage in leukocytes (Comet assay). Preloading of yeast with HEGM for up to 4 h significantly protected the cells from lethality of chronic H2O2-exposure, as expressed in better survival. Absence of genotoxicity and demonstration of an antigenotoxic and antioxidant potential suggest that HEGM or some substances contained in it may hold promise for pharmaceutical or nutraceutical application. PMID:27042187

  15. Antioxidant and DNA Damage Protecting Activity of Exopolysaccharides from the Endophytic Bacterium Bacillus cereus SZ1.

    PubMed

    Zheng, Li Ping; Zou, Tin; Ma, Yan Jun; Wang, Jian Wen; Zhang, Yu Qing

    2016-01-01

    An endophytic bacterium was isolated from the Chinese medicinal plant Artemisia annua L. The phylogenetic and physiological characterization indicated that the isolate, strain SZ-1, was Bacillus cereus. The endophyte could produce an exopolysaccharide (EPS) at 46 mg/L. The 1,1-diphenyl-2-picrylhydracyl (DPPH) radical scavenging activity of the EPS reached more than 50% at 3-5 mg/mL. The EPS was also effective in scavenging superoxide radical in a concentration dependent fashion with an EC50 value of 2.6 mg/mL. The corresponding EC50 for scavenging hydroxyl radical was 3.1 mg/mL. Moreover, phenanthroline-copper complex-mediated chemiluminescent emission of DNA damage was both inhibited and delayed by EPS. The EPS at 0.7-1.7 mg/mL also protected supercoiled DNA strands in plasmid pBR322 against scission induced by Fenton-mediated hydroxyl radical. The preincubation of PC12 cells with the EPS prior to H₂O₂ exposure increased the cell survival and glutathione (GSH) level and catalase (CAT) activities, and decreased the level of malondialdehyde (MDA) and lactate dehydrogenase (LDH) activity in a dose-dependent manner, suggesting a pronounced protective effect against H₂O₂-induced cytotoxicity. Our study indicated that the EPS could be useful for preventing oxidative DNA damage and cellular oxidation in pharmaceutical and food industries. PMID:26861269

  16. Lactobacillus protects the integrity of intestinal epithelial barrier damaged by pathogenic bacteria

    PubMed Central

    Yu, Qinghua; Yuan, Lixia; Deng, Jun; Yang, Qian

    2015-01-01

    Pathogens invade intestinal mucosal barrier through phagocytosis of antigen presenting cells (dendritic cell, microfold cells), or through the invasion into the intestinal epithelial directly. Some pathogens could damage the cell junction between epithelial cells and use the paracellular pathway as an entrance to invade. Moreover, some Lactobacillus could inhibit the adhesion of the pathogens and protect the integrity of the cell junction and mucosal barrier. This research focused on the potential therapeutic effect of Lactobacillus fructosus (L. fructosus) C2 to attenuate ETEC K88 or S. typhimurium SL1344 induced changes to mucosal barrier. The results demonstrated that treatment of polarized Caco-2 cells with L. fructosus C2 reduced the permeation of dextran, and expression of IL-8, p-ERK, and p-JNK when cells were infected with pathogenic bacteria. The findings indicated that L. fructosus C2 exerted a protective effect against the damage to the integrity of Caco-2 cells by ETEC or S. typhimurium infection. PMID:25859435

  17. Protective activity of green tea against free radical- and glucose-mediated protein damage.

    PubMed

    Nakagawa, Takako; Yokozawa, Takako; Terasawa, Katsutoshi; Shu, Seiji; Juneja, Lekh Raj

    2002-04-10

    Protein oxidation and glycation are posttranslational modifications that are implicated in the pathological development of many age-related disease processes. This study investigated the effects of green tea extract, and a green tea tannin mixture and its components, on protein damage induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (a free radical generator) and glucose in in vitro assay systems. We found that green tea extract can effectively protect against protein damage, and showed that its action is mainly due to tannin. In addition, it was shown that the chemical structures of tannin components are also involved in this activity, suggesting that the presence of the gallate group at the 3 position plays the most important role in the protective activity against protein oxidation and glycation, and that there is also a contribution by the hydroxyl group at the 5' position in the B ring and the sterical structure. These findings demonstrate the mechanisms of the usefulness of green tea in protein oxidation- and glycation-associated diseases.

  18. DNA damage protective effect of honey-sweetened cashew apple nectar in Drosophila melanogaster.

    PubMed

    Silva, Robson Alves da; Dihl, Rafael Rodrigues; Dias, Lucas Pinheiro; Costa, Maiane Papke; Abreu, Bianca Regina Ribas de; Cunha, Kênya Silva; Lehmann, Mauricio

    2016-01-01

    Fruits and derivatives, such as juices, are complex mixtures of chemicals, some of which may have mutagenic and/or carcinogenic potential, while others may have antimutagenic and/or anticancer activities. The modulating effects of honey-sweetened cashew apple nectar (HSCAN), on somatic mutation and recombination induced by ethyl methanesulfonate (EMS) and mitomycin C (MMC) were evaluated with the wing spot test in Drosophila melanogaster using co- and post-treatment protocols. Additionally, the antimutagenic activity of two HSCAN components, cashew apple pulp and honey, in MMC-induced DNA damage was also investigated. HSCAN reduced the mutagenic activity of both EMS and MMC in the co-treatment protocol, but had a co-mutagenic effect when post-administered. Similar results were also observed with honey on MMC mutagenic activity. Cashew apple pulp was effective in exerting protective or enhancing effects on the MMC mutagenicity, depending on the administration protocol and concentration used. Overall, these results indicate that HSCAN, cashew apple and honey seem capable of modulating not only the events that precede the induced DNA damages, but also the Drosophila DNA repair processes involved in the correction of EMS and MMC-induced damages. PMID:27560988

  19. DNA damage protective effect of honey-sweetened cashew apple nectar in Drosophila melanogaster

    PubMed Central

    da Silva, Robson Alves; Dihl, Rafael Rodrigues; Dias, Lucas Pinheiro; Costa, Maiane Papke; de Abreu, Bianca Regina Ribas; Cunha, Kênya Silva; Lehmann, Mauricio

    2016-01-01

    Abstract Fruits and derivatives, such as juices, are complex mixtures of chemicals, some of which may have mutagenic and/or carcinogenic potential, while others may have antimutagenic and/or anticancer activities. The modulating effects of honey-sweetened cashew apple nectar (HSCAN), on somatic mutation and recombination induced by ethyl methanesulfonate (EMS) and mitomycin C (MMC) were evaluated with the wing spot test in Drosophila melanogaster using co- and post-treatment protocols. Additionally, the antimutagenic activity of two HSCAN components, cashew apple pulp and honey, in MMC-induced DNA damage was also investigated. HSCAN reduced the mutagenic activity of both EMS and MMC in the co-treatment protocol, but had a co-mutagenic effect when post-administered. Similar results were also observed with honey on MMC mutagenic activity. Cashew apple pulp was effective in exerting protective or enhancing effects on the MMC mutagenicity, depending on the administration protocol and concentration used. Overall, these results indicate that HSCAN, cashew apple and honey seem capable of modulating not only the events that precede the induced DNA damages, but also the Drosophila DNA repair processes involved in the correction of EMS and MMC-induced damages. PMID:27560988

  20. XPD localizes in mitochondria and protects the mitochondrial genome from oxidative DNA damage.

    PubMed

    Liu, Jing; Fang, Hongbo; Chi, Zhenfen; Wu, Zan; Wei, Di; Mo, Dongliang; Niu, Kaifeng; Balajee, Adayabalam S; Hei, Tom K; Nie, Linghu; Zhao, Yongliang

    2015-06-23

    Xeroderma pigmentosum group D (XPD/ERCC2) encodes an ATP-dependent helicase that plays essential roles in both transcription and nucleotide excision repair of nuclear DNA, however, whether or not XPD exerts similar functions in mitochondria remains elusive. In this study, we provide the first evidence that XPD is localized in the inner membrane of mitochondria, and cells under oxidative stress showed an enhanced recruitment of XPD into mitochondrial compartment. Furthermore, mitochondrial reactive oxygen species production and levels of oxidative stress-induced mitochondrial DNA (mtDNA) common deletion were significantly elevated, whereas capacity for oxidative damage repair of mtDNA was markedly reduced in both XPD-suppressed human osteosarcoma (U2OS) cells and XPD-deficient human fibroblasts. Immunoprecipitation-mass spectrometry analysis was used to identify interacting factor(s) with XPD and TUFM, a mitochondrial Tu translation elongation factor was detected to be physically interacted with XPD. Similar to the findings in XPD-deficient cells, mitochondrial common deletion and oxidative damage repair capacity in U2OS cells were found to be significantly altered after TUFM knock-down. Our findings clearly demonstrate that XPD plays crucial role(s) in protecting mitochondrial genome stability by facilitating an efficient repair of oxidative DNA damage in mitochondria.

  1. XPD localizes in mitochondria and protects the mitochondrial genome from oxidative DNA damage

    PubMed Central

    Liu, Jing; Fang, Hongbo; Chi, Zhenfen; Wu, Zan; Wei, Di; Mo, Dongliang; Niu, Kaifeng; Balajee, Adayabalam S.; Hei, Tom K.; Nie, Linghu; Zhao, Yongliang

    2015-01-01

    Xeroderma pigmentosum group D (XPD/ERCC2) encodes an ATP-dependent helicase that plays essential roles in both transcription and nucleotide excision repair of nuclear DNA, however, whether or not XPD exerts similar functions in mitochondria remains elusive. In this study, we provide the first evidence that XPD is localized in the inner membrane of mitochondria, and cells under oxidative stress showed an enhanced recruitment of XPD into mitochondrial compartment. Furthermore, mitochondrial reactive oxygen species production and levels of oxidative stress-induced mitochondrial DNA (mtDNA) common deletion were significantly elevated, whereas capacity for oxidative damage repair of mtDNA was markedly reduced in both XPD-suppressed human osteosarcoma (U2OS) cells and XPD-deficient human fibroblasts. Immunoprecipitation-mass spectrometry analysis was used to identify interacting factor(s) with XPD and TUFM, a mitochondrial Tu translation elongation factor was detected to be physically interacted with XPD. Similar to the findings in XPD-deficient cells, mitochondrial common deletion and oxidative damage repair capacity in U2OS cells were found to be significantly altered after TUFM knock-down. Our findings clearly demonstrate that XPD plays crucial role(s) in protecting mitochondrial genome stability by facilitating an efficient repair of oxidative DNA damage in mitochondria. PMID:25969448

  2. Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

    PubMed Central

    Kip, Gülay; Çelik, Ali; Bilge, Mustafa; Alkan, Metin; Kiraz, Hasan Ali; Özer, Abdullah; Şıvgın, Volkan; Erdem, Özlem; Arslan, Mustafa; Kavutçu, Mustafa

    2015-01-01

    was significantly higher in the DIR group than in the DIRD and C groups. Conclusion Our results confirm that dexmedetomidine has protective effects against the lung damage resulting from I/R in diabetic rats. Future studies conducted to evaluate the effects of the use of dexmedetomidine on damage to various organs following different I/R durations may help understanding possible protective effects of dexmedetomidine and underlying mechanisms in tissue damage related to I/R injury. PMID:26387799

  3. Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles

    SciTech Connect

    Rezvanfar, Mohammad Amin; Rezvanfar, Mohammad Ali; Shahverdi, Ahmad Reza; Ahmadi, Abbas; Baeeri, Maryam; Mohammadirad, Azadeh; Abdollahi, Mohammad

    2013-02-01

    Cisplatin (CIS), an anticancer alkylating agent, induces DNA adducts and effectively cross links the DNA strands and so affects spermatozoa as a male reproductive toxicant. The present study investigated the cellular/biochemical mechanisms underlying possible protective effect of selenium nano-particles (Nano-Se) as an established strong antioxidant with more bioavailability and less toxicity, on reproductive toxicity of CIS by assessment of sperm characteristics, sperm DNA integrity, chromatin quality and spermatogenic disorders. To determine the role of oxidative stress (OS) in the pathogenesis of CIS gonadotoxicity, the level of lipid peroxidation (LPO), antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and peroxynitrite (ONOO) as a marker of nitrosative stress (NS) and testosterone (T) concentration as a biomarker of testicular function were measured in the blood and testes. Thirty-two male Wistar rats were equally divided into four groups. A single IP dose of CIS (7 mg/kg) and protective dose of Nano-Se (2 mg/kg/day) were administered alone or in combination. The CIS-exposed rats showed a significant increase in testicular and serum LPO and ONOO level, along with a significant decrease in enzymatic antioxidants levels, diminished serum T concentration and abnormal histologic findings with impaired sperm quality associated with increased DNA damage and decreased chromatin quality. Coadministration of Nano-Se significantly improved the serum T, sperm quality, and spermatogenesis and reduced CIS-induced free radical toxic stress and spermatic DNA damage. In conclusion, the current study demonstrated that Nano-Se may be useful to prevent CIS-induced gonadotoxicity through its antioxidant potential. Highlights: ► Cisplatin (CIS) affects spermatozoa as a male reproductive toxicant. ► Effect of Nano-Se on CIS-induced spermatotoxicity was investigated. ► CIS-exposure induces oxidative sperm DNA damage

  4. Mitochondrial Peroxiredoxin-3 protects against hyperglycemia induced myocardial damage in Diabetic cardiomyopathy.

    PubMed

    Arkat, Silpa; Umbarkar, Prachi; Singh, Sarojini; Sitasawad, Sandhya L

    2016-08-01

    Mitochondrial oxidative stress has emerged as a key contributor towards the development of diabetic cardiomyopathy. Peroxiredoxin-3 (Prx-3), a mitochondrial antioxidant, scavenges H2O2 and offers protection against ROS related pathologies. We observed a decrease in the expression of Prx-3 in the hearts of streptozotocin (STZ) induced diabetic rats, and also high glucose treated H9c2 cardiac cells, which may augment oxidative stress mediated damage. Hence we hypothesized that overexpression of Prx-3 could prevent the cardiac damage associated with diabetes. In this study we used quercetin (QUE) to achieve Prx-3 induction in vivo, while a Prx-3 overexpressing H9c2 cell line was employed for carrying out in vitro studies. Diabetes was induced in Wistar rats by a single intraperitoneal injection of STZ. Quercetin (50mg/kg body weight) was delivered orally to hyperglycemic and age matched control rats for 2 months. Quercetin treatment induced the myocardial expression of Prx-3 but not Prx-5 both in control and STZ rats. Prx-3 induction by quercetin prevented diabetes induced oxidative stress as confirmed by decrease in expression of markers such as 4-HNE and mitochondrial uncoupling protein, UCP-3. It was also successful in reducing cardiac cell apoptosis, hypertrophy and fibrosis leading to amelioration of cardiac contractility defects. Overexpression of Prx-3 in cultured H9c2 cardiac cells could significantly diminish high glucose inflicted mitochondrial oxidative damage and apoptosis, thus strengthening our hypothesis. These results suggest that diabetes induced cardiomyopathy can be prevented by elevating Prx-3 levels thereby providing extensive protection to the diabetic heart. PMID:27393003

  5. Beneficial protective effect of pramipexole on light-induced retinal damage in mice.

    PubMed

    Shibagaki, Keiichi; Okamoto, Kazuyoshi; Katsuta, Osamu; Nakamura, Masatsugu

    2015-10-01

    We investigated the effects of pramipexole, a potent dopamine receptor D2/D3 agonist, on light-induced retinal damage in mice, H2O2-induced retinal pigment epithelium ARPE-19 cell injury in humans, and hydroxyl radical scavenging activity in a cell-free system. Pramipexole (0.1 and 1 mg/kg body weight) was orally administered to mice 1 h before light exposure (5000 lux, 2 h). Electrophysiological and morphologic studies were performed to evaluate the effects of the pramipexole on light-induced retinal damage in mice. Pramipexole significantly prevented the reduction of the a- and b-wave electroretinogram (ERG) amplitudes caused by light exposure in a dose-dependent manner. In parallel, damage to the inner and outer segments (IS/OS) of the photoreceptors, loss of photoreceptor nuclei, and the number of Tdt-mediated dUTP nick-end labeling (TUNEL)-positive cells in the outer nuclear layer (ONL) caused by light exposure were notably ameliorated by pramipexole. Additionally, pramipexole suppressed H2O2-induced ARPE-19 cell death in vitro in a concentration-dependent manner. The effect of pramipexole was significant at concentrations of 10(-6) M or higher. Pramipexole also significantly prevented H2O2-induced activation of caspases-3/7 and the intracellular accumulation of reactive oxygen species (ROS) in a concentration-dependent manner ranging from 10(-5) to 10(-3) M. Furthermore, pramipexole increased the scavenging activity toward a hydroxyl radical generated from H2O2 in a Fenton reaction. Our results suggest that pramipexole protects against light-induced retinal damage as an antioxidant and that it may be a novel and effective therapy for retinal degenerative disorders, such as dry age-related macular degeneration.

  6. Pharmacologic approaches to protection against radiation-induced lethality and other damage.

    PubMed Central

    Weiss, J F

    1997-01-01

    Studies on mechanisms of radioprotection are leading to a more rational use of protectors for different applications. In considering the feasibility of radioprotectors that act through various mechanisms, it is necessary to distinguish the application needed, e.g., protection against accidental external or internal exposures, acute high-dose radiation injury or low doses over a long period, high-LET radiation exposures during space flight, and protection of normal tissues of cancer patients who are undergoing therapy. Protectors generally are classified as either sulfhydryl compounds, other antioxidants, or receptor-mediated agents (e.g., bioactive lipids, cytokines, and growth factors). This review focuses on comparative radioprotection and toxicity studies in mice using the most effective phosphorothioate agents designated as WR-compounds and other classes of protectors. The superiority of phosphorothioates (WR-2721, WR-151327) as radioprotectors appears to be related to their high affinity for DNA and the similarity in structure of phosphorothioate metabolites to polyamines, and their effects on processes related to DNA structure and synthesis. Drug tolerance levels are available from clinical trials using WR-2721 (amifostine) and provide a basis for discussions of the disadvantages of phosphorothioate administration outside a clinical setting. In this regard, arguments are presented against the current use of WR-2721 by Department of Energy personnel for planned radiation exposures during emergencies. Future research may demonstrate, however, that pharmacologic agents could be useful in accident scenarios, especially when used in combination with therapeutic measures. Assessment of potential prophylactic measures should consider compatibility with therapeutic measures currently in use or ones that might be available in the future for the treatment of radiation injuries. These include antiemetics, purified stem cells, granulocyte colony-stimulating factor, and

  7. Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues

    NASA Technical Reports Server (NTRS)

    Griko, Y. V.; Yan, Xiaoli

    2016-01-01

    Exposure to high doses of ionizing radiation produces both acute and late effects on the collagenized tissues and have profound effects on wound healing. Because of the crucial practical importance for new radioprotective agents, our study has been focused on evaluation of the efficacy of non-toxic naturally occurring compounds to protect tissue integrity against high-dose gamma radiation. Here, we demonstrate that molecular integrity of collagen may serve as a sensitive biological marker for quantitative evaluation of molecular damage to collagenized tissue and efficacy of radioprotective agents. Increasing doses of gamma radiation (0-50kGy) result in progressive destruction of the native collagen fibrils, which provide a structural framework, strength, and proper milieu for the regenerating tissue. The strategy used in this study involved the thermodynamic specification of all structural changes in collagenized matrix of skin, aortic heart valve, and bone tissue induced by different doses and conditions of g-irradiation. This study describes a simple biophysical approach utilizing the Differential Scanning Calorimetry (DSC) to characterize the structural resistance of the aortic valve matrix exposed to different doses of g-irradiation. It allows us to identify the specific response of each constituent as well as to determine the influence of the different treatments on the characteristic parameters of protein structure. We found that pyruvate, a substance that naturally occurs in the body, provide significant protection (up to 80%) from biochemical and biomechanical damage to the collagenized tissue through the effective targeting of reactive oxygen species. The recently discovered role of pyruvate in the cell antioxidant defense to O2 oxidation, and its essential constituency in the daily human diet, indicate that the administration of pyruvate-based radioprotective formulations may provide safe and effective protection from deleterious effects of ionizing

  8. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal events during mid-loop operations, Appendices E (Sections E.1--E.8). Volume 2, Part 3A

    SciTech Connect

    Chu, T.L.; Musicki, Z.; Kohut, P.

    1994-06-01

    During 1989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the potential risks during low power and shutdown operations. The program includes two parallel projects being performed by Brookhaven National Laboratory (BNL) and Sandia National Laboratories (SNL). Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The objective of this report is to document the approach utilized in the Surry plant and discuss the results obtained. A parallel report for the Grand Gulf plant is prepared by SNL. This study shows that the core-damage frequency during mid-loop operation at the Surry plant is comparable to that of power operation. The authors recognize that there is very large uncertainty in the human error probabilities in this study. This study identified that only a few procedures are available for mitigating accidents that may occur during shutdown. Procedures written specifically for shutdown accidents would be useful.

  9. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal events during mid-loop operations, Appendices A--D. Volume 2, Part 2

    SciTech Connect

    Chu, T.L.; Musicki, Z.; Kohut, P.

    1994-06-01

    During 1989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the Potential risks during low Power and shutdown operations. The program includes two parallel projects being performed by Brookhaven National Laboratory (BNL) and Sandia National Laboratories (SNL). Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the Plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The objective of this report is to document the approach utilized in the Surry plant and discuss the results obtained. A parallel report for the Grand Gulf plant is prepared by SNL. This study shows that the core-damage frequency during mid-loop operation at the Surry plant is comparable to that of power operation. We recognize that there is very large uncertainty in the human error probabilities in this study. This study identified that only a few procedures are available for mitigating accidents that may occur during shutdown. Procedures written specifically for shutdown accidents would be useful. This document, Volume 2, Pt. 2 provides appendices A through D of this report.

  10. A Low-Dose Electron Diffraction Assay for Protection of Protein Structure against Damage from Drying

    NASA Astrophysics Data System (ADS)

    Massover, William H.

    2004-04-01

    A new assay using low-dose electron diffraction to measure the protection of protein structure against damage from drying is described. When thin single crystals of catalase are dried within water alone, low-dose electron diffraction yields no Bragg spots. Drying within an experimental aqueous solution that permits detection of diffraction spots thereby indicates a positive result, and the extent of these Bragg reflections into the high angle range gives a quantitative measure of the degree of protection. Bragg spots out to 3.7 3.9 [Angstrom capital A, ring] are recorded for drying within 100 mM solutions of the known structure-preserving sugars, sucrose, tannin, and trehalose. The ability of trehalose to maintain native protein structure during drying starts between 10 and 25 mM, and changes only slightly at concentrations above this threshold; with drying in 150-mM trehalose, catalase crystals yield diffraction spots out to 3.7 [Angstrom capital A, ring]. Drying within the organic nonsugar polymer polyvinylpyrrolidone gives Bragg spots to 4.0 [Angstrom capital A, ring]. This new assay should be useful to measure the unexamined structure-preserving capabilities of modified sugars, other nonsugars, and mixtures to identify which protective matrix maintains native protein structure to the greatest extent during drying; electron crystallography using that optimal matrix should yield protein structure at improved levels of high resolution.

  11. Chlorella protects against hydrogen peroxide-induced pancreatic β-cell damage.

    PubMed

    Lin, Chia-Yu; Huang, Pei-Jane; Chao, Che-Yi

    2014-12-01

    Oxidative stress has been implicated in the etiology of pancreatic β-cell dysfunction and diabetes. Studies have shown that chlorella could be important in health promotion or disease prevention through its antioxidant capacity. However, whether chlorella has a cytoprotective effect in pancreatic β-cells remains to be elucidated. We investigated the protective effects of chlorella on H2O2-induced oxidative damage in INS-1 (832/13) cells. Chlorella partially restored cell viability after H2O2 toxicity. To further investigate the effects of chlorella on mitochondria function and cellular oxidative stress, we analyzed mitochondria membrane potential, ATP concentrations, and cellular levels of reactive oxygen species (ROS). Chlorella prevented mitochondria disruption and maintained cellular ATP levels after H2O2 toxicity. It also normalized intracellular levels of ROS to that of control in the presence of H2O2. Chlorella protected cells from apoptosis as indicated by less p-Histone and caspase 3 activation. In addition, chlorella not only enhanced glucose-stimulated insulin secretion (GSIS), but also partially restored the reduced GSIS after H2O2 toxicity. Our results suggest that chlorella is effective in amelioration of cellular oxidative stress and destruction, and therefore protects INS-1 (832/13) cells from H2O2-induced apoptosis and increases insulin secretion. Chlorella should be studied for use in the prevention or treatment of diabetes.

  12. Protective Role of Comfrey Leave Extracts on UV-induced Zebrafish Fin Damage

    PubMed Central

    Cheng, Chien-Chung; Chou, Chi-Yuan; Chang, Yao-Chin; Wang, Hsuan-Wen; Wen, Chi-Chung; Chen, Yau-Hung

    2014-01-01

    In zebrafish, UV exposure leads to fin malformation phenotypes including fin reduction or absence. The present study evaluated UV-protective activities of comfrey leaves extracts in a zebrafish model by recording fin morphological changes. Chemopreventive effects of comfrey leave extracts were evaluated using Kaplan-Meier analysis and Cox proportional hazards regression. The results showed that (1) the mean times of return to normal fin in the UV+comfrey (50 and 100 ppm) groups were 3.43 and 2.86 days and were quicker compared with that in the UV only group (4.21 days); (2) zebrafish fins in the UV+comfrey (50 and 100 ppm) groups were 2.05 and 3.25 times more likely to return to normal than those in the UV only group; and (3) comfrey leave extracts had UV-absorbance abilities and significantly reduced ROS production in UV-exposed zebrafish embryos, which may attenuate UV-mediated apoptosis. In conclusion, comfrey leaves extracts may have the potential to be developed as UV-protective agents to protect zebrafish embryos from UV-induced damage. PMID:25352712

  13. Resorption Protection. Anthocyanins Facilitate Nutrient Recovery in Autumn by Shielding Leaves from Potentially Damaging Light Levels

    PubMed Central

    Hoch, William A.; Singsaas, Eric L.; McCown, Brent H.

    2003-01-01

    The resorption protection hypothesis, which states that anthocyanins protect foliar nutrient resorption during senescence by shielding photosynthetic tissues from excess light, was tested using wild-type (WT) and anthocyanin-deficient mutants of three deciduous woody species, Cornus sericea, Vaccinium elliottii (Chapmn.), and Viburnum sargentii (Koehne). WT Betula papyrifera (Marsh) was included to compare the senescence performance of a species that does not produce anthocyanins in autumn. Plants were subjected to three environmental regimes during senescence: an outdoor treatment; a 5-d high-stress (high light and low temperature) treatment followed by transfer to a low-stress environment and a low-stress treatment that served as control. In the outdoor treatment, the appearance of anthocyanins in senescing leaves of WT plants was concomitant with the development of photo-inhibition in mutant plants of all three anthocyanin-producing species. In the high-stress environment, WT plants maintained higher photochemical efficiencies than mutants and were able to recover when transferred to the low-stress environment, whereas mutant leaves dropped while still green and displayed signs of irreversible photooxidative damage. Nitrogen resorption efficiencies and proficiencies of all mutants in both stressful treatments were significantly lower than the WT counterparts. B. papyrifera displayed photochemical efficiencies and nitrogen resorption performance comparable with the highest of the anthocyanin-producing species in all three senescing environments, indicating a photoprotective strategy divergent from the other species studied. These results strongly support the resorption protection hypothesis of anthocyanins in senescing leaves. PMID:14526111

  14. A redox hydrogel protects hydrogenase from high-potential deactivation and oxygen damage

    NASA Astrophysics Data System (ADS)

    Plumeré, Nicolas; Rüdiger, Olaf; Oughli, Alaa Alsheikh; Williams, Rhodri; Vivekananthan, Jeevanthi; Pöller, Sascha; Schuhmann, Wolfgang; Lubitz, Wolfgang

    2014-09-01

    Hydrogenases are nature's efficient catalysts for both the generation of energy via oxidation of molecular hydrogen and the production of hydrogen via the reduction of protons. However, their O2 sensitivity and deactivation at high potential limit their applications in practical devices, such as fuel cells. Here, we show that the integration of an O2-sensitive hydrogenase into a specifically designed viologen-based redox polymer protects the enzyme from O2 damage and high-potential deactivation. Electron transfer between the polymer-bound viologen moieties controls the potential applied to the active site of the hydrogenase and thus insulates the enzyme from excessive oxidative stress. Under catalytic turnover, electrons provided from the hydrogen oxidation reaction induce viologen-catalysed O2 reduction at the polymer surface, thus providing self-activated protection from O2. The advantages of this tandem protection are demonstrated using a single-compartment biofuel cell based on an O2-sensitive hydrogenase and H2/O2 mixed feed under anode-limiting conditions.

  15. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1: Analysis of core damage frequency from internal events during mid-loop operations. Appendix E (Sections E.9-E.16), Volume 2, Part 3B

    SciTech Connect

    Chu, T.L.; Musicki, Z.; Kohut, P.; Yang, J.; Bozoki, G.; Hsu, C.J.; Diamond, D.J.; Wong, S.M.; Bley, D.; Johnson, D.

    1994-06-01

    Traditionally, probabilistic risk assessments (PRA) of severe accidents in nuclear power plants have considered initiating events potentially occurring only during full power operation. Some previous screening analyses that were performed for other modes of operation suggested that risks during those modes were small relative to full power operation. However, more recent studies and operational experience have implied that accidents during low power and shutdown could be significant contributors to risk. Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The scope of the program includes that of a level-3 PRA. In phase 2, mid-loop operation was selected as the plant configuration to be analyzed based on the results of the phase 1 study. The objective of the phase 2 study is to perform a detailed analysis of the potential accident scenarios that may occur during mid-loop operation, and compare the results with those of NUREG-1150. The scope of the level-1 study includes plant damage state analysis, and uncertainty analysis. Volume 1 summarizes the results of the study. Internal events analysis is documented in Volume 2. It also contains an appendix that documents the part of the phase 1 study that has to do with POSs other than mid-loop operation. Internal fire and internal flood analyses are documented in Volumes 3 and 4. A separate study on seismic analysis, documented in Volume 5, was performed for the NRC by Future Resources Associates, Inc. Volume 6 documents the accident progression, source terms, and consequence analysis.

  16. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit-1: Analysis of core damage frequency from internal events during mid-loop operations. Appendices F-H, Volume 2, Part 4

    SciTech Connect

    Chu, T.L.; Musicki, Z.; Kohut, P.; Yang, J.; Bozoki, G.; Hsu, C.J.; Diamond, D.J.; Bley, D.; Johnson, D.; Holmes, B.

    1994-06-01

    Traditionally, probabilistic risk assessments (PRA) of severe accidents in nuclear power plants have considered initiating events potentially occurring only during full power operation. Some previous screening analyses that were performed for other modes of operation suggested that risks during those modes were small relative to full power operation. However, more recent studies and operational experience have implied that accidents during low power and shutdown could be significant contributors to risk. Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The scope of the program includes that of a level-3 PRA. In phase 2, mid-loop operation was selected as the plant configuration to be analyzed based on the results of the phase 1 study. The objective of the phase 2 study is to perform a detailed analysis of the potential accident scenarios that may occur during mid-loop operation, and compare the results with those of NUREG-1150. The scope of the level-1 study includes plant damage state analysis, and uncertainty analysis. Volume 1 summarizes the results of the study. Internal events analysis is documented in Volume 2. It also contains an appendix that documents the part of the phase 1 study that has to do with POSs other than mid-loop operation. Internal fire and internal flood analyses are documented in Volumes 3 and 4. A separate study on seismic analysis, documented in Volume 5, was performed for the NRC by Future Resources Associates, Inc. Volume 6 documents the accident progression, source terms, and consequence analysis.

  17. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit-1: Analysis of core damage frequency from internal events during mid-loop operations. Appendix I, Volume 2, Part 5

    SciTech Connect

    Chu, T.L.; Musicki, Z.; Kohut, P.; Yang, J.; Bozoki, G.; Hsu, C.J.; Diamond, D.J.; Bley, D.; Johnson, D.; Holmes, B.

    1994-06-01

    Traditionally, probabilistic risk assessments (PRA) of severe accidents in nuclear power plants have considered initiating events potentially occurring only during full power operation. Some previous screening analyses that were performed for other modes of operation suggested that risks during those modes were small relative to full power operation. However, more recent studies and operational experience have implied that accidents during low power and shutdown could be significant contributors to risk. During 1989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the potential risks during low power and shutdown operations. The program includes two parallel projects being performed by Brookhaven National Lab. (BNL) and Sandia National Labs. (SNL). Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The objective of this volume of the report is to document the approach utilized in the level-1 internal events PRA for the Surry plant, and discuss the results obtained. A phased approach was used in the level-1 program. In phase 1, which was completed in Fall 1991, a coarse screening analysis examining accidents initiated by internal events (including internal fire and flood) was performed for all plant operational states (POSs). The objective of the phase 1 study was to identify potential vulnerable plant configurations, to characterize (on a high, medium, or low basis) the potential core damage accident scenarios, and to provide a foundation for a detailed phase 2 analysis.

  18. Water extracts of tree Hypericum sps. protect DNA from oxidative and alkylating damage and enhance DNA repair in colon cells.

    PubMed

    Ramos, Alice A; Marques, Filipe; Fernandes-Ferreira, Manuel; Pereira-Wilson, Cristina

    2013-01-01

    Diet may induce colon carcinogenesis through oxidative or alkylating DNA damage. However, diet may also contain anticarcinogenic compounds that contribute to cancer prevention. DNA damage prevention and/or induction of repair are two important mechanisms involved in cancer chemoprevention by dietary compounds. Hypericum sps. are widely used in traditional medicine to prepare infusions due to their beneficial digestive and neurologic effects. In this study, we investigated the potential of water extracts from three Hypericum sps. and some of their main phenolic compounds to prevent and repair oxidative and alkylating DNA damage in colon cells. The results showed that water extracts of Hypericum perforatum, Hypericum androsaemum, Hypericum undulatum, quercetin and rutin have protective effect against oxidative DNA damage in HT29 cells. Protective effect was also observed against alkylating DNA damage induced by methyl-methanesulfonate, except for H. androsaemum. With regard to alkylating damage repair H. perforatum, H. androsaemum and chlorogenic acid increased repair of alkylating DNA damage by base excision repair pathway. No effect was observed on nucleotide excision repair pathway. Antigenotoxic effects of Hypericum sps. may contribute to colon cancer prevention and the high amount of phenolic compounds present in Hypericum sps. play an important role in DNA protective effects.

  19. Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea.

    PubMed

    Liu, L; Chen, Y; Qi, J; Zhang, Y; He, Y; Ni, W; Li, W; Zhang, S; Sun, S; Taketo, M M; Wang, L; Chai, R; Li, H

    2016-01-01

    Recent studies have reported the role of Wnt/β-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/β-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator β-catenin in HCs, which allowed us to investigate the role of Wnt/β-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of β-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of β-catenin in HCs reduced HC loss both in vivo and in vitro. We then showed that loss of β-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while β-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of β-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast, β-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that β-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/β-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death.

  20. Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea

    PubMed Central

    Liu, L; Chen, Y; Qi, J; Zhang, Y; He, Y; Ni, W; Li, W; Zhang, S; Sun, S; Taketo, M M; Wang, L; Chai, R; Li, H

    2016-01-01

    Recent studies have reported the role of Wnt/β-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/β-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator β-catenin in HCs, which allowed us to investigate the role of Wnt/β-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of β-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of β-catenin in HCs reduced HC loss both in vivo and in vitro. We then showed that loss of β-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while β-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of β-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast, β-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that β-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/β-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death. PMID:26962686

  1. Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival.

    PubMed

    Tinkum, Kelsey L; Stemler, Kristina M; White, Lynn S; Loza, Andrew J; Jeter-Jones, Sabrina; Michalski, Basia M; Kuzmicki, Catherine; Pless, Robert; Stappenbeck, Thaddeus S; Piwnica-Worms, David; Piwnica-Worms, Helen

    2015-12-22

    Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.

  2. [Microflora of damaged ferroconcrete structures under the conditions of inhibitory protection].

    PubMed

    Kopteva, Zh P; Zanina, V V; Purish, L M; Piliashenko-Novokhatnyĭ, A I; Kozlova, I A

    2004-01-01

    Thionic, sulphate-reducing, denitrifying and ammonifying bacteria widely distributed in the sewer system on various structure elements have been isolated from damaged ferroconcrete samples. Effect of protective materials on microbe-induced corrosion of metal famework of concrete samples has been studied. Selective effect of corrosion inhibitors and coatings on the growth of corrosion-active bacteria of sulphur and nitrogen cycle has been revealed. It is shown that acid medium formed by thionic bacteria is more aggressive than ammonium-hydrosulphide one formed by denitrifying and sulphate-reducing bacteria. It has been established that the corrosion inhibitor--pyrquin, organosilicon coating CO-FMI and epoxyorganosilicon coating 4sk are most effective materials as to the action of thionic bacteria--dangerous agents of ferroconcrete aerobic corrosion. PMID:15554300

  3. [Microflora of damaged ferroconcrete structures under the conditions of inhibitory protection].

    PubMed

    Kopteva, Zh P; Zanina, V V; Purish, L M; Piliashenko-Novokhatnyĭ, A I; Kozlova, I A

    2004-01-01

    Thionic, sulphate-reducing, denitrifying and ammonifying bacteria widely distributed in the sewer system on various structure elements have been isolated from damaged ferroconcrete samples. Effect of protective materials on microbe-induced corrosion of metal famework of concrete samples has been studied. Selective effect of corrosion inhibitors and coatings on the growth of corrosion-active bacteria of sulphur and nitrogen cycle has been revealed. It is shown that acid medium formed by thionic bacteria is more aggressive than ammonium-hydrosulphide one formed by denitrifying and sulphate-reducing bacteria. It has been established that the corrosion inhibitor--pyrquin, organosilicon coating CO-FMI and epoxyorganosilicon coating 4sk are most effective materials as to the action of thionic bacteria--dangerous agents of ferroconcrete aerobic corrosion.

  4. Electron flow through biological molecules: Does hole hopping protect proteins from oxidative damage?

    PubMed Central

    Winkler, Jay R.; Gray, Harry B.

    2016-01-01

    Biological electron transfers often occur between metal-containing cofactors that are separated by very large molecular distances. Employing photosensitizer-modified iron and copper proteins, we have shown that single-step electron tunneling can occur on nanosecond to microsecond timescales at distances between 15 and 20 angstroms. We also have shown that charge transport can occur over even longer distances by hole hopping (multistep tunneling) through intervening tyrosines and tryptophans. In this Perspective, we advance the hypothesis that such hole hopping through Tyr/Trp chains could protect oxygenase, dioxygenase, and peroxidase enzymes from oxidative damage. In support of this view, by examining the structures of P450 (CYP102A) and 2OG-Fe (TauD) enzymes, we have identified candidate Tyr/Trp chains that could transfer holes from uncoupled high-potential intermediates to reductants in contact with protein surface sites. PMID:26537399

  5. Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival

    PubMed Central

    Tinkum, Kelsey L.; Stemler, Kristina M.; White, Lynn S.; Loza, Andrew J.; Jeter-Jones, Sabrina; Michalski, Basia M.; Kuzmicki, Catherine; Pless, Robert; Stappenbeck, Thaddeus S.; Piwnica-Worms, David; Piwnica-Worms, Helen

    2015-01-01

    Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy. PMID:26644583

  6. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

    SciTech Connect

    Chen, Haw-Wen; Huang, Chin-Shiu; Li, Chien-Chun; Lin, Ai-Hsuan; Huang, Yu-Ju; Wang, Tsu-Shing; Yao, Hsien-Tsung; Lii, Chong-Kuei

    2014-10-01

    Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl{sub 4}) at day 6. Andrographolide pretreatment suppressed CCl{sub 4}-induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense

  7. Protective effects of resveratrol against UVA-induced damage in ARPE19 cells.

    PubMed

    Chan, Chi-Ming; Huang, Cheng-Hua; Li, Hsin-Ju; Hsiao, Chien-Yu; Su, Ching-Chieh; Lee, Pei-Lan; Hung, Chi-Feng

    2015-01-01

    Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE) cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS) and generate oxidative injury; oxidative injury to the retinal pigment epithelium has been implicated to play a contributory role in age-related macular degeneration (AMD). Studies showed that resveratrol, an abundant and active component of red grapes, can protect several cell types from oxidative stress. In this study, adult RPE cells being treated with different concentrations of resveratrol were used to evaluate the protective effect of resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through flow cytometry analysis, we found that the generation of intracellular H2O2 induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a concentration-dependent manner. Results of Western blot analysis demonstrated that resveratrol lowered the activation of UVA-induced extracellular signal-regulated kinase, c-jun-NH2 terminal kinase and p38 kinase in RPE cells. In addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2) expression in RPE cells pretreated with resveratrol. Our observations suggest that resveratrol is effective in preventing RPE cells from being damaged by UVA radiation, and is worth considering for further development as a chemoprotective agent for the prevention of early AMD. PMID:25775159

  8. Treatment with nicardipine protects brain in an animal model of hypertension-induced damage.

    PubMed

    Amenta, Francesco; Tomassoni, Daniele

    2004-05-01

    Control of blood pressure protects from the development of cerebrovascular lesions and vascular dementia (VaD). This study has assessed the influence of treatment with the dihydropyridine-type Ca2+ antagonist nicardipine on brain microanatomical changes in spontaneously hypertensive rats (SHR). SHR were treated from 16th to 26th week of age with hypotensive (3 mg/Kg/day) or non-hypotensive (0.1 mg/Kg/day) doses of nicardipine, with the non-dihydropyridine-type vasodilator hydralazine (10 mg/kg/day) or with vehicle (control group). Untreated age-matched Wistar Kyoto (WKY) rats were used as a normotensive reference group. Brain volume, number of neurons, glial fibrillary-acidic protein (GFAP)-immunoreactive astrocytes and neurofilament 200 KDa (NFP)-immunoreactivity (IR) were assessed in frontal and occipital cortex, hippocampus and striatum. A decrease of volume and number of nerve cells and a loss of NFP-IR was found in the frontal and occipital cortex and in the CA1 subfield of hippocampus and in the striatum of SHR. Treatment with nicardipine countered microanatomical changes occurring in SHR, whereas hydralazine displayed a less pronounced effect. Comparatively, the non-hypotensive dose of nicardipine was less active than the hypotensive one. The observation that equihypotensive doses of nicardipine or hydralazine did not protect brain in the same way from hypertensive brain damage suggests that lowering blood pressure is per se not enough for affording neuroprotection. The demonstration of neuroprotective effect of nicardipine suggests an use of the compound in situations in which hypertension is accompanied by the risk of brain damage.

  9. Mechanisms of isoproterenol-induced cardiac mitochondrial damage: protective actions of melatonin.

    PubMed

    Mukherjee, Debasri; Ghosh, Arnab K; Dutta, Mousumi; Mitra, Elina; Mallick, Sanjaya; Saha, Bhaskar; Reiter, Russel J; Bandyopadhyay, Debasish

    2015-04-01

    Mitochondrial dysfunction due to oxidative damage is the key feature of several diseases. We have earlier reported mitochondrial damage resulting from the generation of oxidative stress as a major pathophysiological effect of isoproterenol (ISO)-induced myocardial ischemia in rats. That melatonin is an antioxidant that ameliorates oxidative stress in experimental animals as well as in humans is well established. We previously demonstrated that melatonin provides cardioprotection against ISO-induced myocardial injury as a result of its antioxidant properties. The mechanism of ISO-induced cardiac mitochondrial damage and protection by melatonin, however, remains to be elucidated in vitro. In this study, we provide evidence that ISO causes dysfunction of isolated goat heart mitochondria. Incubation of cardiac mitochondria with increasing concentrations of ISO decreased mitochondrial succinate dehydrogenase (SDH) activity, which plays a pivotal role in mitochondrial bioenergetics, as well as altered the activities of other key enzymes of the Kreb's cycle and the respiratory chain. Co-incubation of ISO-challenged mitochondria with melatonin prevented the alterations in enzyme activity. That these changes in mitochondrial energy metabolism were due to the perpetration of oxidative stress by ISO was evident from the increased levels of lipid peroxidation and decreased reduced glutathione/oxidized glutathione ratio. ISO-induced oxidative stress also altered mitochondrial redox potential and brought about changes in the activity of the antioxidant enzymes manganese superoxide dismutase and glutathione peroxidase, eventually leading to alterations in total ATPase activity and membrane potential. Melatonin ameliorated these changes likely through its antioxidant abilities suggesting a possible mechanism of cardioprotection by this indole against ISO-induced myocardial injury. PMID:25652673

  10. Protective effect of histamine microinjected into cerebellar fastigial nucleus on stress gastric mucosal damage in rats.

    PubMed

    Qiao, Xiao; Yang, Jun; Fei, Su-Juan; Zhu, Jin-Zhou; Zhu, Sheng-Ping; Liu, Zhang-Bo; Li, Ting-Ting; Zhang, Jian-Fu

    2015-12-10

    In the study, we investigated the effect of histamine microinjected into cerebellar fastigial nucleus (FN) on stress gastric mucosal damage (SGMD), and its mechanisms in rats. The model of SGMD was established by restraining and water (21±1°C)-immersion for 3h. The gastric mucosal damage index (GMDI) indicated the severity of gastric mucosal damage. Histamine or receptor antagonist was microinjected into the FN. The decussation of superior cerebellar peduncle (DSCP) and the lateral hypothalamic area (LHA) were destroyed, respectively. The pathological changes of gastric mucosa were evaluated using biological signal acquisition system, Laser-Doppler flowmeter, and western blotting. We found that the microinjection of histamine (0.05, 0.5, and 5μg) into FN significantly attenuated the SGMD, in a dose-dependent manner, whereas, the microinjection of histamine H2 receptor antagonist, ranitidine, and glutamic acid decarboxylase antagonist, 3-mercaptopropionic acid (3-MPA) exacerbated the SGMD. The protective effect of histamine on SGMD was abolished by electrical lesion of DSCP or chemical ablation of LHA. The microinjection of histamine decreased the discharge frequency of the greater splanchnic nerve, and the gastric mucosal blood flow was increased. In addition, the cellular proliferation was enhanced, but the cellular apoptosis was reduced in the gastric mucosa. Also the pro-apoptosis protein, Bax, and caspase-3 were down-regulated, and the anti-apoptosis protein, Bcl-2 was up-regulated following microinjection of histamine. In conclusion, the FN participated in the regulation of SGMD after histamine microinjected into FN, and cerebellar-hypothalamic circuits (include: DSCP, LHA) contribute to the process, which may provide a new therapeutic strategy for SGMD.

  11. Hyperoside protects human primary melanocytes against H2O2-induced oxidative damage

    PubMed Central

    YANG, BIN; YANG, QIN; YANG, XIN; YAN, HONG-BO; LU, QI-PING

    2016-01-01

    Cuscutae semen has been shown to have beneficial effects in the treatment of vitiligo, recorded in the Chinese Pharmacopoeia, whereas the effects of its constituent compounds remains to be elucidated. Using a tetrazolium bromide assay, the present study found that hyperoside (0.5–200 µg/ml) significantly increased the viability of human melanocytes in a time- and dose-dependent manner. The present study used a cell model of hydrogen peroxide (H2O2)-induced oxidative damage to examine the effect of hyperoside on human primary melanocytes. The results demonstrated that hyperoside pretreatment for 2 h decreased cell apoptosis from 54.03±9.11 to 17.46±3.10% in the H2O2-injured melanocytes. The levels of oxidative stress in the mitochondrial membrane potential of the melanocytes increased following hyperoside pretreatment. The mRNA and protein levels of B-cell lymphoma-2/Bcl-2-associated X protein and caspase 3 were regulated by hyperoside, and phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase signaling were also mediated by hyperoside. In conclusion, the results of the present study demonstrated that hyperoside protected the human primary melanocytes against oxidative damage. PMID:27082158

  12. [Protective effect of Radix Salvia Miltiorrhizae on radiation damage of the cochlea].

    PubMed

    Yang, X; Lu, Y; Xie, D

    1999-01-01

    In order to evaluate the preventive and therapeutic effects of Radix Salvia Miltiorrhizae on radiation damage of the cochlea, guinea pigs were divided into 3 groups. Group 1 was treated by radiation added with Radix Salvia Miltiorrhizae. Group 2 was radiated alone, and Group 3 was control. Group 1 and Group 2 were radiated with a single dose of gamma radiation(60 Gy). Morphological and functional observation of the cochleae was performed in two weeks after radiation. The result showed that the changes of complex action potential(CAP) and the cochlear structure were slight in Group 1, but obvious changes were found in Group 2. There was a significant difference in CAP response threshold and incidence of the cochlear hair cell loss between Group 1 and Group 2 (P < 0.01). These results suggest that Radix Salvia Miltiorrhiza may prevent radiation-induced cochlea damage. Its protective mechanisms may be cleaning free radicals, blocking calcium channel and improving microcirculation of the cochlea. PMID:12080686

  13. The polypeptide in Chlamys farreri can protect human dermal fibroblasts from ultraviolet B damage

    NASA Astrophysics Data System (ADS)

    Zhang, Yujiang; Zhan, Songmei; Cao, Pengli; Liu, Ning; Chen, Xuehong; Wang, Yuejun; Wang, Chunbo

    2005-09-01

    To investigate the effect of polypeptide from Chlamys farreri (PCF) on NHDF in vitro, we modeled oxidative damage on normal human dermal fibroblasts (NHDF) exposed to ultraviolet B (UVB). In this study, 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) were tested to measure cell viability. Enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and xanthine oxidase (XOD) were determined biochemically. Total antioxidative capacity (T-AOC) and anti-superoxide anion capacity (A-SAC) were also determined. Ultrastructure of fibroblasts was observed under transmission electron microscope. The results showed that: UVB (1.176×10-4 J/cm2) suppressed the growth of fibroblasts and the introduction of PCF (0.25% 1%) before UVB reduced the suppression in a concentration-dependent manner. PCF could enhance the activities of SOD, GSH-PX and T-AOC as well as A-SAC. Also PCF could inhibit XOD activity, while it did not affect CAT activity. Ultrastructure of fibroblasts were damaged after UVB irradiation, concentration-dependent PCF reduced the destructive effect of UVB on cells. These results indicated that PCF can protect human dermal fibroblasts from being harmed by UVB irradiation via its antioxidant proerty.

  14. Opuntia ficus indica extract protects against chlorpyrifos-induced damage on mice liver.

    PubMed

    Ncibi, Saida; Ben Othman, Mahmoud; Akacha, Amira; Krifi, Mohamed Naceur; Zourgui, Lazhar

    2008-02-01

    This original study investigates the role of Opuntia ficus indica (cactus) cladodes extract against liver damage induced in male SWISS mice by an organophosphorous insecticide, the chlorpyrifos (CPF). Liver damage was evaluated by the measure of its weight and the quantification of some biochemical parameters, such as alanine amino transferase (ALAT), aspartate amino transferase (ASAT), phosphatase alkaline (PAL), lactate dehydrogenase (LDH), cholesterol and albumin in serum by spectrophotometric techniques. The experimental approach lasted 48 h and consisted of 6 treatments of six mice each one; (1) control, (2) 10 mg/kg (b.w) CPF, (3) 10mg/kg (b.w) CPF with 100 mg/kg (b.w) cactus, (4) 150 mg/kg (b.w)CPF, (5) 150 mg/kg (b.w) CPF with 1.5 g/kg cactus, (6) 1.5 g/kg cactus. Both chlorpyrifos and cactus were administrated orally via gavages. Our results showed that CPF affects significantly all parameters studied. However, when this pesticide was administrated associated to cactus, we noticed a recovery of all their levels. In the other hand, cactus alone did not affect the studied parameters. These results allow us to conclude firstly that CPF is hepatotoxic and secondly that Opuntia ficus indica stem extract protects the liver and decreases the toxicity induced by this organophosphorous pesticide.

  15. Heme oxygenase-1-derived bilirubin protects endothelial cells against high glucose-induced damage.

    PubMed

    He, Meihua; Nitti, Mariapaola; Piras, Sabrina; Furfaro, Anna Lisa; Traverso, Nicola; Pronzato, Maria Adelaide; Mann, Giovanni E

    2015-12-01

    Hyperglycemia and diabetes are associated with endothelial cell dysfunction arising from enhanced oxidative injury, leading to the progression of diabetic vascular pathologies. The redox-sensitive transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a master regulator of antioxidant genes, such as heme oxygenase-1 (HO-1), involved in cellular defenses against oxidative stress. We have investigated the pathways involved in high glucose-induced activation of HO-1 in endothelial cells and examined the molecular mechanisms underlying cytoprotection. Elevated d-glucose increased intracellular generation of reactive oxygen species (ROS), leading to nuclear translocation of Nrf2 and HO-1 expression in bovine aortic endothelial cells, with no changes in cell viability. Superoxide scavenging and inhibition of endothelial nitric oxide synthase (eNOS) abrogated upregulation of HO-1 expression by elevated glucose. Inhibition of HO-1 increased the sensitivity of endothelial cells to high glucose-mediated damage, while addition of bilirubin restored cell viability. Our findings establish that exposure of endothelial cells to high glucose leads to activation of endogenous antioxidant defense genes via the Nrf2/ARE pathway. Upregulation of HO-1 provides cytoprotection against high glucose-induced oxidative stress through the antioxidant properties of bilirubin. Modulation of the Nrf2 pathway in the early stages of diabetes may thus protect against sustained damage by hyperglycemia during progression of the disease.

  16. Protective effect of black raspberry seed containing anthocyanins against oxidative damage to DNA, protein, and lipid.

    PubMed

    Choi, Mi-Hee; Shim, Soon-Mi; Kim, Gun-Hee

    2016-02-01

    This study aimed to determine bioactive components and radical scavenging capacity of black raspberry seed extracts as byproducts obtaining during the juice (FSE) and wine (WSE) making process. Cyanidin-3-O-rutinoside was identified as a major anthocyanin and the total anthocyanin contents of fresh and wine seed were 78.24 and 41.61 mg/100 g of dry weight, respectively. The total phenolic and flavonoid contents of FSE and WSE were 2.31 g gallic acid equivalent (GAE) and 360.95 mg catechin equivalent (CE), and 2.44 g GAE and 379.54 mg CE per 100 g dry weight, respectively. The oxygen radical absorbance capacity (ORAC) values were 1041.9 μM TE/g for FSE and 1060.4 μM TE/g for WSE. Pretreatment of the FSE and WSE inhibited the generation of intracellular reactive oxygen species (ROS), DNA and protein damage induced by hydroxyl radicals, and Fe(3+)/ascorbic acid-induced lipid peroxidation in a dose dependent manner. WSE more effectively protected from oxidative damage than FSE. Results from the current study suggest that black raspberry seeds as byproducts from juice and wine processing could be potential sources for natural antioxidants. PMID:27162401

  17. Opuntia ficus indica extract protects against chlorpyrifos-induced damage on mice liver.

    PubMed

    Ncibi, Saida; Ben Othman, Mahmoud; Akacha, Amira; Krifi, Mohamed Naceur; Zourgui, Lazhar

    2008-02-01

    This original study investigates the role of Opuntia ficus indica (cactus) cladodes extract against liver damage induced in male SWISS mice by an organophosphorous insecticide, the chlorpyrifos (CPF). Liver damage was evaluated by the measure of its weight and the quantification of some biochemical parameters, such as alanine amino transferase (ALAT), aspartate amino transferase (ASAT), phosphatase alkaline (PAL), lactate dehydrogenase (LDH), cholesterol and albumin in serum by spectrophotometric techniques. The experimental approach lasted 48 h and consisted of 6 treatments of six mice each one; (1) control, (2) 10 mg/kg (b.w) CPF, (3) 10mg/kg (b.w) CPF with 100 mg/kg (b.w) cactus, (4) 150 mg/kg (b.w)CPF, (5) 150 mg/kg (b.w) CPF with 1.5 g/kg cactus, (6) 1.5 g/kg cactus. Both chlorpyrifos and cactus were administrated orally via gavages. Our results showed that CPF affects significantly all parameters studied. However, when this pesticide was administrated associated to cactus, we noticed a recovery of all their levels. In the other hand, cactus alone did not affect the studied parameters. These results allow us to conclude firstly that CPF is hepatotoxic and secondly that Opuntia ficus indica stem extract protects the liver and decreases the toxicity induced by this organophosphorous pesticide. PMID:17980473

  18. Pyridoxamine protects proteins from damage by hypohalous acids in vitro and in vivo.

    PubMed

    Madu, Hartman; Avance, Josh; Chetyrkin, Sergei; Darris, Carl; Rose, Kristie Lindsey; Sanchez, Otto A; Hudson, Billy; Voziyan, Paul

    2015-12-01

    Diabetes is characterized, in part, by activation of toxic oxidative and glycoxidative pathways that are triggered by persistent hyperglycemia and contribute to diabetic complications. Inhibition of these pathways may benefit diabetic patients by delaying the onset of complications. One such inhibitor, pyridoxamine (PM), had shown promise in clinical trials. However, the mechanism of PM action in vivo is not well understood. We have previously reported that hypohalous acids can cause disruption of the structure and function of renal collagen IV in experimental diabetes (K.L. Brown et al., Diabetes 64:2242-2253, 2015). In the present study, we demonstrate that PM can protect protein functionality from hypochlorous and hypobromous acid-derived damage via a rapid direct reaction with and detoxification of these hypohalous acids. We further demonstrate that PM treatment can ameliorate specific hypohalous acid-derived structural and functional damage to the renal collagen IV network in a diabetic animal model. These findings suggest a new mechanism of PM action in diabetes, namely sequestration of hypohalous acids, which may contribute to known therapeutic effects of PM in human diabetic nephropathy.

  19. The protective effect of clay minerals against damage to adsorbed DNA induced by cadmium and mercury.

    PubMed

    Hou, Yakun; Wu, Pingxiao; Zhu, Nengwu

    2014-01-01

    The adsorption of Salmon Sperm DNA on three kinds of raw clay (rectorite, montmorillonite and sericite) was investigated as a function of pH, ionic strength and the concentrations of DNA and phosphate ions in solution. The DNA adsorption was reduced in the following order: rectorite>montmorillonite>sericite. Based on these findings, there is a strong evidence that the mechanisms for DNA adsorption on clay involve electrostatic forces, cation bridging and ligand exchange. Cyclic voltammetry (CV) and UV-vis absorption and fluorescence spectroscopy were used to compare the properties of unbound DNA and the absorbed DNA on rectorite, both in the absence and presence of Cd(2+) and Hg(2+) inaqueous solutions. The interaction of heavy metals with the unbound DNA was evidenced by the disappearance of reduction peaks in CV, a small bathochromic shift in UV-vis spectroscopy and an incomplete quenching in the emission spectra. Such changes were not observed in the DNA-rectorite hybrids, which is evidence that adsorption on the clay can reduce the extent of the DNA damage caused by heavy metals. Therefore, in these experience the rectorite played an important role in protecting DNA against Cd(2+) and Hg(2+) induced damage.

  20. Common Practice Lightning Strike Protection Characterization Technique to Quantify Damage Mechanisms on Composite Substrates

    NASA Technical Reports Server (NTRS)

    Szatkowski, George N.; Dudley, Kenneth L.; Koppen, Sandra V.; Ely, Jay J.; Nguyen, Truong X.; Ticatch, Larry A.; Mielnik, John J.; Mcneill, Patrick A.

    2013-01-01

    To support FAA certification airworthiness standards, composite substrates are subjected to lightning direct-effect electrical waveforms to determine performance characteristics of the lightning strike protection (LSP) conductive layers used to protect composite substrates. Test results collected from independent LSP studies are often incomparable due to variability in test procedures & applied practices at different organizations, which impairs performance correlations between different LSP data sets. Under a NASA supported contract, The Boeing Company developed technical procedures and documentation as guidance in order to facilitate a test method for conducting universal common practice lightning strike protection test procedures. The procedures obtain conformity in future lightning strike protection evaluations to allow meaningful performance correlations across data sets. This universal common practice guidance provides the manufacturing specifications to fabricate carbon fiber reinforced plastic (CFRP) test panels, including finish, grounding configuration, and acceptable methods for pretest nondestructive inspection (NDI) and posttest destructive inspection. The test operations guidance elaborates on the provisions contained in SAE ARP5416 to address inconsistencies in the generation of damage protection performance data, so as to provide for maximum achievable correlation across capable lab facilities. In addition, the guidance details a direct effects test bed design to aid in quantification of the multi-physical phenomena surrounding a lightning direct attachment supporting validation data requirements for the development of predictive computational modeling. The lightning test bed is designed to accommodate a repeatable installation procedure to secure the test panel and eliminate test installation uncertainty. It also facilitates a means to capture the electrical waveform parameters in 2 dimensions, along with the mechanical displacement and thermal

  1. [Study of blue light induced DNA damage of retinal pigment epithelium(RPE) cells and the protection of vitamin C].

    PubMed

    Zhou, Jian Wei; Ren, Guo Liang; Zhang, Xiao Ming; Zhu, Xi; Lin, Hai Yan; Zhou, Ji Lin

    2003-10-01

    To evaluate protection of vitamin C on blue light-induced DNA damage of human retinal pigment epithelium (RPE) cells. The cultured RPE cells were divided into 3 groups: Control group (no blue light exposure), blue light exposure group (blue light exposure for 20 minutes) and blue light exposure + vitamin C group (blue light exposure + 100 mumol/L vitamin C). Travigen's comet assay kit and Euclid comet assay software were used to assay the DNA damage levels. The DNA percentage in the tail of electrophoretogram in the three groups were 18.44%, 54.42% and 32.43% respectively (p < 0.01). Tail moments were 8.2, 48.3, and 18.4 respectively (p < 0.01). Blue light could induce DNA damage to RPE cells but vitamin C could protect the RPE cells from the blue light-induced DNA damage.

  2. Disaccharides Protect Antigens from Drying-Induced Damage in Routinely Processed Tissue Sections.

    PubMed

    Boi, Giovanna; Scalia, Carla Rossana; Gendusa, Rossella; Ronchi, Susanna; Cattoretti, Giorgio

    2016-01-01

    Drying of the tissue section, partial or total, during immunostaining negatively affects both the staining of tissue antigens and the ability to remove previously deposited antibody layers, particularly during sequential rounds of de-staining and re-staining for multiple antigens. The cause is a progressive loss of the protein-associated water up to the removal of the non-freezable water, a step which abolishes the immunoavailability of the epitope. In order to describe and prevent these adverse effects, we tested, among other substances, sugars, which are known to protect unicellular organisms from freezing and dehydration, and stabilize drugs and reagents in solid state form in medical devices. Disaccharides (lactose, sucrose) prevented the air drying-induced antigen masking and protected tissue-bound antigens and antibodies from air drying-induced damage. Complete removal of the bound antibody layers by chemical stripping was permitted if lactose was present during air drying. Lactose, sucrose and other disaccharides prevent air drying artifacts, allow homogeneous, consistent staining and the reuse of formalin-fixed, paraffin-embedded tissue sections for repeated immunostaining rounds by guaranteeing constant staining quality in suboptimal hydration conditions.

  3. The protective role of neocuproine against cardiac damage in isolated perfused rat hearts.

    PubMed

    Applebaum, Y J; Kuvin, J; Borman, J B; Uretzky, G; Chevion, M

    1990-01-01

    The effect of neocuproine on cardiac injury was studied using retrogradely perfused isolated rat hearts in two experimental systems. In the first system, where hydrogen peroxide-induced damage was studied, neocuproine at the range of 40-175 microM provided protection at the level of 70-85%, as demonstrated by the reduced loss in the peak systolic pressure (P), in +dP/dt and in -dP/dt. In the second system, where ischemia/reperfusion-induced arrhythmias were studied, neocuproine (42 microM) provided a marked protection against cardiac injury as demonstrated by the lowering of the incidence in irreversible ventricular fibrillation, by decreasing the duration of ventricular fibrillation and by the concomitant increase of the duration of normal sinus rhythm, and by improving the post-ischemic recovery of P, +dP/dt and -dP/dt. Free radicals have already been implicated as causative agents in cardiac injury resulting from either hydrogen peroxide or ischemia followed by reperfusion. Additionally, iron and copper have already been shown to drastically exacerbate the injurious effects of free radicals. Thus, the results reported here with neocuproine, a highly effective chelator for both iron and copper, as well as with adventitious copper and with the combination of neocuproine and copper, are in accord with the mediatory role of transition metals in enhancing the deleterious effects induced by free radicals.

  4. Oral Administration of Fermented Soymilk Products Protects the Skin of Hairless Mice against Ultraviolet Damage

    PubMed Central

    Kano, Mitsuyoshi; Kubota, Norihiro; Masuoka, Norie; Hori, Tetsuji; Miyazaki, Kouji; Ishikawa, Fumiyasu

    2016-01-01

    The protective effect of isoflavones on skin damage from ultraviolet (UV) radiation and their bioavailability were investigated in ovariectomized hairless mice fed diets composed of fermented soymilk containing aglycone forms of isoflavones or control soymilk containing glucose-conjugated forms of isoflavones. The erythema intensity of dorsal skin was significantly higher in ovariectomized mice than in sham-operated mice (p < 0.05). The erythema intensity and epidermal thickness of dorsal skin were significantly lower in the fermented soymilk diet group than in the control diet group (each p < 0.05). Levels of cyclobutane pyrimidine dimers in dorsal skin were significantly lower in the fermented soymilk diet group than in the control group (p < 0.05). Serum and dorsal skin isoflavone concentrations were significantly higher in the fermented soymilk diet group than in the soymilk diet group (p < 0.05). These results indicate that oral administration of a fermented soymilk diet increases isoflavone concentrations in the blood and skin, effectively scavenging the reactive oxygen species generated by UV irradiation and exerting an estrogen-like activity, with a consequent protective effect on skin photodamage in hairless mice. PMID:27556484

  5. Oral Administration of Fermented Soymilk Products Protects the Skin of Hairless Mice against Ultraviolet Damage.

    PubMed

    Kano, Mitsuyoshi; Kubota, Norihiro; Masuoka, Norie; Hori, Tetsuji; Miyazaki, Kouji; Ishikawa, Fumiyasu

    2016-01-01

    The protective effect of isoflavones on skin damage from ultraviolet (UV) radiation and their bioavailability were investigated in ovariectomized hairless mice fed diets composed of fermented soymilk containing aglycone forms of isoflavones or control soymilk containing glucose-conjugated forms of isoflavones. The erythema intensity of dorsal skin was significantly higher in ovariectomized mice than in sham-operated mice (p < 0.05). The erythema intensity and epidermal thickness of dorsal skin were significantly lower in the fermented soymilk diet group than in the control diet group (each p < 0.05). Levels of cyclobutane pyrimidine dimers in dorsal skin were significantly lower in the fermented soymilk diet group than in the control group (p < 0.05). Serum and dorsal skin isoflavone concentrations were significantly higher in the fermented soymilk diet group than in the soymilk diet group (p < 0.05). These results indicate that oral administration of a fermented soymilk diet increases isoflavone concentrations in the blood and skin, effectively scavenging the reactive oxygen species generated by UV irradiation and exerting an estrogen-like activity, with a consequent protective effect on skin photodamage in hairless mice. PMID:27556484

  6. γ-Oryzanol protects against acute cadmium-induced oxidative damage in mice testes.

    PubMed

    Spiazzi, Cristiano C; Manfredini, Vanusa; Barcellos da Silva, Fabiana E; Flores, Erico M M; Izaguirry, Aryele P; Vargas, Laura M; Soares, Melina B; Santos, Francielli W

    2013-05-01

    Cadmium is a non-essential heavy metal that is present at low levels mainly in food and water and also in cigar smoke. The present study evaluated the testicular damage caused by acute cadmium exposure and verified the protective role of γ-oryzanol (ORY). Mice were administrated with a single dose of 2.5mg/kg of CdCl2, and then treated with ORY (50mM in canola oil, 5mL/kg). Testes were removed after 24h and tested for lipid peroxidation (TBARS), protein carbonylation, DNA breakage, ascorbic acid, cadmium and non-proteic thiols contents, and for the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and δ-aminolevulic acid dehydratase (δ-ALA-D). Cadmium presented a significant alteration in all parameters, except GPx and CAT activities. Therapy reduced in a slight degree cadmium concentration in testes (around 23%). ORY restored SOD and GST activities as well as TBARS production to the control levels. Furthermore, ORY partially recovered δ-ALA-D activity inhibited by cadmium. This study provides the first evidence on the therapeutic properties of ORY in protecting against cadmium-induced testicular toxicity. PMID:23395783

  7. Ocular Aldehyde Dehydrogenases: Protection against Ultraviolet Damage and Maintenance of Transparency for Vision

    PubMed Central

    Chen, Ying; Thompson, David C.; Koppaka, Vindhya; Jester, James V.; Vasiliou, Vasilis

    2012-01-01

    Aldehyde dehydrogenase (ALDH) enzymes catalyze the NAD(P)+-dependent oxidation of a wide variety of endogenous and exogenous aldehydes to their corresponding acids. Some members of the ALDH superfamily of enzymes are abundantly expressed in the mammalian cornea and lens in a taxon-specific manner. Considered to be corneal and lens crystallins, they confer protective and transparent properties upon these ocular tissues. ALDH3A1 is highly expressed in the cornea of most mammals, with the exception of rabbit that expresses exclusively ALDH1A1 in the cornea. ALDH1A1 is present in both the cornea and lens of several animal species. As a result of their catalytic and non-catalytic functions, ALDH3A1 and ALDH1A1 proteins protect inner ocular tissues from ultraviolet radiation and reactive oxygen-induced damage. In addition, these corneal crystallins contribute to cellular transparency in corneal stromal keratocytes, supporting a structural role of these ALDH proteins. A putative regulatory function of ALDH3A1 on corneal cell proliferation has also been proposed. Finally, the three retinaldehye dehydrogenases cooperatively mediate retinoic acid signaling during the eye development. PMID:23098688

  8. Disaccharides Protect Antigens from Drying-Induced Damage in Routinely Processed Tissue Sections.

    PubMed

    Boi, Giovanna; Scalia, Carla Rossana; Gendusa, Rossella; Ronchi, Susanna; Cattoretti, Giorgio

    2016-01-01

    Drying of the tissue section, partial or total, during immunostaining negatively affects both the staining of tissue antigens and the ability to remove previously deposited antibody layers, particularly during sequential rounds of de-staining and re-staining for multiple antigens. The cause is a progressive loss of the protein-associated water up to the removal of the non-freezable water, a step which abolishes the immunoavailability of the epitope. In order to describe and prevent these adverse effects, we tested, among other substances, sugars, which are known to protect unicellular organisms from freezing and dehydration, and stabilize drugs and reagents in solid state form in medical devices. Disaccharides (lactose, sucrose) prevented the air drying-induced antigen masking and protected tissue-bound antigens and antibodies from air drying-induced damage. Complete removal of the bound antibody layers by chemical stripping was permitted if lactose was present during air drying. Lactose, sucrose and other disaccharides prevent air drying artifacts, allow homogeneous, consistent staining and the reuse of formalin-fixed, paraffin-embedded tissue sections for repeated immunostaining rounds by guaranteeing constant staining quality in suboptimal hydration conditions. PMID:26487185

  9. Antioxidant, cytotoxic, antitumor, and protective DNA damage metabolites from the red sea brown alga Sargassum sp

    PubMed Central

    Ayyad, Seif-Eldin N.; Ezmirly, Saleh T.; Basaif, Salim A.; Alarif, Walied M.; Badria, Adel F.; Badria, Farid A.

    2011-01-01

    Background: Macroalgae can be viewed as a potential antioxidant and anti-inflammatory sources owing to their capability of producing compounds for its protection from environmental factors such as heat, pollution, stress, oxygen concentration, and UV radiations. Objective: To isolate major compounds which are mainly responsible for the pharmacological activity of brown alga under investigation, Sargassum sp. Materials and Methods: Algal material was air dried, extracted with a mixture of organic solvents, and fractionated with different adsorbents. The structures of obtained pure compounds were elucidated with different spectroscopic techniques, and two pure materials were tested for protection of DNA from damage, antioxidant, antitumor, and cytotoxicity. Results: Four pure compounds were obtained, of which fucosterol (1) and fucoxanthin (4) were tested; it was found that fucoxanthin has strong antioxidant and cytotoxicity against breast cancer (MCF-7) with IC50 = 11.5 μg/ml. Conclusion: The naturally highly conjugated safe compound fucoxanthin could be used as antioxidant and as an antitumor compound. PMID:22022163

  10. Control of Trx1 redox state modulates protection against methyl methanesulfonate-induced DNA damage via stabilization of p21.

    PubMed

    Gu, Li; Gao, Wei; Yang, Hui Min; Wang, Bei Bei; Wang, Xiao Na; Xu, Jianguo; Zhang, Hong

    2016-01-01

    Thioredoxin 1 (Trx1) is known to play an important role in protecting against cell death. However, the mechanism for control of Trx1 in cell death resulting from DNA damage has not been fully investigated. In this study, we used the DNA-damaging agent methyl methanesulfonate (MMS) to investigate the protective effects of Trx1 against DNA damage and cell death in HEK293 cells. We found that MMS application caused dose-dependent changes in the Trx1 redox state determined by redox western blotting. At lower concentrations, both reduced and oxidized Trx1 were observed, whereas the reduced band was fully oxidized at the higher concentration. Trx1 overexpression and small interfering RNA knockdown in cells revealed that reduced Trx1 after exposure to lower doses of MMS attenuated DNA damage, assessed by comet assay, and level of the DNA-damage marker histone γ-H2AX, possibly through scavenging intracellular ROS and an increase in p21 protein level via enhancing its stability. However, oxidized Trx1 lost its protective ability to DNA damage in response to higher concentration of MMS. Corresponding to the redox state control of Trx1, cell death induced by different dose of MMS was also found, by inhibiting phosphorylations of p38 and 4E-BP1. These results indicate that reduced Trx1 plays important protective roles against MMS-induced DNA damage and cell death, suggesting that cell protection is regulated by the intracellular redox state. Control of the redox state of Trx1 and its regulating proteins may offer a novel therapeutic strategy for the control of cancer.

  11. Low levels of methylmercury induce DNA damage in rats: protective effects of selenium.

    PubMed

    Grotto, Denise; Barcelos, Gustavo R M; Valentini, Juliana; Antunes, Lusânia M G; Angeli, José Pedro F; Garcia, Solange C; Barbosa, Fernando

    2009-03-01

    In this study we examined the possible antigenotoxic effect of selenium (Se) in rats chronically exposed to low levels of methylmercury (MeHg) and the association between glutathione peroxidase (GSH-Px) activity and DNA lesions (via comet assay) in the same exposed animals. Rats were divided into six groups as follows: (Group I) received water; (Group II) received MeHg (100 mug/day); (Group III) received Se (2 mg/L drinking water); (Group IV) received Se (6 mg/L drinking water); (Group V) received MeHg (100 mug/day) and Se (2 mg/L drinking water); (Group VI) received MeHg (100 mug/day) and Se (6 mg/L drinking water). Total treatment time was 100 days. GSH-Px activity was determined spectrophotometrically and DNA damage was determined by comet assay. Mean GSH-Px activity in groups I, II, III, IV, V and VI were, respectively: 40.19 +/- 17.21; 23.63 +/- 6.04; 42.64 +/- 5.70; 38.50 +/- 7.15; 34.54 +/- 6.18 and 41.39 +/- 11.67 nmolNADPH/min/gHb. DNA damage was represented by a mean score from 0 to 300; the results for groups I, II, III, IV, V and VI were, respectively: 6.87 +/- 3.27; 124.12 +/- 13.74; 10.62 +/- 3.81; 13.25 +/- 1.76; 86.87 +/- 11.95 and 76.25 +/- 7.48. There was a significant inhibition of GSH-Px activity in group II compared with group I (P < 0.05). Groups V and VI did not show a difference in enzyme activity compared with groups III and IV, showing the possible protective action of Se. Comet assay presented a significant difference in DNA migration between group II and group I (P < 0.0001). Groups V and VI showed a significant reduction in MeHg-induced genotoxicity (P < 0.001) when compared with group II. A negative correlation (r = -0.559, P < 0.05) was found between GSH-Px activity and DNA lesion, showing that the greater the DNA damage, the lower the GSH-Px activity. Our findings demonstrated the oxidative and genotoxic properties of MeHg, even at low doses. Moreover, Se co-administration reestablished GSH-Px activity and reduced DNA damage.

  12. [The change in efficiency of protective measures for reduction of 137Cs accumulation by agricultural plants in various periods after the Chernobyl accident].

    PubMed

    Panov, A V; Aleksakhin, R M; Muzalevskaia, A A

    2011-01-01

    Dynamics of 137Cs transfer factors to plants and the effects of protective measures on this radionuclide accumulation in the agricultural production is estimated on the example of the south-western regions of Bryansk District. Three periods in decreasing the 137Cs content in plants during 20 years after the Chernobyl accident are identified. The contribution of radionuclide decay, natural biogeochemical processes and protective measures aimed at reduction of the 137Cs accumulation in agricultural plants during various periods after radioactive fallout is shown. Maximum permissible levels of 137Cs contamination of cultivated lands, where crop products meeting current standards may be obtained, at different scopes of protective measures on radioactive-contaminated territories are forecasted. Periods after radioactive fallout, when crop and forage products meeting radiological standards are obtained, are assessed. PMID:21520624

  13. [The change in efficiency of protective measures for reduction of 137Cs accumulation by agricultural plants in various periods after the Chernobyl accident].

    PubMed

    Panov, A V; Aleksakhin, R M; Muzalevskaia, A A

    2011-01-01

    Dynamics of 137Cs transfer factors to plants and the effects of protective measures on this radionuclide accumulation in the agricultural production is estimated on the example of the south-western regions of Bryansk District. Three periods in decreasing the 137Cs content in plants during 20 years after the Chernobyl accident are identified. The contribution of radionuclide decay, natural biogeochemical processes and protective measures aimed at reduction of the 137Cs accumulation in agricultural plants during various periods after radioactive fallout is shown. Maximum permissible levels of 137Cs contamination of cultivated lands, where crop products meeting current standards may be obtained, at different scopes of protective measures on radioactive-contaminated territories are forecasted. Periods after radioactive fallout, when crop and forage products meeting radiological standards are obtained, are assessed.

  14. Protective Effects of Tinospora crispa Stem Extract on Renal Damage and Hemolysis during Plasmodium berghei Infection in Mice.

    PubMed

    Nutham, Narain; Sakulmettatham, Sakuna; Klongthalay, Suwit; Chutoam, Palatip; Somsak, Voravuth

    2015-01-01

    Renal damage and hemolysis induced by malaria are associated with mortality in adult patients. It has been speculated that oxidative stress condition induced by malaria infection is involved in its pathology. Thus, we aimed to investigate the protective effects of Tinospora crispa stem extract on renal damage and hemolysis during Plasmodium berghei infection. T. crispa stem extract was prepared using hot water method and used for oral treatment in mice. Groups of ICR mice were infected with 1 × 10(7) parasitized erythrocytes of P. berghei ANKA by intraperitoneal injection and given the extracts (500, 1000, and 2000 mg/kg) twice a day for 4 consecutive days. To assess renal damage and hemolysis, blood urea nitrogen (BUN), creatinine, and hematocrit (%Hct) levels were then evaluated, respectively. Malaria infection resulted in renal damage and hemolysis as indicated by increasing of BUN and creatinine and decreasing of %Hct, respectively. However, protective effects on renal damage and hemolysis were observed in infected mice treated with these extracts at doses of 1000 and 2000 mg/kg. In conclusion, T. crispa stem extract exerted protective effects on renal damage and hemolysis induced by malaria infection. This plant may work as potential source in the development of variety of herbal formulations for malarial treatment. PMID:26600953

  15. Protective Effects of Tinospora crispa Stem Extract on Renal Damage and Hemolysis during Plasmodium berghei Infection in Mice

    PubMed Central

    Nutham, Narain; Sakulmettatham, Sakuna; Klongthalay, Suwit; Chutoam, Palatip; Somsak, Voravuth

    2015-01-01

    Renal damage and hemolysis induced by malaria are associated with mortality in adult patients. It has been speculated that oxidative stress condition induced by malaria infection is involved in its pathology. Thus, we aimed to investigate the protective effects of Tinospora crispa stem extract on renal damage and hemolysis during Plasmodium berghei infection. T. crispa stem extract was prepared using hot water method and used for oral treatment in mice. Groups of ICR mice were infected with 1 × 107 parasitized erythrocytes of P. berghei ANKA by intraperitoneal injection and given the extracts (500, 1000, and 2000 mg/kg) twice a day for 4 consecutive days. To assess renal damage and hemolysis, blood urea nitrogen (BUN), creatinine, and hematocrit (%Hct) levels were then evaluated, respectively. Malaria infection resulted in renal damage and hemolysis as indicated by increasing of BUN and creatinine and decreasing of %Hct, respectively. However, protective effects on renal damage and hemolysis were observed in infected mice treated with these extracts at doses of 1000 and 2000 mg/kg. In conclusion, T. crispa stem extract exerted protective effects on renal damage and hemolysis induced by malaria infection. This plant may work as potential source in the development of variety of herbal formulations for malarial treatment. PMID:26600953

  16. The efficacy of post porosity plasma protection against vacuum-ultraviolet damage in porous low-k materials

    NASA Astrophysics Data System (ADS)

    Lionti, K.; Darnon, M.; Volksen, W.; Magbitang, T.; Dubois, G.

    2015-03-01

    As of today, plasma damage remains as one of the main challenges to the reliable integration of porous low-k materials into microelectronic devices at the most aggressive node. One promising strategy to limit damage of porous low-k materials during plasma processing is an approach we refer to as post porosity plasma protection (P4). In this approach, the pores of the low-k material are filled with a sacrificial agent prior to any plasma treatment, greatly minimizing the total damage by limiting the physical interactions between plasma species and the low-k material. Interestingly, the contribution of the individual plasma species to the total plasma damage is not fully understood. In this study, we investigated the specific damaging effect of vacuum-ultraviolet (v-UV) photons on a highly porous, k = 2.0 low-k material and we assessed the P4 protective effect against them. It was found that the impact of the v-UV radiation varied depending upon the v-UV emission lines of the plasma. More importantly, we successfully demonstrated that the P4 process provides excellent protection against v-UV damage.

  17. The efficacy of post porosity plasma protection against vacuum-ultraviolet damage in porous low-k materials

    SciTech Connect

    Lionti, K.; Volksen, W.; Darnon, M.; Magbitang, T.; Dubois, G.

    2015-03-21

    As of today, plasma damage remains as one of the main challenges to the reliable integration of porous low-k materials into microelectronic devices at the most aggressive node. One promising strategy to limit damage of porous low-k materials during plasma processing is an approach we refer to as post porosity plasma protection (P4). In this approach, the pores of the low-k material are filled with a sacrificial agent prior to any plasma treatment, greatly minimizing the total damage by limiting the physical interactions between plasma species and the low-k material. Interestingly, the contribution of the individual plasma species to the total plasma damage is not fully understood. In this study, we investigated the specific damaging effect of vacuum-ultraviolet (v-UV) photons on a highly porous, k = 2.0 low-k material and we assessed the P4 protective effect against them. It was found that the impact of the v-UV radiation varied depending upon the v-UV emission lines of the plasma. More importantly, we successfully demonstrated that the P4 process provides excellent protection against v-UV damage.

  18. A novel strategy of natural plant ferritin to protect DNA from oxidative damage during iron oxidation.

    PubMed

    Liao, Xiayun; Lv, Chenyan; Zhang, Xiuqing; Masuda, Taro; Li, Meiliang; Zhao, Guanghua

    2012-07-15

    Plant ferritin is a naturally occurring heteropolymer in plastids, where Fe(2+) is oxidatively deposited into the protein. However, the effect of this process on the coexistence of DNA and plant ferritin in the plastids is unknown. To investigate this effect, we built a system in which various plant ferritins and DNA coexist, followed by treatment with ferrous ions under aerobic conditions. Interestingly, naturally occurring soybean seed ferritin (SSF), a heteropolymer with an H-1/H-2 ratio of 1 to 1 in the apo form, completely protected DNA from oxidative damage during iron oxidative deposition into protein, and a similar result was obtained with its recombinant form, but not with its homopolymeric counterparts, apo rH-1 and apo rH-2. We demonstrate that the difference in DNA protection between heteropolymeric and homopolymeric plant ferritins stems from their different strategies to control iron chemistry during the above oxidative process. For example, the detoxification reaction occurs only in the presence of apo heteropolymeric SSF (hSSF), thereby preventing the production of hydroxyl radicals. In contrast, hydroxyl radicals are apparently generated via the Fenton reaction when apo rH-1 or rH-2 is used instead of apo hSSF. Thus, a combination of H-1 and H-2 subunits in hSSF seems to impart a unique DNA-protective function to the protein, which was previously unrecognized. This new finding advances our understanding of the structure and function of ferritin and of the widespread occurrence of heteropolymeric plant ferritin in nature. PMID:22580341

  19. Protective Effect of Psidium guajava in Arsenic-induced Oxidative Stress and Cytological Damage in Rats.

    PubMed

    Tandon, Neeraj; Roy, Manju; Roy, Sushovan; Gupta, Neelu

    2012-09-01

    This study was undertaken to evaluate the protective effect of aqueous extract of Psidium guajava leaves against sodium arsenite-induced toxicity in experimental rats. Animals were divided into four groups. Control group received arsenic free distilled water and three treatment groups (II, III, and IV) exposed to the arsenic (NaAsO(2)) (20 mg/kg b.wt) through drinking water. Group III and IV were administered a daily oral dose of P. guajava leaf extract 50 and 100 mg/kg b.wt. (AEPG(50) and AEPG(100)) for the period of 6 weeks. Blood samples and organs were collected at the end of the experiment. Arsenic exposure resulted in significant rise in lipid peroxidation (LPO) levels in erythrocyte, liver, kidney, and brain. In addition toxin decreased (P<0.05) the level of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities in the studied tissues. Residual effect of arsenic in various tissues was also observed. Histopathological results revealed mild to severe type of necrosis and degenerative changes in kidney and liver of arsenic intoxicated animals. Cytological alteration in brain tissue was also observed. Treatment with AEPG(100) (aqueous extract of P. guajava) @100 mg/kg body weight) significantly restored activities of oxidative stress markers like LPO levels, GSH levels, SOD, and CAT activities but having the limited protective activity of the herbal extract was observed on tissues architecture. It is therefore concluded that prophylactic co-administration of AEPG could provide specific protection from oxidative injury and to some extent on tissue damage. PMID:23293461

  20. Dietary spices protect against hydrogen peroxide-induced DNA damage and inhibit nicotine-induced cancer cell migration.

    PubMed

    Jayakumar, R; Kanthimathi, M S

    2012-10-01

    Spices are rich sources of antioxidants due to the presence of phenols and flavonoids. In this study, the DNA protecting activity and inhibition of nicotine-induced cancer cell migration of 9 spices were analysed. Murine fibroblasts (3T3-L1) and human breast cancer (MCF-7) cells were pre-treated with spice extracts and then exposed to H₂O₂ and nicotine. The comet assay was used to analyse the DNA damage. Among the 9 spices, ginger, at 50 μg/ml protected against 68% of DNA damage in 3T3-L1 cells. Caraway, cumin and fennel showed statistically significant (p<0.05) DNA protecting activity. Treatment of MCF-7 cells with nicotine induced cell migration, whereas pre-treatment with spices reduced this migration. Pepper, long pepper and ginger exhibited a high rate of inhibition of cell migration. The results of this study prove that spices protect DNA and inhibit cancer cell migration. PMID:25005983

  1. Ultraviolet damage to the eye revisited: eye-sun protection factor (E-SPF®), a new ultraviolet protection label for eyewear

    PubMed Central

    Behar-Cohen, Francine; Baillet, Gilles; de Ayguavives, Tito; Garcia, Paula Ortega; Krutmann, Jean; Peña-García, Pablo; Reme, Charlotte; Wolffsohn, James S

    2014-01-01

    Ultraviolet (UV) radiation potentially damages the skin, the immune system, and structures of the eye. A useful UV sun protection for the skin has been established. Since a remarkable body of evidence shows an association between UV radiation and damage to structures of the eye, eye protection is important, but a reliable and practical tool to assess and compare the UV-protective properties of lenses has been lacking. Among the general lay public, misconceptions on eye-sun protection have been identified. For example, sun protection is mainly ascribed to sunglasses, but less so to clear lenses. Skin malignancies in the periorbital region are frequent, but usual topical skin protection does not include the lids. Recent research utilized exact dosimetry and demonstrated relevant differences in UV burden to the eye and skin at a given ambient irradiation. Chronic UV effects on the cornea and lens are cumulative, so effective UV protection of the eyes is important for all age groups and should be used systematically. Protection of children’s eyes is especially important, because UV transmittance is higher at a very young age, allowing higher levels of UV radiation to reach the crystalline lens and even the retina. Sunglasses as well as clear lenses (plano and prescription) effectively reduce transmittance of UV radiation. However, an important share of the UV burden to the eye is explained by back reflection of radiation from lenses to the eye. UV radiation incident from an angle of 135°–150° behind a lens wearer is reflected from the back side of lenses. The usual antireflective coatings considerably increase reflection of UV radiation. To provide reliable labeling of the protective potential of lenses, an eye-sun protection factor (E-SPF®) has been developed. It integrates UV transmission as well as UV reflectance of lenses. The E-SPF® compares well with established skin-sun protection factors and provides clear messages to eye health care providers and to

  2. Protective effects of curcumin and vitamin E against chlorpyrifos-induced lung oxidative damage.

    PubMed

    Hassani, S; Sepand, M R; Jafari, A; Jaafari, J; Rezaee, R; Zeinali, M; Tavakoli, F; Razavi-Azarkhiavi, K

    2015-06-01

    There are increasing concerns regarding the toxic effects of chlorpyrifos (CPF) on human health. Curcumin (CUR) is a yellow pigment isolated from turmeric ground rhizome of Curcuma longa Linn., which has been identified as an antioxidant agent. This study was designed to examine the protective effect of CUR and vitamin E (Vit E) on CPF-induced lung toxicity. Rats were divided into seven groups: control, CPF (13.5 mg/kg, orally), CPF + CUR (100 and 300 mg/kg, respectively, orally), CPF + α-tocopherol (Vit E, 150 mg/kg, intraperitoneally), CPF and CUR (100 and 300 mg/kg, respectively) in combination with α-tocopherol. The regimens were administered once daily for 28 days. At the end of the treatment period, lungs were collected for evaluation of oxidative factors and histopathological parameters. CUR and Vit E led to a decrease in lipid peroxidation in the lungs of the CPF-injected animals (48% and 51%, respectively). Glutathione peroxidase inhibited by CPF (91.9 nmol/min/mg protein) was induced again by CUR and Vit E (167.1 and 171.8 nmol/min/mg protein). CUR and Vit E caused a significant induction of superoxide dismutase (103.4 U/mg protein). Catalase activity almost returned to normalcy in CPF-intoxicated rats subjected to CUR + Vit E treatment (p < 0.001). Lung sections from CPF-treated rats displayed histopathological damages, while coadministration of CUR and Vit E resulted in apparently normal morphology with a significant decrease in injuries (p < 0.05). Our findings revealed that coadministration of Vit E and CUR to CPF-treated animals prevents the oxidative damages in the lung tissues. PMID:25233897

  3. Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells.

    PubMed

    Perona, Marina; Dagrosa, María A; Pagotto, Romina; Casal, Mariana; Pignataro, Omar P; Pisarev, Mario A; Juvenal, Guillermo J

    2013-03-01

    Many epidemiologic studies have shown that the exposure to high external radiation doses increases thyroid neoplastic frequency, especially when given during childhood or adolescence. The use of radioprotective drugs may decrease the damage caused by radiation therapy and therefore could be useful to prevent the development of thyroid tumors. The aim of this study was to investigate the possible application of 6-propyl-2-thiouracil (PTU) as a radioprotector in the thyroid gland. Rat thyroid epithelial cells (FRTL-5) were exposed to different doses of γ irradiation with or without the addition of PTU, methimazole (MMI), reduced glutathione (GSH) and perchlorate (KClO4). Radiation response was analyzed by clonogenic survival assay. Cyclic AMP (cAMP) levels were measured by radioimmunoassay (RIA). Apoptosis was quantified by nuclear cell morphology and caspase 3 activity assays. Intracellular reactive oxygen species (ROS) levels were measured using the fluorescent dye 2',7'-dichlorofluorescein-diacetate. Catalase, superoxide dismutase and glutathione peroxidase activities were also determined. Pretreatment with PTU, MMI and GSH prior to irradiation significantly increased the surviving cell fraction (SF) at 2 Gy (P < 0.05), while no effect was observed with KClO4. An increase in extracellular levels of cAMP was found only in PTU treated cells in a dose and time-dependent manner. Cells incubated with agents that stimulate cAMP (forskolin and dibutyril cAMP) mimicked the effect of PTU on SF. Moreover, pretreatment with the inhibitor of protein kinase A, H-89, abolished the radioprotective effect of PTU. PTU treatment diminished radiation-induced apoptosis and protected cells against radiation-induced ROS elevation and suppression of the antioxidant enzyme's activity. PTU was found to radioprotect normal thyroid cells through cAMP elevation and reduction in both apoptosis and radiation-induced oxidative stress damage.

  4. Protective effects of different antioxidants against cadmium induced oxidative damage in rat testis and prostate tissues.

    PubMed

    Jahan, Sarwat; Zahra, Asia; Irum, Umaira; Iftikhar, Natasha; Ullah, Hizb

    2014-08-01

    The present study was performed to determine the effects of different antioxidants on testicular histopathology and oxidative damage induced by cadmium (Cd) in rat testis and prostate. Twenty five rats were equally divided into five groups (n = 5/group). The control group was injected subcutaneously with saline while the Cd alone treated group received a subcutaneous injection of 0.2 mg/kg CdCl(2). Other groups were treated with sulphoraphane (25 µg/rat), vitamin E (75 mg/kg), and Ficus Religiosa plant extract (100 mg/kg) orally along with subcutaneous injections of 0.2 mg/kg CdCl(2) for fifteen days. Oxidative damage in the testicular and prostate tissues were assessed by the estimation of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and glutathione reductase (GSR) activity. Lipid peroxidation (TBARS), protein estimation, and histomorphology were also assessed. Cadmium exposure caused a significant decrease in antioxidant enzymes like CAT, POD, SOD, GSR, protein concentrations, and a marked increase in TBARS activity in rat testis and prostate. Histological examination of adult male rat testes showed a disruption in the arrangement of seminiferous tubules along with a reduction in the number of germ cells, Leydig cells, tunica albuginea thickness, diameter of seminiferous tubules, and height of germinal epithelium. Co-treatment with vitamin E, sulphoraphane, and Ficus religiosa were found to be effective in reversing Cd induced toxicity, representing potential therapeutic options to protect the reproductive tissues from the detrimental effects of Cd toxicity. PMID:24758558

  5. Protective action of erythropoietin on neuronal damage induced by activated microglia.

    PubMed

    Wenker, Shirley D; Chamorro, María E; Vittori, Daniela C; Nesse, Alcira B

    2013-04-01

    Inflammation is a physiological defense response, but may also represent a potential pathological process in neurological diseases. In this regard, microglia have a crucial role in either progression or amelioration of degenerative neuronal damage. Because of the role of hypoxia in pro-inflammatory mechanisms in the nervous system, and the potential anti-inflammatory protective effect of erythropoietin (Epo), we focused our investigation on the role of this factor on activation of microglia and neuroprotection. Activation of microglial cells (EOC-2) was achieved by chemical hypoxia induced by cobalt chloride (CoCl2 ) and characterized by increased levels of nitrite, tumor necrosis factor-α and reactive oxygen species production, as well as up-regulation of inducible nitric oxide synthase expression. Under these conditions, cell proliferation data and proliferating cell nuclear antigen (PCNA) staining demonstrated a mitogenic effect of chemical hypoxia. Even though pre-treatment with Epo did not prevent nitrite production, inducible nitric oxide synthase protein expression or tumor necrosis factor-α secretion, it prevented the oxidative stress induced by CoCl2 as well as cell proliferation. Neuronal cells (SH-SY5Y) cultured in the presence of conditioned medium from activated EOC-2 cells or macrophages (RAW 264.7) developed significant apoptosis, an effect that was abolished by Epo via Epo/Epo receptor activation. The results show that even though Epo did not exert a direct anti-inflammatory effect on microglia activation, it did increase the resistance of neurons to subsequent damage from pro-inflammatory agents. In addition to its anti-apoptotic ability, the Epo antioxidant effect may have an indirect influence on neuronal survival by modulation of the pro-inflammatory environment. PMID:23384249

  6. Swim training does not protect mice from skeletal muscle oxidative damage following a maximum exercise test.

    PubMed

    Barreto, Tatiane Oliveira; Cleto, Lorena Sabino; Gioda, Carolina Rosa; Silva, Renata Sabino; Campi-Azevedo, Ana Carolina; de Sousa-Franco, Junia; de Magalhães, José Carlos; Penaforte, Claudia Lopes; Pinto, Kelerson Mauro de Castro; Cruz, Jader dos Santos; Rocha-Vieira, Etel

    2012-07-01

    We investigated whether swim training protects skeletal muscle from oxidative damage in response to a maximum progressive exercise. First, we investigated the effect of swim training on the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), in the gastrocnemius muscle of C57Bl/6 mice, 48 h after the last training session. Mice swam for 90 min, twice a day, for 5 weeks at 31°C (± 1°C). The activities of SOD and CAT were increased in trained mice (P < 0.05) compared to untrained group. However, no effect of training was observed in the activity of GPx. In a second experiment, trained and untrained mice were submitted to a maximum progressive swim test. Compared to control mice (untrained, not acutely exercised), malondialdehyde (MDA) levels were increased in the skeletal muscle of both trained and untrained mice after maximum swim. The activity of GPx was increased in the skeletal muscle of both trained and untrained mice, while SOD activity was increased only in trained mice after maximum swimming. CAT activity was increased only in the untrained compared to the control group. Although the trained mice showed increased activity of citrate synthase in skeletal muscle, swim performance was not different compared to untrained mice. Our results show an imbalance in the activities of SOD, CAT and GPx in response to swim training, which could account for the oxidative damage observed in the skeletal muscle of trained mice in response to maximum swim, resulting in the absence of improved exercise performance.

  7. Protective effect of an aphrodisiac herb Tribulus terrestris Linn on cadmium-induced testicular damage

    PubMed Central

    Rajendar, B.; Bharavi, K.; Rao, G. S.; Kishore, P.V.S; Kumar, P. Ravi; Kumar, C.S.V Satish; Patel, T. Pankaj

    2011-01-01

    tissue. Co-treatment with eTT and α-tocopherol significantly reduced the Cd burden in the testes along with reversal of the Cd-induced changes. Conclusions: eTT exhibited protective effect against Cd-induced testicular damage. The protective effect appears to be mediated through inhibition of testicular tissue peroxidation by antioxidant and metal chelator activity and also, may be indirectly by stimulating the testosterone production from Leydig cells. PMID:22022002

  8. Pregnane X receptor protects HepG2 cells from BaP-induced DNA damage.

    PubMed

    Naspinski, Christine; Gu, Xinsheng; Zhou, Guo-Dong; Mertens-Talcott, Susanne U; Donnelly, Kirby C; Tian, Yanan

    2008-07-01

    Pregnane X receptor (PXR) is a nuclear receptor that coordinately regulates transcriptional expression of both phase I and phase II metabolizing enzymes. PXR plays an important role in the pharmacokinetics of a broad spectrum of endogenous and xenobiotic compounds and appears to have evolved in part to protect organisms from toxic xenobiotics. Metabolism of benzo[a]pyrene (BaP), a well-established carcinogen and ubiquitous environmental contaminant, can result in either detoxification or bioactivation to its genotoxic forms. Therefore, PXR could modulate the genotoxicity of BaP by changing the balance of the metabolic pathways in favor of BaP detoxification. To examine the role of PXR in BaP genotoxicity, BaP-DNA adduct formation was measured by 32P-postlabeling in BaP-treated parental HepG2 cells and human PXR-transfected HepG2 cells. The presence of transfected PXR significantly reduced the level of adducts relative to parental cells by 50-65% (p < 0.001), demonstrating that PXR protects liver cells from genotoxicity induced by exposure to BaP. To analyze potential PXR-regulated detoxification pathways in liver cells, a panel of genes involved in phase I and phase II metabolism and excretion was surveyed with real-time quantitative reverse transcription PCR. The messenger RNA levels of CYP1A2, GSTA1, GSTA2, GSTM1, UGT1A6, and BCRP (ABCG2) were significantly higher in cells overexpressing PXR, independent of exposure to BaP. In addition, the total GST enzymatic activity, which favors the metabolic detoxification of BaP, was significantly increased by the presence of PXR (p < 0.001), independent of BaP exposure. Taken together, these results suggest that PXR plays an important role in protection against DNA damage by polycyclic aromatic hydrocarbons (PAHs) such as BaP, and that these protective effects may be through a coordinated regulation of genes involved in xenobiotic metabolism.

  9. Antioxidant activity of Coriandrum sativum and protection against DNA damage and cancer cell migration

    PubMed Central

    2013-01-01

    Background Coriandrum sativum is a popular culinary and medicinal herb of the Apiaceae family. Health promoting properties of this herb have been reported in pharmacognostical, phytochemical and pharmacological studies. However, studies on C. sativum have always focused on the aerial parts of the herb and scientific investigation on the root is limited. The aim of this research was to investigate the antioxidant and anticancer activities of C. sativum root, leaf and stem, including its effect on cancer cell migration, and its protection against DNA damage, with special focus on the roots. Methods Powdered roots, leaves and stems of C. sativum were extracted through sequential extraction using hexane, dichloromethane, ethyl acetate, methanol and water. Total phenolic content, FRAP and DPPH radical scavenging activities were measured. Anti-proliferative activitiy on the breast cancer cell line, MCF-7, was assayed using the MTT assay. Activities of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, and of the caspases-3, -8 and -9 were assayed on treatment with the extract. Cell cycle progression was analysed using flow cytometry. The scratch motility assay was used to assess inhibition of MCF-7 cell migration. DNA damage in 3 T3-L1 fibroblasts was evaluated by the comet assay. The components in the extract were identified by HPLC and GC-MS. Results The ethyl acetate extract of C. sativum roots showed the highest antiproliferative activity on MCF-7 cells (IC50 = 200.0 ± 2.6 μg/mL) and had the highest phenolic content, FRAP and DPPH scavenging activities among the extracts. C. sativum root inhibited DNA damage and prevented MCF-7 cell migration induced by H2O2, suggesting its potential in cancer prevention and inhibition of metastasis. The extract exhibited anticancer activity in MCF-7 cells by affecting antioxidant enzymes possibly leading to H2O2 accumulation, cell cycle arrest at the G2/M phase and apoptotic cell death by

  10. Integrated Sensing and Material Damage Identification in Metallic and Ceramic Thermal Protection Systems Using Vibration and Wave Propagation Data

    SciTech Connect

    Sundararaman, S.; White, J.; Jiang, H.; Adams, D.; Jata, K.

    2006-03-06

    Global thermal and impact material damage mechanisms in metallic and ceramic thermal protection systems are detected, located, and quantified using four complementary methods for sensing and data interrogation. First, spatial-temporal beamforming algorithms are used to process active elastic waves measured from remote sensor arrays in two different equilibrium positions of a gamma Ti-Al sheet to localize simulated thermal damage. Damage is located even when it is behind the sensor array and on the edge of the panel; results are shown to be dependent on the equilibrium position considered. Second, an active virtual force method is implemented in a honeycomb Al-Al sandwich panel instrumented with a distributed piezo sensor and actuator array to identify impact and thermal damage using frequency response inversion. Damage is quantified and is similarly diagnosed regardless of the excitation location. Third, passive acoustic transmission measurements through a homogeneous baffled Al panel subject to launch-type sound pressure variations are used to detect and locate material damage. The frequency range with highest transmission is shown to be optimal for damage detection. Fourth, thermal damage in a wrapped ceramic tile with a mock strain isolation pad is identified using active propagating waves. Remote actuation and sensing on the bulkhead and the tile backside are shown to be sufficient for detection even when variability is present in the data.

  11. Protective effects of acteoside against X‑ray‑induced damage in human skin fibroblasts.

    PubMed

    Yang, Jianhua; Yan, Yao; Liu, Huibin; Wang, Jianhua; Hu, Junping

    2015-08-01

    To investigate the protective effects of acteoside against apoptosis induced by X-ray radiation in human skin fibroblasts (HSFs), the cells were divided into the following groups: Control group; X-ray radiation group; acteoside group, in which the confluent cells were preincubated with 50 μg/ml acteoside for 2 h followed by radiation; and positive control group, in which the cells were preincubated with 50 μg/ml paeoniflorin followed by radiation. For the radiation, HSF cells preincubated with acteoside or paeoniflorin were exposed to X-ray beams at a dose-rate of 3 Gy/min (16 Gy in total). Cell viability, apoptosis and intracellular alteration of redox were monitored by MTT and flow cytometry. Compared with the radiation group, the number of cells arrested at the G0/G1 phase was significantly reduced in the acteoside and paeoniflorin groups, respectively (P<0.05). X-ray radiation induced marked apoptosis in HSF cells and acteoside reversed this effect. Compared with the radiation group, the generation of intracellular reactive oxygen species (ROS) was abrogated by pre-incubation with acteoside or paeoniflorin (P<0.05). In addition, the upregulation of pro-caspase-3 induced by radiation was reversed by acteoside or paeoniflorin. Radiation could induce upregulation of Bax and downregulation of Bcl-2; however, it was reversed completely after administration of acteoside or paeoniflorin. Furthermore, the enhanced expression of ERK and JNK induced by radiation was reversed by acteoside or paeoniflorin. Acteoside could protect the cells from X-ray induced damage through enhancing the scavenging activity of ROS, decreasing the Bax/Bcl-2 ratio and downregulating the activity of procaspase-3, as well as modulating the mitogen-activated protein kinase signaling pathways.

  12. Cholesterol synthesis inhibitors protect against platelet-activating factor-induced neuronal damage

    PubMed Central

    Bate, Clive; Rumbold, Louis; Williams, Alun

    2007-01-01

    Background Platelet-activating factor (PAF) is implicated in the neuronal damage that accompanies ischemia, prion disease and Alzheimer's disease (AD). Since some epidemiological studies demonstrate that statins, drugs that reduce cholesterol synthesis, have a beneficial effect on mild AD, we examined the effects of two cholesterol synthesis inhibitors on neuronal responses to PAF. Methods Primary cortical neurons were treated with cholesterol synthesis inhibitors (simvastatin or squalestatin) prior to incubation with different neurotoxins. The effects of these drugs on neuronal cholesterol levels and neuronal survival were measured. Immunoblots were used to determine the effects of simvastatin or squalestatin on the distribution of the PAF receptor and an enzyme linked immunoassay was used to quantify the amounts of PAF receptor. Results PAF killed primary neurons in a dose-dependent manner. Pre-treatment with simvastatin or squalestatin reduced neuronal cholesterol and increased the survival of PAF-treated neurons. Neuronal survival was increased 50% by 100 nM simvastatin, or 20 nM squalestatin. The addition of mevalonate restored cholesterol levels, and reversed the protective effect of simvastatin. Simvastatin or squalestatin did not affect the amounts of the PAF receptor but did cause it to disperse from within lipid rafts. Conclusion Treatment of neurons with cholesterol synthesis inhibitors including simvastatin and squalestatin protected neurons against PAF. Treatment caused a percentage of the PAF receptors to disperse from cholesterol-sensitive domains. These results raise the possibility that the effects of statins on neurodegenerative disease are, at least in part, due to desensitisation of neurons to PAF. PMID:17233902

  13. Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism

    PubMed Central

    LI, SHUANG; WANG, SU; GUO, ZHI-GANG; HUANG, NING; ZHAO, FAN-RONG; ZHU, MO-LI; MA, LI-JUAN; LIANG, JIN-YING; ZHANG, YU-LIN; HUANG, ZHONG-LIN; WAN, GUANG-RUI

    2015-01-01

    The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism. PMID:26640531

  14. The Flaxseed-Derived Lignan Phenolic Secoisolariciresinol Diglucoside (SDG) Protects Non-Malignant Lung Cells from Radiation Damage

    PubMed Central

    Velalopoulou, Anastasia; Tyagi, Sonia; Pietrofesa, Ralph A.; Arguiri, Evguenia; Christofidou-Solomidou, Melpo

    2015-01-01

    Plant phenolic compounds are common dietary antioxidants that possess antioxidant and anti-inflammatory properties. Flaxseed (FS) has been reported to be radioprotective in murine models of oxidative lung damage. Flaxseed’s protective properties are attributed to its main biphenolic lignan, secoisolariciresinol diglucoside (SDG). SDG is a free radical scavenger, shown in cell free systems to protect DNA from radiation-induced damage. The objective of this study was to investigate the in vitro radioprotective efficacy of SDG in murine lung cells. Protection against irradiation (IR)-induced DNA double and single strand breaks was assessed by γ-H2AX labeling and alkaline comet assay, respectively. The role of SDG in modulating the levels of cytoprotective enzymes was evaluated by qPCR and confirmed by Western blotting. Additionally, effects of SDG on clonogenic survival of irradiated cells were evaluated. SDG protected cells from IR-induced death and ameliorated DNA damage by reducing mean comet tail length and percentage of γ-H2AX positive cells. Importantly, SDG significantly increased gene and protein levels of antioxidant HO-1, GSTM1 and NQO1. Our results identify the potent radioprotective properties of the synthetic biphenolic SDG, preventing DNA damage and enhancing the antioxidant capacity of normal lung cells; thus, rendering SDG a potential radioprotector against radiation exposure. PMID:26703588

  15. The Flaxseed-Derived Lignan Phenolic Secoisolariciresinol Diglucoside (SDG) Protects Non-Malignant Lung Cells from Radiation Damage.

    PubMed

    Velalopoulou, Anastasia; Tyagi, Sonia; Pietrofesa, Ralph A; Arguiri, Evguenia; Christofidou-Solomidou, Melpo

    2016-01-01

    Plant phenolic compounds are common dietary antioxidants that possess antioxidant and anti-inflammatory properties. Flaxseed (FS) has been reported to be radioprotective in murine models of oxidative lung damage. Flaxseed's protective properties are attributed to its main biphenolic lignan, secoisolariciresinol diglucoside (SDG). SDG is a free radical scavenger, shown in cell free systems to protect DNA from radiation-induced damage. The objective of this study was to investigate the in vitro radioprotective efficacy of SDG in murine lung cells. Protection against irradiation (IR)-induced DNA double and single strand breaks was assessed by γ-H2AX labeling and alkaline comet assay, respectively. The role of SDG in modulating the levels of cytoprotective enzymes was evaluated by qPCR and confirmed by Western blotting. Additionally, effects of SDG on clonogenic survival of irradiated cells were evaluated. SDG protected cells from IR-induced death and ameliorated DNA damage by reducing mean comet tail length and percentage of γ-H2AX positive cells. Importantly, SDG significantly increased gene and protein levels of antioxidant HO-1, GSTM1 and NQO1. Our results identify the potent radioprotective properties of the synthetic biphenolic SDG, preventing DNA damage and enhancing the antioxidant capacity of normal lung cells; thus, rendering SDG a potential radioprotector against radiation exposure.

  16. Salivary α-amylase, serum albumin, and myoglobin protect against DNA-damaging activities of ingested dietary agents in vitro

    PubMed Central

    Hossain, M. Zulfiquer; Patel, Kalpesh; Kern, Scott E.

    2014-01-01

    Potent DNA-damaging activities were seen in vitro from dietary chemicals found in coffee, tea, and liquid smoke. A survey of tea varieties confirmed genotoxic activity to be widespread. Constituent pyrogallol-like polyphenols (PLPs) such as epigallocatechin-3-gallate (EGCG), pyrogallol, and gallic acid were proposed as a major source of DNA-damaging activities, inducing DNA double-strand breaks in the p53R assay, a well characterized assay sensitive to DNA strand breaks, and comet assay. Paradoxically, their consumption does not lead to the kind of widespread cellular toxicity and acute disease that might be expected from genotoxic exposure. Existing physiological mechanisms could limit DNA damage from dietary injurants. Serum albumin and salivary α-amylase are known to bind EGCG. Salivary α-amylase, serum albumin, and myoglobin, but not salivary proline-rich proteins, reduced damage from tea, coffee, and PLPs, but did not inhibit damage from the chemotherapeutics etoposide and camptothecin. This represents a novel function for saliva in addition to its known functions including protection against tannins. Cell populations administered repeated pyrogallol exposures had abatement of measured DNA damage by two weeks, indicating an innate cellular adaptation. We suggest that layers of physiological protections may exist toward natural dietary products to which animals have had high-level exposure over evolution. PMID:24842839

  17. cAMP-Inhibits Cytoplasmic Phospholipase A₂ and Protects Neurons against Amyloid-β-Induced Synapse Damage.

    PubMed

    Bate, Clive; Williams, Alun

    2015-01-01

    A key event in Alzheimer's disease (AD) is the production of amyloid-β (Aβ) peptides and the loss of synapses. In cultured neurons Aβ triggered synapse damage as measured by the loss of synaptic proteins. α-synuclein (αSN), aggregates of which accumulate in Parkinson's disease, also caused synapse damage. Synapse damage was associated with activation of cytoplasmic phospholipase A₂ (cPLA₂), an enzyme that regulates synapse function and structure, and the production of prostaglandin (PG) E₂. In synaptosomes PGE₂ increased concentrations of cyclic adenosine monophosphate (cAMP) which suppressed the activation of cPLA₂ demonstrating an inhibitory feedback system. Thus, Aβ/αSN-induced activated cPLA₂ produces PGE₂ which increases cAMP which in turn suppresses cPLA₂ and, hence, its own production. Neurons pre-treated with pentoxifylline and caffeine (broad spectrum phosphodiesterase (PDE) inhibitors) or the PDE4 specific inhibitor rolipram significantly increased the Aβ/αSN-induced increase in cAMP and consequently protected neurons against synapse damage. The addition of cAMP analogues also inhibited cPLA₂ and protected neurons against synapse damage. These results suggest that drugs that inhibit Aβ-induced activation of cPLA₂ and cross the blood-brain barrier may reduce synapse damage in AD. PMID:26389963

  18. cAMP-Inhibits Cytoplasmic Phospholipase A2 and Protects Neurons against Amyloid-β-Induced Synapse Damage

    PubMed Central

    Bate, Clive; Williams, Alun

    2015-01-01

    A key event in Alzheimer’s disease (AD) is the production of amyloid-β (Aβ) peptides and the loss of synapses. In cultured neurons Aβ triggered synapse damage as measured by the loss of synaptic proteins. α-synuclein (αSN), aggregates of which accumulate in Parkinson’s disease, also caused synapse damage. Synapse damage was associated with activation of cytoplasmic phospholipase A2 (cPLA2), an enzyme that regulates synapse function and structure, and the production of prostaglandin (PG) E2. In synaptosomes PGE2 increased concentrations of cyclic adenosine monophosphate (cAMP) which suppressed the activation of cPLA2 demonstrating an inhibitory feedback system. Thus, Aβ/αSN-induced activated cPLA2 produces PGE2 which increases cAMP which in turn suppresses cPLA2 and, hence, its own production. Neurons pre-treated with pentoxifylline and caffeine (broad spectrum phosphodiesterase (PDE) inhibitors) or the PDE4 specific inhibitor rolipram significantly increased the Aβ/αSN-induced increase in cAMP and consequently protected neurons against synapse damage. The addition of cAMP analogues also inhibited cPLA2 and protected neurons against synapse damage. These results suggest that drugs that inhibit Aβ-induced activation of cPLA2 and cross the blood–brain barrier may reduce synapse damage in AD. PMID:26389963

  19. Protective effect of persimmon (Diospyros kaki) peel proanthocyanidin against oxidative damage under H2O2-induced cellular senescence.

    PubMed

    Lee, Young A; Cho, Eun Ju; Yokozawa, Takako

    2008-06-01

    8-Hydroxy-2'-deoxyguanosine (8-OHdG), one of the most abundant oxidative DNA adducts, is used as an indicator of oxidative DNA damage associated with aging. Among homologs of the silent information regulator (Sir), sirtuin 1 (SIRT1) is suggested as a regulator of the apoptotic response to DNA damage. Since it has been suggested that the aging process can be delayed by the attenuation of oxidative damage such as DNA damage or SIRT1 modulation, we focused on the protective effect against cellular oxidative damage of persimmon peel, a proanthocyanidin-rich food, in relation to its level of polymerization. We confirmed that 8-OHdG expression in TIG-1 human fibroblasts was increased by treatment with 300 microM H2O2 for 2 h. On the other hand, the nuclear SIRT1 level was decreased in H2O2-treated as compared with non-pretreated cells. However, pretreatments with polymers and oligomers led to a decrease in 8-OHdG and elevation in nuclear SIRT1 expression in a concentration-dependent manner. In particular, oligomers exerted a stronger effect. The present study supports the protective potential of proanthocyanidin from persimmon peel against oxidative damage under the aging process, and suggests that the polymerization of proanthocyanidin plays an important role in retarding aging in a cellular senescence model.

  20. Mitochondrial anti-oxidant protects IEX-1 deficient mice from organ damage during endotoxemia.

    PubMed

    Ramsey, Haley; Wu, Mei X

    2014-12-01

    Sepsis, a leading cause of mortality in intensive care units worldwide, is often a result of overactive and systemic inflammation following serious infections. We found that mice lacking immediate early responsive gene X-1 (IEX-1) were prone to lipopolysaccharide (LPS) -induced endotoxemia. A nonlethal dose of LPS provoked numerous aberrations in IEX-1 knockout (KO) mice including pancytopenia, increased serum aspartate aminotransferase (AST), and lung neutrophilia, concurrent with liver and kidney damage, followed by death. Given these results, in conjunction with a proven role for IEX-1 in the regulation of reactive oxygen species (ROS) homeostasis during stress, we pre-treated IEX-1 KO mice with Mitoquinone (MitoQ), a mitochondrion-based antioxidant prior to LPS injection. The treatment significantly reduced ROS formation in circulatory cells and protected against pancytopenia and multiple organ failure, drastically increasing the survival rate of IEX-1 KO mice challenged by this low dose of LPS. This study confirms significant contribution of mitochondrial ROS to the etiology of sepsis. PMID:25466275

  1. Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage

    PubMed Central

    Li, Xiao-Qiang; Tian, Wen; Liu, Xiao-Xiao; Zhang, Kai; Huo, Jun-Cheng; Liu, Wen-Juan; Li, Ping; Xiao, Xiong; Zhao, Ming-Gao; Cao, Wei

    2016-01-01

    Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM). This study aimed to explore the effects of corosolic acid (CA) on the renal damage of DM and the mechanisms behind these effects. The renoprotective effect of CA was investigated in type 1 diabetic rats and db/db mice. The kidneys and glomerular mesangial cells (GMCs) were used to study the proliferation of GMCs by immunostaining and MTT assay. Further immunoblotting, siRNA, qPCR analysis, and detecting of NADPH oxidase activity and reactive oxygen species (ROS) generation were performed to explore relevant molecular mechanisms. In CA-treated diabetic animals, diabetes-induced albuminuria, increased serum creatinine and blood urea nitrogen were significantly attenuated, and glomerular hypertrophy, mesangial expansion and fibrosis were ameliorated. Furthermore, CA significantly inhibited proliferation of GMCs and phosphorylation of ERK1/2 and p38 MAPK in both diabetic animals and high glucose (HG)-induced GMCs. CA also normalized Δψm and inhibited HG-induced NADPH oxidase activity, ROS generation and NOX4, NOX2, p22phox and p47phox expression. More importantly, CA inhibited GMC proliferation mediated by NADPH/ERK1/2 and p38 MAPK signaling pathways. These findings suggest that CA exert the protective effect on DN by anti-proliferation resulted from inhibition of p38 MAPK- and NADPH-mediated inactivation of ERK1/2. PMID:27229751

  2. Acetone Extract of Almond Hulls Provides Protection against Oxidative Damage and Membrane Protein Degradation.

    PubMed

    Meshkini, Azadeh

    2016-06-01

    Several studies have revealed that among foods, the consumption of edible nuts has beneficial effects on health which are attributed to their high content of potent antioxidants. Among nuts, the whole seed of the almond (Prunus dulcis) has been demonstrated to possess potent free radical scavenging activity, which is related to the presence of phenolic compounds. The aim of the current study is to evaluate the polyphenol content and the antioxidant ability of almond hull, which is an agriculture solid waste. The present results revealed that among different extraction methods, the acetone extract of almond hulls has a high content of phenolic and flavonoid compounds and a high antioxidant ability, which were determined by using the phosphomolybdenum method and by measuring the potency of the antioxidant, respectively. Moreover, the experimental data disclosed that the acetone extract of almond hulls provides protection against the oxidative damage and the membrane protein degradation that are caused in human erythrocytes by hydrogen peroxide. These phenomena may likely be due to the recruitment of antioxidants by cell membranes and/or translocation to cytosol. Overall, almond hull extract could be considered as a natural source of antioxidants, and its consumption could have a positive effect on human health. PMID:27342887

  3. The protective effect of Malva sylvestris on rat kidney damaged by vanadium

    PubMed Central

    2011-01-01

    Background The protective effect of the common mallow (Malva sylvestris) decoction on renal damages in rats induced by ammonium metavanadate poisoning was evaluated. On the one hand, vanadium toxicity is associated to the production of reactive oxygen species, causing a lipid peroxidation and an alteration in the enzymatic antioxidant defence. On the other hand, many medicinal plants are known to possess antioxidant and radical scavenging properties, thanks to the presence of flavonoids. These properties were confirmed in Malva sylvestris by two separate methods; namely, the Diphenyl-2-picrylhydrazyl assay and the Nitroblue Tetrazolium reduction assay. Results In 80 rats exposed to ammonium metavanadate (0.24 mmol/kg body weight in drinking water) for 90 days, lipid peroxidation levels and superoxide dismutase, catalase and glutathione peroxidase activities were measured in kidney. A significant increase in the formation of free radicals and antioxidant enzyme activities was noticed. In addition, a histological examination of kidney revealed a structural deterioration of the renal cortical capsules and a shrinking of the Bowman space. In animals intoxicated by metavanadate but also given a Malva sylvestris decoction (0.2 g dry mallow/kg body weight), no such pathologic features were observed: lipid peroxidation levels, antioxidant enzyme activities and histological features appeared normal as compared to control rats. Conclusion Malva sylvestris is proved to have a high antioxidative potential thanks to its richness in phenolic compounds. PMID:21513564

  4. Antioxidant and DNA damage protecting potentials of polysaccharide extracted from Phellinus baumii using a delignification method.

    PubMed

    Jin, Qun-Li; Zhang, Zuo-Fa; Lv, Guo-Ying; Cai, Wei-Ming; Cheng, Jun-Wen; Wang, Jian-Gong; Fan, Lei-Fa

    2016-11-01

    A delignification method was employed to extract the polysaccharide from the fruiting body of Phellinus baumii. The three parameters, processing temperature, ratio of water to raw material and amount of acetic acid every time were optimized using the Box-Behnken design. As a result, the optimal extraction conditions were: processing temperature 70.3°C, ratio of water to raw material of 34.7mL/g and amount of acetic acid of 0.32mL every time. Under these conditions, the highest yield of polysaccharide (10.28%) was obtained. The main fraction (PPB-2) purified from PPB was composed of fucose, arabinose, galactose, glucose, xylose and mannose, while glucose was the predominant monosaccharide. PPB-2 exhibited noticeable antioxidant activity and strong protection against oxidative DNA damage. These findings implied that acid-chlorite delignification was a superior method to extract the polysaccharide from P. baumii and PPB-2 may be useful for cancer chemoprevention. PMID:27516306

  5. Mulberry Fruit Extract Protects against Memory Impairment and Hippocampal Damage in Animal Model of Vascular Dementia

    PubMed Central

    Kaewkaen, Pratchaya; Tong-un, Terdthai; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Kaewrueng, Wiroje; Wongcharoenwanakit, Sathaporn

    2012-01-01

    Nowadays, the preventive strategy of vascular dementia, one of the challenge problems of elderly, has received attention due to the limitation of therapeutic efficacy. In this study, we aimed to determine the protective effect and possible mechanism of action of mulberry fruit extract on memory impairment and brain damage in animal model of vascular dementia. Male Wistar rats, weighing 300–350 g, were orally given mulberry extract at doses of 2, 10 and 50 mg/kg at a period of 7 days before and 21 days after the occlusion of right middle cerebral artery (Rt.MCAO). It was found that rats subjected to mulberry fruits plus Rt.MCAO showed the enhanced memory, the increased densities of neuron, cholinergic neuron, Bcl-2-immunopositive neuron together with the decreased oxidative stress in hippocampus. Taken all data together, the cognitive enhancing effect of mulberry fruit extract observed in this study might be partly associated with the increased cholinergic function and its neuroprotective effect in turn occurs partly via the decreased oxidative stress and apoptosis. Therefore, mulberry fruit is the potential natural cognitive enhancer and neuroprotectant. However, further researches are essential to elucidate the possible active ingredient. PMID:22952555

  6. Resveratrol Protects PC12 Cell against 6-OHDA Damage via CXCR4 Signaling Pathway

    PubMed Central

    Zhang, Jing; Fan, Wenchuang; Wang, Hui; Bao, Lihua; Li, Guibao; Li, Tao; Song, Shouyang; Li, Hongyu; Hao, Jing; Sun, Jinhao

    2015-01-01

    Resveratrol, herbal nonflavonoid polyphenolic compound naturally derived from grapes, has long been acknowledged to possess extensive biological and pharmacological properties including antioxidant and anti-inflammatory ones and may exert a neuroprotective effect on neuronal damage in neurodegenerative diseases. However, the underlying molecular mechanisms remain undefined. In the present study, we intended to investigate the neuroprotective effects of resveratrol against 6-OHDA-induced neurotoxicity of PC12 cells and further explore the possible mechanisms involved. For this purpose, PC12 cells were exposed to 6-OHDA in the presence of resveratrol (0, 12.5, 25, and 50 μM). The results showed that resveratrol increased cell viability, alleviated the MMP reduction, and reduced the number of apoptotic cells as measured by MTT assay, JC-1 staining, and Hoechst/PI double staining (all p < 0.01). Immunofluorescent staining and Western blotting revealed that resveratrol averts 6-OHDA induced CXCR4 upregulation (p < 0.01). Our results demonstrated that resveratrol could effectively protect PC12 cells from 6-OHDA-induced oxidative stress and apoptosis via CXCR4 signaling pathway. PMID:26681969

  7. SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage.

    PubMed

    Tseng, Anne H H; Shieh, Shyan-Shu; Wang, Danny Ling

    2013-10-01

    Progressive accumulation of defective mitochondria is a common feature of aged cells. SIRT3 is a NAD(+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. FOXO3 is a direct target of SIRT3 and functions as a forkhead transcription factor to govern diverse cellular responses to stress. Here we show that hydrogen peroxide induces SIRT3 to deacetylate FOXO3 at K271 and K290, followed by the upregulation of a set of genes that are essential for mitochondrial homeostasis (mitochondrial biogenesis, fission/fusion, and mitophagy). Consequently, SIRT3-mediated deacetylation of FOXO3 modulates mitochondrial mass, ATP production, and clearance of defective mitochondria. Thus, mitochondrial quantity and quality are ensured to maintain mitochondrial reserve capacity in response to oxidative damage. Maladaptation to oxidative stress is a major risk factor underlying aging and many aging-related diseases. Hence, our finding that SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative stress provides a possible direction for aging-delaying therapies and disease intervention.

  8. Characterization of pumpkin polysaccharides and protective effects on streptozotocin-damaged islet cells.

    PubMed

    Zhu, Hong-Yan; Chen, Guang-Tong; Meng, Guo-Liang; Xu, Ji-Liang

    2015-03-01

    The polysaccharides from pumpkin fruit (PP) were obtained and purified by hot-water extraction, anion-exchange chromatography, and gel column chromatography. The physicochemical properties of PP were determined by gel filtration chromatography, gas chromatography, fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. Results indicated that the molecular weight of PP was about 23 kDa and PP was composed of D-Arabinose, D-Mannose, D-Glucose, and D-Galactose with a molar ratio of 1 : 7.79 : 70.32 : 7.05. FTIR and NMR spectra indicated that PP was the polysaccharide containing pyranose ring. Additionally, PP protected islets cells from streptozotocin (STZ) injury in vitro via increasing the levels of super-oxide dismutase (SOD) and malondialdehyde (MDA) and reducing the production of NO. The experiment of reverse transcriptase-polymerase chain reaction further proved that PP inhibited apoptosis via modulating the expression of Bax/Bcl-2 in STZ-damaged islet cells. In conclusion, PP could be explored as a novel agent for the treatment of diabetes mellitus.

  9. Acetone Extract of Almond Hulls Provides Protection against Oxidative Damage and Membrane Protein Degradation.

    PubMed

    Meshkini, Azadeh

    2016-06-01

    Several studies have revealed that among foods, the consumption of edible nuts has beneficial effects on health which are attributed to their high content of potent antioxidants. Among nuts, the whole seed of the almond (Prunus dulcis) has been demonstrated to possess potent free radical scavenging activity, which is related to the presence of phenolic compounds. The aim of the current study is to evaluate the polyphenol content and the antioxidant ability of almond hull, which is an agriculture solid waste. The present results revealed that among different extraction methods, the acetone extract of almond hulls has a high content of phenolic and flavonoid compounds and a high antioxidant ability, which were determined by using the phosphomolybdenum method and by measuring the potency of the antioxidant, respectively. Moreover, the experimental data disclosed that the acetone extract of almond hulls provides protection against the oxidative damage and the membrane protein degradation that are caused in human erythrocytes by hydrogen peroxide. These phenomena may likely be due to the recruitment of antioxidants by cell membranes and/or translocation to cytosol. Overall, almond hull extract could be considered as a natural source of antioxidants, and its consumption could have a positive effect on human health.

  10. Alpinia protocatechuic acid protects against oxidative damage in vitro and reduces oxidative stress in vivo.

    PubMed

    Shi, Gui-Fang; An, Li-Jia; Jiang, Bo; Guan, Shui; Bao, Yong-Ming

    2006-08-01

    In this study, the neuroprotective effects of Alpinia protocatechuic acid (PCA), a phenolic compound isolated from the dried fruits of Alpinia Oxyphylla Miq. was found. The protective effect of Alpinia PCA against H2O2-induced oxidative damage on PC12 cells was investigated by measuring cell viability via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Rats were injected intraperitoneally with Alpinia PCA at a dose of 5mg/kg per day for 7 days, behavioral testing was performed in Y-maze. In order to make clear the neuroprotective mechanism of Alpinia PCA, the activities of endogenous antioxidants and the content of lipid peroxide in brain were assayed. The results proved that Alpinia PCA significantly prevented the H2O2-induced reduction in cell survival, improved the cognition of aged rats, reduced the content of lipid peroxide, increased the activity of glutathione peroxidase and superoxide dismutase. All these suggested that Alpinia PCA was a potential neuroprotective agent and its neuroprotective effects were achieved at least partly by promoting endogenous antioxidant enzymatic activities and inhibiting free radical generation.

  11. The protective effect of qiancao naomaitong mixture on neuronal damage and cerebral ischemia/reperfusion injury.

    PubMed

    Lu, Juan; Li, Yi-Hang; Zhan, Xia; Li, Guang; Chen, Zhe; Chen, Xi

    2016-10-01

    Context Qiancao Naomaitong Mixture (QNM) is mainly used to treat ischemic stroke patients in the clinic. Objective This study evaluates the protective effect of QNM on neuronal damage in vitro, and clarifies the underlying mechanism against cerebral ischemia-reperfusion (I/R) injury in vivo. Materials and methods Activity assay of caspase 3 (C-3) and caspase 8 (C-8) were measured with microplate reader and cell apoptosis was investigated. Cerebral I/R injury was induced by MCAO model. QNM groups were given at 0.27, 0.54 and 1.08 mL/100 g body weight. The weight ratio of cerebral infarction tissue was obtained. The cytokine levels in serum and brain tissue were measured using ELISA. Results Compared with the OGD group (C-3: 29.69 ± 5.63, C-8: 74.05 ± 6.86), 100 mg/mL QNM (C-3: 19.80 ± 2.62, C-8: 48.94 ± 6.41) and 200 mg/mL QNM (C-3: 16.28 ± 4.55, C-8: 41.08 ± 4.05) treatments decreased C-3 and C-8 activities significantly, and inhibited apoptosis of SH-SY5Y cells. The weight ratios of cerebral tissues in low, medium and high dose groups were 17.33 ± 5.1%, 17.78 ± 5.4% and 14.25 ± 4.2%, respectively, significantly lower than in control group. QNM also improved the cytokine levels in serum and brain tissue. In addition, histological examination indicated that dense neuropil and largely surviving neurons were seen in treated rats. Conclusion QNM exerted protective effect by inhibiting the cell apoptosis in vitro. The protective mechanisms of QNM were associated with its properties of anti-apoptosis and antioxidation as well as improved neuronal nutrition in I/R rats. PMID:26987389

  12. The Effects of Foam Thermal Protection System on the Damage Tolerance Characteristics of Composite Sandwich Structures for Launch Vehicles

    NASA Technical Reports Server (NTRS)

    Nettles, A. T.; Hodge, A. J.; Jackson, J. R.

    2011-01-01

    For any structure composed of laminated composite materials, impact damage is one of the greatest risks and therefore most widely tested responses. Typically, impact damage testing and analysis assumes that a solid object comes into contact with the bare surface of the laminate (the outer ply). However, most launch vehicle structures will have a thermal protection system (TPS) covering the structure for the majority of its life. Thus, the impact response of the material with the TPS covering is the impact scenario of interest. In this study, laminates representative of the composite interstage structure for the Ares I launch vehicle were impact tested with and without the planned TPS covering, which consists of polyurethane foam. Response variables examined include maximum load of impact, damage size as detected by nondestructive evaluation techniques, and damage morphology and compression after impact strength. Results show that there is little difference between TPS covered and bare specimens, except the residual strength data is higher for TPS covered specimens.

  13. Apurinic/Apyrimidinic Endonuclease 1 Upregulation Reduces Oxidative DNA Damage and Protects Hippocampal Neurons from Ischemic Injury

    PubMed Central

    Leak, Rehana K.; Li, Peiying; Zhang, Feng; Sulaiman, Hassan H.; Weng, Zhongfang; Wang, Guohua; Stetler, R. Anne; Shi, Yejie; Cao, Guodong

    2015-01-01

    Abstract Aims: Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme that participates in base-excision repair of oxidative DNA damage and in the redox activation of transcription factors. We tested the hypothesis that APE1 upregulation protects neuronal structure and function against transient global cerebral ischemia (tGCI). Results: Upregulation of APE1 by low-dose proton irradiation (PI) or by transgene overexpression protected hippocampal CA1 neurons against tGCI-induced cell loss and reduced apurinic/apyrimidinic sites and DNA fragmentation. Conversely, APE1 knockdown attenuated the protection afforded by PI and ischemic preconditioning. APE1 overexpression inhibited the DNA damage response, as evidenced by lower phospho-histone H2A and p53-upregulated modulator of apoptosis levels. APE1 overexpression also partially rescued dendritic spines and attenuated the decrease in field excitatory postsynaptic potentials in hippocampal CA1. Presynaptic and postsynaptic markers were reduced after tGCI, and this effect was blunted in APE1 transgenics. The Morris water maze test revealed that APE1 protected against learning and memory deficits for at least 27 days post-injury. Animals expressing DNA repair-disabled mutant APE1 (D210A) exhibited more DNA damage than wild-type controls and were not protected against tGCI-induced cell loss. Innovation: This is the first study that thoroughly characterizes structural and functional protection against ischemia after APE1 upregulation by measuring synaptic markers, electrophysiological function, and long-term neurological deficits in vivo. Furthermore, disabling the DNA repair activity of APE1 was found to abrogate its protective impact. Conclusion: APE1 upregulation, either endogenously or through transgene overexpression, protects DNA, neuronal structures, synaptic function, and behavioral output from ischemic injury. Antioxid. Redox Signal. 22, 135–148. PMID:24180454

  14. Thermal hydraulic features of the TMI accident

    NASA Astrophysics Data System (ADS)

    Tolman, B.

    1985-10-01

    The Three Mile island (TMI)-2 accident resulted in extensive core damage and recent data confirms that the reactor vessel was challenged from molten core materials. A hypothesized TMI accident scenario is presented that consistently explains the TMI data and is also consistent with research findings from independent severe fuel damage experiments. The TMI data will prove useful in confirming our understanding of severe core damage accidents under realistic reactor systems conditions. This understanding will aid in addressing safety and regulatory issues related to severe core damage accidents in light water reactors.

  15. Protective role of hydrogen-rich water on aspirin-induced gastric mucosal damage in rats

    PubMed Central

    Zhang, Jing-Yao; Wu, Qi-Fei; Wan, Yong; Song, Si-Dong; Xu, Jia; Xu, Xin-Sen; Chang, Hu-Lin; Tai, Ming-Hui; Dong, Ya-Feng; Liu, Chang

    2014-01-01

    AIM: To investigate the role of the hydrogen-rich water (HRW) in the prevention of aspirin-induced gastric mucosal injury in rats. METHODS: Forty male rats were allocated into four groups: normal control group, HRW group, aspirin group, and HRW plus aspirin group. The protective efficacy was tested by determining the gastric mucosal damage score. Malondialdehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO), interleukin (IL)-06 and tumor necrosis factor (TNF)-α in gastric tissues were evaluated. The serum levels of IL-1β and TNF-α were also detected. Histopathology of gastric tissues and localization of Cyclooxygenase 2 (COX-2) were detected using hematoxylin and eosin staining and immunohistochemistry, respectively. RESULTS: Pretreatment with HRW obviously reduced aspirin-induced gastric damage scores (4.04 ± 0.492 vs 2.10 ± 0.437, P < 0.05). The oxidative stress levels of MDA and MPO in the gastric tissues increased significantly in the aspirin-treated group compared with the HRW group (2.43 ± 0.145 vs 1.79 ± 0.116 nmol/mg prot, P < 0.05 and 2.53 ± 0.238 vs 1.40 ± 0.208 U/g tissue, P < 0.05, respectively). HRW could obviously elevated the SOD levels in the gastric tissues (37.94 ± 8.44 vs 59.55 ± 9.02 nmol/mg prot, P < 0.05). Pretreatment with HRW significantly reduced IL-06 and TNF-α in the gastric tissues (46.65 ± 5.50 vs 32.15 ± 4.83 pg/mg, P < 0.05 and 1305.08 ± 101.23 vs 855.96 ± 93.22 pg/mg, P < 0.05), and IL-1β and TNF-α in the serum (505.38 ± 32.97 vs 343.37 ± 25.09 pg/mL, P < 0.05 and 264.53 ± 28.63 vs 114.96 ± 21.79 pg/mL, P < 0.05) compared to treatment with aspirin alone. HRW could significantly decrease the COX-2 expression in the gastric tissues (staining score: 8.4 ± 2.1 vs 2.9 ± 1.5, P < 0.05). CONCLUSION: HRW pretreatment alleviated the aspirin-induced gastric lesions by inhibiting the oxidative stress, inflammatory reaction and reducing the COX-2 in the gastric tissues. PMID:24587639

  16. Molecular mechanisms of silk gland damage caused by phoxim exposure and protection of phoxim-induced damage by cerium chloride in Bombyx mori.

    PubMed

    Li, Bing; Sun, Qingqing; Yu, Xiaohong; Xie, Yi; Hong, Jie; Zhao, Xiaoyang; Sang, Xuezi; Shen, Weide; Hong, Fashui

    2015-09-01

    It is known that exposure to organophosphorus pesticides (OP) including phoxim can produce oxidative stress, neurotoxicity, and greatly attenuate cocooning rate in the silkworm, Bombyx mori. Cerium treatment has been demonstrated to relieve phoxim-induced toxicity in B. mori; however, very little is known about the molecular mechanisms of silk gland injury due to OP exposure and protection of gland damage due to cerium pretreatment. The aim of this study was to evaluate silk gland damage and its molecular mechanisms in phoxim-induced silkworm toxicity and the protective mechanisms of cerium following exposure to phoxim. The results showed that phoxim exposure resulted in severe gland damage, reductions in protein synthesis and the cocooning rate of silkworms. Cerium (Ce) attenuated gland damage caused by phoxim, promoted protein synthesis, increased the antioxidant capacity of the gland and increased the cocooning rate of B. mori. Furthermore, digital gene expression data suggested that phoxim exposure led to significant up-regulation of 714 genes and down-regulation of 120 genes. Of these genes, 122 were related to protein metabolism, specifically, the down-regulated Ser2, Ser3, Fib-L, P25, and CYP450. Ce pretreatment resulted in up-regulation of 162 genes, and down-regulation of 141 genes, importantly, Ser2, Ser3, Fib-L, P25, and CYP333B8 were up-regulated. Treatment with CeCl3 + phoxim resulted in higher levels of Fib-L, P25, Ser2, Ser3, CAT, TPx, and CYP333B8 expression in the silk gland of silkworms. These findings indicated that Ce increased cocooning rate via the promotion of silk protein synthesis-related gene expression in the gland under phoxim-induced toxicity. These findings may expand the application of rare earths in sericulture.

  17. Evaluation of Antioxidant and DNA Damage Protection Activity of the Hydroalcoholic Extract of Desmostachya bipinnata L. Stapf

    PubMed Central

    Bhimathati, Solomon Sunder Raj

    2014-01-01

    Desmostachya bipinnata Stapf (Poaceae/Gramineae) is an official drug of ayurvedic pharmacopoeia. Various parts of this plant were used extensively in traditional and folklore medicine to cure various human ailments. The present study was aimed to evaluate the antioxidant and DNA damage protection activity of hydroalcoholic extract of Desmostachya bipinnata both in vitro and in vivo, to provide scientific basis for traditional usage of this plant. The extract showed significant antioxidant activity in a dose-dependent manner with an IC50 value of 264.18 ± 3.47 μg/mL in H2O2 scavenging assay and prevented the oxidative damage to DNA in presence of DNA damaging agent (Fenton's reagent) at a concentration of 50 μg/mL. Also, the presence of extract protected yeast cells in a dose-dependent manner against DNA damaging agent (Hydroxyurea) in spot assay. Moreover, the presence of extract exhibited significant antioxidant activity in vivo by protecting yeast cells against oxidative stressing agent (H2O2). Altogether, the results of current study revealed that Desmostachya bipinnata is a potential source of antioxidants and lends pharmacological credence to the ethnomedical use of this plant in traditional system of medicine, justifying its therapeutic application for free-radical-induced diseases. PMID:24574873

  18. In vitro free radical scavenging and DNA damage protective property of Coriandrum sativum L. leaves extract.

    PubMed

    Harsha, S N; Anilakumar, K R

    2014-08-01

    Coriandrum sativum L. (coriander), an everyday spice in the Indian kitchen is known to add flavor to the cuisine. It is an annual herb belonging to the Apiaceae (Umbellifera) family. The hydro-alcohol extract of Coriandrum sativum L. at the dose of 1 mg/ml was subjected to a series of in vitro assays viz. 2, 2'- diphenyl-1-picrylhydrazyl, lipid peroxidation by thiobarbituric acid, reducing power and nitric oxide (NO) radical scavenging in order to study its antioxidant efficacy in detail. The amount of flavonoids in 70% ethanol extract was found to be 44.5 μg and that of the total phenols was 133.74 μg gallic acid equivalents per mg extract. The extracts of the leaves showed metal chelating power, with IC50 values, 368.12 μg/ml where as that of standard EDTA was 26.7 μg/ml. The IC50 values for 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid radical scavenging was 222 μg/ml where as that of standard ascorbic acid was 22.6 μg/ml. The NO scavenging activity of the extract of the leaves showed IC50 value of 815.6 μg/ml; at the same time the standard BHA had 49.1 μg/ml. All the plant extracts provided DNA damage protection; however, the protection provided at the dose of 8 μg/ml was comparable to that of standard gallic acid. The Coriandrum sativum leaf extract was able to prevent in vitro lipid peroxidation with IC50 values; 589.6 μg/ml where as that of standard BHA was 16.3 μg/ml. Our results also showed significant ferric reducing power indicating the hydrogen donating ability of the extract. This study indicated the potential of the leaf extract as a source of natural antioxidants or nutraceuticals that could be of use in food industry with potential application to reduce oxidative stress in living system. PMID:25114344

  19. In vitro free radical scavenging and DNA damage protective property of Coriandrum sativum L. leaves extract.

    PubMed

    Harsha, S N; Anilakumar, K R

    2014-08-01

    Coriandrum sativum L. (coriander), an everyday spice in the Indian kitchen is known to add flavor to the cuisine. It is an annual herb belonging to the Apiaceae (Umbellifera) family. The hydro-alcohol extract of Coriandrum sativum L. at the dose of 1 mg/ml was subjected to a series of in vitro assays viz. 2, 2'- diphenyl-1-picrylhydrazyl, lipid peroxidation by thiobarbituric acid, reducing power and nitric oxide (NO) radical scavenging in order to study its antioxidant efficacy in detail. The amount of flavonoids in 70% ethanol extract was found to be 44.5 μg and that of the total phenols was 133.74 μg gallic acid equivalents per mg extract. The extracts of the leaves showed metal chelating power, with IC50 values, 368.12 μg/ml where as that of standard EDTA was 26.7 μg/ml. The IC50 values for 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid radical scavenging was 222 μg/ml where as that of standard ascorbic acid was 22.6 μg/ml. The NO scavenging activity of the extract of the leaves showed IC50 value of 815.6 μg/ml; at the same time the standard BHA had 49.1 μg/ml. All the plant extracts provided DNA damage protection; however, the protection provided at the dose of 8 μg/ml was comparable to that of standard gallic acid. The Coriandrum sativum leaf extract was able to prevent in vitro lipid peroxidation with IC50 values; 589.6 μg/ml where as that of standard BHA was 16.3 μg/ml. Our results also showed significant ferric reducing power indicating the hydrogen donating ability of the extract. This study indicated the potential of the leaf extract as a source of natural antioxidants or nutraceuticals that could be of use in food industry with potential application to reduce oxidative stress in living system.

  20. Green tea protects against psoralen plus ultraviolet A-induced photochemical damage to skin.

    PubMed

    Zhao, J F; Zhang, Y J; Jin, X H; Athar, M; Santella, R M; Bickers, D R; Wang, Z Y

    1999-12-01

    The use of psoralens combined with exposure to ultraviolet A radiation is a major form of treatment for psoriasis and a number of other common skin diseases. Although psoralen plus ultraviolet A treatment is highly effective, careful follow-up cohort studies have shown that it greatly increases risk for the development of cutaneous squamous cell carcinoma and melanoma. Strategies to reduce the risk of cancer development in psoralen plus ultraviolet A-treated populations are highly desirable. In prior studies, we demonstrated that green tea and constituent polyphenols protect against ultraviolet B-induced carcinogenesis and reduce the growth rate of established tumors in skin. In this study, we show that pre- and post-treatment with standardized green tea extract in psoralen plus ultraviolet A treatment populations abrogates the psoralen plus ultraviolet A-induced photochemical damage to skin. Intact mouse and human skin and reconstituted human skin were employed to assess the effect of both topical and oral administration of standardized green tea extract against psoralen plus ultraviolet A-induced photodamage. Oral administration of standardized green tea extract prior to and during multiple psoralen plus ultraviolet A treatments reduced hyperplasia and hyperkeratosis in murine skin. Standardized green tea extract treatment also inhibited accumulation of c-fos and p53 protein induction following a single exposure to psoralen plus ultraviolet A. c-fos and p53 positive cells in psoralen plus ultraviolet A-treated skin were found to be increased by 55.4 +/- 13. 6% and 62.3 +/- 10.5%, respectively, compared with saline-treated unexposed control skin. Oral administration of 0.4 or 0.8% standardized green tea extract inhibited c-fos protein accumulation by 18.5% and 46.2% (p < 0.05), respectively, and p53 protein accumulation by 26.1% and 54.3% (p < 0.05), respectively. Similarly proliferating cell nuclear antigen staining, a marker of cell proliferation was induced (73

  1. Protection against radiation-induced testicular damage in Swiss albino mice by Mentha piperita (Linn.).

    PubMed

    Samarth, Ravindra M; Samarth, Meenakshi

    2009-04-01

    The protective effects of Mentha piperita leaf extract against radiation-induced damage in testis of Swiss albino mice have been studied. Animals (Male Swiss albino mice) were given M. piperita leaf extract orally (1 g/kg body weight/day) for three consecutive days before radiation exposure (8 Gy gamma-radiation). Mice were autopsied at 1, 3, 7, 14, and 30 days after irradiation to evaluate the radiomodulatory effect in terms of histological alterations, lipid peroxidation, and acid and alkaline phosphatases levels in testis. Radiation treatment showed reduction in the testis weight during all days of observation, however, in the M. piperita leaf extract-pretreated irradiated group there was a significant increase in testis weight. Radiation treatment induced moderate to severe testicular atrophy with degeneration of germ cells in seminiferous tubules. The tubules were shrunken and greatly depleted of germ cells. Sertoli cells with few germ cells were observed in the lumen. However, animals pre-treated with M. piperita leaf extract and exposed to radiation showed normal testicular morphology with regular arrangement of germ cells and slight degeneration of seminiferous epithelium. Significant decreases in the lipid peroxidation and acid phosphatase level and increase in level of alkaline phosphatase were observed in testis. The M. piperita leaf extract showed high amount of phenolic content, flavonoids content and flavonols. The results of the present study suggest that M. piperita has a significant radioprotective effect and the amount of phenolic compounds, the content of flavonoids and flavonols of M. piperita leaf extract may be held responsible for radioprotective effect due to their antioxidant and radical scavenging activity.

  2. DCT protects human melanocytic cells from UVR and ROS damage and increases cell viability.

    PubMed

    Ainger, Stephen A; Yong, Xuan L; Wong, Shu S; Skalamera, Dubravka; Gabrielli, Brian; Leonard, J Helen; Sturm, Richard A

    2014-12-01

    Dopachrome tautomerase (DCT) is involved in the formation of the photoprotective skin pigment eumelanin and has also been shown to have a role in response to apoptotic stimuli and oxidative stress. The effect of DCT on UVR DNA damage responses and survival pathways in human melanocytic cells was examined by knockdown experiments using melanoma cells, neonatal foreskin melanoblasts (MB) in monoculture and in co-culture with human keratinocytes. MB cell strains genotyped as either MC1R WT or MC1R RHC homozygotes, which are known to be deficient in DCT, were transduced with lentivirus vectors for either DCT knockdown or overexpression. We found melanoma cell survival was reduced by DCT depletion and by UVR over time. UVR-induced p53 and pp53-Ser15 levels were reduced with DCT depletion. Knockdown of DCT in MC1R WT and MC1R RHC MB cells reduced their survival after UVR exposure, whereas increased DCT protein levels enhanced survival. DCT depletion reduced p53 and pp53-Ser15 levels in WM266-4 melanoma and MC1R WT MB cells, while MC1R RHC MB cells displayed variable levels. Both MC1R WT and RHC genotypes of MB cells were responsive to UVR at 3 h with increases in both p53 and pp53-Ser15 proteins. MC1R WT MB cell strains in coculture with keratinocytes have an increased cell survival after UVR exposure when compared to those in monoculture, a protective effect which appears to be conferred by the keratinocytes.

  3. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    PubMed

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity.

  4. Protective Effects of Gallic Acid against Streptozotocin-induced Oxidative Damage in Rat Striatum.

    PubMed

    Naghizadeh, B; Mansouri, M T

    2015-10-01

    The present study aimed to investigate the protective effects of gallic acid (GA) against ICV STZ-induced oxidative damage in the rat striatum. Animals were randomly divided into 4 groups (8 each). Group 1 (Sham), were injected ICV on day 1 and 3 with artificial CSF and treated with normal saline (2 ml/kg, p.o.). Group 2 (sham+GA), were injected ICV on day 1 and 3 with artificial CSF and treated with GA (30 mg/kg, p.o.) for 26 days. Group 3 (lesion) were injected with ICV-STZ (3 mg/kg bilaterally, on day 1 and 3) and received normal saline (2 ml/kg, p.o.) as vehicle. Group 4 (lesion+GA), were injected with ICV-STZ (3 mg/kg bilaterally, on day 1 and 3) and treated with gallic acid (30 mg/kg, p.o.) once daily for 26 days starting 5 days before the first injection of ICV STZ. The homogenized striatum was used for measuring thiobarbituric acid reactive species (TBARS) and total thiol contents, glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) activities. The results showed that ICV STZ-injection increased the level of TBARS (+69.3%) and decreased total thiol concentration (-48.8%), GPx (-47.3%), CAT (-47.1%) and SOD (-30.7%) activities. In contrast, chronic administration of GA significantly prevented the biochemical alterations in the ICV-STZ rats. These findings highlight the beneficial role of GA via enhancement of cerebral antioxidant defense system.

  5. Neuronal oxidative injury and dendritic damage induced by carbofuran: Protection by memantine

    SciTech Connect

    Gupta, Ramesh C. . E-mail: ramesh.gupta@murraystate.edu; Milatovic, Snjezana; Dettbarn, Wolf-D.; Aschner, Michael; Milatovic, Dejan

    2007-03-15

    Carbamate insecticides mediate their neurotoxicity by acetylcholinesterase (AChE) inactivation. Male Sprague-Dawley rats acutely intoxicated with the carbamate insecticide carbofuran (1.5 mg/kg, sc) developed hypercholinergic signs within 5-7 min of exposure, with maximal severity characterized by seizures within 30-60 min, lasting for about 2 h. At the time of peak severity, compared with controls, AChE was maximally inhibited (by 82-90%), radical oxygen species (ROS) markers (F{sub 2}-isoprostanes, F{sub 2}-IsoPs; and F{sub 4}-neuroprostanes, F{sub 4}-NeuroPs) were elevated 2- to 3-fold, and the radical nitrogen species (RNS) marker citrulline was elevated 4- to 8-fold in discrete brain regions (cortex, amygdala, and hippocampus). In addition, levels of high-energy phosphates (HEPs) were significantly reduced (ATP, by 43-56%; and phosphocreatine, by 37-48%). Values of total adenine nucleotides and total creatine compounds declined markedly (by 41-56% and 35-45%, respectively), while energy charge potential remained unchanged. Quantitative morphometric analysis of pyramidal neurons of the hippocampal CA1 region revealed significant decreases in dendritic lengths (by 64%) and spine density (by 60%). Pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonist memantine (18 mg/kg, sc), in combination with atropine sulfate (16 mg/kg, sc), significantly attenuated carbofuran-induced changes in AChE activity and levels of F{sub 2}-IsoPs and F{sub 4}-NeuroPs, declines in HEPs, as well as the alterations in morphology of hippocampal neurons. MEM and ATS pretreatment also protected rats from carbofuran-induced hypercholinergic behavioral activity, including seizures. These findings support the involvement of ROS and RNS in seizure-induced neuronal injury and suggest that memantine by preventing carbofuran-induced neuronal hyperactivity blocks pathways associated with oxidative damage in neurons.

  6. Protective effect of Ugni molinae Turcz against oxidative damage of human erythrocytes.

    PubMed

    Suwalsky, M; Orellana, P; Avello, M; Villena, F

    2007-01-01

    Ugni molinae Turcz, also known as "Murtilla", is a plant that grows in the south of Chile. Infusions of its leaves have long been used in traditional native herbal medicine. The chemical composition of the leaves indicates the presence of polyphenols, which have antioxidant properties. In the present work, the antioxidant properties of U. molinae were evaluated in human erythrocytes exposed in vitro to oxidative stress induced by HClO. The experiments were carried out by scanning electron microscopy (SEM) and hemolysis measurements. The SEM observations showed that HClO induced a morphological alteration in the red blood cells from a discoid to an echinocytic form. According to the bilayer couple hypothesis, the formation of echinocytes indicates that HClO was inserted in the outer leaflet of the erythrocyte membrane. However, a concentration as low as 10 microM gallic acid equivalents (GAE) U. molinae aqueous extract neutralized the shape change effect of HClO applied in a concentration as high as 0.25 mM. The significant protection of U. molinae aqueous extract was also shown in the hemolysis experiments. In fact, very low concentrations of the extract considerably reduced the deleterious capacity of HClO to induce hemolysis in red blood cells. It is concluded that the location of the extract components into the membrane bilayer and the resulting restriction on its fluidity might hinder the diffusion of HClO and its consequent damaging effects. This conclusion can also imply that this restriction could apply to the diffusion of free radicals into cell membranes and the subsequent decrease of the kinetics of free radical reactions. PMID:17030381

  7. Nebivolol, a β1-adrenergic blocker, protects from peritoneal membrane damage induced during peritoneal dialysis

    PubMed Central

    Abensur, Hugo; Albar-Vizcaino, Patricia; Parra, Emilio González; Sandoval, Pilar; Ramírez, Laura García; del Peso, Gloria; Acedo, Juan Manuel; Bajo, María A.; Selgas, Rafael; Tomero, José A. Sánchez; López-Cabrera, Manuel; Aguilera, Abelardo

    2016-01-01

    Peritoneal dialysis (PD) is a form of renal replacement treatment, which employs the peritoneal membrane (PM) to eliminate toxins that cannot be removed by the kidney. The procedure itself, however, contributes to the loss of the PM ultrafiltration capacity (UFC), leading consequently to the technique malfunction. β-blockers have been considered deleterious for PM due to their association with loss of UFC and induction of fibrosis. Herein we analyzed the effects of Nebivolol, a new generation of β1-blocker, on PM alterations induced by PD fluids (PDF). In vitro: We found that mesothelial cells (MCs) express β1-adrenergic receptor. MCs were treated with TGF-β to induce mesothelial-to-mesenchymal transition (MMT) and co-treated with Nebivolol. Nebivolol reversed the TGF-β effects, decreasing extracellular matrix synthesis, and improved the fibrinolytic capacity, decreasing plasminogen activator inhibitor-1 (PAI-1) and increasing tissue-type plasminogen activator (tPA) supernatant levels. Moreover, Nebivolol partially inhibited MMT and decreased vascular endothelial growth factor (VEGF) and IL-6 levels in supernatants. In vivo: Twenty-one C57BL/6 mice were divided into 3 groups. Control group carried a catheter without PDF infusion. Study group received intraperitoneally PDF and oral Nebivolol during 30 days. PDF group received PDF alone. Nebivolol maintained the UFC and reduced PM thickness, MMT and angiogenesis promoted by PDF. It also improved the fibrinolytic capacity in PD effluents decreasing PAI-1 and IL-8 and increased tPA levels. Conclusion: Nebivolol protects PM from PDF-induced damage, promoting anti-fibrotic, anti-angiogenic, anti-inflammatory and pro-fibrinolytic effects. PMID:27102153

  8. Protective Role of Glucagon-Like Peptide-1 Against High-Glucose-Induced Endothelial Oxidative Damage

    PubMed Central

    Guo, Lixin; Qiao, Yue; Zhang, Lina; Pan, Qi

    2015-01-01

    Abstract To investigate the protective effect of glucagon-like peptide-1 (GLP-1) against cell damage induced by high glucose. Human umbilical vein endothelial cells (HUVECs) were divided into control group (5.5 mmol/L) and high glucose groups (19, 33, or 47 mmol/L), which were cultured with different concentrations of glucose for 48 hours, respectively. Cell viability was measured with MTT assay. Levels of intracellular reactive oxygen species (ROS) were monitored by flow cytometry and apoptotic cell death was measured by staining with Annexin V-FITC and propidium iodide. Cultured cells were detected with intercellular adhesion molecule 1 (ICAM-1), VCAM-1, and JNK on protein. Compared with the control group, cell viability was decreased by 20% and 37%, respectively, when cultured under 33 and 47 mM, while increased in different GLP-1-treated groups (0.01 L, 0.1, 1, and 10 nmol/L). The GLP-1 treatment significantly reduced the ROS level of high glucose treatment group but not impact on the control group. Meanwhile, the level of apoptosis was elevated in the high glucose treatment group. Early apoptosis was significantly reversed in the GLP-1-treated group (0.1, 1, and 10 nmol/L). Late apoptosis was uniquely decreased in the GLP-1 concentrations of 10 nmol/L. Furthermore, GLP-1 could also reduce the protein levels of ICAM-1, VCAM-1, and phospho JNK in the endothelial cells with high glucose treatment. GLP-1 could inhibit cell apoptosis and reduce ROS generation and JNK-Bax signaling pathway activation, which were induced by high glucose treatment. PMID:26632709

  9. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    PubMed

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity. PMID:26485141

  10. The pristine atomic structure of MoS2 monolayer protected from electron radiation damage by graphene

    NASA Astrophysics Data System (ADS)

    Algara-Siller, Gerardo; Kurasch, Simon; Sedighi, Mona; Lehtinen, Ossi; Kaiser, Ute

    2013-11-01

    Materials can, in principle, be imaged at the level of individual atoms with aberration-corrected transmission electron microscopy. However, such resolution can be attained only with very high electron doses. Consequently, radiation damage is often the limiting factor when characterizing sensitive materials. Here, we demonstrate a simple and an effective method to increase the electron radiation tolerance of materials by using graphene as protective coating. This leads to an improvement of three orders of magnitude in the radiation tolerance of monolayer MoS2. Further on, we construct samples in different heterostructure configurations to separate the contributions of different radiation damage mechanisms.

  11. Aloin Protects Skin Fibroblasts from Heat Stress-Induced Oxidative Stress Damage by Regulating the Oxidative Defense System

    PubMed Central

    Wang, Yu-Ren; Tsai, Hsin-I; Yu, Huang-Ping

    2015-01-01

    Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system. PMID:26637174

  12. Aloin Protects Skin Fibroblasts from Heat Stress-Induced Oxidative Stress Damage by Regulating the Oxidative Defense System.

    PubMed

    Liu, Fu-Wei; Liu, Fu-Chao; Wang, Yu-Ren; Tsai, Hsin-I; Yu, Huang-Ping

    2015-01-01

    Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system. PMID:26637174

  13. Aerothermal performance and damage tolerance of a Rene 41 metallic standoff thermal protection system at Mach 6.7

    NASA Technical Reports Server (NTRS)

    Avery, D. E.

    1984-01-01

    A flight-weight, metallic thermal protection system (TPS) model applicable to Earth-entry and hypersonic-cruise vehicles was subjected to multiple cycles of both radiant and aerothermal heating in order to evaluate its aerothermal performance, structural integrity, and damage tolerance. The TPS was designed for a maximum operating temperature of 2060 R and featured a shingled, corrugation-stiffened corrugated-skin heat shield of Rene 41, a nickel-base alloy. The model was subjected to 10 radiant heating tests and to 3 radiant preheat/aerothermal tests. Under radiant-heating conditions with a maximum surface temperature of 2050 R, the TPS performed as designed and limited the primary structure away from the support ribs to temperatures below 780 R. During the first attempt at aerothermal exposure, a failure in the panel-holder test fixture severely damaged the model. However, two radiant preheat/aerothermal tests were made with the damaged model to test its damage tolerance. During these tests, the damaged area did not enlarge; however, the rapidly increasing structural temperature measuring during these tests indicates that had the damaged area been exposed to aerodynamic heating for the entire trajectory, an aluminum burn-through would have occurred.

  14. Hyperprolinemia induces DNA, protein and lipid damage in blood of rats: antioxidant protection.

    PubMed

    Ferreira, Andréa G K; Scherer, Emilene B; da Cunha, Aline A; Manfredini, Vanusa; Biancini, Giovana Brondani; Vanzin, Camila Simioni; Vargas, Carmen R; Wyse, Angela T S

    2014-09-01

    The present study investigated the effects of hyperprolinemia on oxidative damage to biomolecules (protein, lipids and DNA) and the antioxidant status in blood of rats. The influence of the antioxidants on the effects elicited by proline was also examined. Wistar rats received two daily injections of proline and/or vitamin E plus C (6th-28th day of life) and were killed 12h after the last injection. Results showed that hyperprolinemia induced a significant oxidative damage to proteins, lipids and DNA demonstrated by increased carbonyl content, malondialdehyde levels and a greater damage index in comet assay, respectively. The concomitant antioxidants administration to proline treatment completely prevented oxidative damage to proteins, but partially prevented lipids and DNA damage. We also observed that the non-enzymatic antioxidant potential was decreased by proline treatment and partially prevented by antioxidant supplementation. The plasma levels of vitamins E and C significantly increased in rats treated exogenously with these vitamins but, interestingly, when proline was administered concomitantly with vitamin E plus C, the levels of these vitamins were similar to those found in plasma of control and proline rats. Our findings suggest that hyperprolinemia promotes oxidative damage to the three major classes of macromolecules in blood of rats. These effects were accomplished by decrease in non-enzymatic antioxidant potential and decrease in vitamins administered exogenously, which significantly decreased oxidative damage to biomolecules studied. These data suggest that antioxidants may be an effective adjuvant therapeutic to limit oxidative damage caused by proline.

  15. Hyperprolinemia induces DNA, protein and lipid damage in blood of rats: antioxidant protection.

    PubMed

    Ferreira, Andréa G K; Scherer, Emilene B; da Cunha, Aline A; Manfredini, Vanusa; Biancini, Giovana Brondani; Vanzin, Camila Simioni; Vargas, Carmen R; Wyse, Angela T S

    2014-09-01

    The present study investigated the effects of hyperprolinemia on oxidative damage to biomolecules (protein, lipids and DNA) and the antioxidant status in blood of rats. The influence of the antioxidants on the effects elicited by proline was also examined. Wistar rats received two daily injections of proline and/or vitamin E plus C (6th-28th day of life) and were killed 12h after the last injection. Results showed that hyperprolinemia induced a significant oxidative damage to proteins, lipids and DNA demonstrated by increased carbonyl content, malondialdehyde levels and a greater damage index in comet assay, respectively. The concomitant antioxidants administration to proline treatment completely prevented oxidative damage to proteins, but partially prevented lipids and DNA damage. We also observed that the non-enzymatic antioxidant potential was decreased by proline treatment and partially prevented by antioxidant supplementation. The plasma levels of vitamins E and C significantly increased in rats treated exogenously with these vitamins but, interestingly, when proline was administered concomitantly with vitamin E plus C, the levels of these vitamins were similar to those found in plasma of control and proline rats. Our findings suggest that hyperprolinemia promotes oxidative damage to the three major classes of macromolecules in blood of rats. These effects were accomplished by decrease in non-enzymatic antioxidant potential and decrease in vitamins administered exogenously, which significantly decreased oxidative damage to biomolecules studied. These data suggest that antioxidants may be an effective adjuvant therapeutic to limit oxidative damage caused by proline. PMID:24980685

  16. Fortilin potentiates the peroxidase activity of Peroxiredoxin-1 and protects against alcohol-induced liver damage in mice

    PubMed Central

    Chattopadhyay, Abhijnan; Pinkaew, Decha; Doan, Hung Q.; Jacob, Reed B.; Verma, Sunil K.; Friedman, Hana; Peterson, Alan C.; Kuyumcu-Martinez, Muge N.; McDougal, Owen M.; Fujise, Ken

    2016-01-01

    Fortilin, a pro-survival molecule, inhibits p53-induced apoptosis by binding to the sequence-specific DNA-binding domain of the tumor suppressor protein and preventing it from transcriptionally activating Bax. Intriguingly, fortilin protects cells against ROS-induced cell death, independent of p53. The signaling pathway through which fortilin protects cells against ROS-induced cell death, however, is unknown. Here we report that fortilin physically interacts with the antioxidant enzyme peroxiredoxin-1 (PRX1), protects it from proteasome-mediated degradation, and keeps it enzymatically active by blocking its deactivating phosphorylation by Mst1, a serine/threonine kinase. At the whole animal level, the liver-specific overexpression of fortilin reduced PRX1 phosphorylation in the liver, enhanced PRX1 activity, and protected the transgenic animals against alcohol-induced, ROS-mediated, liver damage. These data suggest the presence of a novel oxidative-stress-handling pathway where the anti-p53 molecule fortilin augments the peroxidase PRX1 by protecting it against degradation and inactivation of the enzyme. Fortilin-PRX1 interaction in the liver could be clinically exploited further to prevent acute alcohol-induced liver damage in humans. PMID:26726832

  17. Fortilin potentiates the peroxidase activity of Peroxiredoxin-1 and protects against alcohol-induced liver damage in mice.

    PubMed

    Chattopadhyay, Abhijnan; Pinkaew, Decha; Doan, Hung Q; Jacob, Reed B; Verma, Sunil K; Friedman, Hana; Peterson, Alan C; Kuyumcu-Martinez, Muge N; McDougal, Owen M; Fujise, Ken

    2016-01-01

    Fortilin, a pro-survival molecule, inhibits p53-induced apoptosis by binding to the sequence-specific DNA-binding domain of the tumor suppressor protein and preventing it from transcriptionally activating Bax. Intriguingly, fortilin protects cells against ROS-induced cell death, independent of p53. The signaling pathway through which fortilin protects cells against ROS-induced cell death, however, is unknown. Here we report that fortilin physically interacts with the antioxidant enzyme peroxiredoxin-1 (PRX1), protects it from proteasome-mediated degradation, and keeps it enzymatically active by blocking its deactivating phosphorylation by Mst1, a serine/threonine kinase. At the whole animal level, the liver-specific overexpression of fortilin reduced PRX1 phosphorylation in the liver, enhanced PRX1 activity, and protected the transgenic animals against alcohol-induced, ROS-mediated, liver damage. These data suggest the presence of a novel oxidative-stress-handling pathway where the anti-p53 molecule fortilin augments the peroxidase PRX1 by protecting it against degradation and inactivation of the enzyme. Fortilin-PRX1 interaction in the liver could be clinically exploited further to prevent acute alcohol-induced liver damage in humans. PMID:26726832

  18. Protection of radiation induced DNA and membrane damages by total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst.

    PubMed

    Smina, T P; Maurya, D K; Devasagayam, T P A; Janardhanan, K K

    2015-05-25

    The total triterpenes isolated from the fruiting bodies of Ganoderma lucidum was examined for its potential to prevent γ-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on γ-radiation-induced DNA strand breaks in pBR 322 plasmid DNA in vitro and human peripheral blood lymphocytes ex vivo were evaluated. The protective effect of total triterpenes against γ-radiation-induced micronuclei formations in mice bone marrow cells in vivo were also evaluated. The results indicated the significant effectiveness of Ganoderma triterpenes in protecting the DNA and membrane damages consequent to the hazardous effects of radiation. The findings suggest the potential use of Ganoderma triterpenes in radio therapy. PMID:25824410

  19. Protection of radiation induced DNA and membrane damages by total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst.

    PubMed

    Smina, T P; Maurya, D K; Devasagayam, T P A; Janardhanan, K K

    2015-05-25

    The total triterpenes isolated from the fruiting bodies of Ganoderma lucidum was examined for its potential to prevent γ-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on γ-radiation-induced DNA strand breaks in pBR 322 plasmid DNA in vitro and human peripheral blood lymphocytes ex vivo were evaluated. The protective effect of total triterpenes against γ-radiation-induced micronuclei formations in mice bone marrow cells in vivo were also evaluated. The results indicated the significant effectiveness of Ganoderma triterpenes in protecting the DNA and membrane damages consequent to the hazardous effects of radiation. The findings suggest the potential use of Ganoderma triterpenes in radio therapy.

  20. Protective Effect of Sinapine against Hydroxyl Radical-Induced Damage to Mesenchymal Stem Cells and Possible Mechanisms.

    PubMed

    Li, Xican; Han, Lu; Li, Yunrong; Zhang, Jing; Chen, Jiemin; Lu, Wenbiao; Zhao, Xiaojun; Lai, Yingtao; Chen, Dongfeng; Wei, Gang

    2016-01-01

    As a phenolic alkaloid occurring in Cruciferous plants, sinapine was observed to protect mesenchymal stem cells (MSCs) against ·OH-induced damage in this study. It was also found to prevent DNA from damage, to scavenge various free radicals (·OH, ·O2(-), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt) (ABTS)(+·), and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·)), and to reduce Cu(2+) to Cu(+). To further explore the mechanism, the end-product of sinapine reaction with DPPH· was determined using HPLC-electrospray ionization (ESI)-MS/MS and HPLC-diode array detector (DAD). Four molecular ion peaks (m/z 701, 702, 703, and 351) in HPLC-ESI-MS/MS analysis indicated a radical adduct formation (RAF) pathway; while a bathochromic shift (λ(max) 334→475 nm) in HPLC-DAD indicated the formation of quinone as the oxidized product of the phenolic -OH group. Based on these results, it may be concluded that, (i) sinapine can effectively protect against ·OH-induced damage to DNA and MSCs; such protective effect may provide evidence for a potential role for sinapine in MSC transplantation therapy, and be responsible for the beneficial effects of Cruciferous plants. (ii) The possible mechanism for sinapine to protect against ·OH-induced oxidative damage is radical-scavenging, which is thought to be via hydrogen atom (H·) transfer (HAT) (or sequential electron (e) proton transfer (SEPT))→RAF pathways.

  1. Sperm fucosyltransferase-5 mediates spermatozoa-oviductal epithelial cell interaction to protect human spermatozoa from oxidative damage.

    PubMed

    Huang, Venus Wenxin; Lee, Cheuk-Lun; Lee, Yin-Lau; Lam, Kevin K W; Ko, Jennifer K Y; Yeung, William S B; Ho, Pak-Chung; Chiu, Philip C N

    2015-06-01

    Oxidative damage by reactive oxygen species (ROS) is a major cause of sperm dysfunction. Excessive ROS generation reduces fertilization and enhances DNA damage of spermatozoa. Interaction between spermatozoa and oviductal epithelial cells improves the fertilizing ability of and reduces chromatin damage in spermatozoa. Our previous data showed that oviductal epithelial cell membrane proteins interact with the human spermatozoa and protect them from ROS-induced reduction in sperm motility, membrane integrity and DNA integrity. Sperm fucosyltransferase-5 (sFUT5) is a membrane carbohydrate-binding protein on human spermatozoa. In this study, we demonstrate for the first time that sFUT5 is involved in human spermatozoa-oviduct interaction and the beneficial effects of such interaction on the fertilizing ability of human spermatozoa. Anti-sFUT5 antibody-treated spermatozoa had reduced binding to oviductal membrane proteins. It is consistent with the result that affinity-purified sFUT5 is bound to the epithelial lining of human oviduct and to the immortalized human oviductal epithelial cell line, OE-E6/E7. Pretreatment of spermatozoa with anti-sFUT5 antibody and oviductal membrane proteins with sFUT5 suppressed the protective action of oviductal membrane proteins against ROS/cryopreservation-induced oxidative damage in spermatozoa. Asialofetuin, a reported sFUT5 substrate, can partly mimic the protective effect of oviductal epithelial cell membrane proteins on sperm motility, membrane and DNA integrity. The results enhance our understanding on the protective mechanism of oviduct on sperm functions.

  2. Protection from UV-B damage of mosquito larvicidal toxins from Bacillus thuringiensis subsp. israelensis expressed in Anabaena PCC 7120.

    PubMed

    Manasherob, Robert; Ben-Dov, Eitan; Xiaoqiang, Wu; Boussiba, Sammy; Zaritsky, Arieh

    2002-09-01

    A transgenic strain of the nitrogen-fixing filamentous cyanobacterium Anabaena PCC 7120 protected expressed delta-endotoxin proteins of Bacillus thuringiensis subsp. israelensis from damage inflicted by UV-B, a sunlight component that penetrates Earth's ozone layer. This organism, which serves as a food source to mosquito larvae and could multiply in their breeding sites, may solve the environment-imposed limitations of B. thuringiensis subsp. israelensis as a mosquito biological control agent.

  3. Plasma from human volunteers subjected to remote ischemic preconditioning protects human endothelial cells from hypoxia-induced cell damage.

    PubMed

    Weber, Nina C; Riedemann, Isabelle; Smit, Kirsten F; Zitta, Karina; van de Vondervoort, Djai; Zuurbier, Coert J; Hollmann, Markus W; Preckel, Benedikt; Albrecht, Martin

    2015-03-01

    Short repeated cycles of peripheral ischemia/reperfusion (I/R) can protect distant organs from subsequent prolonged I/R injury; a phenomenon known as remote ischemic preconditioning (RIPC). A RIPC-mediated release of humoral factors might play a key role in this protection and vascular endothelial cells are potential targets for these secreted factors. In the present study, RIPC-plasma obtained from healthy male volunteers was tested for its ability to protect human umbilical endothelial cells (HUVEC) from hypoxia-induced cell damage. 10 healthy male volunteers were subjected to a RIPC-protocol consisting of 4 × 5 min inflation/deflation of a blood pressure cuff located at the upper arm. Plasma was collected before (T0; control), directly after (T1) and 1 h after (T2) the RIPC procedure. HUVEC were subjected to 24 h hypoxia damage and simultaneously incubated with 5% of the respective RIPC-plasma. Cell damage was evaluated by lactate dehydrogenase (LDH)-measurements. Western blot experiments of hypoxia inducible factor 1 alpha (HIF1alpha), phosphorylated signal transducer and activator of transcription 5 (STAT5), protein kinase B (AKT) and extracellular signal-related kinase 1/2 (ERK-1/2) were performed. Furthermore, the concentrations of hVEGF were evaluated in the RIPC-plasma by sandwich ELISA. Hypoxia-induced cell damage was significantly reduced by plasma T1 (p = 0.02 vs T0). The protective effect of plasma T1 was accompanied by an augmentation of the intracellular HIF1alpha (p = 0.01 vs T0) and increased phosphorylation of ERK-1/2 (p = 0.03 vs T0). Phosphorylation of AKT and STAT5 remained unchanged. Analysis of the protective RIPC-plasma T1 showed significantly reduced levels of hVEGF (p = 0.01 vs T0). RIPC plasma protects endothelial cells from hypoxia-induced cell damage and humoral mediators as well as intracellular HIF1alpha may be involved.

  4. Protective effect of infrared-A radiation against damage induced by UVB radiation in the melan-a cell line.

    PubMed

    Portantiolo Lettnin, Aline; Teixeira Santos Figueiredo Salgado, Mariana; Gonsalez Cruz, Camila; Manoel Rodrigues da Silva-Júnior, Flávio; Cunha Gonzalez, Vinícius; de Souza Votto, Ana Paula; Santos Trindade, Gilma; de Moraes Vaz Batista Filgueira, Daza

    2016-10-01

    The present work evaluated the infrared-A (IR-A) protective effect using a light-emitting diode (LED) lamp against the cytotoxic effects of ultraviolet B radiation (UVB). Effects on cell viability (Trypan blue assay), DNA damage (comet assay), lipid peroxidation (FOX method), reactive oxygen species production and antioxidant capacity were analyzed in melan-a, a non-tumoral murine melanocytic cell line. To define the doses used in the interaction experiments between IR-A+UVB, dose/response curves were made after exposure to IR-A or UVB. The IR-A dose chosen was 0.8J/cm(2) because this dose caused no significant inhibition of proliferation effects and viability decreased. For UVB exposure, a dose of 0.015J/cm(2), which showed a decrease in viable cell number by approximately 50% in relation to control until 72h, was selected. For IR-A+UVB, cell proliferation recovery was showed, decreasing DNA damage and lipid peroxide content when compared to UVB alone. Besides, the results obtained for ROS and antioxidant capacity showed that the protection observed was probably not related to decreased oxidative stress. In conclusion, non-thermal IR-A was capable of protecting the melan-a cells from UVB induced damage. PMID:27567083

  5. Protective effect of infrared-A radiation against damage induced by UVB radiation in the melan-a cell line.

    PubMed

    Portantiolo Lettnin, Aline; Teixeira Santos Figueiredo Salgado, Mariana; Gonsalez Cruz, Camila; Manoel Rodrigues da Silva-Júnior, Flávio; Cunha Gonzalez, Vinícius; de Souza Votto, Ana Paula; Santos Trindade, Gilma; de Moraes Vaz Batista Filgueira, Daza

    2016-10-01

    The present work evaluated the infrared-A (IR-A) protective effect using a light-emitting diode (LED) lamp against the cytotoxic effects of ultraviolet B radiation (UVB). Effects on cell viability (Trypan blue assay), DNA damage (comet assay), lipid peroxidation (FOX method), reactive oxygen species production and antioxidant capacity were analyzed in melan-a, a non-tumoral murine melanocytic cell line. To define the doses used in the interaction experiments between IR-A+UVB, dose/response curves were made after exposure to IR-A or UVB. The IR-A dose chosen was 0.8J/cm(2) because this dose caused no significant inhibition of proliferation effects and viability decreased. For UVB exposure, a dose of 0.015J/cm(2), which showed a decrease in viable cell number by approximately 50% in relation to control until 72h, was selected. For IR-A+UVB, cell proliferation recovery was showed, decreasing DNA damage and lipid peroxide content when compared to UVB alone. Besides, the results obtained for ROS and antioxidant capacity showed that the protection observed was probably not related to decreased oxidative stress. In conclusion, non-thermal IR-A was capable of protecting the melan-a cells from UVB induced damage.

  6. Short-term psychosocial stress protects photoreceptors from damage via corticosterone-mediated activation of the AKT pathway.

    PubMed

    Forkwa, Tembei K; Neumann, Inga D; Tamm, Ernst R; Ohlmann, Andreas; Reber, Stefan O

    2014-02-01

    Apoptotic death of photoreceptors in hereditary retinal degenerations can be prevented by neuroprotective molecules. Here, we report that adrenal glucocorticoids (GC) released during psychosocial stress protect photoreceptors from apoptosis after light damage. Psychosocial stress is known to be the main type of stressor humans are exposed to and was induced here in mice by 10h of chronic subordinate colony housing (CSC). Photoreceptor damage was generated by subsequent exposure to white light. Short-term psychosocial stress prior to illumination significantly reduced the number of apoptotic photoreceptors, an effect that was absent in adrenalectomized (ADX) mice. The neuroprotective effect was completely restored in ADX mice substituted with GC. Moreover, phosphorylation of retinal AKT increased following CSC or exogenous GC treatment, an effect that was again absent in ADX mice exposed to CSC. Finally, inhibition of AKT signaling with triciribine blocked the stress- and GC-mediated neuroprotective effects on photoreceptors. In summary, we provide evidence that 1) short-term psychosocial stress protects photoreceptors from light-induced damage and 2) the protective effect is most likely mediated by GC-induced activation of the AKT signaling pathway.

  7. Protective effects of guarana (Paullinia cupana Mart. var. Sorbilis) against DEN-induced DNA damage on mouse liver.

    PubMed

    Fukumasu, H; Avanzo, J L; Heidor, R; Silva, T C; Atroch, A; Moreno, F S; Dagli, M L Z

    2006-06-01

    Guarana (Paullinia cupana Mart. var. Sorbilis) is a plant originally from Brazil, which is rich in tannins. Some tannins are known to present protective effects against DNA damage. This study was performed to investigate the anti-genotoxic/cytotoxic properties of guarana in hepatocytes of mice injected with N-nitrosodiethylamine (DEN). The protective effect of guarana was evaluated both by comet assay and DNA smear fragmentation technique in two month-old female BALB/c mice. These were treated previously with 2.0 mg/g bw of guarana for 16 days and then injected with DEN (160 microg/g body weight) to induce DNA damage. The DEN-only treated group presented higher comet image length than the guarana plus DEN and untreated groups (116.06+/-5.0 microm, 104.09+/-3.3 microm and 93.28+/-14.4 microm, respectively; p<0.01). Guarana treatment presented a 52.54% reduction in comet image length when animals were exposed to DEN (p<0.05). DNA samples from the guarana plus DEN group clearly showed less EtBr fluorescence intensity when compared to the DEN-only group, reinforcing the comet assay data. These results show, for the first time, that guarana has a protective effect against DEN-induced DNA damage in mouse liver.

  8. Biological properties of Alsidium corallinum and its potential protective effects against damage caused by potassium bromate in the mouse liver.

    PubMed

    Ben Saad, Hajer; Kharrat, Nadia; Krayem, Najeh; Boudawara, Ons; Boudawara, Tahia; Zeghal, Najiba; Ben Amara, Ibtissem

    2016-02-01

    In the course of searching for hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine red alga Alsidium corallinum (A. corallinum) against potassium bromate (KBrO3)-induced liver damage in adult mice was investigated. The in vitro antioxidant and antibacterial properties of A. corallinum were firstly investigated. Then, A. corallinum was tested in vivo for its potential protective effects against damage caused by KBrO3 in mice models divided into four groups: controls, KBrO3, KBrO3 + A. corallinum, and A. corallinum. Our results demonstrated the rich composition of A. corallinum in antioxidant compounds like phenolics, flavonoids, anthocyanins, polysaccharides, chlorophyll and carotenoids. Its antioxidant activity was also confirmed using β-carotene bleaching by linoleic acid assay, reducing sugar test and trolox equivalent antioxidant capacity. The ethanolic extract of A. corallinum also showed good inhibition of the tested bacteria. The coadministration of the red alga associated to the KBrO3 alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers and plasma biochemical parameters, when compared to the KBrO3-treated mice. These results were confirmed by the improvement of histological and molecular changes. Treatment with A. corallinum prevented liver damage induced by KBrO3, thus protecting the body against free radicals and reducing inflammation and hypercholesterolemia risks.

  9. Protective and damaging effects of stress mediators: central role of the brain

    PubMed Central

    McEwen, Bruce S.

    2006-01-01

    The mind involves the whole body, and two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Stress is a condition of the mind-body interaction, and a factor in the expression of disease that differs among individuals. It is not just the dramatic stressful events that exact their toll, but rather the many events of daily life that elevate and sustain activities of physiological systems and cause sleep deprivation, overeating, and other health-damaging behaviors, producing the feeling of being “stressed out.” Over time, this results in wear and tear on the body, which is called “allostatic load,” and it reflects not only the impact of life experiences but also of genetic load, individual lifestyle habits reflecting items such as diet, exercise, and substance abuse, and developmental experiences that set life-long patterns of behavior and physiological reactivity. Hormones associated with stress and allostatic load protect the body in the short run and promote adaptation by the process known as allostasis, but in the long run allostatic load causes changes in the body that can lead to disease. The brain is the key organ of stress, allostasis, and allostatic load, because it determines what is threatening and therefore stressful, and also determines the physiological and behavioral responses. Brain regions such as the hippocampus, amygdala, and prefrontal cortex respond to acute and chronic stress by undergoing structural remodeling, which alters behavioral and physiological responses. Translational studies in humans with structural and functional imaging reveal smaller hippocampal volume in stress-related conditions, such as mild cognitive impairment in aging and prolonged major depressive illness, as well as in individuals with low self-esteem. Alterations in amygdala and prefrontal cortex are also reported. Besides Pharmaceuticals, approaches to alleviate chronic stress and reduce

  10. Protective Effect of SAHA against LPS-induced Liver Damage in Rodents

    PubMed Central

    Zhao, Yili; Zhou, Peter; Liu, Baoling; Bambakidis, Ted; Mazitschek, Ralph; Alam, Hasan B.; Li, Yongqing

    2014-01-01

    BACKGROUND Lipopolysaccharide (LPS) has a deleterious effect on several organs including the liver and eventually leads to endotoxic shock and death. LPS-induced hepatotoxicity is characterized by disturbed intracellular redox balance and excessive reactive oxygen species (ROS) accumulation, leading to liver injury. We have shown that treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACI), improves survival in a murine model of LPS-induced shock, but the protective effect of SAHA against liver damage remains unknown. The goal of this study was to investigate the mechanism underlying SAHA action in murine livers. METHOD Male C57BL/6J mice (6-8 weeks) weighing 20-25 g were randomly divided into three groups: (A) a sham group was given isotonic sodium chloride solution (10 μL/g body weight, intraperitoneal, i.p.) with DMSO (1 μl/g body weight, i.p.); (B) a LPS group was challenged with LPS (20 mg/kg, i.p.) dissolved in isotonic sodium chloride solution with DMSO; (C) a LPS plus SAHA group was treated with SAHA (50 mg/kg, i.p.) dissolved in DMSO immediately after injection of LPS (20 mg/kg, i.p.). Mice were anesthetized, and their livers were harvested 6 or 24 hours after injection to analyze whether SAHA affected production of reactive oxygen species (ROS) and activation of apoptotic proteins in the liver cells of challenged mice. RESULTS SAHA counteracted LPS-induced production of ROS (thiobarbituric acid reactive substances (TBARS) and nitrite) and reversed an LPS-induced decrease in antioxidant enzyme, glutathione (GSH). SAHA also attenuated LPS-induced hepatic apoptosis. Moreover, SAHA inhibited activation of the redox-sensitive kinase, apoptosis signal-regulating kinase-1 (ASK1), and the mitogen-activated protein kinases (MAPKs) p38 and Jun N-terminal kinase (JNK). CONCLUSION Our data indicates, for the first time, that SAHA is capable of alleviating LPS-induced hepatotoxicity and suggests that a blockade of the upstream

  11. Protective Effects of Gelam Honey against Oxidative Damage in Young and Aged Rats

    PubMed Central

    Sahhugi, Zulaikha; Jubri, Zakiah

    2014-01-01

    Aging is characterized by progressive decline in physiological and body function due to increase in oxidative damage. Gelam honey has been accounted to have high phenolic and nonphenolic content to attenuate oxidative damage. This study was to determine the effect of local gelam honey on oxidative damage of aged rats. Twenty-four male Spraque-Dawley rats were divided into young (2 months) and aged (19 months) groups. Each group was further divided into control (fed with plain water) and supplemented with 2.5 mg/kg body weight of gelam honey for 8 months. DNA damage level was determined by comet assay and plasma malondialdehyde (MDA) by high performance liquid chromatography (HPLC). The activity of blood and cardiac antioxidant enzymes was determined by spectrophotometer. The DNA damage and MDA level were reduced in both gelam honey supplemented groups. Gelam honey increases erythrocytes CAT and cardiac SOD activities in young and cardiac CAT activity in young and aged groups. The DNA damage was increased in the aged group compared to young group, but reduced at the end of the study. The decline of oxidative damage in rats supplemented with gelam honey might be through the modulation of antioxidant enzyme activities. PMID:25505937

  12. Zingerone protects against stannous chloride-induced and hydrogen peroxide-induced oxidative DNA damage in vitro.

    PubMed

    Rajan, Iyappan; Narayanan, Nithya; Rabindran, Remitha; Jayasree, P R; Manish Kumar, P R

    2013-12-01

    In this paper, we report the dose-dependent antioxidant activity and DNA protective effects of zingerone. At 500 μg/mL, the DPPH radical scavenging activity of zingerone and ascorbic acid as a standard was found to be 86.7 and 94.2 % respectively. At the same concentration, zingerone also showed significant reducing power (absorbance 0.471) compared to that of ascorbic acid (absorbance 0.394). The in vitro toxicity of stannous chloride (SnCl2) was evaluated using genomic and plasmid DNA. SnCl2-induced degradation of genomic DNA was found to occur at a concentration of 0.8 mM onwards with complete degradation at 1.02 mM and above. In the case of plasmid DNA, conversion of supercoiled DNA into the open circular form indicative of DNA nicking activity was observed at a concentration of 0.2 mM onwards; complete conversion was observed at a concentration of 1.02 mM and above. Zingerone was found to confer protection against SnCl2-induced oxidative damage to genomic and plasmid DNA at concentrations of 500 and 750 μg/mL onwards, respectively. This protective effect was further confirmed in the presence of UV/H2O2-a known reactive oxygen species (ROS) generating system-wherein protection by zingerone against ROS-mediated DNA damage was observed at a concentration of 250 μg/mL onwards in a dose-dependent manner. This study clearly indicated the in vitro DNA protective property of zingerone against SnCl2-induced, ROS-mediated DNA damage.

  13. Protective effect of naringin, a citrus flavonoid, against colchicine-induced cognitive dysfunction and oxidative damage in rats.

    PubMed

    Kumar, Anil; Dogra, Samrita; Prakash, Atish

    2010-08-01

    Alzheimer's disease is a neurodegenerative disorder. Central administration of colchicine is well known to cause cognitive impairment and oxidative damage, which simulates sporadic dementia of the Alzheimer type in humans. The present study has been designed to investigate the protective effects of naringin against the colchicine-induced cognitive impairment and oxidative damage in rats. Colchicine (15 microg/5 microL), administered intracerebroventricularly, resulted in poor memory retention in both the Morris water maze and elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant decrease in acetylcholinesterase activity. Naringin (40 and 80 mg/kg, p.o.) treatment was given daily for a period of 25 days beginning 4 days prior to colchicine administration. Chronic treatment with naringin caused significant improvement in the cognitive performance and attenuated oxidative damage, as evidenced by lowering of malondialdehyde level and nitrite concentration and restoration of superoxide dismutase, catalase, glutathione S-transferase, and reduced glutathione levels, and acetylcholinesterase activity compared to control. The present study highlights the therapeutic potential of naringin against colchicine-induced cognitive impairment and associated oxidative damage. PMID:20673063

  14. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1. Volume 5: Analysis of core damage frequency from seismic events during mid-loop operations

    SciTech Connect

    Budnitz, R.J.; Davis, P.R.; Ravindra, M.K.; Tong, W.H.

    1994-08-01

    In 1989 the US Nuclear Regulatory Commission (NRC) initiated an extensive program to examine carefully the potential risks during low-power and shutdown operations. The program included two parallel projects, one at Brookhaven National Laboratory studying a pressurized water reactor (Surry Unit 1) and the other at Sandia National Laboratories studying a boiling water reactor (Grand Gulf). Both the Brookhaven and Sandia projects have examined only accidents initiated by internal plant faults--so-called ``internal initiators.`` This project, which has explored the likelihood of seismic-initiated core damage accidents during refueling shutdown conditions, is complementary to the internal-initiator analyses at Brookhaven and Sandia. This report covers the seismic analysis at Surry Unit 1. All of the many systems modeling assumptions, component non-seismic failure rates, and human error rates that were used in the internal-initiator study at Surry have been adopted here, so that the results of the two studies can be as comparable as possible. Both the Brookhaven study and this study examine only two shutdown plant operating states (POSs) during refueling outages at Surry, called POS 6 and POS 10, which represent mid-loop operation before and after refueling, respectively. This analysis has been limited to work analogous to a level-1 seismic PRA, in which estimates have been developed for the core-damage frequency from seismic events during POSs 6 and 10. The results of the analysis are that the core-damage frequency of earthquake-initiated accidents during refueling outages in POS 6 and POS 10 is found to be low in absolute terms, less than 10{sup {minus}6}/year.

  15. Evaluation of potential severe accidents during low power and shutdown operations at Grand Gulf, Unit 1. Volume 5: Analysis of core damage frequency from seismic events for plant operational state 5 during a refueling outage

    SciTech Connect

    Budnitz, R.J.; Davis, P.R.; Ravindra, M.K.; Tong, W.H.

    1994-08-01

    In 1989 the US Nuclear Regulatory Commission (NRC) initiated an extensive program to examine carefully the potential risks during low-power and shutdown operations. The program included two parallel projects, one at Sandia National Laboratories studying a boiling water reactor (Grand Gulf), and the other at Brookhaven National Laboratory studying a pressurized water reactor (Surry Unit 1). Both the Sandia and Brookhaven projects have examined only accidents initiated by internal plant faults---so-called ``internal initiators.`` This project, which has explored the likelihood of seismic-initiated core damage accidents during refueling outage conditions, is complementary to the internal-initiator analyses at Brookhaven and Sandia. This report covers the seismic analysis at Grand Gulf. All of the many systems modeling assumptions, component non-seismic failure rates, and human effort rates that were used in the internal-initiator study at Grand Gulf have been adopted here, so that the results of the study can be as comparable as possible. Both the Sandia study and this study examine only one shutdown plant operating state (POS) at Grand Gulf, namely POS 5 representing cold shutdown during a refueling outage. This analysis has been limited to work analogous to a level-1 seismic PRA, in which estimates have been developed for the core-damage frequency from seismic events during POS 5. The results of the analysis are that the core-damage frequency for earthquake-initiated accidents during refueling outages in POS 5 is found to be quite low in absolute terms, less than 10{sup {minus}7}/year.

  16. The determinants of fishing vessel accident severity.

    PubMed

    Jin, Di

    2014-05-01

    The study examines the determinants of fishing vessel accident severity in the Northeastern United States using vessel accident data from the U.S. Coast Guard for 2001-2008. Vessel damage and crew injury severity equations were estimated separately utilizing the ordered probit model. The results suggest that fishing vessel accident severity is significantly affected by several types of accidents. Vessel damage severity is positively associated with loss of stability, sinking, daytime wind speed, vessel age, and distance to shore. Vessel damage severity is negatively associated with vessel size and daytime sea level pressure. Crew injury severity is also positively related to the loss of vessel stability and sinking.

  17. The determinants of fishing vessel accident severity.

    PubMed

    Jin, Di

    2014-05-01

    The study examines the determinants of fishing vessel accident severity in the Northeastern United States using vessel accident data from the U.S. Coast Guard for 2001-2008. Vessel damage and crew injury severity equations were estimated separately utilizing the ordered probit model. The results suggest that fishing vessel accident severity is significantly affected by several types of accidents. Vessel damage severity is positively associated with loss of stability, sinking, daytime wind speed, vessel age, and distance to shore. Vessel damage severity is negatively associated with vessel size and daytime sea level pressure. Crew injury severity is also positively related to the loss of vessel stability and sinking. PMID:24473412

  18. Protective effects of acetaminophen on ibuprofen-induced gastric mucosal damage in rats with associated suppression of matrix metalloproteinase.

    PubMed

    Fukushima, Eriko; Monoi, Noriyuki; Mikoshiba, Shigeo; Hirayama, Yutaka; Serizawa, Tetsushi; Adachi, Kiyo; Koide, Misao; Ohdera, Motoyasu; Murakoshi, Michiaki; Kato, Hisanori

    2014-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal damage as a side effect. Acetaminophen, widely used as an analgesic and antipyretic drug, has gastroprotective effects against gastric lesions induced by absolute ethanol and certain NSAIDs. However, the mechanisms that underlie the gastroprotective effects of acetaminophen have not yet been clarified. In the present study, we examined the role and protective mechanism of acetaminophen on ibuprofen-induced gastric damage in rats. Ibuprofen and acetaminophen were administered orally, and the gastric mucosa was macroscopically examined 4 hours later. Acetaminophen decreased ibuprofen-induced gastric damage in a dose-dependent manner. To investigate the mechanisms involved, transcriptome analyses of the ibuprofen-damaged gastric mucosa were performed in the presence and absence of acetaminophen. Ingenuity pathway analysis (IPA) software revealed that acetaminophen suppressed the pathways related to cellular assembly and inflammation, whereas they were highly activated by ibuprofen. On the basis of gene classifications from the IPA Knowledge Base, we identified the following five genes that were related to gastric damage and showed significant changes in gene expression: interleukin-1β (IL-1β), chemokine (C-C motif) ligand 2 (CCL2), matrix metalloproteinase-10 (MMP-10), MMP-13, and FBJ osteosarcoma oncogene (FOS). Expression of these salient genes was confirmed using real-time polymerase chain reaction. The expression of MMP-13 was the most reactive to the treatments, showing strong induction by ibuprofen and suppression by acetaminophen. Moreover, MMP-13 inhibitors decreased ibuprofen-induced gastric damage. In conclusion, these results suggest that acetaminophen decreases ibuprofen-induced gastric mucosal damage and that the suppression of MMP-13 may play an important role in the gastroprotective effects of acetaminophen.

  19. Protective activity of butyrate on hydrogen peroxide-induced DNA damage in isolated human colonocytes and HT29 tumour cells.

    PubMed

    Rosignoli, P; Fabiani, R; De Bartolomeo, A; Spinozzi, F; Agea, E; Pelli, M A; Morozzi, G

    2001-10-01

    Epidemiological studies support the involvement of short-chain fatty acids (SCFA) in colon physiology and the protective role of butyrate on colon carcinogenesis. Among the possible mechanisms by which butyrate may exert its anti-carcinogenicity an antioxidant activity has been recently suggested. We investigated the effects of butyrate and mixtures of SCFA (butyrate, propionate and acetate) on DNA damage induced by H(2)O(2) in isolated human colonocytes and in two human colon tumour cell lines (HT29 and HT29 19A). Human colonocytes were isolated from endoscopically obtained samples and the DNA damage was assessed by the comet assay. H(2)O(2) induced DNA damage in normal colonocytes in a dose-dependent manner which was statistically significant at concentrations over 10 microM. At 15 microM H(2)O(2) DNA damage in HT29 and HT29 19A cells was significantly lower than that observed in normal colonocytes (P < 0.01). Pre-incubation of the cells with physiological concentrations of butyrate (6.25 and 12.5 mM) reduced H(2)O(2) (15 microM) induced damage by 33 and 51% in human colonocytes, 45 and 75% in HT29 and 30 and 80% in HT29 19A, respectively. Treatment of cells with a mixture of 25 mM acetate + 10.4 mM propionate + 6.25 mM butyrate did not induce DNA damage, while a mixture of 50 mM acetate + 20.8 mM propionate + 12.5 mM butyrate was weakly genotoxic only towards normal colonocytes. However, both mixtures were able to reduce the H(2)O(2)-induced DNA damage by about 50% in all cell types. The reported protective effect of butyrate might be important in pathogenetic mechanisms mediated by reactive oxygen species, and aids understanding of the apparent protection toward colorectal cancer exerted by dietary fibres, which enhance the butyrate bioavailability in the colonic mucosa. PMID:11577008

  20. The effect of phytosterol protects rats against 4-nitrophenol-induced liver damage.

    PubMed

    Chen, Jiaqin; Song, Meiyan; Li, Yansen; Zhang, Yonghui; Taya, Kazuyoshi; Li, ChunMei

    2016-01-01

    We investigated the effect of phytosterol (PS) in regard to liver damage induced by 4-nitrophenol (PNP). Twenty rats were randomly divided into four groups (Control, PS, PNP, and PNP+PS). The PS and PNP+PS groups were pretreated with PS for one week. The PNP and PNP+PS groups were injected subcutaneously with PNP for 28 days. The control group received a basal diet and was injected with vehicle alone. Treatment with PS prevented the elevation of the total bilirubin levels, as well as an increase in serum alkaline transaminase and aspartate transaminase, which are typically caused by PNP-induced liver damage. Histopathologically showed that liver damage was significantly mitigated by PS treatment. However, there was no significant change in antioxidant enzyme activities, and the Nrf2-antioxidant system was not activated after treatment with PS. These results suggest that PS could mitigate liver damage induced by PNP, but does not enhance antioxidant capacity. PMID:26748050

  1. The protective effect of M40401, a superoxide dismutase mimetic, on post-ischemic brain damage in Mongolian gerbils

    PubMed Central

    Mollace, Vincenzo; Iannone, Michelangelo; Muscoli, Carolina; Palma, Ernesto; Granato, Teresa; Modesti, Andrea; Nisticò, Robert; Rotiroti, Domenicantonio; Salvemini, Daniela

    2003-01-01

    Background Overproduction of free radical species has been shown to occur in brain tissues after ischemia-reperfusion injury. However, most of free radical scavengers known to antagonize oxidative damage (e.g. superoxide dismutase, catalase), are unable to protect against ischemia-reperfusion brain injury when given in vivo, an effect mainly due to their difficulty to gain access to brain tissues. Here we studied the effect of a low molecular weight superoxide dismutase mimetic (M40401) in brain damage subsequent to ischemia-reperfusion injury in Mongolian gerbils. Results In animals undergoing ischemia-reperfusion injury, neuropathological and ultrastructural changes were monitored for 1–7 days either in the presence or in the absence of M40401 after bilateral common carotid artery occlusion (BCCO). Administration of M40401 (1–40 mg/kg, given i.p. 1 h after BCCO) protected against post-ischemic, ultrastructural and neuropathological changes occurring within the hippocampal CA1 area. The protective effect of M40401 was associated with a significant reduction of the levels of malondialdehyde (MDA; a marker of lipid peroxidation) in ischemic brain tissues after ischemia-reperfusion. Conclusion Taken together, these results demonstrate that M40401 provides protective effects when given early after the induction of ischemia-reperfusion of brain tissues and suggest the possible use of such compounds in the treatment of neurological dysfunction subsequent to cerebral flow disturbances. PMID:12809567

  2. Concentration-Dependent Protection by Ethanol Extract of Propolis against γ-Ray-Induced Chromosome Damage in Human Blood Lymphocytes

    PubMed Central

    Montoro, A.; Barquinero, J. F.; Almonacid, M.; Montoro, A.; Sebastià, N.; Verdú, G.; Sahuquillo, V.; Serrano, J.; Saiz, M.; Villaescusa, J. I.; Soriano, J. M.

    2011-01-01

    Radioprotection with natural products may be relevant to the mitigation of ionizing radiation-induced damage in mammalian systems; in this sense, propolis extracts have shown effects such as antioxidant, antitumoral, anti-inflammatory, and immunostimulant. We report for the first time a cytogenetic study to evaluate the radioprotective effect, in vitro, of propolis against radiation-induced chromosomal damage. Lymphocytes were cultured with increasing concentrations of ethanol extract of propolis (EEP), including 20, 40, 120, 250, 500, 750, 1000, and 2000 μg mL−1 and then exposed to 2 Gy γ-rays. A significant and concentration-dependent decrease is observed in the frequency of chromosome aberrations in samples treated with EEP. The protection against the formation of dicentrics was concentration-dependent, with a maximum protection at 120 μg mL−1 of EEP. The observed frequency of dicentrics is described as negative exponential function, indicating that the maximum protectible fraction of dicentrics is approximately 44%. Free radical scavenging and antioxidant activities are the mechanisms that these substances use to protect cells from ionizing radiation. PMID:20981159

  3. Alkali production associated with malolactic fermentation by oral streptococci and protection against acid, oxidative, or starvation damage.

    PubMed

    Sheng, Jiangyun; Baldeck, Jeremiah D; Nguyen, Phuong T M; Quivey, Robert G; Marquis, Robert E

    2010-07-01

    Alkali production by oral streptococci is considered important for dental plaque ecology and caries moderation. Recently, malolactic fermentation (MLF) was identified as a major system for alkali production by oral streptococci, including Streptococcus mutans. Our major objectives in the work described in this paper were to further define the physiology and genetics of MLF of oral streptococci and its roles in protection against metabolic stress damage. L-Malic acid was rapidly fermented to L-lactic acid and CO(2) by induced cells of wild-type S. mutans, but not by deletion mutants for mleS (malolactic enzyme) or mleP (malate permease). Mutants for mleR (the contiguous regulator gene) had intermediate capacities for MLF. Loss of capacity to catalyze MLF resulted in loss of capacity for protection against lethal acidification. MLF was also found to be protective against oxidative and starvation damage. The capacity of S. mutans to produce alkali from malate was greater than its capacity to produce acid from glycolysis at low pH values of 4 or 5. MLF acted additively with the arginine deiminase system for alkali production by Streptococcus sanguinis, but not with urease of Streptococcus salivarius. Malolactic fermentation is clearly a major process for alkali generation by oral streptococci and for protection against environmental stresses.

  4. Lunasin peptide purified from Solanum nigrum L. protects DNA from oxidative damage by suppressing the generation of hydroxyl radical via blocking fenton reaction.

    PubMed

    Jeong, Jin Boo; De Lumen, Ben O; Jeong, Hyung Jin

    2010-07-01

    Oxidative DNA damage is the most critical factor implicated in carcinogenesis and other disorders. However, the protective effects of lunasin against oxidative DNA damage have not yet reported. In this study, we report here the protective effect of lunasin purified from Solanum nigrum L. against oxidative DNA. Lunasin protected DNA from the oxidative damage induced by Fe(2+) ion and hydroxyl radical. To better understand the mechanism for the protective effect of lunasin against DNA damage, the abilities to chelate Fe(2+), scavenge the generated hydroxyl radical and block the generation of hydroxyl radical were evaluated. Although it did not scavenge generated hydroxyl radical, lunasin blocked the generation of hydroxyl radical by chelating Fe(2+) ion. We conclude that lunasin protects DNA from oxidation by blocking fenton reaction between Fe(2+) and H(2)O(2) by chelating Fe(2+) and that consumption of lunasin may play an important role in the chemoprevention for the oxidative carcinogenesis. PMID:20083341

  5. Antioxidant activity of herbaceous plant extracts protect against hydrogen peroxide-induced DNA damage in human lymphocytes

    PubMed Central

    2013-01-01

    Background Herbaceous plants containing antioxidants can protect against DNA damage. The purpose of this study was to evaluate the antioxidant substances, antioxidant activity, and protection of DNA from oxidative damage in human lymphocytes induced by hydrogen peroxide (H2O2). Our methods used acidic methanol and water extractions from six herbaceous plants, including Bidens alba (BA), Lycium chinense (LC), Mentha arvensis (MA), Plantago asiatica (PA), Houttuynia cordata (HC), and Centella asiatica (CA). Methods Antioxidant compounds such as flavonol and polyphenol were analyzed. Antioxidant activity was determined by the inhibition percentage of conjugated diene formation in a linoleic acid emulsion system and by trolox-equivalent antioxidant capacity (TEAC) assay. Their antioxidative capacities for protecting human lymphocyte DNA from H2O2-induced strand breaks was evaluated by comet assay. Results The studied plants were found to be rich in flavonols, especially myricetin in BA, morin in MA, quercetin in HC, and kaemperol in CA. In addition, polyphenol abounded in BA and CA. The best conjugated diene formation inhibition percentage was found in the acidic methanolic extract of PA. Regarding TEAC, the best antioxidant activity was generated from the acidic methanolic extract of HC. Water and acidic methanolic extracts of MA and HC both had better inhibition percentages of tail DNA% and tail moment as compared to the rest of the tested extracts, and significantly suppressed oxidative damage to lymphocyte DNA. Conclusion Quercetin and morin are important for preventing peroxidation and oxidative damage to DNA, and the leaves of MA and HC extracts may have excellent potential as functional ingredients representing potential sources of natural antioxidants. PMID:24279749

  6. Histaminergic neurons protect the developing hippocampus from kainic acid-induced neuronal damage in an organotypic coculture system.

    PubMed

    Kukko-Lukjanov, Tiina-Kaisa; Soini, Sanna; Taira, Tomi; Michelsen, Kimmo A; Panula, Pertti; Holopainen, Irma E

    2006-01-25

    The central histaminergic neuron system inhibits epileptic seizures, which is suggested to occur mainly through histamine 1 (H1) and histamine 3 (H3) receptors. However, the importance of histaminergic neurons in seizure-induced cell damage is poorly known. In this study, we used an organotypic coculture system and confocal microscopy to examine whether histaminergic neurons, which were verified by immunohistochemistry, have any protective effect on kainic acid (KA)-induced neuronal damage in the developing hippocampus. Fluoro-Jade B, a specific marker for degenerating neurons, indicated that, after the 12 h KA (5 microM) treatment, neuronal damage was significantly attenuated in the hippocampus cultured together with the posterior hypothalamic slice containing histaminergic neurons [HI plus HY (POST)] when compared with the hippocampus cultured alone (HI) or with the anterior hypothalamus devoid of histaminergic neurons. Moreover, alpha-fluoromethylhistidine, an inhibitor of histamine synthesis, eliminated the neuroprotective effect in KA-treated HI plus HY (POST), and extracellularly applied histamine (1 nM to 100 microM) significantly attenuated neuronal damage only at 1 nM concentration in HI. After the 6 h KA treatment, spontaneous electrical activity registered in the CA1 subregion contained significantly less burst activity in HI plus HY (POST) than in HI. Finally, in KA-treated slices, the H3 receptor antagonist thioperamide enhanced the neuroprotective effect of histaminergic neurons, whereas the H1 receptor antagonists triprolidine and mepyramine dose-dependently decreased the neuroprotection in HI plus HY (POST). Our results suggest that histaminergic neurons protect the developing hippocampus from KA-induced neuronal damage, with regulation of neuronal survival being at least partly mediated through H1 and H3 receptors.

  7. Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage

    PubMed Central

    Srivastava, Amit Kumar; Bhatnagar, Priyanka; Singh, Madhulika; Mishra, Sanjay; Kumar, Pradeep; Shukla, Yogeshwer; Gupta, Kailash Chand

    2013-01-01

    In spite of proficient results of several phytochemicals in preclinical settings, the conversion rate from bench to bedside is not very encouraging. Many reasons are attributed to this limited success, including inefficient systemic delivery and bioavailability under in vivo conditions. To achieve improved efficacy, polyphenolic constituents of black (theaflavin [TF]) and green (epigallocatechin-3-gallate [EGCG]) tea in poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) were entrapped with entrapment efficacy of ~18% and 26%, respectively. Further, their preventive potential against 7,12-dimethylbenzanthracene (DMBA)-induced DNA damage in mouse skin using DNA alkaline unwinding assay was evaluated. Pretreatment (topically) of mouse skin with either TF or EGCG (100 μg/mouse) doses exhibits protection of 45.34% and 28.32%, respectively, against DMBA-induced DNA damage. However, pretreatment with TF-loaded PLGA-NPs protects against DNA damage 64.41% by 1/20th dose of bulk, 71.79% by 1/10th dose of bulk, and 72.46% by 1/5th dose of bulk. Similarly, 51.28% (1/20th of bulk), 57.63% (1/10th of bulk), and 63.14% (1/5th of bulk) prevention was noted using EGCG-loaded PLGA-NP doses. These results showed that tea polyphenol-loaded PLGA-NPs have ~30-fold dose-advantage than bulk TF or EGCG doses. Additionally, TF- or EGCG-loaded PLGA-NPs showed significant potential for induction of DNA repair genes (XRCC1, XRCC3, and ERCC3) and suppression of DNA damage responsive genes (p53, p21, MDM2, GADD45α, and COX-2) as compared with respective bulk TF or EGCG doses. Taken together, TF- or EGCG-loaded PLGA-NPs showed a superior ability to prevent DMBA-induced DNA damage at much lower concentrations, thus opening a new dimension in chemoprevention research. PMID:23717041

  8. Red blood cells protect endothelial cells against H/sub 2/O/sub 2/-mediated but not hyperoxia-induced damage

    SciTech Connect

    Tsan, M.F.; White, J.E.

    1988-07-01

    We studied the effect of intact red blood cells on the exogenous H/sub 2/O/sub 2/-mediated damage as well as on the hyperoxia-induced injury of cultured endothelial cells. Red blood cells protected endothelial cells against H/sub 2/O/sub 2/-mediated injury efficiently, but had no effect on the hyperoxia-induced damage. Failure of red blood cells to protect endothelial cells against hyperoxia-induced injury was not due to hemolysis. Furthermore, hyperoxia-exposed red blood cells were still capable of protecting endothelial cells against H/sub 2/O/sub 2/-mediated damage.

  9. Acetyl salicylic acid protected against heat stress damage in chicken myocardial cells and may associate with induced Hsp27 expression.

    PubMed

    Wu, Di; Xu, Jiao; Song, Erbao; Tang, Shu; Zhang, Xiaohui; Kemper, N; Hartung, J; Bao, Endong

    2015-07-01

    We investigated whether acetyl salicylic acid (ASA) protects chicken myocardial cells from heat stress-mediated damage in vivo and whether the induction of Hsp27 expression is connected with this function. Pathological changes, damage-related enzyme levels, and Hsp27 expression were studied in chickens following heat stress (40 ± 1 °C for 0, 1, 2, 3, 5, 7, 10, 15, or 24 h, respectively) with or without ASA administration (1 mg/kg BW, 2 h prior). Appearance of pathological lesions such as degenerations and karyopyknosis as well as the myocardial damage-related enzyme activation indicated that heat stress causes considerable injury to the myocardial cells in vivo. Myocardial cell injury was most serious in chickens exposed to heat stress without prior ASA administration; meanwhile, ASA pretreatment acted protective function against high temperature-induced injury. Hsp27 expression was induced under all experimental conditions but was one-fold higher in the ASA-pretreated animals (0.3138 ± 0.0340 ng/mL) than in untreated animals (0.1437 ± 0.0476 ng/mL) 1 h after heat stress exposure, and such an increase was sustained over the length of the experiment. Our findings indicate that pretreatment with ASA protects chicken myocardial cells from acute heat stress in vivo with almost no obvious side effects, and this protection may involve an enhancement of Hsp27 expression. However, the detailed mechanisms underlying this effect require further investigation.

  10. Protective effect of C. sativa leaf extract against UV mediated-DNA damage in a human keratinocyte cell line.

    PubMed

    Almeida, I F; Pinto, A S; Monteiro, C; Monteiro, H; Belo, L; Fernandes, J; Bento, A R; Duarte, T L; Garrido, J; Bahia, M F; Sousa Lobo, J M; Costa, P C

    2015-03-01

    Toxic effects of ultraviolet (UV) radiation on skin include protein and lipid oxidation, and DNA damage. The latter is known to play a major role in photocarcinogenesis and photoaging. Many plant extracts and natural compounds are emerging as photoprotective agents. Castanea sativa leaf extract is able to scavenge several reactive species that have been associated to UV-induced oxidative stress. The aim of this work was to analyze the protective effect of C. sativa extract (ECS) at different concentrations (0.001, 0.01, 0.05 and 0.1 μg/mL) against the UV mediated-DNA damage in a human keratinocyte cell line (HaCaT). For this purpose, the cytokinesis-block micronucleus assay was used. Elucidation of the protective mechanism was undertaken regarding UV absorption, influence on (1)O₂ mediated effects or NRF2 activation. ECS presented a concentration-dependent protective effect against UV-mediated DNA damage in HaCaT cells. The maximum protection afforded (66.4%) was achieved with the concentration of 0.1 μg/mL. This effect was found to be related to a direct antioxidant effect (involving (1)O₂) rather than activation of the endogenous antioxidant response coordinated by NRF2. Electrochemical studies showed that the good antioxidant capacity of the ECS can be ascribed to the presence of a pool of different phenolic antioxidants. No genotoxic or phototoxic effects were observed after incubation of HaCaT cells with ECS (up to 0.1 μg/mL). Taken together these results reinforce the putative application of this plant extract in the prevention/minimization of UV deleterious effects on skin.

  11. Low concentrations of flavonoids are protective in rat H4IIE cells whereas high concentrations cause DNA damage and apoptosis.

    PubMed

    Wätjen, Wim; Michels, Gudrun; Steffan, Bärbel; Niering, Petra; Chovolou, Yvonni; Kampkötter, Andreas; Tran-Thi, Quynh-Hoa; Proksch, Peter; Kahl, Regine

    2005-03-01

    Dietary flavonoids possess a wide spectrum of biochemical and pharmacological actions and are assumed to protect human health. These actions, however, can be antagonistic, and some health claims are mutually exclusive. The antiapoptotic actions of flavonoids may protect against neurodegenerative diseases, whereas their proapoptotic actions could be used for cancer chemotherapy. This study was undertaken to determine whether a cytoprotective dose range of flavonoids could be differentiated from a cytotoxic dose range. Seven structurally related flavonoids were tested for their ability to protect H4IIE rat hepatoma cells against H(2)O(2)-induced damage on the one hand and to induce cellular damage on their own on the other hand. All flavonoids proved to be good antioxidants in a cell-free assay. However, their pharmacologic activity did not correlate with in vitro antioxidant potential but rather with cellular uptake. For quercetin and fisetin, which were readily taken up into the cells, protective effects against H(2)O(2)-induced cytotoxicity, DNA strand breaks, and apoptosis were detected at concentrations as low as 10-25 micromol/L. On the other hand, these flavonoids induced cytotoxicity, DNA strand breaks, oligonucleosomal DNA fragmentation, and caspase activation at concentrations between 50 and 250 micromol/L. Published data on quercetin pharmacokinetics in humans suggest that a dietary supplement of 1-2 g of quercetin may result in plasma concentrations between 10 and 50 micromol/L. Our data suggest that cytoprotective concentrations of some flavonoids are lower by a factor of 5-10 than their DNA-damaging and proapoptotic concentrations.

  12. 49 CFR 192.355 - Customer meters and regulators: Protection from damage.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Customer meters and regulators: Protection from... Meters, Service Regulators, and Service Lines § 192.355 Customer meters and regulators: Protection from... that houses a customer meter or regulator at a place where vehicular traffic is anticipated, must...

  13. 49 CFR 192.355 - Customer meters and regulators: Protection from damage.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Customer meters and regulators: Protection from... Meters, Service Regulators, and Service Lines § 192.355 Customer meters and regulators: Protection from... that houses a customer meter or regulator at a place where vehicular traffic is anticipated, must...

  14. 49 CFR 192.355 - Customer meters and regulators: Protection from damage.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Customer meters and regulators: Protection from... Meters, Service Regulators, and Service Lines § 192.355 Customer meters and regulators: Protection from... that houses a customer meter or regulator at a place where vehicular traffic is anticipated, must...

  15. Anti-oxidative protection against iron overload-induced liver damage in mice by Cajanus cajan (L.) Millsp. leaf extract.

    PubMed

    Sarkar, Rhitajit; Hazra, Bibhabasu; Mandal, Nripendranath

    2013-02-01

    In view of the contribution of iron deposition in the oxidative pathologic process of liver disease, the potential of 70% methanolic extract of C. cajan leaf (CLME) towards antioxidative protection against iron-overload-induced liver damage in mice has been investigated. DPPH radical scavenging and protection of Fenton reaction induced DNA damage was conducted in vitro. Post oral administration of CLME to iron overloaded mice, the levels of antioxidant and serum enzymes, hepatic iron, serum ferritin, lipid peroxidation, and protein carbonyl and hydroxyproline contents were measured, in comparison to deferasirox treated mice. Oral treatment of the plant extract effectively lowered the elevated levels of liver iron, lipid peroxidation, protein carbonyl and hydroxyproline. There was notable increment in the dropped levels of hepatic antioxidants. The dosage of the plant extract not only made the levels of serum enzymes approach normal value, but also counteracted the overwhelmed serum ferritin level. The in vitro studies indicated potential antioxidant activity of CLME. The histopathological observations also substantiated the ameliorative function of the plant extract. Accordingly, it is suggested that Cajanus cajan leaf can be a useful herbal remedy to suppress oxidative damage caused by iron overload. PMID:23923610

  16. Hemerythrins in the microaerophilic bacterium Campylobacter jejuni help protect key iron–sulphur cluster enzymes from oxidative damage

    PubMed Central

    Kendall, John J; Barrero-Tobon, Angelica M; Hendrixson, David R; Kelly, David J

    2014-01-01

    Microaerophilic bacteria are adapted to low oxygen environments, but the mechanisms by which their growth in air is inhibited are not well understood. The citric acid cycle in the microaerophilic pathogen Campylobacter jejuni is potentially vulnerable, as it employs pyruvate and 2-oxoglutarate:acceptor oxidoreductases (Por and Oor), which contain labile (4Fe-4S) centres. Here, we show that both enzymes are rapidly inactivated after exposure of cells to a fully aerobic environment. We investigated the mechanisms that might protect enzyme activity and identify a role for the hemerythrin HerA (Cj0241). A herA mutant exhibits an aerobic growth defect and reduced Por and Oor activities after exposure to 21% (v/v) oxygen. Slow anaerobic recovery of these activities after oxygen damage was observed, but at similar rates in both wild-type and herA strains, suggesting the role of HerA is to prevent Fe-S cluster damage, rather than promote repair. Another hemerythrin (HerB; Cj1224) also plays a protective role. Purified HerA and HerB exhibited optical absorption, ligand binding and resonance Raman spectra typical of μ-oxo-bridged di-iron containing hemerythrins. We conclude that oxygen lability and poor repair of Por and Oor are major contributors to microaerophily in C. jejuni; hemerythrins help prevent enzyme damage microaerobically or during oxygen transients. PMID:24245612

  17. Protective role of diallyl tetrasulfide on cadmium-induced testicular damage in adult rats: a biochemical and histological study.

    PubMed

    Ponnusamy, Murugavel; Pari, Leelavinothan

    2011-06-01

    Cadmium (Cd)-induced oxidative damage is the most serious problem that leads to reproductive system failure in both human and animals. Our previous studies indicate that diallyl tetrasulfide (DTS) from garlic has the cytoprotective and antioxidant activity against Cd-induced toxicity in vivo and in vitro. The present investigation was carried out to find the influence of DTS on peroxidative damage induced by Cd in rat testes. The Cd-exposed rat testis showed a significant (p < 0.05) decrease in testes to body weight ratio, along with a significant (p < 0.05) increase in Cd accumulation, lipid peroxidation and protein carbonyl levels. In Cd-exposed rats, we also observed a significant (p < 0.05) decrease in the activities of antioxidant (superoxide dismutase, catalase and glutathione peroxidase) and glutathione metabolizing (glutathione-S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase) enzymes as well as reduced levels of non-enzymic (reduced glutathione, ascorbate and total sulphydryl groups) antioxidants. In contrast, treatment with DTS (40 mg/kg body weight orally) significantly (p < 0.05) reduced the accumulation of Cd and lipid peroxidation markers and also significantly improved the activities of antioxidant defense system in testes. Testicular protection by DTS is further substantiated by remarkable reduction of Cd-induced pathological changes. Our study has revealed that DTS renders protection against Cd-induced testicular injury by reducing Cd-mediated oxidative damage. PMID:21245201

  18. Protective effects of carvacrol and pomegranate against methotrexate-induced intestinal damage in rats

    PubMed Central

    Türkcü, Gül; Alabalık, Ulaş; Keleş, Ayşe Nur; Bozkurt, Mehtap; İbiloğlu, İbrahim; Fırat, Uğur; Büyükbayram, Hüseyin

    2015-01-01

    Objective: The purpose of this experimental study was to evaluate the efficacy of carvacrol (CVR) and pomegranate (PMG) against methotrexate (MTX)-induced intestinal damage using histopathological and immunohistochemical techniques. Methods: Thirty-two male Sprague-Dawley rats, weighing 195-250 g, were divided into four groups: control, MTX treatment alone, MTX plus CVR and MTX plus PMG. A single dose of CVR (73 mg/kg) was administered intraperitoneally to group III on the first day of the experiment, PMG (225 mg/kg/day) was administered orogastrically (with a gavage needle) once daily for 7 days and a single dose of MTX (20 mg/kg) was administered intraperitoneally on the second day of the experiment. Intestinal tissues were obtained on 8th day, and examined for villus damage, crypt damage, and inflammation. Ki-67 and Caspase 3 staining was used for immunohistochemical evaluation. Results: MTX treatment induced villus shortening and fusion, epithelial atrophy, crypt loss, inflammatory infiltrate in the lamina propria, and goblet cell depletion. The CVR and PMG decreased the severity of intestinal damage caused by MTX treatment. In the MTX-received group, significant inflammatory cell infiltration was observed in the lamina propria. Compared to the MTX-received group, the PMG and CVR groups showed less villus and crypt damage and less inflammation in the lamina propria. Fewer Ki-67 positive cells were observed in the crypts of the MTX-received groups compared to the control group. There were more Ki-67 positive cells in the CVR and PMG groups compared to MTX group. The MTX-received group exhibited more caspase-3 positive cells than the control group, and the number of caspase-3 positive cells were decreased in the CVR and PMG treated groups. Conclusion: This study is the first to show that PMG and CVR decrease MTX-related damage and apoptotic activity in intestinal tissue. PMID:26629037

  19. 50 CFR 25.72 - Reporting of accidents.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., but in no event later than 24 hours after the accident, by the persons involved, to the refuge manager... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Reporting of accidents. 25.72 Section 25... Reporting of accidents. Accidents involving damage to property, injury to the public or injury to...

  20. 50 CFR 25.72 - Reporting of accidents.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., but in no event later than 24 hours after the accident, by the persons involved, to the refuge manager... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Reporting of accidents. 25.72 Section 25... Reporting of accidents. Accidents involving damage to property, injury to the public or injury to...

  1. New regulations for radiation protection for work involving radioactive fallout emitted by the TEPCO Fukushima Daiichi APP accident: application expansion to recovery and reconstruction work.

    PubMed

    Yasui, Shojiro

    2014-01-01

    The accident at the Fukushima Daiichi Atomic Power Plant that accompanied the Great East Japan Earthquake on March 11, 2011 released a large amount of radioactive material. To rehabilitate the contaminated areas, the government of Japan decided to carry out decontamination work. In April 2012, the Nuclear Emergency Response Headquarters (NERH) started dividing the restricted areas into three sub-areas based on the ambient dose rate. In accordance with the rearrangement of the restricted area, NERH decided to allow resumption of business activities, including manufacturing and farming, as well as operation of hospitals, welfare facilities, and shops and related subordinate tasks, such as maintenance, repair, and transportation. As a result, the government needed regulations for radiation protection for workers engaged in those activities. The issues that arose in the deliberation of the regulations were distilled into two points: 1) whether radiation protection systems established for a planned exposure situation should apply to construction and agricultural work activities in an existing exposure situation, and 2) how to simplify the regulation in accordance with the nature of the work activities. Further research and development concerning the following issues are warranted: a) the relationship between the radioactive concentrations of materials handled and the risk of internal exposure, and b) the relationship between the radioactive concentration of the soil and the surface contamination level.

  2. Analysis of damaging effects of laser-plasma accelerated shrapnels on protecting glass shield

    NASA Astrophysics Data System (ADS)

    Martinkova, Michaela; Kalal, Milan; Shmatov, Mikhail L.

    2013-11-01

    Analysis of the damage caused by laser plasma accelerated fragments of metal target was performed. Measured as well as calculated parameters of craters and shrapnel found in BK7 glass blastshield are presented. Method applied for the measurement of parameters of craters is described. Potential damage of optical elements by the so-called striking cores (high-velocity stable objects arising due to collapse of cones or some other target parts toward their axes) that can be generated in IFE related experiments is evaluated.

  3. Protective effect of apricot (Prunus armeniaca L.) on hepatic steatosis and damage induced by carbon tetrachloride in Wistar rats.

    PubMed

    Ozturk, Feral; Gul, Mehmet; Ates, Burhan; Ozturk, I Cetin; Cetin, Asli; Vardi, Nigar; Otlu, Ali; Yilmaz, Ismet

    2009-12-01

    The present study was planned to investigate the protective effect of 10 % and 20 % apricot-containing feed on carbon tetrachloride (CCl4)-induced hepatic steatosis and damage. Adult male Wistar rats (n 42) were divided into six groups of seven each, as follows: control group; CCl4 group; CCl4+10 % apricot group; CCl4+20 % apricot group; 10 % apricot group; 20 % apricot group. All apricot groups were fed with 10 % or 20 % apricot-containing feed for 5 months. CCl4 injections were applied to the CCl4 groups at the dose of 1 mg/kg for 3 d at the end of 5 months. In the CCl4 group, vacuolated hepatocytes and hepatic necrosis were seen, especially in the centrilobular area. Hepatocytes showed an oedematous cytoplasmic matrix, large lipid globules and degenerated organelles. The area of liver injury was found significantly decreased with apricot feeding. Malondialdehyde and total glutathione levels and catalase, superoxide dismutase and glutathione peroxidase activities were significantly changed in the CCl4 group and indicated increased oxidative stress. Apricot feeding decreased this oxidative stress and ameliorated histological damage. We concluded that apricot feeding had beneficial effects on CCl4-induced liver steatosis and damage probably due to its antioxidant nutrient (beta-carotene and vitamin) contents and high radical-scavenging capacity. Dietary intake of apricot can reduce the risk of liver steatosis and damage caused by free radicals.

  4. Protective activity of C-geranylflavonoid analogs from Paulownia tomentosa against DNA damage in 137Cs irradiated AHH-1 cells.

    PubMed

    Moon, Hyung-In; Jeong, Min Ho; Jo, Wol Soon

    2014-09-01

    Radiotherapy is an important form of treatment for a wide range of cancers, but it can damage DNA and cause adverse effects. We investigated if the diplacone analogs of P. tomentosa were radio-protective in a human lymphoblastoid cell line (AHH-1). Four geranylated flavonoids, diplacone, 3'-O-methyl-5'-hydroxydiplacone, 3'-O-methyl-5'-O-methyldiplacone and 3'-O-methyldiplacol, were tested for their antioxidant and radio-protective effects. Diplacone analogs effectively scavenged free radicals and inhibited radiation-induced DNA strand breaks in vitro. They significantly decreased levels of reactive oxygen species and cellular DNA damage in 2 Gy-irradiated AHH-1 cells. Glutathione levels and superoxide dismutase activity in irradiated AHH-1 cells increased significantly after treatment with these analogs. The enhanced biological anti-oxidant activity and radioprotective activity of diplacone analogs maintained the survival of irradiated AHH-1 cells in a clonogenic assay. These data suggest that diplacone analogs may protect healthy tissue surrounding tumor cells during radiotherapy to ensure better control of radiotherapy and allow higher doses of radiotherapy to be employed. PMID:25918796

  5. Protective effect of the isoflavone equol against DNA damage induced by ultraviolet radiation to hairless mouse skin.

    PubMed

    Widyarini, Sitarina

    2006-09-01

    Equol, an isoflavonoid metabolite produced from the dietary isoflavone daidzein by the gut microflora in mammals, has been found to protect not only against ultraviolet (UV) radiation-induced cutaneous inflammation and photoimmune suppression, but also have antiphotocarcinogenic properties in mice. Because the state of DNA damage has been correlated with suppression of the immune system and photocarcinogenesis, we have therefore examined the potential of equol to offer protection from solar-simulated UV (SSUV) radiation-induced DNA damage in hairless mice by the immunohistochemical approach using monoclonal antibody specific for cyclobutane pyrimidine dimers (CPDs; H3 antibody). Topical application of 20 microM equol lotion, which was applied both before and after SSUV significantly reduced the number of CPDs. This reduction was evident immediately after SSUV exposure, at 1 h after exposure, and at 24 h after exposure, revealing 54%, 50%, and 26% reduction in CPDs, respectively. When the same concentration was applied for 5 consecutive days after SSUV exposure, there was no significant difference in the reduction of CPDs immediately after SSUV irradiation or at 1 hour afterwards, but there were significant reductions of 23% and 42% at 24 and 48 h after SSUV exposure, respectively. Despite apparently reducing the number of CPDs post-SSUV, topically applied equol did not appear to increase the rate of dimer removal. To conclude, equol applied topically prior to SSUV irradiation offers protection against CPD formation in hairless mice, possibly by acting as a suncreen and thus inhibiting DNA photodamage.

  6. Protective effect of dietary potassium against cardiovascular damage in salt-sensitive hypertension: possible role of its antioxidant action.

    PubMed

    Ando, Katsuyuki; Matsui, Hiromitsu; Fujita, Megumi; Fujita, Toshiro

    2010-01-01

    It is well known that high salt intake induces hypertension and cardiovascular damage, while dietary potassium supplementation counteracts these harmful effects. Actually, the protective effect of potassium is strengthened with excess salt as compared with salt depletion. Although the precise mechanisms have not been fully elucidated, in our previous reports, the antihypertensive effect of dietary potassium was accompanied by sympathetic nerve inhibition in salt-sensitive hypertension. Also, potassium supplement suppressed salt-induced insulin resistance. These effects of dietary potassium can explain its cardio- and vasculo-protective action in addition to the potassium supplementation induced decreased salt-induced rise in blood pressure. On the other hand, salt-sensitive hypertension is associated with reactive oxygen species (ROS) overproduction. Moreover, sympathoexcitation can be induced by central ROS upregulation and insulin resistance can be caused by ROS excess in the target organs of insulin, such as skeletal muscle. Conversely, the seemingly different actions of potassium can be explained by the antioxidant effect of dietary potassium; in our recent studies, potassium supplementation inhibits salt-induced progress of cardiac diastolic dysfunction and vascular neointima formation by cuff placement around arteries, associated with the inhibition of regional ROS overproduction, in salt-sensitive hypertension. Thus, it is possible that dietary potassium protects against salt-induced cardiovascular damage by the reduction of ROS generation and by central sympatholytic action and amelioration of insulin resistance induced through its antioxidant effect.

  7. Protective effects of ethanolic extract of rosemary against lead-induced hepato-renal damage in rabbits.

    PubMed

    Mohamed, Wafaa A M; Abd-Elhakim, Yasmina M; Farouk, Sameh M

    2016-09-01

    In traditional medicine, Rosmarinus officinalis L. leaf is used as a curative herbal therapy for the treatment of several diseases. The protective effects of rosemary in toxic effects of some environmental pollutants are known. However, there is paucity of information about its protective effects on lead acetate (LD) toxicity. To assess the protection of rosemary ethanolic extracts (REE) on LD-induced hepato- and nephro-toxicity, male albino rabbits were treated with REE (30mg/kg) and/or LD (30mg LD/kg) by gavage administration for 30 days. The total phenolic compound content in REE was estimated using Folin-Ciocalteu's assay and phyto-constituents were isolated and identified using gas chromatographic and mass spectrometry (GC-MS) analysis. The protective effect of REE in LD-induced liver and renal dysfunction and blood cells was evaluated by estimating blood biomarkers of liver and renal damage, histological, and biochemical examinations. Antioxidant enzyme activities, lipid peroxidation biomarker, protein and glycogen contents were estimated in both liver and kidney homogenates. The GC-MS analysis revealed that REE is rich in phenolic compounds including camphor, phytol, borneol, caryophyllene oxide, isopulegol, thymol, and verbenone. REE pre-treatment significantly (P<0.05) suppressed levels of LD induced hepatic and renal damage products as well as lipid peroxidation. In contrast, pre-treatment using REE significantly (P<0.05) decreased LD-induced depletion of antioxidant enzymes, protein, and glycogen content. Additionally, REE preserved blood cells and their structure and renal and hepatic architecture. In conclusion, these findings revealed that REE protects from toxic effects of LD possibly through its free radical-scavenging and antioxidant activities.

  8. Protective effects of ethanolic extract of rosemary against lead-induced hepato-renal damage in rabbits.

    PubMed

    Mohamed, Wafaa A M; Abd-Elhakim, Yasmina M; Farouk, Sameh M

    2016-09-01

    In traditional medicine, Rosmarinus officinalis L. leaf is used as a curative herbal therapy for the treatment of several diseases. The protective effects of rosemary in toxic effects of some environmental pollutants are known. However, there is paucity of information about its protective effects on lead acetate (LD) toxicity. To assess the protection of rosemary ethanolic extracts (REE) on LD-induced hepato- and nephro-toxicity, male albino rabbits were treated with REE (30mg/kg) and/or LD (30mg LD/kg) by gavage administration for 30 days. The total phenolic compound content in REE was estimated using Folin-Ciocalteu's assay and phyto-constituents were isolated and identified using gas chromatographic and mass spectrometry (GC-MS) analysis. The protective effect of REE in LD-induced liver and renal dysfunction and blood cells was evaluated by estimating blood biomarkers of liver and renal damage, histological, and biochemical examinations. Antioxidant enzyme activities, lipid peroxidation biomarker, protein and glycogen contents were estimated in both liver and kidney homogenates. The GC-MS analysis revealed that REE is rich in phenolic compounds including camphor, phytol, borneol, caryophyllene oxide, isopulegol, thymol, and verbenone. REE pre-treatment significantly (P<0.05) suppressed levels of LD induced hepatic and renal damage products as well as lipid peroxidation. In contrast, pre-treatment using REE significantly (P<0.05) decreased LD-induced depletion of antioxidant enzymes, protein, and glycogen content. Additionally, REE preserved blood cells and their structure and renal and hepatic architecture. In conclusion, these findings revealed that REE protects from toxic effects of LD possibly through its free radical-scavenging and antioxidant activities. PMID:27449700

  9. Protection against cellular damage in the rat heart by hyperosmotic solutions.

    PubMed

    Harding, R J; Duncan, C J

    1999-10-01

    In this comparative study, rat hearts were perfused at 37 degrees C with three clearly defined protocols: the Ca2+ paradox, the O(2) paradox, and with 20 mM caffeine. Each protocol involved an initial priming (Ca(2+)(0) depletion or anoxia; stage 1) and subsequent full activation (Ca(2+)(0) repletion, caffeine or reoxygenation; stage 2) of the damage system of the sarcolemma. Creatine kinase release in stage 2 was completely inhibited (P < 0.001) in all three protocols when 420 mOsm was added to the perfusion medium throughout the experiments, or only during stage 1, or only during stage 2. Increasing the perfusion pressure in the Ca2+ paradox significantly (P < 0.001) exacerbated creatine kinase release, although this was still completely inhibited at 28 degrees C. Amiloride (1 mM) inhibited creatine kinase release completely at 40 cm of water pressure but only some 50% at 80 cm of water pressure. It is suggested that the transmembrane damage system needs to be uncoupled or deactivated by modifying its relationship with the cytosol or with the underlying cytoskeleton by hyperosmotic cell shrinkage for only one of the stages in all three protocols to block the damage pathway. Increased perfusion pressure has the opposite effect and exacerbates damage. PMID:10527760

  10. The protective effects of Prunus armeniaca L (apricot) against methotrexate-induced oxidative damage and apoptosis in rat kidney.

    PubMed

    Vardi, Nigar; Parlakpinar, Hakan; Ates, Burhan; Cetin, Asli; Otlu, Ali

    2013-09-01

    This study was conducted to evaluate a possible protective role of apricot in apoptotic cell death induced by methotrexate (MTX) and renal damage by different histological and biochemical parameters. Twenty-eight rats were divided into four groups, control, apricot, methotrexate, and apricot + methotrexate. Methotrexate induced renal failure, as shown by significant serum creatinine and urea elevation. Additionally, the results indicated that methotrexate significantly induced lipid peroxidation and reduced antioxidant activities in rats. In contrast, apricot significantly prevented toxic effects of methotrexate via increased catalase, superoxide dismutase, and glutathione levels but decreased formation of malondialdehyde. Also, it was determined that exposure to methotrexate leads to significant histological damage in kidney tissue such as glomerulosclerosis and apoptosis. On the other hand, these effects can be eliminated with apricot diet. These data indicate that apricot may be useful in preventing undesirable effects of MTX such as nephrotoxicity.

  11. On the efficiency of Gore-Tex layer for brain protection from shock wave damage in cranioplasty

    NASA Astrophysics Data System (ADS)

    Saito, T.; Voinovich, P. A.; Nakagawa, A.; Hosseini, S. H. R.; Takayama, K.; Hirano, T.

    2004-11-01

    The effectiveness of a Gore-Tex layer for protecting soft tissue from damage in shock wave therapy is investigated analytically, numerically and experimentally. Analytical considerations based on the fundamentals of wave dynamics and two-dimensional numerical simulations based on the elastodynamic equations are carried out for underwater shock wave propagation and interaction with Gore-Tex membrane models of different complexity. The results clearly demonstrate that considerable attenuation of shock waves with Gore-Tex is due to the air trapped inside the membrane. The experimental results confirm that a Gore-Tex sheet placed in the liquid reduces the transmitted shock wave peak overpressure significantly, by up to two orders of magnitude. Another experimental series reveals what kind of damage in the rat brain tissue can be caused by shock waves of different intensity.

  12. Protective immunity and lack of histopathological damage two years after DNA vaccination against infectious hematopoietic necrosis virus in trout

    USGS Publications Warehouse

    Kurath, Gael; Garver, Kyle A.; Corbeil, Serge; Elliott, Diane G.; Anderson, Eric D.; LaPatra, Scott E.

    2006-01-01

    The DNA vaccine pIHNw-G encodes the glycoprotein of the fish rhabdovirus infectious hematopoietic necrosis virus (IHNV). Vaccine performance in rainbow trout was measured 3, 6, 13, 24, and 25 months after vaccination. At three months all fish vaccinated with 0.1 μg pIHNw-G had detectable neutralizing antibody (NAb) and they were completely protected from lethal IHNV challenge with a relative percent survival (RPS) of 100% compared to control fish. Viral challenges at 6, 13, 24, and 25 months post-vaccination showed protection with RPS values of 47–69%, while NAb seroprevalence declined to undetectable levels. Passive transfer experiments with sera from fish after two years post-vaccination were inconsistent but significant protection was observed in some cases. The long-term duration of protection observed here defined a third temporal phase in the immune response to IHNV DNA vaccination, characterized by reduced but significant levels of protection, and decline or absence of detectable NAb titers. Examination of multiple tissues showed an absence of detectable long-term histopathological damage due to DNA vaccination.

  13. Triple-Layer Plastic Bags Protect Dry Common Beans (Phaseolus vulgaris) Against Damage by Acanthoscelides obtectus (Coleoptera: Chrysomelidae) During Storage.

    PubMed

    Mutungi, C; Affognon, H D; Njoroge, A W; Manono, J; Baributsa, D; Murdock, L L

    2015-10-01

    Fumigated dry common beans (Phaseolus vulgaris L.) that were artificially infested with Acanthoscelides obtectus Say, and others that were not artificially infested, were stored in hermetic triple-layer PICS (Lela Agro, Kano, Nigeria) or woven polypropylene (PP) bags for 6 mo at ambient laboratory temperature conditions of 22.6 ± 1.9°C and 60.1 ± 4.3% relative humidity. In an additional trial, beans contained in PP bags were treated with Actellic Super dust before introducing A. obtectus. Moisture content, number of live adult A. obtectus, seed damage, weight loss, and seed germination were determined at monthly intervals. At 6 mo, beans stored in PICS bags retained higher moisture than those stored in PP bags, but in all treatments the moisture level remained below that recommended for safe storage of beans. In the PICS bags, proliferation of A. obtectus did not proceed and at 6 mo, beans stored in these bags did not have insect-inflicted seed damage or weight loss. In contrast, seed damage and weight loss in PP bags exceeded economic threshold after 1 mo in the absence of Actellic Super dust (Syngenta Crop protection AG, Basle, Switzerland), and after 2 mo in the presence of it. Germination of beans stored in PP bags decreased greatly whereas the beans stored in PICS bags did not show reduced germination. Chemical free storage of common beans in PICS bags protects them against damage by A. obtectus.

  14. Protective effects of lemongrass (Cymbopogon citratus STAPF) essential oil on DNA damage and carcinogenesis in female Balb/C mice.

    PubMed

    Bidinotto, Lucas T; Costa, Celso A R A; Salvadori, Daisy M F; Costa, Mirtes; Rodrigues, Maria A M; Barbisan, Luís F

    2011-08-01

    This study investigated the protective effect of oral treatment with lemongrass (Cymbopogon citratus STAPF) essential oil (LGEO) on leukocyte DNA damage induced by N-methyl-N-nitrosurea (MNU). Also, the anticarcinogenic activity of LGEO was investigated in a multi-organ carcinogenesis bioassay induced by 7,12-dimethylbenz(a)antracene, 1,2-dimethylhydrazine and N-butyl-N-(4-hydroxibuthyl)nitrosamine in Balb/C female Balb/c mice (DDB-initiated mice). In the short-term study, the animals were allocated into three groups: vehicle group (negative control), MNU group (positive control) and LGEO 500 mg kg⁻¹ (five times per week for 5 weeks) plus MNU group (test group). Blood samples were collected to analyze leukocyte DNA damage by comet assay 4 h after each MNU application at the end of weeks 3 and 5. The LGEO 500 mg kg⁻¹ treated group showed significantly lower (P < 0.01) leukocyte DNA damage than its respective positive group exposed to MNU alone at week 3. In the medium-term study, DDB-initiated mice were allocated into three groups: vehicle group (positive control) and LGEO 125 or 500 mg kg⁻¹ (five times per week for 6 weeks; test groups). At week 20, all animals were euthanized and mammary glands, colon and urinary bladder were processed for histopathological analyses for detection of preneoplastic and neoplastic lesions. A slight non-significant effect of treatment with LGEO 500 mg kg⁻¹ in reducing development of alveolar and ductal mammary hyperplasia was found (P = 0.075). Our findings indicate that lemongrass essential oil provided protective action against MNU-induced DNA damage and a potential anticarcinogenic activity against mammary carcinogenesis in DDB-initiated female Balb/C mice.

  15. Protective effects of peony root extract and its components on neuron damage in the hippocampus induced by the cobalt focus epilepsy model.

    PubMed

    Tsuda, T; Sugaya, A; Ohguchi, H; Kishida, N; Sugaya, E

    1997-08-01

    Protective effects of peony root extract and its components on neuron damage in the CA1 area of the hippocampus induced by the cobalt focus epilepsy model were examined. Neuron damage in the CA1 area of the hippocampus and frequent spike discharges induced by application of metallic cobalt to the cerebral cortex of rats were completely prevented when peony root extract was continuously administered orally at 1 g/kg/day for 30 days prior to cobalt application. Component crude gallotannin fraction showed marked but incomplete protective action. A combination of crude gallotannin fraction and paeoniflorin showed complete protective action in the same way as peony root extract against neuron damage although use of paeoniflorin alone had no effect. These findings together with our previous reports indicate that peony root extract and its component, gallotannin, have excellent protective effects on neuron damage in addition to anticonvulsant action by prior oral administration.

  16. Protective Efficacy of Alpha-lipoic Acid against AflatoxinB1-induced Oxidative Damage in the Liver

    PubMed Central

    Li, Y.; Ma, Q. G.; Zhao, L. H.; Guo, Y. Q.; Duan, G. X.; Zhang, J. Y.; Ji, C.

    2014-01-01

    Alpha-lipoic acid (α-LA) is not only involved in energy metabolism, but is also a powerful antioxidant that can protect against hepatic oxidative stress induced by some drugs, toxins, or under various physiological and pathophysiological conditions. Here, we investigated the effect of α-LA against liver oxidative damage in broilers exposed to aflatoxin B1 (AFB1). Birds were randomly divided into four groups and assigned different diets: basal diet, 300 mg/kg α-LA supplementation in basal diet, diet containing 74 μg/kg AFB1, and 300 mg/kg α-LA supplementation in diet containing 74 μg/kg AFB1, for 3 weeks. The results revealed that the addition of 300 mg/kg α-LA protected against the liver function damage of broilers induced by chronic low dose of AFB1 as estimated by a significant (p<0.05) change in levels of plasma total protein, albumin, alkaline phosphatase and the activities of liver glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. The histopathological analysis also showed that liver tissues were injured in the AFB1 diet, but this effect was alleviated by the addition of 300 mg/kg α-LA. Additionally, AFB1 induced a profound elevation of oxidative stress in birds, as indicated by an increase in malondialdehyde level, a decrease in glutathione peroxidase activity and a depletion of the glutathione content in the liver. All of these negative effects were inhibited by treatment with α-LA. Our results suggest that the inhibition of AFB1-induced excess production of lipid peroxides and the maintenance of intracellular antioxidant status may play important roles in the protective effects of α-LA against AFB1-induced oxidative damage in the liver. PMID:25050030

  17. Liv.52 protects HepG2 cells from oxidative damage induced by tert-butyl hydroperoxide.

    PubMed

    Vidyashankar, S; K Mitra, S; Nandakumar, Krishna S

    2010-01-01

    Oxidative stress induced by toxicants is known to cause various complications in the liver. Herbal drug such as Liv.52 is found to have hepatoprotective effect. However, the biochemical mechanism involved in the Liv.52 mediated protection against toxicity is not well elucidated using suitable in vitro models. Hence, in the present study, the hepatoprotective effect of Liv.52 against oxidative damage induced by tert-butyl hydroperoxide (t-BHP) in HepG2 cells was evaluated in order to relate in vitro antioxidant activity with cytoprotective effects. Cytotoxicity was measured by MTT assay. Antioxidant effect of Liv.52 was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, ferric-reducing antioxidant power (FRAP) assay, and lipid peroxidation and measurement of non-enzymic and antioxidant enzymes in HepG2 cells exposed to t-BHP over a period of 24 h. The results obtained indicate that t-BHP induced cell damage in HepG2 cells as shown by significant increase in lipid peroxidation as well as decreased levels of reduced glutathione (GSH). Liv.52 significantly decreased toxicity induced by t-BHP in HepG2 cells. Liv.52 was also significantly decreased lipid peroxidation and prevented GSH depletion in HepG2 cells induced by t-BHP. Therefore, Liv.52 appeared to be important for cell survival when exposed to t-BHP. The protective effect of Liv.52 against cell death evoked by t-BHP was probably achieved by preventing intracellular GSH depletion and lipid peroxidation. The results showed protective effect of Liv.52 against oxidative damage induced in HepG2 cells. Hence, taken together, these findings derived from the present study suggest the beneficial effect of Liv.52 in regulating oxidative stress induced in liver by toxicants.

  18. Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats.

    PubMed

    Pradeep, Kannampalli; Park, Sang Hyun; Ko, Kyong Cheol

    2008-06-10

    Oxidative stress plays a pivotal role in the pathogenesis and progression of gamma-irradiation induced cellular damage and the administration of dietary antioxidants has been suggested to protect against the subsequent tissue damage. Here, we present the data to explore the hepatoprotective and antioxidant effect of hesperidin, a naturally occurring citrus flavanoglycone, against gamma-irradiation induced oxidative damage in the liver of rats. Healthy male Sprague-Dawley rats were exposed to gamma-irradiation (1 Gy, 3 Gy and 5 Gy) and were administered hesperidin (50 mg/kg and 100 mg/kg, b.w, orally) for 7 days post irradiation. The changes in body weight, liver weight, spleen index, serum and liver aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and serum ceruloplasmin levels were determined along with differences in the liver histopathology. Liver thiobarbuturic acid reactive substance as an index for lipid peroxidation and the levels of enzymatic antioxidants like superoxide dismutase, catalase, glutathione peroxidase and the status of non-enzymatic antioxidants as an index for oxidative stress were also determined. Exposure to gamma-irradiation resulted in hepatocellular damage in a dose-dependent manner, featuring a significantly decreased body weight and liver weight and higher levels of serum AST, ALT, ALP, LDH and gamma-GT levels and a simultaneous decrease in their levels in the liver tissue. Oxidative stress was evidenced by elevated levels of lipid peroxidation and a decrease in the levels of key enzymatic and non-enzymatic antioxidants in the liver. However, the gamma-irradiation induced toxic effects were dramatically and dose-dependently inhibited by hesperidin treatment as observed by the restoration in the altered levels of the marker enzymes, lipid peroxidation, enzymatic and non-enzymatic antioxidants. The results of the biochemical

  19. Antioxidant activity and protective effect of Clitoria ternatea flower extract on testicular damage induced by ketoconazole in rats*

    PubMed Central

    Iamsaard, Sitthichai; Burawat, Jaturon; Kanla, Pipatpong; Arun, Supatcharee; Sukhorum, Wannisa; Sripanidkulchai, Bungorn; Uabundit, Nongnut; Wattathorn, Jintanaporn; Hipkaeo, Wiphawi; Fongmoon, Duriya; Kondo, Hisatake

    2014-01-01

    Background: Ketoconazole (KET), an antifungal drug, has adverse effects on the male reproductive system. Pre-treatments with antioxidant plant against testicular damage induced by KET are required. The flowers of Clitoria ternatea (CT) are proven to have hepatoprotective potential. However, the protective effect on KET-induced testicular damage has not been reported. Objective: To investigate the protective effect of CT flower extracts with antioxidant activity on male reproductive parameters including sperm concentration, serum testosterone level, histopathology of the testis, and testicular tyrosine phosphorylation levels in rats induced with KET. Methods: The antioxidant activity of CT flower extracts was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Male rats were treated with CT flower extracts (10, 50, or 100 mg/kg BW) or distilled water via a gastric tube for 28 d (preventive period: Days 1–21) and induced by KET (100 mg/kg BW) via intraperitoneal injection for 7 d (induction period: Days 22–28). After the experiment, all animals were examined for the weights of the testis, epididymis plus vas deferens and seminal vesicle, serum testosterone levels, sperm concentration, histological structures and diameter of testis, and testicular tyrosine phosphorylation levels by immunoblotting. Results: The CT flower extracts had capabilities for DPPH scavenging and high reducing power. At 100 mg/kg BW, the extract had no toxic effects on the male reproductive system. Significantly, in CT+KET groups, CT flower extracts (50 and 100 mg/kg BW) alleviated the reduction of reproductive organ weight parameters, testosterone levels, and sperm concentration. In addition, CT flower extracts gave protection from testicular damage in KET-induced rats. Moreover, in the CT100+KET group, CT flower extracts significantly enhanced the expression of a testicular 50-kDa tyrosine phosphorylated protein compared with that of

  20. Precursors to potential severe core damage accidents: 1992, a status report; Volume 18: Appendices B, C, D, E, F, and G

    SciTech Connect

    1993-12-01

    This document is part of a report which documents 1992 operational events selected as accident sequence precursors. This report describes the 27 precursors identified from the 1992 licensee event reports. It also describe containment-related events; {open_quote}interesting{close_quote} events; potentially significant events that were considered impractical to analyze; copies of the licensee event reports which were cited in the cases above; and comments from the licensee and NRC in response to the preliminary reports.

  1. [Protecting Safety During Dust Fires and Dust Explosions - The Example of the Formosa Fun Coast Water Park Accident].

    PubMed

    Hsieh, Ming-Hong; Wu, Jia-Wun; Li, Ya-Cing; Tang, Jia-Suei; Hsieh, Chun-Chien

    2016-02-01

    This paper will explore the fire and explosion characteristics of cornstarch powder as well as strategies for protecting the safety of people who are involved a dust fire or dust explosion. We discuss the 5 elements of dust explosions and conduct tests to analyze the fire and explosion characteristics of differently colored powders (yellow, golden yellow, pink, purple, orange and green). The results show that, while all of the tested powders were difficult to ignite, low moisture content was associated with significantly greater risks of ignition and flame spread. We found the auto-ignition temperature (AIT) of air-borne cornstarch powder to be between 385°C and 405°C, with yellow-colored cornstarch powder showing the highest AIT and pink-colored cornstarch powder showing the lowest AIT. The volume resistivity of all powder samples was approximately 108 Ω.m, indicating that they were nonconductive. Lighters and cigarettes are effective ignition sources, as their lit temperatures are higher than the AIT of cornstarch powder. In order to better protect the safety of individuals at venues where cornstarch powder is released, explosion control measures such as explosion containment facilities, vents, and explosion suppression and isolation devices should be installed. Furthermore, employees that work at these venues should be better trained in explosion prevention and control measures. We hope this article is a reminder to the public to recognize the fire and explosion characteristics of flammable powders as well as the preventive and control measures for dust explosions. PMID:26813056

  2. [Protecting Safety During Dust Fires and Dust Explosions - The Example of the Formosa Fun Coast Water Park Accident].

    PubMed

    Hsieh, Ming-Hong; Wu, Jia-Wun; Li, Ya-Cing; Tang, Jia-Suei; Hsieh, Chun-Chien

    2016-02-01

    This paper will explore the fire and explosion characteristics of cornstarch powder as well as strategies for protecting the safety of people who are involved a dust fire or dust explosion. We discuss the 5 elements of dust explosions and conduct tests to analyze the fire and explosion characteristics of differently colored powders (yellow, golden yellow, pink, purple, orange and green). The results show that, while all of the tested powders were difficult to ignite, low moisture content was associated with significantly greater risks of ignition and flame spread. We found the auto-ignition temperature (AIT) of air-borne cornstarch powder to be between 385°C and 405°C, with yellow-colored cornstarch powder showing the highest AIT and pink-colored cornstarch powder showing the lowest AIT. The volume resistivity of all powder samples was approximately 108 Ω.m, indicating that they were nonconductive. Lighters and cigarettes are effective ignition sources, as their lit temperatures are higher than the AIT of cornstarch powder. In order to better protect the safety of individuals at venues where cornstarch powder is released, explosion control measures such as explosion containment facilities, vents, and explosion suppression and isolation devices should be installed. Furthermore, employees that work at these venues should be better trained in explosion prevention and control measures. We hope this article is a reminder to the public to recognize the fire and explosion characteristics of flammable powders as well as the preventive and control measures for dust explosions.

  3. A putative Leishmania DNA polymerase theta protects the parasite against oxidative damage

    PubMed Central

    Fernández-Orgiler, Abel; Martínez-Jiménez, María I.; Alonso, Ana; Alcolea, Pedro J.; Requena, Jose M.; Thomas, María C.; Blanco, Luis; Larraga, Vicente

    2016-01-01

    Leishmania infantum is a protozoan parasite that is phagocytized by human macrophages. The host macrophages kill the parasite by generating oxidative compounds that induce DNA damage. We have identified, purified and biochemically characterized a DNA polymerase θ from L. infantum (LiPolθ), demonstrating that it is a DNA-dependent DNA polymerase involved in translesion synthesis of 8oxoG, abasic sites and thymine glycol lesions. Stably transfected L. infantum parasites expressing LiPolθ were significantly more resistant to oxidative and interstrand cross-linking agents, e.g. hydrogen peroxide, cisplatin and mitomycin C. Moreover, LiPolθ-overexpressing parasites showed an increased infectivity toward its natural macrophage host. Therefore, we propose that LiPolθ is a translesion synthesis polymerase involved in parasite DNA damage tolerance, to confer resistance against macrophage aggression. PMID:27131366

  4. Phenolic compounds of Chromolaena odorata protect cultured skin cells from oxidative damage: implication for cutaneous wound healing.

    PubMed

    Phan, T T; Wang, L; See, P; Grayer, R J; Chan, S Y; Lee, S T

    2001-12-01

    Extracts from the leaves of Chromolaena odorata have been shown to be beneficial for treatment of wounds. The crude ethanol extract of the plant had been demonstrated to be a powerful antioxidant to protect fibroblasts and keratinocytes in vitro. In this study, the most active compounds were fractionated and identified from the crude extract using liquid chromatography coupled with UV spectroscopy and mass spectrometry. The antioxidant effects of purified fractions on cultured fibroblasts and keratinocytes were investigated using colorimetric and lactate hydrogenase release assay. The results showed that the phenolic acids present (protocatechuic, p-hydroxybenzoic, p-coumaric, ferulic and vanillic acids) and complex mixtures of lipophilic flavonoid aglycones (flavanones, flavonols, flavones and chalcones) were major and powerful antioxidants to protect cultured skin cells against oxidative damage. In conclusion, the extract from C odorata contains a mixture of powerful antioxidant compounds that may be one of potential mechanism contributing to enhanced wound healing.

  5. Protective effect of Indigofera aspalathoides against CCl4-induced hepatic damage in rats.

    PubMed

    Rajkapoor, B; Jayakar, B; Kavimani, S; Murugesh, N

    2006-01-01

    The alcoholic extract of stem of Indigofera aspalathoides was evaluated for its antihepatotoxic activity against CCl(4)-induced hepatic damage in rats. The activity was evaluated by using biochemical parameters, such as serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin and gama glutamate transpeptidase (GGTP). The histopathological changes of liver sample were compared with respective control. The extract showed remarkable hepatoprotective effect.

  6. Nucleoside-nucleotide free diet protects rat colonic mucosa from damage induced by trinitrobenzene sulphonic acid.

    PubMed Central

    Adjei, A A; Morioka, T; Ameho, C K; Yamauchi, K; Kulkarni, A D; Al-Mansouri, H M; Kawajiri, A; Yamamoto, S

    1996-01-01

    BACKGROUND: Growing evidence suggests that intestinal recovery from injury induced by radiation, endotoxin, and protein deficiency is improved by the ingestion of nucleosides and nucleotides. AIM: This study examined the effect of dietary nucleosides and nucleotides supplementation on trinitrobenzene sulphonic acid induced colonic damage in experimental colitis. METHODS: Sprague-Dawley rats were randomised into two groups and fed nucleic acid free 20% casein diet (control) or this diet supplemented with 0.5% nucleoside-nucleotide mixture for four weeks. On the second week, colonic inflammation was induced in rats by intracolonic administration of 0.25 ml of 50% ethanol containing 25 mg of trinitrobenzene sulphonic acid. Additionally, other sets of rats were treated with 0.25 ml of 50% ethanol, 25 mg of trinitrobenzene sulphonic acid in 0.25 ml saline, or 0.25 ml of 0.9% saline. RESULTS: After two weeks, colon weight, macroscopic and microscopic damage scores, were significantly greater (p < 0.05) in the nucleoside-nucleotide supplemented group compared with the non-supplemented control groups. The same variables seen in the trinitrobenzene sulphonic acid-ethanol group fed nucleoside-nucleotide free diet were greater (p < 0.05) than in the rest of the groups fed nucleoside-nucleotide free diet and treated with ethanol, trinitrobenzene sulphonic acid in saline, or saline. Histologically, segmental ulceration and inflammation associated with significantly increased infiltration of polymorphonuclear leucocytes, macrophages, lymphocytes, fibroblasts were observed in the supplemented group compared with the controls. In the nucleoside-nucleotide supplemented group the epithelial damage, mucosal erosion, oedema, and coagulative necrosis of the muscularis propria was more extensive in comparison to the non-supplemented control groups. CONCLUSIONS: This study suggests that dietary nucleosides and nucleotides may aggravate colonic damage and inflammation in chemically

  7. Radiotherapy Accidents

    NASA Astrophysics Data System (ADS)

    Mckenzie, Alan

    A major benefit of a Quality Assurance system in a radiotherapy centre is that it reduces the likelihood of an accident. For over 20 years I have been the interface in the UK between the Institute of Physics and Engineering in Medicine and the media — newspapers, radio and TV — and so I have learned about radiotherapy accidents from personal experience. In some cases, these accidents did not become public and so the hospital cannot be identified. Nevertheless, lessons are still being learned.

  8. How caterpillar-damaged plants protect themselves by attracting parasitic wasps.

    PubMed Central

    Turlings, T C; Loughrin, J H; McCall, P J; Röse, U S; Lewis, W J; Tumlinson, J H

    1995-01-01

    Parasitic and predatory arthropods often prevent plants from being severely damaged by killing herbivores as they feed on the plants. Recent studies show that a variety of plants, when injured by herbivores, emit chemical signals that guide natural enemies to the herbivores. It is unlikely that herbivore-damaged plants initiate the production of chemicals solely to attract parasitoids and predators. The signaling role probably evolved secondarily from plant responses that produce toxins and deterrents against herbivores and antibiotics against pathogens. To effectively function as signals for natural enemies, the emitted volatiles should be clearly distinguishable from background odors, specific for prey or host species that feed on the plant, and emitted at times when the natural enemies forage. Our studies on the phenomena of herbivore-induced emissions of volatiles in corn and cotton plants and studies conducted by others indicate that (i) the clarity of the volatile signals is high, as they are unique for herbivore damage, produced in relatively large amounts, and easily distinguishable from background odors; (ii) specificity is limited when different herbivores feed on the same plant species but high as far as odors emitted by different plant species and genotypes are concerned; (iii) the signals are timed so that they are mainly released during the daytime, when natural enemies tend to forage, and they wane slowly after herbivory stops. PMID:7753779

  9. 40 CFR 68.168 - Five-year accident history.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 15 2011-07-01 2011-07-01 false Five-year accident history. 68.168 Section 68.168 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.168 Five-year accident...

  10. 40 CFR 68.168 - Five-year accident history.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Five-year accident history. 68.168 Section 68.168 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.168 Five-year accident...

  11. 40 CFR 68.168 - Five-year accident history.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 16 2012-07-01 2012-07-01 false Five-year accident history. 68.168 Section 68.168 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.168 Five-year accident...

  12. 40 CFR 68.168 - Five-year accident history.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 16 2013-07-01 2013-07-01 false Five-year accident history. 68.168 Section 68.168 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.168 Five-year accident...

  13. 40 CFR 68.168 - Five-year accident history.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 16 2014-07-01 2014-07-01 false Five-year accident history. 68.168 Section 68.168 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.168 Five-year accident...

  14. Coenzyme Q10 protects astrocytes from ROS-induced damage through inhibition of mitochondria-mediated cell death pathway.

    PubMed

    Jing, Li; He, Mao-Tao; Chang, Yue; Mehta, Suresh L; He, Qing-Ping; Zhang, Jian-Zhong; Li, P Andy

    2015-01-01

    Coenzyme Q10 (CoQ10) acts by scavenging reactive oxygen species to protect neuronal cells against oxidative stress in neurodegenerative diseases. The present study was designed to examine whether CoQ10 was capable of protecting astrocytes from reactive oxygen species (ROS) mediated damage. For this purpose, ultraviolet B (UVB) irradiation was used as a tool to induce ROS stress to cultured astrocytes. The cells were treated with 10 and 25 μg/ml of CoQ10 for 3 or 24 h prior to the cells being exposed to UVB irradiation and maintained for 24 h post UVB exposure. Cell viability was assessed by MTT conversion assay. Mitochondrial respiration was assessed by respirometer. While superoxide production and mitochondrial membrane potential were measured using fluorescent probes, levels of cytochrome C (cyto-c), cleaved caspase-9, and caspase-8 were detected using Western blotting and/or immunocytochemistry. The results showed that UVB irradiation decreased cell viability and this damaging effect was associated with superoxide accumulation, mitochondrial membrane potential hyperpolarization, mitochondrial respiration suppression, cyto-c release, and the activation of both caspase-9 and -8. Treatment with CoQ10 at two different concentrations started 24 h before UVB exposure significantly increased the cell viability. The protective effect of CoQ10 was associated with reduction in superoxide, normalization of mitochondrial membrane potential, improvement of mitochondrial respiration, inhibition of cyto-c release, suppression of caspase-9. Furthermore, CoQ10 enhanced mitochondrial biogenesis. It is concluded that CoQ10 may protect astrocytes through suppression of oxidative stress, prevention of mitochondrial dysfunction, blockade of mitochondria-mediated cell death pathway, and enhancement of mitochondrial biogenesis. PMID:25552930

  15. Thymoquinone protects cultured hippocampal and human induced pluripotent stem cells-derived neurons against α-synuclein-induced synapse damage.

    PubMed

    Alhebshi, A H; Odawara, A; Gotoh, M; Suzuki, I

    2014-06-01

    The seeds of Nigella sativa are used worldwide to treat various diseases and ailments. Thymoquinone (TQ) that is present in the essential oil of these seeds mediates most of the plant's diverse therapeutic effects. The present study aimed to determine whether TQ protects against α-synuclein (αSN)-induced synaptic toxicity in rat hippocampal and human induced pluripotent stem cell (hiPSC)-derived neurons. Here, we report that αSN decreased the level of synaptophysin, a protein used as an indicator of synaptic density, in cultured hippocampal and hiPSC-derived neurons. However, simultaneous treatment with αSN and TQ protected neurons against αSN-induced synapse damage, as revealed by immunostaining. Moreover, administration of TQ efficiently induced protection in these cells against αSN-induced inhibition of synaptic vesicle recycling in hippocampal and hiPSC-derived neurons as well as against mutated P123H β-synuclein (βSN) in hippocampal neurons, as revealed by experiments using the fluorescent dye FM1-43. Using a multielectrode array, we further demonstrated that the treatment of hiPSC-derived neurons with αSN induced a reduction in spontaneous firing activity, and cotreatment with αSN and TQ partially reversed this loss. These results suggest that TQ protects cultured rat primary hippocampal and hiPSC-derived neurons against αSN-induced synaptic toxicity and could be a promising therapeutic agent for patients with Parkinson's disease and dementia with Lewy bodies.

  16. The Protective Effect of Grape-Seed Proanthocyanidin Extract on Oxidative Damage Induced by Zearalenone in Kunming Mice Liver

    PubMed Central

    Long, Miao; Yang, Shu-Hua; Han, Jian-Xin; Li, Peng; Zhang, Yi; Dong, Shuang; Chen, Xinliang; Guo, Jiayi; Wang, Jun; He, Jian-Bin

    2016-01-01

    Although grape-seed proanthocyanidin extract (GSPE) demonstrates strong anti-oxidant activity, little research has been done to clearly reveal the protective effects on the hepatotoxicity caused by zearalenone (ZEN). This study is to explore the protective effect of GSPE on ZEN-induced oxidative damage of liver in Kunming mice and the possible protective molecular mechanism of GSPE. The results indicated that GSPE could greatly reduce the ZEN-induced increase of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. GSPE also significantly decreased the content of MDA but enhanced the activities of antioxidant enzymes SOD and GSH-Px. The analysis indicated that ZEN decreased both mRNA expression levels and protein expression levels of nuclear erythroid2-related factor2 (Nrf2). Nrf2 is considered to be an essential antioxidative transcription factor, as downstream GSH-Px, γ-glutamyl cysteine synthetase (γ-GCS), hemeoxygenase-1 (HO-1), and quinone oxidoreductase 1 (NQO1) decreased simultaneously, whereas the pre-administration of GSPE groups was shown to elevate these expressions. The results indicated that GSPE exerted a protective effect on ZEN-induced hepatic injury and the mechanism might be related to the activation of the Nrf2/ARE signaling pathway. PMID:27231898

  17. High Throughput Screening Identifies a Novel Compound Protecting Cardiomyocytes from Doxorubicin-Induced Damage

    PubMed Central

    Gergely, Szabolcs; Hegedűs, Csaba; Lakatos, Petra; Kovács, Katalin; Gáspár, Renáta; Csont, Tamás; Virág, László

    2015-01-01

    Antracyclines are effective antitumor agents. One of the most commonly used antracyclines is doxorubicin, which can be successfully used to treat a diverse spectrum of tumors. Application of these drugs is limited by their cardiotoxic effect, which is determined by a lifetime cumulative dose. We set out to identify by high throughput screening cardioprotective compounds protecting cardiomyocytes from doxorubicin-induced injury. Ten thousand compounds of ChemBridge's DIVERSet compound library were screened to identify compounds that can protect H9C2 rat cardiomyocytes against doxorubicin-induced cell death. The most effective compound proved protective in doxorubicin-treated primary rat cardiomyocytes and was further characterized to demonstrate that it significantly decreased doxorubicin-induced apoptotic and necrotic cell death and inhibited doxorubicin-induced activation of JNK MAP kinase without having considerable radical scavenging effect or interfering with the antitumor effect of doxorubicin. In fact the compound identified as 3-[2-(4-ethylphenyl)-2-oxoethyl]-1,2-dimethyl-1H-3,1-benzimidazol-3-ium bromide was toxic to all tumor cell lines tested even without doxorubicine treatment. This benzimidazole compound may lead, through further optimalization, to the development of a drug candidate protecting the heart from doxorubicin-induced injury. PMID:26137186

  18. Protection against hydrogen peroxide induced oxidative damage in rat erythrocytes by Mangifera indica L. peel extract.

    PubMed

    Ajila, C M; Prasada Rao, U J S

    2008-01-01

    Phytochemicals such as polyphenols and carotenoids are gaining importance because of their contribution to human health and their multiple biological effects such as antioxidant, antimutagenic, anticarcinogenic and cytoprotective activities and other therapeutic properties. Mango peel is a major by-product in pulp industry and it contains various bioactive compounds like polyphenols, carotenoids and others. In the present study, the protective effect of peel extracts of unripe and ripe mango fruits of two varieties namely, Raspuri and Badami on hydrogen peroxide induced hemolysis, lipid peroxidation, degradation of membrane proteins and its morphological changes are reported. The oxidative hemolysis of rat erythrocytes by hydrogen peroxide was inhibited by mango peel extract in a dose dependent manner. The IC(50) value for lipid peroxidation inhibition on erythrocyte ghost membrane was found to be in the range of 4.5-19.3 microg gallic acid equivalents. The mango peel extract showed protection against membrane protein degradation caused by hydrogen peroxide. Morphological changes to erythrocyte membrane caused by hydrogen peroxide were protected by mango peel extract. The results demonstrated that mango peel extracts protected erythrocytes against oxidative stress and may impart health benefits and it could be used as a valuable food ingredient or a nutraceutical product.

  19. Protective Effects of Danhong Injection against Cerebral Damage during On-Pump Coronary Artery Bypass Graft Surgery

    PubMed Central

    Xuejuan, Zhang; Jietao, Zhang; Di, Han; Yu, Zheng; Xiaozi, Guo; Yunfa, Li; Lihua, Dong

    2015-01-01

    To explore the protective effects of Danhong injection against cerebral damage during on-pump coronary artery bypass graft surgery and its mechanism. Methods. Fifty patients scheduled for on-pump CABG surgery were randomly divided into Danhong injection group (group D) and control group (group C). Group D was given Danhong injection while group C was given the same volume of normal saline when the artery was cut open. Jugular bulb blood right before the operation began (T1), when body temperature rewarming to 36°C (T2), 30 min after the termination of cardiopulmonary bypass (T3), and 6 hrs after the termination of CPB (T4) was collected. The superoxide dismutase activity by using xanthine oxidase method and concentration determination of malondialdehyde were examined. Results. In group C, SOD activity was less at T2–T4 than at T1. It was also less active comparatively in group D at T2–T4. The MDA concentration increased in both groups but was more obvious in group C. Levels of TNF-α, IL-6, IL-8, and IL-10 increased in both groups C and D at T3 and T4, compared to T1. Conclusions. Danhong injection shows significant protective effects against cerebral damage during on-pump coronary artery bypass graft surgery. PMID:26798399

  20. Tumor necrosis factor alpha protects heart cultures against hypoxic damage via activation of PKA and phospholamban to prevent calcium overload.

    PubMed

    El-Ani, Dalia; Philipchik, Irena; Stav, Hagit; Levi, Moran; Zerbib, Jordana; Shainberg, Asher

    2014-11-01

    This study aims to elucidate the mechanisms by which tumor necrosis factor alpha (TNFα) provides protection from hypoxic damage to neonatal rat cardiomyocyte cultures. We show that when intracellular Ca(2+) ([Ca(2+)]i) levels are elevated by extracellular Ca(2+) ([Ca(2+)]o) or by hypoxia, then TNFα decreased [Ca(2+)]i in individual cardiomyocytes. However, TNFα did not reduce [Ca(2+)]i after its increase by thapsigargin, (a SERCA2a inhibitor), indicating that TNFα attenuates Ca(2+) overload through Ca(2+) uptake by SERCA2a. TNFα did not reduce [Ca(2+)]i, following its elevation when [Ca(2+)]o levels were elevated in TNFα receptor knock-out mice. H-89, a protein kinase A (PKA) inhibitor, attenuated the protective effect of TNFα when the cardiomyoctyes were subjected to hypoxia, as determined by lactate dehydrogenase (LDH) and creatine kinase (CK) released and from the cardiomyocytes. Moreover, when the levels of [Ca(2+)]i were increased by hypoxia, H-89, but not KN93, (a calmodulin kinase II inhibitor), prevented the reduction in [Ca(2+)]i by TNFα. TNFα increased the phosphorylation of PKA in normoxic and hypoxic cardiomyoctes, indicating that the cardioprotective effect of TNFα against hypoxic damage was via PKA activation. Hypoxia decreased phosphorylated phospholamban levels; however, TNFα attenuated this decrease following hypoxia. It is suggested that TNFα activates phospholamban phosphorylation in hypoxic heart cultures via PKA to stimulate SERCA2a activity to limit Ca(2+) overload.

  1. Protective effects of Artocarpus altilis (Moraceae) on cadmium-induced changes in sperm characteristics and testicular oxidative damage in rats.

    PubMed

    Adaramoye, O A; Akanni, O O

    2016-03-01

    Cadmium (Cd) is a major environmental toxicant and an endocrine disruptor. We investigated the protective effects of methanol extract of Artocarpus altilis (AA) against Cd-induced testicular damage in rats while quercetin (Que) served as standard. The total flavonoids and phenolic contents (TFC and TPC), 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl (OH) radicals scavenging activities of AA were determined. In vivo, thirty male Wistar rats were assigned to six groups and orally treated with corn oil (control), Cd alone, Cd+Que, Cd+AA, Que and AA alone. Que and AA were given at doses of 25 and 200 mg kg(-1), respectively, for 3 weeks and challenged with two doses of Cd (1.5 mg kg(-1)). Results showed that TFC and TPC of AA increased with increase in concentration. AA scavenged DPPH and OH radicals in a dose-dependent manner. Administration of Cd significantly increased the relative weight of testis of rats. Lipid peroxidation was significantly increased while antioxidant parameters decreased in testis of Cd-treated rats. Also, Cd-treated rats had significantly reduced sperm count, motility, sialic acid, luteinising hormone and testosterone relative to controls. Pre-treatment with AA or Que significantly attenuated the biochemical alterations observed in Cd-treated rats. Overall, AA protects against Cd-induced testicular damage via antioxidative mechanism. PMID:25912632

  2. Protective effects of Artocarpus altilis (Moraceae) on cadmium-induced changes in sperm characteristics and testicular oxidative damage in rats.

    PubMed

    Adaramoye, O A; Akanni, O O

    2016-03-01

    Cadmium (Cd) is a major environmental toxicant and an endocrine disruptor. We investigated the protective effects of methanol extract of Artocarpus altilis (AA) against Cd-induced testicular damage in rats while quercetin (Que) served as standard. The total flavonoids and phenolic contents (TFC and TPC), 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl (OH) radicals scavenging activities of AA were determined. In vivo, thirty male Wistar rats were assigned to six groups and orally treated with corn oil (control), Cd alone, Cd+Que, Cd+AA, Que and AA alone. Que and AA were given at doses of 25 and 200 mg kg(-1), respectively, for 3 weeks and challenged with two doses of Cd (1.5 mg kg(-1)). Results showed that TFC and TPC of AA increased with increase in concentration. AA scavenged DPPH and OH radicals in a dose-dependent manner. Administration of Cd significantly increased the relative weight of testis of rats. Lipid peroxidation was significantly increased while antioxidant parameters decreased in testis of Cd-treated rats. Also, Cd-treated rats had significantly reduced sperm count, motility, sialic acid, luteinising hormone and testosterone relative to controls. Pre-treatment with AA or Que significantly attenuated the biochemical alterations observed in Cd-treated rats. Overall, AA protects against Cd-induced testicular damage via antioxidative mechanism.

  3. The CDKN1B-RB1-E2F1 pathway protects mouse spermatogonial stem cells from genomic damage

    PubMed Central

    TANAKA, Takashi; KANATSU-SHINOHARA, Mito; SHINOHARA, Takashi

    2015-01-01

    Spermatogonial stem cells (SSCs) undergo self-renewal divisions to provide the foundation for spermatogenesis. Although Rb1 deficiency is reportedly essential for SSC self-renewal, its mechanism has remained unknown. Here we report that Rb1 is critical for cell cycle progression and protection of SSCs from DNA double-strand breaks (DSBs). Cultured SSCs depleted of Cdkn1b proliferated poorly and showed diminished expression of CDK4 and RB1, thereby leading to hypophosphorylation of RB1. Rb1 deficiency induced cell cycle arrest and apoptosis in cultured SSCs, which expressed markers for DNA DSBs. This DNA damage is caused by increased E2F1 activity, the depletion of which decreased DNA DSBs caused by Rb1 deficiency. Depletion of Cdkn1a and Bbc3, which were upregulated by Trp53, rescued Rb1-deficient cells from undergoing cell cycle arrest and apoptosis. These results suggest that the CDKN1B-RB1-E2F1 pathway is essential for SSC self-renewal and protects SSCs against genomic damage. PMID:25959802

  4. Sulforaphane protects against cytokine- and streptozotocin-induced {beta}-cell damage by suppressing the NF-{kappa}B pathway

    SciTech Connect

    Song, Mi-Young; Kim, Eun-Kyung; Moon, Woo-Sung; Park, Jin-Woo; Kim, Hyung-Jin; So, Hong-Seob; Park, Raekil; Kwon, Kang-Beom Park, Byung-Hyun

    2009-02-15

    Sulforaphane (SFN) is an indirect antioxidant that protects animal tissues from chemical or biological insults by stimulating the expression of several NF-E2-related factor-2 (Nrf2)-regulated phase 2 enzymes. Treatment of RINm5F insulinoma cells with SFN increases Nrf2 nuclear translocation and expression of phase 2 enzymes. In this study, we investigated whether the activation of Nrf2 by SFN treatment or ectopic overexpression of Nrf2 inhibited cytokine-induced {beta}-cell damage. Treatment of RIN cells with IL-1{beta} and IFN-{gamma} induced {beta}-cell damage through a NF-{kappa}B-dependent signaling pathway. Activation of Nrf2 by treatment with SFN and induction of Nrf2 overexpression by transfection with Nrf2 prevented cytokine toxicity. The mechanism by which Nrf2 activation inhibited NF-{kappa}B-dependent cell death signals appeared to involve the reduction of oxidative stress, as demonstrated by the inhibition of cytokine-induced H{sub 2}O{sub 2} production. The protective effect of SFN was further demonstrated by the restoration of normal insulin secreting responses to glucose in cytokine-treated rat pancreatic islets. Furthermore, pretreatment with SFN blocked the development of type 1 diabetes in streptozotocin-treated mice.

  5. Protective effects of the extracts of Barringtonia racemosa shoots against oxidative damage in HepG2 cells

    PubMed Central

    Kong, Kin Weng; Mat-Junit, Sarni; Aminudin, Norhaniza; Hassan, Fouad Abdulrahman; Ismail, Amin

    2016-01-01

    Barringtonia racemosa is a tropical plant with medicinal values. In this study, the ability of the water extracts of the leaf (BLE) and stem (BSE) from the shoots to protect HepG2 cells against oxidative damage was studied. Five major polyphenolic compounds consisting of gallic acid, ellagic acid, protocatechuic acid, quercetin and kaempferol were identified using HPLC-DAD and ESI-MS. Cell viability assay revealed that BLE and BSE were non-cytotoxic (cell viabilities >80%) at concentration less than 250 µg/ml and 500 µg/ml, respectively. BLE and BSE improved cellular antioxidant status measured by FRAP assay and protected HepG2 cells against H2O2-induced cytotoxicity. The extracts also inhibited lipid peroxidation in HepG2 cells as well as the production of reactive oxygen species. BLE and BSE could also suppress the activities of superoxide dismutase and catalase during oxidative stress. The shoots of B. racemosa can be an alternative bioactive ingredient in the prevention of oxidative damage. PMID:26839752

  6. Kidney Injury Molecule-1 Protects against Gα12 Activation and Tissue Damage in Renal Ischemia-Reperfusion Injury

    PubMed Central

    Ismail, Ola Z.; Zhang, Xizhong; Wei, Junjun; Haig, Aaron; Denker, Bradley M.; Suri, Rita S.; Sener, Alp; Gunaratnam, Lakshman

    2016-01-01

    Ischemic acute kidney injury is a serious untreatable condition. Activation of the G protein α12 (Gα12) subunit by reactive oxygen species is a major cause of tissue damage during renal ischemia-reperfusion injury. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is highly up-regulated during acute kidney injury, but the physiologic significance of this up-regulation is unclear. Here, we report for the first time that Kim-1 inhibits Gα12 activation and protects mice against renal ischemia-reperfusion injury. We reveal that Kim-1 physically interacts with and inhibits cellular Gα12 activation after inflammatory stimuli, including reactive oxygen species, by blocking GTP binding to Gα12. Compared with Kim-1+/+ mice, Kim-1−/− mice exhibited greater Gα12 and downstream Src activation both in primary tubular epithelial cells after in vitro stimulation with H2O2 and in whole kidneys after unilateral renal artery clamping. Finally, we show that Kim-1–deficient mice had more severe kidney dysfunction and tissue damage after bilateral renal artery clamping, compared with wild-type mice. Our results suggest that KIM-1 is an endogenous protective mechanism against renal ischemia-reperfusion injury through inhibition of Gα12. PMID:25759266

  7. Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model.

    PubMed

    Lin, Wei-Ting; Chen, Ran-Chou; Lu, Wen-Wei; Liu, Shing-Hwa; Yang, Feng-Yi

    2015-04-15

    The protein expressions of neurotrophic factors can be enhanced by low-intensity pulsed ultrasound (LIPUS) stimulation in the brain. The purpose of this study was to demonstrate the protective effect of LIPUS stimulation against aluminum-induced cerebral damage in Alzheimer's disease rat model. LIPUS was administered 7 days before each aluminum chloride (AlCl3) administration, and concomitantly given with AlCl3 daily for a period of 6 weeks. Neurotrophic factors in hippocampus were measured by western blot analysis. Behavioral changes in the Morris water maze and elevated plus maze were examined in rats after administration of AlCl3. Various biochemical analyses were performed to evaluate the extent of brain damages. LIPUS is capable of prompting levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor (VEGF) in rat brain. AlCl3 administration resulted in a significant increase in the aluminum concentration, acetylcholinesterase activity and beta-amyloid (Aβ) deposition in AlCl3 treated rats. LIPUS stimulation significantly attenuated aluminum concentration, acetylcholinesterase activity, Aβ deposition and karyopyknosis in AlCl3 treated rats. Furthermore, LIPUS significantly improved memory retention in AlCl3-induced memory impairment. These experimental results indicate that LIPUS has neuroprotective effects against AlCl3-induced cerebral damages and cognitive dysfunction.

  8. Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model

    NASA Astrophysics Data System (ADS)

    Lin, Wei-Ting; Chen, Ran-Chou; Lu, Wen-Wei; Liu, Shing-Hwa; Yang, Feng-Yi

    2015-04-01

    The protein expressions of neurotrophic factors can be enhanced by low-intensity pulsed ultrasound (LIPUS) stimulation in the brain. The purpose of this study was to demonstrate the protective effect of LIPUS stimulation against aluminum-induced cerebral damage in Alzheimer's disease rat model. LIPUS was administered 7 days before each aluminum chloride (AlCl3) administration, and concomitantly given with AlCl3 daily for a period of 6 weeks. Neurotrophic factors in hippocampus were measured by western blot analysis. Behavioral changes in the Morris water maze and elevated plus maze were examined in rats after administration of AlCl3. Various biochemical analyses were performed to evaluate the extent of brain damages. LIPUS is capable of prompting levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor (VEGF) in rat brain. AlCl3 administration resulted in a significant increase in the aluminum concentration, acetylcholinesterase activity and beta-amyloid (Aβ) deposition in AlCl3 treated rats. LIPUS stimulation significantly attenuated aluminum concentration, acetylcholinesterase activity, Aβ deposition and karyopyknosis in AlCl3 treated rats. Furthermore, LIPUS significantly improved memory retention in AlCl3-induced memory impairment. These experimental results indicate that LIPUS has neuroprotective effects against AlCl3-induced cerebral damages and cognitive dysfunction.

  9. Protective activity of cedron (Aloysia triphylla) infusion over genetic damage induced by cisplatin evaluated by the comet assay technique.

    PubMed

    Zamorano-Ponce, Enrique; Fernández, Julia; Vargas, Gilda; Rivera, Pilar; Carballo, Marta A

    2004-08-30

    Using the comet assay technique, this paper examines the protection from the cisplatin-induced genetic damage in mouse bone marrow cells provided by cedron-leaf infusion. Animals were separated into six groups: (I) untreated, (II) negative control, (III) treated with cedron-leaf infusion (5%), (IV) treated with cisplatin (6 mg/kg b.w.), (V) pretreated with infusion and treated with cisplatin and (VI) positive control (cyclophosphamide, 20 mg/kg b.w.). Based on the tail moment values found, four types of comets were distinguished. No statistical differences (P<0.01) were found between untreated animals, negative control and infusion treated mice. As expected, treatment of mice with a single dose of cis-DDP-induced genetic damage and the pretreatment with infusion prior to cis-DDP injection inhibited the capacity of cisplatin to induce genetic damage. Cell viability was up to 90% in all cases. The results suggest that infusion could exert its in vivo antigenotoxic action by enhancing the antioxidant status of bone marrow cells. The found could be attributed to its scavenging potency towards free radicals. PMID:15294350

  10. Protection against Whole Body γ-Irradiation Induced Oxidative Stress and Clastogenic Damage in Mice by Ginger Essential Oil.

    PubMed

    Jeena, Kottarapat; Liju, Vijayasteltar B; Ramanath, Viswanathan; Kuttan, Ramadasan

    2016-01-01

    Radioprotective effects of ginger essential oil (GEO) on mortality, body weight alteration, hematological parameters, antioxidant status and chromosomal damage were studied in irradiated mice. Regression analysis of survival data in mice exposed to radiation yielded LD50/30 as 7.12 and 10.14 Gy for control (irradiation alone) and experimental (GEO-treated irradiated) mice, respectively, with a dose reduction factor (DRF) of 1.42. In mice exposed to whole-body gamma-irradiation (6 Gy), GEO pre-treatment at 100 and 500 mg/kg b.wt (orally) significantly ameliorated decreased hematological and immunological parameters. Radiation induced reduction in intestinal tissue antioxidant enzyme levels such as superoxide dismutase, catalase, glutathione peroxidase and glutathione was also reversed following administration of GEO. Tissue architecture of small intestine which was damaged following irradiation was improved upon administration of GEO. Anticlastogenic effects of GEO were studied by micronuclei assay, chromosomal aberration and alkaline gel electrophoresis assay. GEO significantly decreased the formation of micronuclei, increased the P/N ratio, inhibited the formation of chromosomal aberrations and protected agaisnt cellular DNA damage in bone marrow cells as revealed by comet assay. These results are supportive of use of GEO as a potential radioprotective compound. PMID:27039766

  11. Protective activity of cedron (Aloysia triphylla) infusion over genetic damage induced by cisplatin evaluated by the comet assay technique.

    PubMed

    Zamorano-Ponce, Enrique; Fernández, Julia; Vargas, Gilda; Rivera, Pilar; Carballo, Marta A

    2004-08-30

    Using the comet assay technique, this paper examines the protection from the cisplatin-induced genetic damage in mouse bone marrow cells provided by cedron-leaf infusion. Animals were separated into six groups: (I) untreated, (II) negative control, (III) treated with cedron-leaf infusion (5%), (IV) treated with cisplatin (6 mg/kg b.w.), (V) pretreated with infusion and treated with cisplatin and (VI) positive control (cyclophosphamide, 20 mg/kg b.w.). Based on the tail moment values found, four types of comets were distinguished. No statistical differences (P<0.01) were found between untreated animals, negative control and infusion treated mice. As expected, treatment of mice with a single dose of cis-DDP-induced genetic damage and the pretreatment with infusion prior to cis-DDP injection inhibited the capacity of cisplatin to induce genetic damage. Cell viability was up to 90% in all cases. The results suggest that infusion could exert its in vivo antigenotoxic action by enhancing the antioxidant status of bone marrow cells. The found could be attributed to its scavenging potency towards free radicals.

  12. Protective Effect of Boric Acid on Oxidative DNA Damage In Chinese Hamster Lung Fibroblast V79 Cell Lines

    PubMed Central

    Yılmaz, Sezen; Ustundag, Aylin; Cemiloglu Ulker, Ozge; Duydu, Yalcın

    2016-01-01

    Objective Many studies have been published on the antioxidative effects of boric acid (BA) and sodium borates in in vitro studies. However, the boron (B) concentrations tested in these in vitro studies have not been selected by taking into account the realistic blood B concentrations in humans due to the lack of comprehensive epidemiological studies. The recently published epidemiological studies on B exposure conducted in China and Turkey provided blood B concentrations for both humans in daily life and workers under extreme exposure conditions in occupational setting. The results of these studies have made it possible to test antioxidative effects of BA in in vitro studies within the concentra- tion range relevant to humans. The aim of this study was to investigate the protective ef- fects of BA against oxidative DNA damage in V79 (Chinese hamster lung fibroblast) cells. The concentrations of BA tested for its protective effect was selected by taking the blood B concentrations into account reported in previously published epidemiological studies. Therefore, the concentrations of BA tested in this study represent the exposure levels for humans in both daily life and occupational settings. Materials and Methods In this experimental study, comet assay and neutral red uptake (NRU) assay methods were used to determinacy to toxicity and genotoxicity of BA and hydrogen peroxide (H2O2). Results The results of the NRU assay showed that BA was not cytotoxic within the tested concentrations (3, 10, 30, 100 and 200 µM). These non-cytotoxic concentrations were used for comet assay. BA pre-treatment significantly reduced (P<0.05, one-way ANOVA) the DNA damaging capacity of H2O2 at each tested BA concentrations in V79 cells. Conclusion Consequently, pre-incubation of V79 cells with BA has significantly reduced the H2O2-induced oxidative DNA damage in V79 cells. The protective effect of BA against oxidative DNA damage in V79 cells at 5, 10, 50, 100 and 200 μM (54, 108, 540

  13. Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in male rat

    PubMed Central

    Dhibi, Sabah; Mbarki, Sakhria; Elfeki, Abdelfettah; Hfaiedh, Najla

    2014-01-01

    Plants have historically been used in treating many diseases. Eucalyptus globules, a rich source of bioactive compounds, and have been shown to possess antioxidative properties. The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of Eucalyptus globulus extract upon acetaminophen-induced damages in kidney. Our study is realized in the Department of Biology, Faculty of Sciences of Sfax (Tunisia). 32 Wistar male rats; were divided into 4 batches: a control group (n=8), a group of rats treated with acetaminophen (goomg/kg) by intraperitoneal injection during 4 days (n=8), a group receiving Eucalyptus globulus extract (130 mg of dry leaves/kg/day) in drinking water during 42 days after 2 hours of acetaminophen administration (during 4 days) (n=8) and group received only Eucalyptus (n=8) during 42 days. After 6 weeks, animals from each group were rapidly sacrificed by decapitation. Blood serum was obtained by centrifugation. Under our experimental conditions, acetaminophen poisoning resulted in an oxidative stress evidenced by statistically significant losses in the activities of catalase (CAT), superoxide-dismutase (SOD), glutathione-peroxidase (GPX) activities and an increase in lipids peroxidation level in renal tissue of acetaminophen-treated group compared with the control group. Acetaminophen also caused kidney damage as evident by statistically significant (p<0.05) increase in levels of creatinine and urea and decreased levels of uric acid and proteins in blood. Histological analysis demonstrated alteration of proximal tubules, atrophy of the glomerule and dilatation of urinary space. Previous administration of plant extract is found to alleviate this acetaminophen-induced damage. PMID:24856382

  14. Ampelopsin protects endothelial cells from hyperglycemia-induced oxidative damage by inducing autophagy via the AMPK signaling pathway.

    PubMed

    Liang, Xinyu; Zhang, Ting; Shi, Linying; Kang, Chao; Wan, Jing; Zhou, Yong; Zhu, Jundong; Mi, Mantian

    2015-01-01

    Diabetic angiopathy is a major diabetes-specific complication that often begins with endothelial dysfunction induced by hyperglycemia; however, the pathological mechanisms of this progression remain unclear. Ampelopsin is a natural flavonol that has strong antioxidant activity, but little information is available regarding its antidiabetic effect. This study focused on the effect of ampelopsin on hyperglycemia-induced oxidative damage and the underlying mechanism of this effect in human umbilical vein endothelial cells (HUVECs). We found that hyperglycemia impaired autophagy in HUVECs through the inhibition of AMP-activated protein kinase (AMPK), which directly led to endothelial cell damage. Ampelopsin significantly attenuated the detrimental effect of hyperglycemia-induced cell dysfunction in a concentration-dependent manner in HUVECs. Ampelopsin significantly upregulated LC3-II, Beclin1, and Atg5 protein levels but downregulated p62 protein levels in HUVECs. Transmission electron microscopy and confocal microscopy indicated that ampelopsin notably induced autophagosomes and LC3-II dots, respectively. Additionally, the autophagy-specific inhibitor 3-MA, as well as Atg5 and Beclin1 siRNA pretreatment, markedly attenuated ampelopsin-induced autophagy, which subsequently abolished the protective effect of ampelopsin against hyperglycemia in HUVECs. Moreover, ampelopsin also increased AMPK activity and inhibited mTOR (mammalian target of rapamycin) complex activation. Ampelopsin-induced autophagy was attenuated by the AMPK antagonist compound C but strengthened by the AMPK agonist AICAR (5-minoimidazole-4-carboxamide ribonucleotide). Furthermore, AMPK siRNA transfection eliminated ampelopsin's alleviation of cell injury induced by hyperglycemia. The protective effect of ampelopsin against hyperglycemia-induced cell damage, which functions by targeting autophagy via AMPK activation, makes it a promising pharmacological treatment for type-2 diabetes.

  15. The protective effects of the traditional Chinese herbs against renal damage induced by extracorporeal shock wave lithotripsy: a clinical study.

    PubMed

    Sheng, Binwu; He, Dalin; Zhao, Jun; Chen, Xingfa; Nan, Xunyi

    2011-04-01

    Extracorporeal shock wave lithotripsy (ESWL)-induced renal damage can occur as a result of multiple mechanisms. We have reported previously that Astragalus membranaceus, Salvia miltiorrhiza, a decoction of six drugs containing rhizoma Rehmanniae preparata and supplements of a few traditional Chinese medicinal herbs for invigorating the kidney and excreting calculus, have a protective effect on renal injury induced by high-energy shock waves (HESW) in rabbits. In this clinical study we further investigate the protective effects of these traditional Chinese herbs against renal damage induced by ESWL. Sixty consenting patients with renal calculus who underwent ESWL treatment were included and randomly assigned to the medication group or control group. Post-ESWL plasma nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA), and serum tumor necrosis factor α (TNF-α) increased significantly in the controls (P < 0.05), while in the medication group, slightly but not significantly elevated levels of plasma ET-1, NO, and serum TNF-α were found. The difference between the groups was statistically significant (P < 0.05). The levels of superoxide dismutase (SOD) decreased gradually in the controls, reaching a trough 72 h after ESWL (P < 0.05), while in the treated group it was unchanged, and remained at a level higher versus the controls (P < 0.05). Plasma NO peaked twice by 72 h and at 1 week in the controls (P < 0.05). Urinary enzymes and β(2)-microglobulin increased significantly and peaked by 24 h and immediately after ESWL (P < 0.05). These values were greater in the controls, and the difference was statistically significant (P < 0.05). This study demonstrates that the preparations of traditional Chinese medicines for invigorating the kidney and excreting calculus can reduce renal tubular damage induced by ESWL, and can shorten the recovery time of renal tubules in human subjects. PMID:20607528

  16. Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage.

    PubMed

    Sun, Zhaorui; Liu, Hongmei; Yang, Zhizhou; Shao, Danbing; Zhang, Wei; Ren, Yi; Sun, Baodi; Lin, Jinfeng; Xu, Min; Nie, Shinan

    2014-09-01

    Intestinal trefoil factor (ITF, also named as trefoil factor 3, TFF3) is a member of the TFF-domain peptide family, which plays an essential role in the regulation of cell survival, cell migration and maintains mucosal epithelial integrity in the gastrointestinal tract. However, the underlying mechanisms and associated molecules remain unclear. The aim of this study was to explore the protective effects of ITF on gastric mucosal epithelium injury and its possible molecular mechanisms of action. In the present study, we show that ITF was able to promote the proliferation and migration of GES-1 cells via a mechanism that involves the PI3K/Akt signaling pathway. Western blot results indicated that ITF induced a dose- and time-dependent increase in the Akt signaling pathway. ITF also plays an essential role in the restitution of GES-1 cell damage induced by lipopolysaccharide (LPS). LPS induced the apoptosis of GES-1 cells, decreased cell viability significantly (P<0.01) and led to epithelial tight junction damage, which is attenuated via ITF treatment. The protective effect of ITF on the integrity of GES-1 was abrogated by inhibition of the PI3K/Akt pathway. Taken together, our results demonstrate that ITF promotes the proliferation and migration of gastric mucosal epithelial cells and preserves gastric mucosal epithelial integrity after damage is mediated by activation of the PI3K/Akt signaling pathway. This study suggested that the PI3K/Akt pathway could act as a key intracellular pathway in the gastric mucosal epithelium that may serve as a therapeutic target to preserve epithelial integrity during injury.

  17. Ground based impact testing of Orbiter thermal protection system materials in support of the Columbia accident investigation

    NASA Astrophysics Data System (ADS)

    Kerr, Justin Hamilton

    On January 16, 2003, the Space Shuttle Columbia (OV-102) was launched for a nominal 16-day mission of microgravity research. Fifteen days and 20 hours after launch, and just 16 minutes before its scheduled landing, the OV-102 vehicle disintegrated during its descent. The entire crew was lost. Film and video cameras located around the launch complex captured images of the vehicle during its ascent. Of note were data that showed a piece of debris strike the port wing at approximately 82 sec after lift-off (T+82). As resulting analysis would show, the source of the debris was the left bipod ramp of the Shuttle external tank. This foam debris struck the Orbiter leading edge at sufficient velocity to breech the thermal protection system (TPS). During reentry at the end of the mission, the hot plasma impinged inside the Orbiter wing and aerodynamic forces ultimately failed the wing structure. This thesis documents the activities conducted to evaluate the effects of foam impact on Orbiter TPS. These efforts were focused on, to the greatest extent practical, replicating the impact event during the STS-107 mission ascent. This thesis fully documents the test program development, methodology, results, analysis, and conclusions to the degree that future investigators can reproduce the tests and understand the basis for decisions made during the development of the tests.

  18. Protective effect of alpha-tocopherol-6-O-phosphate against ultraviolet B-induced damage in cultured mouse skin.

    PubMed

    Nakayama, Satomi; Katoh, Eiko M; Tsuzuki, Toshi; Kobayashi, Shizuko

    2003-08-01

    The ability of the novel water-soluble provitamin E, alpha-tocopherol-6-O-phosphate, to protect against ultraviolet B-induced damage in cultured mouse skin was investigated and compared with the protectiveness of alpha-tocopherol acetate in cultured mouse skin. Pretreatment of skin with 0.5% (9.4 mM) alpha-tocopherol-6-O-phosphate in medium for 3 h significantly prevented such photodamage as sunburn cell formation, DNA degradation, and lipid peroxidation, which were induced in control cultured skin by a single dose of ultraviolet B irradiation at 0 to 40 kJ per m2 (290-380 nm, maximum 312 nm). This protection was greater than that seen with alpha-tocopherol acetate, the most common provitamin E that is used in commercial human skin care products. The concentration of alpha-tocopherol in cultured skin pretreated with 0.5% alpha-tocopherol-6-O-phosphate rose to approximately two to three times that found in the control skin and the reduction in cutaneous alpha-tocopherol that was induced by ultraviolet irradiation was significantly inhibited. In the group pretreated with 0.5% alpha-tocopherol acetate, however, conversion of alpha-tocopherol acetate to alpha-tocopherol was not observed, although the level of provitamin incorporated into the cultured skin was the same as that for alpha-tocopherol-6-O-phosphate. These findings indicated that the enhanced ability of alpha-tocopherol-6-O-phosphate to protect against ultraviolet B-induced skin damage compared with alpha-tocopherol acetate may have been due to alpha-tocopherol-6-O-phosphate's conversion to alpha-tocopherol. Moreover, following pretreatment with a 0.5% alpha-tocopherol-6-O-phosphate, alpha-tocopherol-6-O-phosphate was incorporated into the human skin in a three-dimensional model and 5% of the incorporated alpha-tocopherol-6-O-phosphate was converted to alpha-tocopherol. These results suggest that treatment with the novel provitamin E, alpha-tocopherol-6-O-phosphate may be useful in preventing ultraviolet

  19. Protective effects of antioxidants and anti-inflammatory agents against manganese-induced oxidative damage and neuronal injury

    SciTech Connect

    Milatovic, Dejan; Gupta, Ramesh C.; Yu, Yingchun; Zaja-Milatovic, Snjezana; Aschner, Michael

    2011-11-15

    Exposure to excessive manganese (Mn) levels leads to neurotoxicity, referred to as manganism, which resembles Parkinson's disease (PD). Manganism is caused by neuronal injury in both cortical and subcortical regions, particularly in the basal ganglia. The basis for the selective neurotoxicity of Mn is not yet fully understood. However, several studies suggest that oxidative damage and inflammatory processes play prominent roles in the degeneration of dopamine-containing neurons. In the present study, we assessed the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates and associated neuronal dysfunctions both in vitro and in vivo. Results from our in vitro study showed a significant (p < 0.01) increase in biomarkers of oxidative damage, F{sub 2}-isoprostanes (F{sub 2}-IsoPs), as well as the depletion of ATP in primary rat cortical neurons following exposure to Mn (500 {mu}M) for 2 h. These effects were protected when neurons were pretreated for 30 min with 100 of an antioxidant, the hydrophilic vitamin E analog, trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), or an anti-inflammatory agent, indomethacin. Results from our in vivo study confirmed a significant increase in F{sub 2}-IsoPs levels in conjunction with the progressive spine degeneration and dendritic damage of the striatal medium spiny neurons (MSNs) of mice exposed to Mn (100 mg/kg, s.c.) 24 h. Additionally, pretreatment with vitamin E (100 mg/kg, i.p.) or ibuprofen (140 {mu}g/ml in the drinking water for two weeks) attenuated the Mn-induced increase in cerebral F{sub 2}-IsoPs? and protected the MSNs from dendritic atrophy and dendritic spine loss. Our findings suggest that the mediation of oxidative stress/mitochondrial dysfunction and the control of alterations in biomarkers of oxidative injury, neuroinflammation and synaptodendritic degeneration may provide an effective, multi-pronged therapeutic strategy for protecting dysfunctional dopaminergic

  20. Candu 6 severe core damage accident consequence analysis for steam generator tube rupture scenario using MAAP4-CANDU V4.0.5A: preliminary results

    SciTech Connect

    Petoukhov, S.M.; Awadh, B.; Mathew, P.M.

    2006-07-01

    This paper describes the preliminary results of the consequence analysis for a generic AECL CANDU 6 station, when it undergoes a postulated, low probability Steam Generator multiple Tube Rupture (SGTR) severe accident with assumed unavailability of several critical plant safety systems. The Modular Accident Analysis Program for CANDU (MAAP4-CANDU) code was used for this analysis. The SGTR accident is assumed to begin with the guillotine rupture of 10 steam generator tubes in one steam generator in Primary Heat Transport System (PHTS) loop 1. For the reference case, the following systems were assumed unavailable: moderator and shield cooling, emergency core cooling, crash cool-down, and main and auxiliary feed water. Two additional cases were analyzed, one with the crash cool-down system available, and another with the crash cool-down and the auxiliary feed water systems available. The three scenarios considered in this study show that most of the initial fission product inventory would be retained within the containment by various fission product retention mechanisms. For the case where the crash cool-down system was credited but the auxiliary feed water systems were not credited, the total mass of volatile fission products released to the environment including stable and radioactive isotopes was about four times more than in the reference case, because fission products could be released directly from the PHTS to the environment through the Main Steam Safety Valves (MSSVs), bypassing the containment. For the case where the crash cool-down and auxiliary feed water systems were credited, the volatile fission product release to the environment was insignificant, because the fission product release was substantially mitigated by scrubbing in the water pool in the secondary side of the steam generator (SG). (authors)

  1. Image Processing and control of a programmable spatial light modulator for optic damage protection

    SciTech Connect

    Awwal, A; Leach, R; Brunton, G; Tse, E; Matone, J; Heebner, J

    2010-12-06

    The heart of the National Ignition Facility is a megajoule-class laser system consisting of 192 beams used to drive inertial confinement fusion reactions. A recently installed system of programmable, liquid-crystal-based spatial light modulators adds the capability of arbitrarily shaping the spatial beam profiles in order to enhance operational flexibility. Its primary intended use is for introducing 'blocker' obscurations shadowing isolated flaws on downstream optical elements that would otherwise be damaged by high fluence laser illumination. Because an improperly shaped blocker pattern can lead to equipment damage, both the position and shape of the obscurations must be carefully verified prior to high-fluence operations. An automatic alignment algorithm is used to perform detection and estimation of the imposed blocker centroid positions compared to their intended locations. Furthermore, in order to minimize the spatially-varying nonlinear response of the device, a calibration of the local magnification is performed at multiple sub-image locations. In this paper, we describe the control and associated image processing of this device that helps to enhance the safety and longevity of the overall system.

  2. Accumulation of Flavonols over Hydroxycinnamic Acids Favors Oxidative Damage Protection under Abiotic Stress.

    PubMed

    Martinez, Vicente; Mestre, Teresa C; Rubio, Francisco; Girones-Vilaplana, Amadeo; Moreno, Diego A; Mittler, Ron; Rivero, Rosa M

    2016-01-01

    Efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Although multiple pathways, enzymes, and antioxidants are present in plants, their exact roles during different stress responses remain unclear. Here, we report on the characterization of the different antioxidant mechanisms of tomato plants subjected to heat stress, salinity stress, or a combination of both stresses. All the treatments applied induced an increase of oxidative stress, with the salinity treatment being the most aggressive, resulting in plants with the lowest biomass, and the highest levels of H2O2 accumulation, lipid peroxidation, and protein oxidation. However, the results obtained from the transcript expression study and enzymatic activities related to the ascorbate-glutathione pathway did not fully explain the differences in the oxidative damage observed between salinity and the combination of salinity and heat. An exhaustive metabolomics study revealed the differential accumulation of phenolic compounds depending on the type of abiotic stress applied. An analysis at gene and enzyme levels of the phenylpropanoid metabolism concluded that under conditions where flavonols accumulated to a greater degree as compared to hydroxycinnamic acids, the oxidative damage was lower, highlighting the importance of flavonols as powerful antioxidants, and their role in abiotic stress tolerance.

  3. Photo-damage, photo-protection and age-related macular degeneration.

    PubMed

    Marquioni-Ramella, Melisa D; Suburo, Angela M

    2015-09-26

    Age-related macular degeneration (AMD) is a degenerative retinal disease that causes blindness in people 60-65 years and older, with the highest prevalence appearing in people 90 years-old or more. Epidemiological estimates indicate that the number of cases is increasing, and will almost double in the next 20 years. Preventive measures require precise etiological knowledge. This is quite difficult, since AMD is a multifactorial condition with intricate relationships between causes and risk factors. In this review, we describe the impact of light on the structure and physiology of the retina and the pigment epithelium, taking into account the continuous exposure to natural and artificial light sources along the life of an individual. A large body of experimental evidence demonstrates the toxic effects of some lighting conditions on the retina and the pigment epithelium, and consensus exists about the importance of photo-oxidation phenomena in the causality chain between light and retinal damage. Here, we analyzed the transmission of light to the retina, and compared the aging human macula in healthy and diseased retinas, as shown by histology and non-invasive imaging systems. Finally, we have compared the putative retinal photo-sensitive molecular structures that might be involved in the genesis of AMD. The relationship between these compounds and retinal damage supports the hypothesis of light as an important initiating cause of AMD.

  4. Environmental enrichment protects the retina from early diabetic damage in adult rats.

    PubMed

    Dorfman, Damián; Aranda, Marcos L; González Fleitas, María Florencia; Chianelli, Mónica S; Fernandez, Diego C; Sande, Pablo H; Rosenstein, Ruth E

    2014-01-01

    Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Available treatments are not completely effective. We analyzed the effect of environmental enrichment on retinal damage induced by experimental diabetes in adult Wistar rats. Diabetes was induced by an intraperitoneal injection of streptozotocin. Three days after vehicle or streptozotocin injection, animals were housed in enriched environment or remained in a standard environment. Retinal function (electroretinogram, and oscillatory potentials), retinal morphology, blood-retinal barrier integrity, synaptophysin, astrocyte and Müller cell glial fibrillary acidic protein, vascular endothelial growth factor, tumor necrosis factor-α, and brain-derived neurotrophic factor levels, as well as lipid peroxidation were assessed in retina from diabetic animals housed in standard or enriched environment. Environmental enrichment preserved scotopic electroretinogram a-wave, b-wave and oscillatory potential amplitude, avoided albumin-Evan's blue leakage, prevented the decrease in retinal synaptophysin and astrocyte glial fibrillary acidic protein levels, the increase in Müller cell glial fibrillary acidic protein, vascular endothelial growth factor and tumor necrosis factor-α levels, as well as oxidative stress induced by diabetes. In addition, enriched environment prevented the decrease in retinal brain-derived neurotrophic factor levels induced by experimental diabetes. When environmental enrichment started 7 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that enriched environment could attenuate the early diabetic damage in the retina from adult rats.

  5. Photo-damage, photo-protection and age-related macular degeneration.

    PubMed

    Marquioni-Ramella, Melisa D; Suburo, Angela M

    2015-09-26

    Age-related macular degeneration (AMD) is a degenerative retinal disease that causes blindness in people 60-65 years and older, with the highest prevalence appearing in people 90 years-old or more. Epidemiological estimates indicate that the number of cases is increasing, and will almost double in the next 20 years. Preventive measures require precise etiological knowledge. This is quite difficult, since AMD is a multifactorial condition with intricate relationships between causes and risk factors. In this review, we describe the impact of light on the structure and physiology of the retina and the pigment epithelium, taking into account the continuous exposure to natural and artificial light sources along the life of an individual. A large body of experimental evidence demonstrates the toxic effects of some lighting conditions on the retina and the pigment epithelium, and consensus exists about the importance of photo-oxidation phenomena in the causality chain between light and retinal damage. Here, we analyzed the transmission of light to the retina, and compared the aging human macula in healthy and diseased retinas, as shown by histology and non-invasive imaging systems. Finally, we have compared the putative retinal photo-sensitive molecular structures that might be involved in the genesis of AMD. The relationship between these compounds and retinal damage supports the hypothesis of light as an important initiating cause of AMD. PMID:26198091

  6. Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

    PubMed

    Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

    2016-08-17

    Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase. PMID:27362436

  7. Chronic Fluoride Toxicity and Myocardial Damage: Antioxidant Offered Protection in Second Generation Rats

    PubMed Central

    Basha, Mahaboob P.; Sujitha, N. S.

    2011-01-01

    This experiment was designed to investigate the extent of peroxidative changes and histological alterations in the myocardium of rats exposed to high fluoride for two generations, in addition to ameliorative role of selenium and vitamin E on the above indices. Adult albino Wistar rats were given fluoride through drinking water (200 ppm F) and maintained subsequently for two generations, while they were exposed to fluoride throughout the experiment. Fluoride treatment significantly increased the lipid peroxidation and decreased the activity of antioxidant enzymes, viz., catalase, superoxide dismutase, and glutathione level in auricle and ventricle regions of the heart. Decreased feed and water consumption, organ somatic index and marginal drop in body growth rate were observed. Decreased antioxidant enzymes and increased malondialdehyde levels might be related to oxidative damage that occurs variably in the myocardium of rats. Biochemical changes were supported by the histological observations, which also revealed that chronic exposure to fluoride causes damage to the myocardium. Results of this study can be taken as an index of cardio-toxicity in rats exposed to water fluoridation. Further, oral supplementation of selenium and vitamin E not only inhibited oxidative stress but also enhanced the activities of antioxidant enzymes. Administration of antioxidants during fluoride exposure significantly overcame cardiac fluoride toxicity and therefore may be a therapeutic strategy for fluorotic victims. PMID:21976813

  8. Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium.

    PubMed

    Amanuma, Yusuke; Ohashi, Shinya; Itatani, Yoshiro; Tsurumaki, Mihoko; Matsuda, Shun; Kikuchi, Osamu; Nakai, Yukie; Miyamoto, Shin'ichi; Oyama, Tsunehiro; Kawamoto, Toshihiro; Whelan, Kelly A; Nakagawa, Hiroshi; Chiba, Tsutomu; Matsuda, Tomonari; Muto, Manabu

    2015-01-01

    Acetaldehyde is an ethanol-derived definite carcinogen that causes oesophageal squamous cell carcinoma (ESCC). Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that eliminates acetaldehyde, and impairment of ALDH2 increases the risk of ESCC. ALDH2 is produced in various tissues including the liver, heart, and kidney, but the generation and functional roles of ALDH2 in the oesophagus remain elusive. Here, we report that ethanol drinking increased ALDH2 production in the oesophagus of wild-type mice. Notably, levels of acetaldehyde-derived DNA damage represented by N(2)-ethylidene-2'-deoxyguanosine were higher in the oesophagus of Aldh2-knockout mice than in wild-type mice upon ethanol consumption. In vitro experiments revealed that acetaldehyde induced ALDH2 production in both mouse and human oesophageal keratinocytes. Furthermore, the N(2)-ethylidene-2'-deoxyguanosine levels increased in both Aldh2-knockout mouse keratinocytes and ALDH2-knockdown human keratinocytes treated with acetaldehyde. Conversely, forced production of ALDH2 sharply diminished the N(2)-ethylidene-2'-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage. PMID:26374466

  9. Accumulation of Flavonols over Hydroxycinnamic Acids Favors Oxidative Damage Protection under Abiotic Stress

    PubMed Central

    Martinez, Vicente; Mestre, Teresa C.; Rubio, Francisco; Girones-Vilaplana, Amadeo; Moreno, Diego A.; Mittler, Ron; Rivero, Rosa M.

    2016-01-01

    Efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Although multiple pathways, enzymes, and antioxidants are present in plants, their exact roles during different stress responses remain unclear. Here, we report on the characterization of the different antioxidant mechanisms of tomato plants subjected to heat stress, salinity stress, or a combination of both stresses. All the treatments applied induced an increase of oxidative stress, with the salinity treatment being the most aggressive, resulting in plants with the lowest biomass, and the highest levels of H2O2 accumulation, lipid peroxidation, and protein oxidation. However, the results obtained from the transcript expression study and enzymatic activities related to the ascorbate-glutathione pathway did not fully explain the differences in the oxidative damage observed between salinity and the combination of salinity and heat. An exhaustive metabolomics study revealed the differential accumulation of phenolic compounds depending on the type of abiotic stress applied. An analysis at gene and enzyme levels of the phenylpropanoid metabolism concluded that under conditions where flavonols accumulated to a greater degree as compared to hydroxycinnamic acids, the oxidative damage was lower, highlighting the importance of flavonols as powerful antioxidants, and their role in abiotic stress tolerance. PMID:27379130

  10. Cytoplasmic localization of p21 protects trophoblast giant cells from DNA damage induced apoptosis.

    PubMed

    de Renty, Christelle; DePamphilis, Melvin L; Ullah, Zakir

    2014-01-01

    Proliferating trophoblast stem cells (TSCs) can differentiate into nonproliferating but viable trophoblast giant cells (TGCs) that are resistant to DNA damage induced apoptosis. Differentiation is associated with selective up-regulation of the Cip/Kip cyclin-dependent kinase inhibitors p57 and p21; expression of p27 remains constant. Previous studies showed that p57 localizes to the nucleus in TGCs where it is essential for endoreplication. Here we show that p27 also remains localized to the nucleus during TSC differentiation where it complements the role of p57. Unexpectedly, p21 localized to the cytoplasm where it was maintained throughout both the G- and S-phases of endocycles, and where it prevented DNA damage induced apoptosis. This unusual status for a Cip/Kip protein was dependent on site-specific phosphorylation of p21 by the Akt1 kinase that is also up-regulated in TGCs. Although cytoplasmic p21 is widespread among cancer cells, among normal cells it has been observed only in monocytes. The fact that it also occurs in TGCs reveals that p57 and p21 serve nonredundant functions, and suggests that the role of p21 in suppressing apoptosis is restricted to terminally differentiated cells.

  11. Environmental Enrichment Protects the Retina from Early Diabetic Damage in Adult Rats

    PubMed Central

    Dorfman, Damián; Aranda, Marcos L.; González Fleitas, María Florencia; Chianelli, Mónica S.; Fernandez, Diego C.; Sande, Pablo H.; Rosenstein, Ruth E.

    2014-01-01

    Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Available treatments are not completely effective. We analyzed the effect of environmental enrichment on retinal damage induced by experimental diabetes in adult Wistar rats. Diabetes was induced by an intraperitoneal injection of streptozotocin. Three days after vehicle or streptozotocin injection, animals were housed in enriched environment or remained in a standard environment. Retinal function (electroretinogram, and oscillatory potentials), retinal morphology, blood-retinal barrier integrity, synaptophysin, astrocyte and Müller cell glial fibrillary acidic protein, vascular endothelial growth factor, tumor necrosis factor-α, and brain-derived neurotrophic factor levels, as well as lipid peroxidation were assessed in retina from diabetic animals housed in standard or enriched environment. Environmental enrichment preserved scotopic electroretinogram a-wave, b-wave and oscillatory potential amplitude, avoided albumin-Evan's blue leakage, prevented the decrease in retinal synaptophysin and astrocyte glial fibrillary acidic protein levels, the increase in Müller cell glial fibrillary acidic protein, vascular endothelial growth factor and tumor necrosis factor-α levels, as well as oxidative stress induced by diabetes. In addition, enriched environment prevented the decrease in retinal brain-derived neurotrophic factor levels induced by experimental diabetes. When environmental enrichment started 7 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that enriched environment could attenuate the early diabetic damage in the retina from adult rats. PMID:25004165

  12. Oxidative DNA damage protective activity, antioxidant and anti-quorum sensing potentials of Moringa oleifera.

    PubMed

    Singh, Brahma N; Singh, B R; Singh, R L; Prakash, D; Dhakarey, R; Upadhyay, G; Singh, H B

    2009-06-01

    The aqueous extract of leaf (LE), fruit (FE) and seed (SE) of Moringa oleifera was assessed to examine the ability to inhibit the oxidative DNA damage, antioxidant and anti-quorum sensing (QS) potentials. It was found that these extracts could significantly inhibit the OH-dependent damage of pUC18 plasmid DNA and also inhibit synergistically with trolox, with an activity sequence of LE > FE > SE. HPLC and MS/MS analysis was carried out, which showed the presence of gallic acid, chlorogenic acid, ellagic acid, ferulic acid, kaempferol, quercetin and vanillin. The LE was with comparatively higher total phenolics content (105.04 mg gallic acid equivalents (GAE)/g), total flavonoids content (31.28 mg quercetin equivalents (QE)/g), and ascorbic acid content (106.95 mg/100 g) and showed better antioxidant activity (85.77%), anti-radical power (74.3), reducing power (1.1 ascorbic acid equivalents (ASE)/ml), inhibition of lipid peroxidation, protein oxidation, OH-induced deoxyribose degradation, and scavenging power of superoxide anion and nitric oxide radicals than did the FE, SE and standard alpha-tocopherol. Eventually, LE and FE were found to inhibit violacein production, a QS-regulated behavior in Chromobacterium violaceum 12472.

  13. Intraperitoneally administered biliverdin protects against UVB-induced skin photo-damage in hairless mice.

    PubMed

    Bai, Bingxue; Liu, Yingdi; You, Yan; Li, Yuzhen; Ma, Liangjuan

    2015-03-01

    Oxidative stress is shown to be responsible for ultraviolet B (UVB) irradiation-induced skin cancer and premature aging. Biliverdin (BVD), a product of heme oxygenase-1, has strong anti-oxidant and anti-inflammatory properties. In the present study, we investigated the effects of BVD on UVB-induced skin photo-damage in hairless mice. Mice were divided into three groups: control group, UVB group (only UVB irradiation) and BVD+UVB group (mice were intraperitoneally injected with BVD before each UVB irradiation). Intraperitoneal BVD injection resulted in a significant photoprotective effect by reducing morphological and histopathological changes to the skin. BVD also exhibited a significant antioxidant effect by increasing the superoxide dismutase (SOD) level and decreasing the thiobarbituric acid reactive substances (TBARS) level compared with the control group. In addition, BVD activated biliverdin reductase (BVR) expression and inhibited the UVB-induced increase of p38 mitogen-activated protein kinase phosphorylation (p-p38MAPK), MMP (matrix metalloproteinase)-1 and MMP-3 expression (p<0.05). It also significantly decreased the interleukin (IL)-6 level compared with the UVB group (p<0.05). In conclusion, these data suggest that the intraperitoneally administered BVD can prevent UVB irradiation-induced skin photo-damage in hairless mice and that this is likely mediated by its antioxidant and anti-inflammatory mechanisms and cell signal regulatory action.

  14. Accumulation of Flavonols over Hydroxycinnamic Acids Favors Oxidative Damage Protection under Abiotic Stress.

    PubMed

    Martinez, Vicente; Mestre, Teresa C; Rubio, Francisco; Girones-Vilaplana, Amadeo; Moreno, Diego A; Mittler, Ron; Rivero, Rosa M

    2016-01-01

    Efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Although multiple pathways, enzymes, and antioxidants are present in plants, their exact roles during different stress responses remain unclear. Here, we report on the characterization of the different antioxidant mechanisms of tomato plants subjected to heat stress, salinity stress, or a combination of both stresses. All the treatments applied induced an increase of oxidative stress, with the salinity treatment being the most aggressive, resulting in plants with the lowest biomass, and the highest levels of H2O2 accumulation, lipid peroxidation, and protein oxidation. However, the results obtained from the transcript expression study and enzymatic activities related to the ascorbate-glutathione pathway did not fully explain the differences in the oxidative damage observed between salinity and the combination of salinity and heat. An exhaustive metabolomics study revealed the differential accumulation of phenolic compounds depending on the type of abiotic stress applied. An analysis at gene and enzyme levels of the phenylpropanoid metabolism concluded that under conditions where flavonols accumulated to a greater degree as compared to hydroxycinnamic acids, the oxidative damage was lower, highlighting the importance of flavonols as powerful antioxidants, and their role in abiotic stress tolerance. PMID:27379130

  15. Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium

    PubMed Central

    Amanuma, Yusuke; Ohashi, Shinya; Itatani, Yoshiro; Tsurumaki, Mihoko; Matsuda, Shun; Kikuchi, Osamu; Nakai, Yukie; Miyamoto, Shin’ichi; Oyama, Tsunehiro; Kawamoto, Toshihiro; Whelan, Kelly A.; Nakagawa, Hiroshi; Chiba, Tsutomu; Matsuda, Tomonari; Muto, Manabu

    2015-01-01

    Acetaldehyde is an ethanol-derived definite carcinogen that causes oesophageal squamous cell carcinoma (ESCC). Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that eliminates acetaldehyde, and impairment of ALDH2 increases the risk of ESCC. ALDH2 is produced in various tissues including the liver, heart, and kidney, but the generation and functional roles of ALDH2 in the oesophagus remain elusive. Here, we report that ethanol drinking increased ALDH2 production in the oesophagus of wild-type mice. Notably, levels of acetaldehyde-derived DNA damage represented by N2-ethylidene-2′-deoxyguanosine were higher in the oesophagus of Aldh2-knockout mice than in wild-type mice upon ethanol consumption. In vitro experiments revealed that acetaldehyde induced ALDH2 production in both mouse and human oesophageal keratinocytes. Furthermore, the N2-ethylidene-2′-deoxyguanosine levels increased in both Aldh2-knockout mouse keratinocytes and ALDH2-knockdown human keratinocytes treated with acetaldehyde. Conversely, forced production of ALDH2 sharply diminished the N2-ethylidene-2′-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage. PMID:26374466

  16. Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL

    PubMed Central

    2014-01-01

    Background Increased levels of the most electronegative type of LDL, L5, have been observed in the plasma of patients with metabolic syndrome (MetS) and ST-segment elevation myocardial infarction and can induce endothelial dysfunction. Because men have a higher predisposition to developing coronary artery disease than do premenopausal women, we hypothesized that LDL electronegativity is increased in men and promotes endothelial damage. Methods L5 levels were compared between middle-aged men and age-matched, premenopausal women with or without MetS. We further studied the effects of gender-influenced LDL electronegativity on aortic cellular senescence and DNA damage in leptin receptor–deficient (db/db) mice by using senescence-associated–β-galactosidase and γH2AX staining, respectively. We also studied the protective effects of 17β-estradiol and genistein against electronegative LDL–induced senescence in cultured bovine aortic endothelial cells (BAECs). Results L5 levels were higher in MetS patients than in healthy subjects (P < 0.001), particularly in men (P = 0.001). LDL isolated from male db/db mice was more electronegative than that from male or female wild-type mice. In addition, LDL from male db/db mice contained abundantly more apolipoprotein CIII and induced more BAEC senescence than did female db/db or wild-type LDL. In the aortas of db/db mice but not wild-type mice, we observed cellular senescence and DNA damage, and the effect was more significant in male than in female db/db mice. Pretreatment with 17β-estradiol or genistein inhibited BAEC senescence induced by male or female db/db LDL and downregulated the expression of lectin-like oxidized LDL receptor-1 and tumor necrosis factor-alpha protein. Conclusion The gender dichotomy of LDL-induced cardiovascular damage may underlie the increased propensity to coronary artery disease in men. PMID:24666525

  17. Cryopreservation of Escherichia coli K12TG1: protection from the damaging effects of supercooling by freezing.

    PubMed

    Simonin, H; Bergaoui, I M; Perrier-Cornet, J M; Gervais, P

    2015-04-01

    Injuries in living cells caused by water freezing during a freeze-thaw process have been extensively reported. In particular, intracellular water freezing has long been incriminated in cell death caused by a high cooling rate, but this supposition could not always be demonstrated. This work aims to discriminate the role of water freezing, dehydration and cold-induced injuries in cellular damage occuring during cryopreservation. For this purpose, Escherichia coli K12TG1 suspensions were maintained in a supercooled or frozen state at -20°C for times ranging from 10 min to 5 h. The supercooled state was maintained for a long period at -20°C by applying a non-injurious isostatic pressure (P<40 MPa). Next, viability and membrane damage were determined by agar plating and fluorescence staining with propidium iodide and bis-oxonol. It was clear that keeping the cell suspensions in the supercooled state had a detrimental effect on both viability and plasma membrane permeability. Conversely, when cells were subjected to cold stress by freezing, the survival rate remained high throughout the experiment, and the cell membranes suffered little damage. Moreover, cells subjected to 5h of osmotic treatments at -20°C, conditions that mimic cryoconcentration upon freezing, and subsequently diluted and thawed suffered little damage. Dehydration due to cryoconcentration upon freezing protects the cells against the deleterious effects of supercooling, especially in the plasma membranes. The decrease in membrane leakage upon dehydration at low temperatures could be linked to differences in the gel state of the membrane revealed by a higher Laurdan general polarization (GP) value.

  18. Polysaccharides purified from Cordyceps cicadae protects PC12 cells against glutamate-induced oxidative damage.

    PubMed

    Olatunji, Opeyemi J; Feng, Yan; Olatunji, Oyenike O; Tang, Jian; Wei, Yuan; Ouyang, Zhen; Su, Zhaoliang

    2016-11-20

    Two polysaccharides CPA-1 and CPB-2 were isolated purified from Cordyceps cicadae by hot water extraction, ethanol precipitation and purification using anion exchange and gel filtration chromatography. Preliminary structural characterization of CPA-1 and CPB-2 were performed. The protective effect of CPA-1 and CPB-2 against glutamate-induced oxidative toxicity in PC12 cells was analyzed. The results indicated that pretreatment of PC12 cells with CPA-1 and CPB-2 significantly increased cell survival, Ca(2+) overload and ROS generation. CPA-1 and CPB-2 also markedly up-regulated the antioxidant status of pretreated PC12 cells. Our results suggested that Cordyceps cicadae polysaccharides can protect PC12 cells against glutamate excitotoxicity and might serve as therapeutic agents for neuronal disorders. PMID:27561486

  19. Protective effects of Commiphora erythraea resin constituents against cellular oxidative damage.

    PubMed

    Marcotullio, Maria Carla; Messina, Federica; Curini, Massimo; Macchiarulo, Antonio; Cellanetti, Marco; Ricci, Donata; Giamperi, Laura; Bucchini, Anahi; Minelli, Alba; Mierla, Anna Lisa; Bellezza, Ilaria

    2011-12-14

    By bioguided fractionation of the hexane extract of Commiphora erythraea resin we isolated four furanosesquiterpenoids that were tested for their protective activity against oxidative stress. Furanodienone and 1,10(15)-furanogermacra-dien-6-ones showed to be potent inhibitors of lipid peroxidation (IC(50) of -0.087 μM), being more active than the methoxylated analogues. Furthermore, using BV2 microglial cells, we found that furanodienone from C. erythraea is able to counteract LPS-induced cell death and decrease LPS-induced NO generation thus protecting microglial cells from LPS-induced cytotoxicity. Finally, docking studies were undertaken to gain insight into the possible binding mode of the isolated compounds at 5-LOX binding site.

  20. Aerial monitoring and environmental protection: aerial photography as an instrument for checking landscape damage

    NASA Astrophysics Data System (ADS)

    Tartara, Patrizia

    2009-09-01

    C.N.R. and University of Salento have realized a Geographical Information System for heritage management of the national territory (landscape) and historical urban settlements. Informations come from bibliography, archives, direct and systematic field survey, different kind of aerial photographs analysis, with the primary aim of knowledge for the establishment of an in existence Cultural Heritage Cadastre, focused to legal protection and exploitation of the sites, not last the correct territory planning.

  1. Reciprocal Paracrine Interactions Between Normal Human Epithelial and Mesenchymal Cells Protect Cellular DNA from Radiation-Induced Damage

    SciTech Connect

    Nakazawa, Yuka; Saenko, Vladimir Rogounovitch, Tatiana; Suzuki, Keiji; Mitsutake, Norisato; Matsuse, Michiko; Yamashita, Shunichi

    2008-06-01

    Purpose: To explore whether interactions between normal epithelial and mesenchymal cells can modulate the extent of radiation-induced DNA damage in one or both types of cells. Methods and Materials: Human primary thyrocytes (PT), diploid fibroblasts BJ, MRC-5, and WI-38, normal human mammary epithelial cells (HMEC), and endothelial human umbilical cord vein endothelial cells (HUV-EC-C), cultured either individually or in co-cultures or after conditioned medium transfer, were irradiated with 0.25 to 5 Gy of {gamma}-rays and assayed for the extent of DNA damage. Results: The number of {gamma}-H2AX foci in co-cultures of PT and BJ fibroblasts was approximately 25% lower than in individual cultures at 1 Gy in both types of cells. Reciprocal conditioned medium transfer to individual cultures before irradiation resulted in approximately a 35% reduction of the number {gamma}-H2AX foci at 1 Gy in both types of cells, demonstrating the role of paracrine soluble factors. The DNA-protected state of cells was achieved within 15 min after conditioned medium transfer; it was reproducible and reciprocal in several lines of epithelial cells and fibroblasts, fibroblasts, and endothelial cells but not in epithelial and endothelial cells. Unlike normal cells, human epithelial cancer cells failed to establish DNA-protected states in fibroblasts and vice versa. Conclusions: The results imply the existence of a network of reciprocal interactions between normal epithelial and some types of mesenchymal cells mediated by soluble factors that act in a paracrine manner to protect DNA from genotoxic stress.

  2. Dose-dependent protective effects of apomorphine against methamphetamine-induced nigrostriatal damage.

    PubMed

    Fornai, F; Battaglia, G; Gesi, M; Orzi, F; Nicoletti, F; Ruggieri, S

    2001-04-13

    (R)-apomorphine is a non-selective dopamine (DA) agonist which is used in the treatment of Parkinson's disease. In addition to symptomatic effects, apomorphine exerts a neuroprotective activity in specific experimental models. For instance, apomorphine prevents experimental parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroprotection obtained with apomorphine does not seem to be related to its dopamine (DA) agonist properties, instead it appears to be grounded on the antioxidant and the free radical scavenging effects of the compound. In this study, we sought to determine whether apomorphine protects against methamphetamine toxicity. We found that apomorphine (1; 5 and 10 mg/kg) dose-dependently protects against methamphetamine- (5 mg/kg X3, 2 h apart) induced striatal DA loss and reduction of tyrosine hydroxylase (TH) activity in the rat striatum. These protective effects are neither due to a decrease in the amount of striatal methamphetamine nor to hypothermia as indicated by measurement of striatal methamphetamine and body temperature at different time intervals after drug administration. The effects of apomorphine were neither opposite to, nor reversed by the DA antagonist haloperidol despite no decrease in body temperature was observed when apomorphine was given in combination with haloperidol. The present data are in line with recent studies suggesting a DA receptor-independent neuroprotective effect of apomorphine on DA neurons and call for further studies aimed at evaluating potential neuroprotective effects of apomorphine in Parkinson's disease.

  3. Protective effect of quercetin on nicotine-induced prooxidant and antioxidant imbalance and DNA damage in Wistar rats.

    PubMed

    Muthukumaran, Shanmugavelu; Sudheer, Adluri Ram; Menon, Venugopal P; Nalini, Namasivayam

    2008-01-14

    We have investigated the protective effect of quercetin (QN) against nicotine-induced prooxidant and antioxidant imbalance in circulation, lung, liver and kidney of experimental rats. The protective effect of QN was compared with N-acetylcysteine (NAC), a well-known antioxidant. Male albino rats of Wistar stain were used for the experimental study. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5mg/kg body weight (5 days a week, for 22 weeks) and QN was given simultaneously by intragastric intubations for 22 weeks. The body weight gain of rats during experimental period was significantly decreased in nicotine treated group, whereas QN co-treated rats significantly increased in their body weight. The levels of lipid peroxidative indices viz., thiobarbituric acid reactive substances and hydroperoxides, and nitric oxide in circulation, lung, liver and kidney of nicotine-treated rats were increased significantly when compared to normal, which were brought down to near normal in QN co-treated group. Endogenous antioxidant status viz., superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione were found to be significantly decreased in circulation, lung, liver and kidney of nicotine-treated group, which were significantly increased in QN-administered groups. The extent of DNA damage (evaluated by comet assay) was significantly increased in circulatory blood of nicotine-treated rats, which was effectively brought down by QN treatment. The protective effect of QN against nicotine toxicity was comparable to that of NAC. Our data suggest that QN exerts its protective effect by modulating the extent of lipid peroxidation and augmenting antioxidant defense system and thus protects the DNA in experimental animals. PMID:18045763

  4. (-)-SCR1693 Protects against Memory Impairment and Hippocampal Damage in a Chronic Cerebral Hypoperfusion Rat Model

    PubMed Central

    Zhu, Xiaoyin; Tian, Jingwei; Sun, Songmei; Dong, Qiuju; Zhang, Fangxi; Zhang, Xiumei

    2016-01-01

    Chronic cerebral hypoperfusion (CCH) is one of the most common causes of vascular dementia (VaD) and is recognised as an etiological factor in the development of Alzheimer’s disease (AD). CCH can induce severe cognitive deficits, as assessed by the water maze task, along with neuronal loss in the hippocampus. However, there are currently no effective, approved pharmacological treatments available for VaD. In the present study, we created a rat model of CCH using bilateral common carotid artery occlusion and found that (-)-SCR1693, a novel compound, prevented rats from developing memory deficits and neuronal damage in the hippocampus by rectifying cholinergic dysfunction and decreasing the accumulation of the phospho-tau protein. These results strongly suggest that (-)-SCR1693 has therapeutic potential for the treatment of CCH-induced VaD. PMID:27349344

  5. Photomultiplier circuit including means for rapidly reducing the sensitivity thereof. [and protection from radiation damage

    NASA Technical Reports Server (NTRS)

    Mcclenahan, J. O. (Inventor)

    1974-01-01

    A simple, reliable and inexpensive control circuit is described for rapidly reducing the bias voltage across one or more of the dynode stages of a photomultiplier, to substantially decrease its sensitivity to incoming light at those times where excess light intensity might damage the tube. The control circuit comprises a switching device, such as a silicon controlled rectifier (SCR), coupled between a pair of the electrodes in the tube, preferably the cathode and first dynode, or the first and second dynodes, the switching device operating in response to a trigger pulse applied to its gate to short circuit the two electrodes. To insure the desired reduction in sensitivity, two switching stages, the devices be employed between two of the electrode stages, the devices being operated simultaneously to short circuit both stages.

  6. Co- and Post-Treatment with Lysine Protects Primary Fish Enterocytes against Cu-Induced Oxidative Damage.

    PubMed

    Li, Xue-Yin; Liu, Yang; Jiang, Wei-Dan; Jiang, Jun; Wu, Pei; Zhao, Juan; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

    2016-01-01

    The aim of the work was primarily to explore the protective activity pathways of lysine against oxidative damage in fish in vivo and in enterocytes in vitro. First, grass carp were fed diets containing six graded levels of lysine (7.1-19.6 g kg-1 diet) for 56 days. Second, the enterocytes were treated with different concentrations of lysine (0-300 mg/L in media) prior to (pre-treatment), along with (co-treatment) or following (post-treatment) with 6 mg/L of Cu for 24 h. The results indicated that lysine improved grass carp growth performance. Meanwhile, lysine ameliorated lipid and protein oxidation by elevating the gene expression and activity of antioxidant enzymes (superoxide dismutase (SOD), glutathioneperoxidase (GPx), glutathione-S-transferase (GST) and reductase (GR)), and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA levels in fish intestine. The in vitro studies showed that co- and post-treatment with lysine conferred significant protection against Cu-induced oxidative damage in fish primary enterocytes as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) OD values, along with alkaline phosphatase (ALP) and lactate dehydrogenase activities, and the depletion of protein carbonyl (PC), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine contents. Moreover, lysine co-treatment decreased the activities and mRNA level of cellular SOD, GPx, GST and GR compared with the Cu-only exposed group. Gene expression of the signalling molecule Nrf2 showed the same pattern as that of SOD activity, whereas Kelch-like ECH-associated protein 1b (Keap1b) followed the opposite trend, indicating that co-treatment with lysine induced antioxidant enzymes that protected against oxidative stress through Nrf2 pathway. In addition, post-treatment with lysine increased proteasomal activity and blocked the Cu-stimulated increase in mRNA levels of GST and associated catalase (CAT) and GST activities (P<0.01 and P<0.001). GR activity and gene

  7. Co- and Post-Treatment with Lysine Protects Primary Fish Enterocytes against Cu-Induced Oxidative Damage

    PubMed Central

    Li, Xue-Yin; Liu, Yang; Jiang, Wei-Dan; Jiang, Jun; Wu, Pei; Zhao, Juan; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

    2016-01-01

    The aim of the work was primarily to explore the protective activity pathways of lysine against oxidative damage in fish in vivo and in enterocytes in vitro. First, grass carp were fed diets containing six graded levels of lysine (7.1–19.6 g kg-1 diet) for 56 days. Second, the enterocytes were treated with different concentrations of lysine (0–300 mg/L in media) prior to (pre-treatment), along with (co-treatment) or following (post-treatment) with 6 mg/L of Cu for 24 h. The results indicated that lysine improved grass carp growth performance. Meanwhile, lysine ameliorated lipid and protein oxidation by elevating the gene expression and activity of antioxidant enzymes (superoxide dismutase (SOD), glutathioneperoxidase (GPx), glutathione-S-transferase (GST) and reductase (GR)), and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA levels in fish intestine. The in vitro studies showed that co- and post-treatment with lysine conferred significant protection against Cu-induced oxidative damage in fish primary enterocytes as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) OD values, along with alkaline phosphatase (ALP) and lactate dehydrogenase activities, and the depletion of protein carbonyl (PC), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine contents. Moreover, lysine co-treatment decreased the activities and mRNA level of cellular SOD, GPx, GST and GR compared with the Cu-only exposed group. Gene expression of the signalling molecule Nrf2 showed the same pattern as that of SOD activity, whereas Kelch-like ECH-associated protein 1b (Keap1b) followed the opposite trend, indicating that co-treatment with lysine induced antioxidant enzymes that protected against oxidative stress through Nrf2 pathway. In addition, post-treatment with lysine increased proteasomal activity and blocked the Cu-stimulated increase in mRNA levels of GST and associated catalase (CAT) and GST activities (P<0.01 and P<0.001). GR activity and gene

  8. Protective role of NecroX-5 against neomycin-induced hair cell damage in zebrafish.

    PubMed

    Song, Jae-Jun; Chang, Jiwon; Choi, Jungim; Im, Gi Jung; Chae, Sung Won; Lee, Seung Hoon; Kwon, Soon-Young; Jung, Hak Hyun; Chung, Ah-Young; Park, Hae-Chul; Choi, June

    2014-02-01

    NecroX-5, one of the derivatives of NecroX series compounds, is a mitochondrial reactive oxygen species and reactive nitrogen species scavenger that inhibits cell death against various kinds of oxidative stresses. The objective of the present study was to evaluate the effects of NecroX-5 on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). Five days post-fertilization, zebrafish larvae were exposed to 125 μM neomycin and one of the following NecroX-5 concentrations for 1 h: 10, 25, 50, and 75 μM. Hair cells within the neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed using fluorescence microscopy (n = 10). The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and 2-[4-(dimethylamino) styryl]-N-ethylpyridiniumiodide (DASPEI) assay were performed for evaluation of apoptosis and mitochondrial damage. Ultrastructural changes were evaluated using scanning electron microscopy. NecroX-5 decreased neomycin-induced hair cell loss in the neuromasts (NecroX-5 50 μM: 13.4 ± 2.0 cells, 125 μM neomycin only: 8.1 ± 1.2 cells; n = 10, P < 0.05) and decreased the TUNEL reaction. The ultrastructural analysis showed that the structures of mitochondria and hair cells within the neuromasts were preserved in zebrafish exposed to 125 μM neomycin and 50 μM NecroX-5. NecroX-5 decreased apoptosis and mitochondrial damage. In conclusion, NecroX-5 attenuated neomycin-induced hair cell loss in zebrafish.

  9. 40 CFR 68.42 - Five-year accident history.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 16 2012-07-01 2012-07-01 false Five-year accident history. 68.42... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.42 Five-year accident history. (a) The owner or operator shall include in the five-year accident history all accidental releases...

  10. 40 CFR 68.42 - Five-year accident history.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 16 2014-07-01 2014-07-01 false Five-year accident history. 68.42... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.42 Five-year accident history. (a) The owner or operator shall include in the five-year accident history all accidental releases...

  11. 40 CFR 68.42 - Five-year accident history.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Five-year accident history. 68.42... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.42 Five-year accident history. (a) The owner or operator shall include in the five-year accident history all accidental releases...

  12. Protection of Clitoria ternatea flower petal extract against free radical-induced hemolysis and oxidative damage in canine erythrocytes.

    PubMed

    Phrueksanan, Wathuwan; Yibchok-anun, Sirinthorn; Adisakwattana, Sirichai

    2014-10-01

    The present study assessed the antioxidant activity and protective ability of Clitoria ternatea flower petal extract (CTE) against in vitro 2,2'-azobis-2-methyl-propanimidamide dihydrochloride (AAPH)-induced hemolysis and oxidative damage of canine erythrocytes. From the phytochemical analysis, CTE contained phenolic compounds, flavonoids, and anthocyanins. In addition, CTE showed antioxidant activity as measured by oxygen radical absorbance capacity (ORAC) method and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. CTE (400 µg/ml) remarkably protected erythrocytes against AAPH-induced hemolysis at 4 h of incubation. Moreover, CTE (400 µg/ml) reduced membrane lipid peroxidation and protein carbonyl group formation and prevented the reduction of glutathione concentration in AAPH-induced oxidation of erythrocytes. The AAPH-induced morphological alteration of erythrocytes from a smooth discoid to an echinocytic form was effectively protected by CTE. The present results contribute important insights that CTE may have the potential to act as a natural antioxidant to prevent free radical-induced hemolysis, protein oxidation and lipid peroxidation in erythrocytes. PMID:25241390

  13. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats.

    PubMed

    Li, Jianzhong; Xu, Jing; Xu, Weiheng; Qi, Yang; Lu, Yiming; Qiu, Lei; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2015-08-12

    Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage.

  14. Protective effects of citrus and rosemary extracts on UV-induced damage in skin cell model and human volunteers.

    PubMed

    Pérez-Sánchez, A; Barrajón-Catalán, E; Caturla, N; Castillo, J; Benavente-García, O; Alcaraz, M; Micol, V

    2014-07-01

    Ultraviolet radiation absorbed by the epidermis is the major cause of various cutaneous disorders, including photoaging and skin cancers. Although topical sunscreens may offer proper skin protection, dietary plant compounds may significantly contribute to lifelong protection of skin health, especially when unconsciously sun UV exposed. A combination of rosemary and citrus bioflavonoids extracts was used to inhibit UV harmful effects on human HaCaT keratinocytes and in human volunteers after oral intake. Survival of HaCaT cells after UVB radiation was higher in treatments using the combination of extracts than in those performed with individual extracts, indicating potential synergic effects. The combination of extracts also decreased UVB-induced intracellular radical oxygen species (ROS) and prevented DNA damage in HaCaT cells by comet assay and decreased chromosomal aberrations in X-irradiated human lymphocytes. The oral daily consumption of 250 mg of the combination by human volunteers revealed a significant minimal erythema dose (MED) increase after eight weeks (34%, p<0.05). Stronger protection was achieved after 12 weeks (56%, p<0.01). The combination of citrus flavonoids and rosemary polyphenols and diterpenes may be considered as an ingredient for oral photoprotection. Their mechanism of action may deserve further attention.

  15. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats

    PubMed Central

    Li, Jianzhong; Xu, Jing; Xu, Weiheng; Qi, Yang; Lu, Yiming; Qiu, Lei; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2015-01-01

    Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage. PMID:26274957

  16. Protection of wheat bran feruloyl oligosaccharides against free radical-induced oxidative damage in normal human erythrocytes.

    PubMed

    Wang, Jing; Sun, Baoguo; Cao, Yanping; Tian, Yuan

    2009-07-01

    The present work assessed the protective effect of water-soluble feruloyl oligosaccharides (FSH), ferulic acid ester of oligosaccharides from wheat bran, against in vitro oxidative damage of normal human erythrocytes induced by a water-soluble free radical initiator, 2,2'-azobis-2-amidinopropane dihydrochloride (AAPH). In the whole process of AAPH-initiated oxidation, hemolysis occurred quickly after the lag time. The rate of hemolysis is correlated dose-dependently with AAPH concentration. Significant decrease in reduced glutathione (GSH) levels of erythrocyte with concomitant enhancement in oxidized gluthione (GSSG) levels was noticed. It was also observed that lipid and protein peroxidation of erythrocytes induced by AAPH was significantly increased, and scanning electron microscopy observations showed that AAPH induced obvious morphological alteration in the erythrocytes from a smooth discoid to an echinocytic form. FSH suppressed depletion of GSH, lipid peroxidation, and methaemoglobin and protein carbonyl group formation of erythrocytes in concentration- and time-dependent manners, remarkably delayed AAPH-induced hemolysis. Morphological changes to erythrocyte caused by AAPH were effectively protected by FSH. It was also observed that FSH could work synergistically with endogenous antioxidants in erythrocytes. These results indicated that FSH efficiently protected normal human erythrocytes against oxidative stress, and they could be used as a potential source of natural antioxidants.

  17. Nardostachys jatamansi extract protects against cytokine-induced β-cell damage and streptozotocin-induced diabetes

    PubMed Central

    Song, Mi-Young; Bae, Ui-Jin; Lee, Bong-Hee; Kwon, Kang-Beom; Seo, Eun-A; Park, Sung-Joo; Kim, Min-Sun; Song, Ho-Joon; Kwon, Keun-Sang; Park, Jin-Woo; Ryu, Do-Gon; Park, Byung-Hyun

    2010-01-01

    AIM: To investigate the anti-diabetogenic mechanism of Nardostachys jatamansi extract (NJE). METHODS: Mice were injected with streptozotocin via a tail vein to induce diabetes. Rat insulinoma RINm5F cells and isolated rat islets were treated with interleukin-1β and interferon-γ to induce cytotoxicity. RESULTS: Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was confirmed by immunohistochemical staining of the islets. The diabetogenic effects of streptozotocin were completely abolished when mice were pretreated with NJE. Inhibition of streptozotocin-induced hyperglycemia by NJE was mediated by suppression of nuclear factor (NF)-κB activation. In addition, NJE protected against cytokine-mediated cytotoxicity. Incubation of RINm5F cells and islets with NJE resulted in a significant reduction in cytokine-induced NF-κB activation and downstream events, inducible nitric oxide synthase expression and nitric oxide production. The protective effect of NJE was further demonstrated by the normal insulin secretion of cytokine-treated islets in response to glucose. CONCLUSION: NJE provided resistance to pancreatic β-cell damage from cytokine or streptozotocin treatment. The β-cell protective effect of NJE is mediated by suppressing NF-κB activation. PMID:20614480

  18. Protection of Clitoria ternatea flower petal extract against free radical-induced hemolysis and oxidative damage in canine erythrocytes.

    PubMed

    Phrueksanan, Wathuwan; Yibchok-anun, Sirinthorn; Adisakwattana, Sirichai

    2014-10-01

    The present study assessed the antioxidant activity and protective ability of Clitoria ternatea flower petal extract (CTE) against in vitro 2,2'-azobis-2-methyl-propanimidamide dihydrochloride (AAPH)-induced hemolysis and oxidative damage of canine erythrocytes. From the phytochemical analysis, CTE contained phenolic compounds, flavonoids, and anthocyanins. In addition, CTE showed antioxidant activity as measured by oxygen radical absorbance capacity (ORAC) method and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. CTE (400 µg/ml) remarkably protected erythrocytes against AAPH-induced hemolysis at 4 h of incubation. Moreover, CTE (400 µg/ml) reduced membrane lipid peroxidation and protein carbonyl group formation and prevented the reduction of glutathione concentration in AAPH-induced oxidation of erythrocytes. The AAPH-induced morphological alteration of erythrocytes from a smooth discoid to an echinocytic form was effectively protected by CTE. The present results contribute important insights that CTE may have the potential to act as a natural antioxidant to prevent free radical-induced hemolysis, protein oxidation and lipid peroxidation in erythrocytes.

  19. Following specific podocyte injury captopril protects against progressive long term renal damage

    PubMed Central

    Zhou, Yu S; Ihmoda, Ihmoda A; Phelps, Richard G; Bellamy, Christopher OS; Turner, A Neil

    2015-01-01

    Background: Angiotensin converting enzyme inhibitors (ACEi) reduce proteinuria and preserve kidney function in proteinuric renal diseases. Their nephroprotective effect exceeds that attributable to lowering of blood pressure alone. This study examines the potential of ACEi to protect from progression of injury after a highly specific injury to podocytes in a mouse model. Methods: We created transgenic (Podo-DTR) mice in which graded specific podocyte injury could be induced by a single injection of diphtheria toxin. Transgenic and wild-type mice were given the ACEi captopril in drinking water, or water alone, commencing 24h after toxin injection. Kidneys were examined histologically at 8 weeks and injury assessed by observers blinded to experimental group. Results: After toxin injection, Podo-DTR mice developed acute proteinuria, and at higher doses transient renal impairment, which subsided within 3 weeks to be followed by a slow glomerular scarring process. Captopril treatment in Podo-DTR line 57 after toxin injection at 5ng/g body weight reduced proteinuria and ameliorated glomerular scarring, matrix accumulation and glomerulosclerosis almost to baseline (toxin: 17%; toxin + ACEi 10%, p<0.04; control 7% glomerular scarring). Podocyte counts were reduced after toxin treatment and showed no recovery irrespective of captopril treatment (7.1 and 7.3 podocytes per glomerular cross section in water and captopril-treated animals compared with 8.2 of wild-type controls, p<0.05). Conclusions: Observations in Podo-DTR mice support the hypothesis that continuing podocyte dysfunction is a key abnormality in proteinuric disease. Our model is ideal for studying strategies to protect the kidney from progressive injury following podocyte depletion. Demonstrable protective effects from captopril occur, despite indiscernible preservation or restoration of podocyte counts, at least after this degree of relatively mild injury. PMID:26629332

  20. Protective role of taurine against genotoxic damage in mice treated with methotrexate and tamoxfine.

    PubMed

    Alam, Sally S; Hafiz, Nagla A; Abd El-Rahim, Abeer H

    2011-01-01

    The genotoxic actions of anti-neoplastic drugs can lead to the development of secondary cancers in patients in extended remission. One of the most attractive approaches to disease prevention involves the use of natural antioxidants to protect tissue against toxic injury. We investigated the modulatory effects of exogenously administered taurine, on the genotoxicity of two well known anti-neoplastic drugs methotrexate (MTX) and tamoxifen (TAM) in Swiss albino mice. The animals were randomly divided into six groups consisting of ten mice each. Two groups were received single intraperitoneal injection of MTX (10 mg/kgb.wt.) and TAM (50 mg/kgb.wt.) to induce genotoxicity. Two other groups were treated orally with taurine (100 mg/kgb.wt.) for nine days prior to MTX and TAM administration. A vehicle treated control group and taurine control groups were also included. The protective effects of taurine were monitored by apoptosis assays and level of reduced glutathione (GSH), a key antioxidant, in liver, chromosomal aberrations in somatic and germ cells as well as sperm count, motility and morphology. The results indicated that taurine pre-treatment showed significant increment in the levels of GSH content, reduction in DNA fragmentation and ladder formation in hepatic tissue, suggesting the antioxidant activity of taurine may reduce the toxic effects of MTX and TAM. Treatment with taurine showed also significant reduction in the frequency of chromosomal aberrations in both somatic and germ cells. Moreover, it increases sperm count and motility, and decreases the incidence of sperm abnormalities. In conclusion, it appears that taurine protects against anti-neoplastic drugs-induced genotoxicity in somatic and germ tissues and may be of therapeutic potential in alleviating the risk of secondary tumors in chemotherapy.

  1. Protective effect of secondary plant metabolites from Ipomoea aquatica Forsk. against carbofuran induced damages.

    PubMed

    Datta, Sanjukta; Sinha, Mahuya; Das, Dipesh; Ghosh, Santinath; Dhar, Pubali

    2013-12-01

    Plausible interactions between food contaminants and natural constituents in vivo and protective effect of polyphenols present in I. aquatica against carbofuran toxicity in Charles Foster rats were evaluated. Determinations based on antioxidant enzyme activities showed significant alterations in glutathione, glutathione peroxidase, superoxide dismutase and catalase in tissues (liver and brain) and plasma of pesticide treated group while polyphenolic extracts from I. aquatica (IAE) attenuated their activities when given alongwith carbofuran. IAE decreased enhanced lipid peroxidation levels in plasma and erythrocyte membrane and cholesterol levels in brain and plasma. IAE also minimized histopathological degenerative changes produced by carbofuran. While single cell gel electrophoresis showed that secondary metabolites in leafy vegetables produced a combinatorial effect with pesticide at cellular level, DNA fragmentation level in bone marrow cells showed a decline in the IAE treated rats. Food safety adversely affected by various chemical contaminants can be retained by plant polyphenols and secondary plant constituents that can be found together in bolus. Therefore, the present study gives an insight into the protective role of naturally found polyphenols against pesticide toxicity. PMID:24579377

  2. Recombinant Reg3β protein protects against streptozotocin-induced β-cell damage and diabetes

    PubMed Central

    Luo, Chen; Yu, Lu-Ting; Yang, Meng-Qi; Li, Xiang; Zhang, Zhi-Yuan; Alfred, Martin O; Liu, Jun-Li; Wang, Min

    2016-01-01

    Regenerating genes (Reg) have been found during the search for factors involved in pancreatic islet regeneration. Our recent study discovered that pancreatic β-cell-specific overexpression of Reg3β protects against streptozotocin (Stz) -induced diabetes in mice. To investigate its potential roles in the treatment of diabetes, we produced a recombinant Reg3β protein and provided evidence that it is active in promoting islet β-cell survival against Stz- triggered cell death. Though ineffective in alleviating preexisting diabetes, pretreatment of recombinant Reg3β was capable of minimizing the Stz-induced hyperglycemia and weight loss, by preserving serum and pancreatic insulin levels, and islet β-cell mass. No obvious changes were observed in the rate of cell proliferation and hypertrophy in α- or acinar-cells after treatment with recombinant Reg3β. The underlying mechanism of Reg3β-mediated protection seems to involve Akt activation which upregulates Bcl-2 and Bcl-xL levels and consequently promotes cell survival. PMID:27767186

  3. Protective Effect of Oral Hesperetin Against Unilateral Striatal 6-Hydroxydopamine Damage in the Rat.

    PubMed

    Kiasalari, Zahra; Khalili, Mohsen; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

    2016-05-01

    Parkinson's disease (PD) is a neurodegenerative disorder due to loss of dopaminergic neurons in the substantia nigra pars compacta (SNC). PD finally leads to incapacitating symptoms including motor and cognitive deficits. This study was undertaken to assess protective effect of the flavanone hesperetin against striatal 6-hydroxydopamine lesion and to explore in more detail some underlying mechanisms including apoptosis, inflammation and oxidative stress. In this research study, intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats received hesperetin (50 mg/kg/day) for 1 week. Hesperetin reduced apomorphine-induced rotational asymmetry and decreased the latency to initiate and the total time on the narrow beam task. It also attenuated striatal malondialdehyde and enhanced striatal catalase activity and GSH content, lowered striatal level of glial fibrillary acidic protein as an index of astrogliosis and increased Bcl2 with no significant change of the nuclear factor NF-kB as a marker of inflammation. Hesperetin treatment was also capable to mitigate nigral DNA fragmentation as an index of apoptosis and to prevent loss of SNC dopaminergic neurons. This study indicated the protective effect of hesperetin in an early model of PD via attenuation of apoptosis, astrogliosis marker and oxidative stress and it may be helpful as an adjuvant therapy for management of PD at its early stages.

  4. Identification of the protective effects of traditional medicinal plants against SDS-induced Drosophila gut damage

    PubMed Central

    Zhou, Yang; Liu, Zonglin; Chen, Yuchen; Jin, Li Hua

    2016-01-01

    Traditional medicinal plants are widely used as immunomodulatory medicines that help improve health. A total of 50 different plants used for the treatment of toxicity were screened for their in vivo protective effects. Flies were fed a standard cornmeal-yeast medium (control group) or the standard medium containing medicinal plant extracts (experimental groups). Assessment of the survival rate was performed by feeding flies with toxic compounds. Gut epithelial cells were analyzed for cell proliferation and death by green fluorescent protein antibodies and 7-aminoactinomycin D staining under the microscope. The expression of antimicrobial peptides (AMPs) was evaluated by the quantitative polymerase chain reaction and the results revealed that after feeding the flies with toxic compounds, aqueous extracts from Codonopsis pilosula (Franch.) Nannf (C. pilosula), Saussurea lappa (Decne.) C.B.Clarke (S. lappa), Imperata cylindrica Beauv.var.major (Nees) C.E. Hubb. (I. cylindrical var. major) and Melia toosendan Sied. Et Zucc. (M.toosendan) increased the fly survival rate, reduced epithelial cell death and improved gut morphology. In addition, C. pilosula extracts induced the antimicrobial peptide levels (Dpt and Mtk) following treatment with sodium dodecyl sulfate (SDS). However, these extracts were not observed to increase SDS-induced cell proliferation in vivo. These results indicate that there are strong protective effects in extracts of C. pilosula, S. lappa, I. cylindrical var. major and M. toosendan on Drosophila intestinal cells among 50 medicinal plants. PMID:27698771

  5. Identification of the protective effects of traditional medicinal plants against SDS-induced Drosophila gut damage

    PubMed Central

    Zhou, Yang; Liu, Zonglin; Chen, Yuchen; Jin, Li Hua

    2016-01-01

    Traditional medicinal plants are widely used as immunomodulatory medicines that help improve health. A total of 50 different plants used for the treatment of toxicity were screened for their in vivo protective effects. Flies were fed a standard cornmeal-yeast medium (control group) or the standard medium containing medicinal plant extracts (experimental groups). Assessment of the survival rate was performed by feeding flies with toxic compounds. Gut epithelial cells were analyzed for cell proliferation and death by green fluorescent protein antibodies and 7-aminoactinomycin D staining under the microscope. The expression of antimicrobial peptides (AMPs) was evaluated by the quantitative polymerase chain reaction and the results revealed that after feeding the flies with toxic compounds, aqueous extracts from Codonopsis pilosula (Franch.) Nannf (C. pilosula), Saussurea lappa (Decne.) C.B.Clarke (S. lappa), Imperata cylindrica Beauv.var.major (Nees) C.E. Hubb. (I. cylindrical var. major) and Melia toosendan Sied. Et Zucc. (M.toosendan) increased the fly survival rate, reduced epithelial cell death and improved gut morphology. In addition, C. pilosula extracts induced the antimicrobial peptide levels (Dpt and Mtk) following treatment with sodium dodecyl sulfate (SDS). However, these extracts were not observed to increase SDS-induced cell proliferation in vivo. These results indicate that there are strong protective effects in extracts of C. pilosula, S. lappa, I. cylindrical var. major and M. toosendan on Drosophila intestinal cells among 50 medicinal plants.

  6. Caffeine metabolites not caffeine protect against riboflavin photosensitized oxidative damage related to skin and eye health.

    PubMed

    Scurachio, R S; Mattiucci, F; Santos, W G; Skibsted, L H; Cardoso, D R

    2016-10-01

    Caffeine metabolites were found to bind riboflavin with dissociation constant in the millimolar region by an exothermic process with positive entropy of reaction, which was found by (1)H NMR and fluorescence spectroscopy to occur predominantly by hydrogen bonding with water being released from riboflavin solvation shell upon caffeine metabolite binding to riboflavin. The caffeine metabolites 1-methyl uric acid and 1,7-dimethyl uric acid were shown by transient absorption laser flash photolysis to be efficient as quenchers of triplet riboflavin with second-order rate constant of 1.4 10(8)Lmol(-1)s(-1) and 1.0 10(8)Lmol(-1)s(-1), respectively, in aqueous solution of pH6.4 at 25°C and more efficient than the other caffeine metabolite 1,7-dimethyl xanthine with second-order rate constant of 4.2 10(7)Lmol(-1)s(-1). Caffeine was in contrast found to be non-reactive towards triplet riboflavin. Caffeine metabolites rather than caffeine seem accordingly important for the observed protective effect against cutaneous melanoma identified for drinkers of regular but not of decaffeinated coffee. The caffeine metabolites, but not caffeine, were by time resolved single photon counting found to quench singlet excited riboflavin through exothermic formation of ground-state precursor complexes indicating importance of hydrogen bounding through keto-enol tautomer's for protection of oxidizable substrates and sensitive structures against riboflavin photosensitization.

  7. Caffeine metabolites not caffeine protect against riboflavin photosensitized oxidative damage related to skin and eye health.

    PubMed

    Scurachio, R S; Mattiucci, F; Santos, W G; Skibsted, L H; Cardoso, D R

    2016-10-01

    Caffeine metabolites were found to bind riboflavin with dissociation constant in the millimolar region by an exothermic process with positive entropy of reaction, which was found by (1)H NMR and fluorescence spectroscopy to occur predominantly by hydrogen bonding with water being released from riboflavin solvation shell upon caffeine metabolite binding to riboflavin. The caffeine metabolites 1-methyl uric acid and 1,7-dimethyl uric acid were shown by transient absorption laser flash photolysis to be efficient as quenchers of triplet riboflavin with second-order rate constant of 1.4 10(8)Lmol(-1)s(-1) and 1.0 10(8)Lmol(-1)s(-1), respectively, in aqueous solution of pH6.4 at 25°C and more efficient than the other caffeine metabolite 1,7-dimethyl xanthine with second-order rate constant of 4.2 10(7)Lmol(-1)s(-1). Caffeine was in contrast found to be non-reactive towards triplet riboflavin. Caffeine metabolites rather than caffeine seem accordingly important for the observed protective effect against cutaneous melanoma identified for drinkers of regular but not of decaffeinated coffee. The caffeine metabolites, but not caffeine, were by time resolved single photon counting found to quench singlet excited riboflavin through exothermic formation of ground-state precursor complexes indicating importance of hydrogen bounding through keto-enol tautomer's for protection of oxidizable substrates and sensitive structures against riboflavin photosensitization. PMID:27611451

  8. Protective Effect of Plantago major Extract against t-BOOH-Induced Mitochondrial Oxidative Damage and Cytotoxicity.

    PubMed

    Mello, Joyce C; Gonzalez, Mariano V D; Moraes, Vivian W R; Prieto, Tatiana; Nascimento, Otaciro R; Rodrigues, Tiago

    2015-01-01

    Plantago major L. produces several chemical substances with anti-inflammatory and analgesic activities and its use in the treatment of oral and throat inflammation in popular medicine is well described. In this study, the antioxidant potential of the Plantago major hydroethanolic extract was screened and its protective action was evaluated against t-BOOH-induced oxidative stress. The extract was obtained by fractionated percolation using 50% ethanolic solution and, after drying, suspended in dimethyl sulfoxide. The chromatographic profile of crude extract was obtained with the identification of some phytochemical markers and the total phenols and flavonoids were quantified. The scavenger activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals was determined and the antioxidant activity in biological systems was evaluated in isolated rat liver mitochondria and HepG2 cells. The extract exhibited a significant free radical scavenger activity at 0.1 mg/mL, and decreased the ROS (reactive oxygen species) generation in succinate-energized mitochondria. Such an effect was associated with the preservation of the intrinsic antioxidant defenses (reduced glutathione and NAD(P)H) against the oxidation by t-BOOH, and also to the protection of membranes from lipid oxidation. The cytoprotective effect of PmHE against t-BOOH induced cell death was also shown. These findings contribute to the understanding of the health benefits attributed to P. major. PMID:26404215

  9. Protective effect of secondary plant metabolites from Ipomoea aquatica Forsk. against carbofuran induced damages.

    PubMed

    Datta, Sanjukta; Sinha, Mahuya; Das, Dipesh; Ghosh, Santinath; Dhar, Pubali

    2013-12-01

    Plausible interactions between food contaminants and natural constituents in vivo and protective effect of polyphenols present in I. aquatica against carbofuran toxicity in Charles Foster rats were evaluated. Determinations based on antioxidant enzyme activities showed significant alterations in glutathione, glutathione peroxidase, superoxide dismutase and catalase in tissues (liver and brain) and plasma of pesticide treated group while polyphenolic extracts from I. aquatica (IAE) attenuated their activities when given alongwith carbofuran. IAE decreased enhanced lipid peroxidation levels in plasma and erythrocyte membrane and cholesterol levels in brain and plasma. IAE also minimized histopathological degenerative changes produced by carbofuran. While single cell gel electrophoresis showed that secondary metabolites in leafy vegetables produced a combinatorial effect with pesticide at cellular level, DNA fragmentation level in bone marrow cells showed a decline in the IAE treated rats. Food safety adversely affected by various chemical contaminants can be retained by plant polyphenols and secondary plant constituents that can be found together in bolus. Therefore, the present study gives an insight into the protective role of naturally found polyphenols against pesticide toxicity.

  10. Epigallocatechin-3-gallate protects rat brain mitochondria against cadmium-induced damage.

    PubMed

    Abib, Renata Torres; Peres, Kaite Cristiane; Barbosa, Anderson Machado; Peres, Tanara Vieira; Bernardes, Angela; Zimmermann, Lizandra Maria; Quincozes-Santos, André; Fiedler, Haidi D; Leal, Rodrigo Bainy; Farina, Marcelo; Gottfried, Carmem

    2011-10-01

    Many health claims have been made about the medicinal benefits of drinking green tea, including neuroprotection. This study mainly focuses on Epigallocatechin 3-gallate (EGCG), a potent antioxidant, which is abundantly found in green tea. Cadmium [Cd(2+)] is a toxic pollutant that leads to neurotoxicity in both animals and humans. Although the entrance of Cd(2+) in the adult central nervous system is limited, developmental neurotoxicity has been evidenced as result of the blood-brain barrier (BBB) immaturity. Moreover, high Cd(2+) levels are known to impair BBB function. Furthermore, the molecular mechanisms related to its neurotoxic properties remain unknown. This study evaluates the potential protective effect of the major green tea polyphenol, EGCG, against Cd(2+)-induced mitotoxicity under in vitro conditions, using mitochondrial-enriched fractions from rat brain. Co-incubation of EGCG with Cd(2+) prevented the Cd(2+)-induced mitochondrial dysfunction (capacity to reduce MTT to formazan). In addition, EGCG completely prevented mitochondrial lipid peroxidation induced by Cd(2+) but did not affect non protein thiols levels. Spectroscopic studies have shown EGCG able to form a chemical complex with Cd(2+), in an equimolar ratio. In this study we demonstrate EGCG effectiveness in protecting against Cd(2+)-induced mitochondrial dysfunction and lipid peroxidation probably due to its antioxidant and chelating effects. PMID:21798304

  11. Noscapine protects OLN-93 oligodendrocytes from ischemia-reperfusion damage: Calcium and nitric oxide involvement.

    PubMed

    Nadjafi, S; Ebrahimi, S-A; Rahbar-Roshandel, N

    2015-12-01

    This study was carried out to evaluate the effects of noscapine, a benzylisoquinoline alkaloid from opium poppy, on oligodendrocyte during ischemia/reperfusion-induced excitotoxic injury. Changes in intracellular calcium levels due to chemical ischemia and nitric oxide (NO) production during ischemia/reperfusion were evaluated as the hallmarks of ischemia-derived excitotoxic event. OLN-93 cell line (a permanent immature rat oligodendrocyte) was used as a model of oligodendrocyte. 30- or 60-minute-oxygen-glucose deprivation/24 hours reperfusion were used to induce excitotoxicity. MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay was used to evaluate cell viability. Ratiometric fluorescence microscopy using Ca(2+)-sensitive indicator Fura-2/AM was utilized to assess intracellular calcium levels. NO production was evaluated by Griess method. Noscapine (4 μM) significantly attenuated intracellular Ca(2+) elevation (P < 0.001). Also, noscapine significantly decreased NO production during a 30-minute oxygen-glucose deprivation/reperfusion (P < 0.01). The inhibitory effect of noscapine (4 μM) on intracellular Ca(2+) was greater than ionotropic glutamate receptors antagonists. Noscapine is protective against ischemia/reperfusion-induced excitotoxic injury in OLN-93 oligodendrocyte. This protective effect seems to be related to attenuation of intracellular Ca(2+) overload and NO production. PMID:26690027

  12. Protective Effect of Plantago major Extract against t-BOOH-Induced Mitochondrial Oxidative Damage and Cytotoxicity.

    PubMed

    Mello, Joyce C; Gonzalez, Mariano V D; Moraes, Vivian W R; Prieto, Tatiana; Nascimento, Otaciro R; Rodrigues, Tiago

    2015-09-25

    Plantago major L. produces several chemical substances with anti-inflammatory and analgesic activities and its use in the treatment of oral and throat inflammation in popular medicine is well described. In this study, the antioxidant potential of the Plantago major hydroethanolic extract was screened and its protective action was evaluated against t-BOOH-induced oxidative stress. The extract was obtained by fractionated percolation using 50% ethanolic solution and, after drying, suspended in dimethyl sulfoxide. The chromatographic profile of crude extract was obtained with the identification of some phytochemical markers and the total phenols and flavonoids were quantified. The scavenger activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals was determined and the antioxidant activity in biological systems was evaluated in isolated rat liver mitochondria and HepG2 cells. The extract exhibited a significant free radical scavenger activity at 0.1 mg/mL, and decreased the ROS (reactive oxygen species) generation in succinate-energized mitochondria. Such an effect was associated with the preservation of the intrinsic antioxidant defenses (reduced glutathione and NAD(P)H) against the oxidation by t-BOOH, and also to the protection of membranes from lipid oxidation. The cytoprotective effect of PmHE against t-BOOH induced cell death was also shown. These findings contribute to the understanding of the health benefits attributed to P. major.

  13. The protective effect of magnesium lithospermate B against glucose-induced intracellular oxidative damage

    SciTech Connect

    Qu, Jian; Ren, Xian; Hou, Rui-ying; Dai, Xing-ping; Zhao, Ying-chun; Xu, Xiao-jing; Zhang, Wei; Zhou, Gan; Zhou, Hong-hao; Liu, Zhao-qian

    2011-07-22

    Highlights: {yields} LAB reduced the ROS production in HEK293T cells cultured under oxidative stress. High dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time-dependent manner. {yields} LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a dose-dependent manner treated with high dose of glucose. {yields} LAB plays an important role against glucose-induced intracellular oxidative damage. {yields} The enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via Nrf2 signal pathway. -- Abstract: Objectives: To investigate the effects of magnesium lithospermate B (LAB) on intracellular reactive oxygen species (ROS) production induced by high dose of glucose or H{sub 2}O{sub 2}, we explored the influences of LAB on the expression of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf2) in HEK293T cells after treatment with high dose of glucose. Materials and methods: The total nuclear proteins in HEK293T cells were extracted with Cytoplasmic Protein Extraction Kit. The ROS level was determined by flow cytometry. The mRNA and protein expression of HO-1 and Nrf2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Results: LAB reduced the ROS production in HEK293T cells cultured under oxidative stress. High dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time-dependent manner. LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a dose-dependent manner treated with high dose of glucose. The amount of Nrf2 translocation was enhanced after cells were pretreated with 50 {mu}mol/L or 100 {mu}mol/L LAB. Silencing of Nrf2 gene eliminated the enhanced expression of HO-1 protein induced by high dose of glucose plus LAB. Conclusions: LAB plays an important role against glucose-induced intracellular oxidative damage. The enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via Nrf2 signal pathway.

  14. Protection of DFP-induced oxidative damage and neurodegeneration by antioxidants and NMDA receptor antagonist

    SciTech Connect

    Zaja-Milatovic, Snjezana; Aschner, Michael

    2009-10-15

    Prophylactic agents acutely administered in response to anticholinesterases intoxication can prevent toxic symptoms, including fasciculations, seizures, convulsions and death. However, anticholinesterases also have long-term unknown pathophysiological effects, making rational prophylaxis/treatment problematic. Increasing evidence suggests that in addition to excessive cholinergic stimulation, organophosphate compounds such as diisopropylphosphorofluoridate (DFP) induce activation of glutamatergic neurons, generation of reactive oxygen (ROS) and nitrogen species (RNS), leading to neurodegeneration. The present study investigated multiple affectors of DFP exposure critical to cerebral oxidative damage and whether antioxidants and NMDA receptor antagonist memantine provide neuroprotection by preventing DFP-induced biochemical and morphometric changes in rat brain. Rats treated acutely with DFP (1.25 mg/kg, s.c.) developed onset of toxicity signs within 7-15 min that progressed to maximal severity of seizures and fasciculations within 60 min. At this time point, DFP caused significant (p < 0.01) increases in biomarkers of ROS (F{sub 2}-isoprostanes, F{sub 2}-IsoPs; and F{sub 4}-neuroprostanes, F{sub 4}-NeuroPs), RNS (citrulline), and declines in high-energy phosphates (HEP) in rat cerebrum. At the same time, quantitative morphometric analysis of pyramidal neurons of the hippocampal CA1 region revealed significant (p < 0.01) reductions in dendritic lengths and spine density. When rats were pretreated with the antioxidants N-tert-butyl-{alpha}-phenylnitrone (PBN, 200 mg/kg, i.p.), or vitamin E (100 mg/kg, i.p./day for 3 days), or memantine (18 mg/kg, i.p.), significant attenuations in DFP-induced increases in F{sub 2}-IsoPs, F{sub 4}-NeuroPs, citrulline, and depletion of HEP were noted. Furthermore, attenuation in oxidative damage following antioxidants or memantine pretreatment was accompanied by rescue from dendritic degeneration of pyramidal neurons in the CA1

  15. Fisetin attenuates hydrogen peroxide-induced cell damage by scavenging reactive oxygen species and activating protective functions of cellular glutathione system.

    PubMed

    Kang, Kyoung Ah; Piao, Mei Jing; Kim, Ki Cheon; Cha, Ji Won; Zheng, Jian; Yao, Cheng Wen; Chae, Sungwook; Hyun, Jin Won

    2014-01-01

    Hydrogen peroxide (H2O2) can induce cell damage by generating reactive oxygen species (ROS), resulting in DNA damage and cell death. The aim of this study is to elucidate the protective effects of fisetin (3,7,3',4',-tetrahydroxy flavone) against H2O2-induced cell damage. Fisetin reduced the level of superoxide anion, hydroxyl radical in cell free system, and intracellular ROS generated by H2O2. Moreover, fisetin protected against H2O2-induced membrane lipid peroxidation, cellular DNA damage, and protein carbonylation, which are the primary cellular outcomes of H2O2 treatment. Furthermore, fisetin increased the level of reduced glutathione (GSH) and expression of glutamate-cysteine ligase catalytic subunit, which is decreased by H2O2. Conversely, a GSH inhibitor abolished the cytoprotective effect of fisetin against H2O2-induced cells damage. Taken together, our results suggest that fisetin protects against H2O2-induced cell damage by inhibiting ROS generation, thereby maintaining the protective role of the cellular GSH system.