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Biomedical subjects

R S Ray

Publications and source records attributed to R S Ray.

At least 19 recordsLinked to original sources

Radiation-induced in vitro phototoxic potential of some fluoroquinolones.

Photosensitizing drugs that can damage cellular biomolecules is a matter of concern. Lomefloxacin, norfloxacin, ofloxacin, and enoxacin (broad-spectrum antibiotics of fluoroquinolone group) are used for the treatment of Gram-positive and Gram-negative bacterial infections. Phototoxicity and possible mechanism of their action was assessed under the exposure of ambient levels of UV-A, UV-B, and sunlight at a concentration generally used in the treatment of various diseases. Singlet oxygen (1O2), superoxide anion radical (O2.-) generation, DNA damage, and lipid peroxidation in human blood were studied. All the fluoroquinolones tested in this study produced 1O2 and O2.- under exposure to UV-A, UV-B, and sunlight depending on the concentrations (0 to 60 microg/mL) of the drugs. Enoxacin showed a higher yield of 1O2 and O2.- than other drugs. These materials also degraded deoxyguanosine and induced lipid peroxidation in vitro under exposure to UV-A, UV-B, and sunlight (depending on the dose of radiation). The formation of the reactive oxygen species (ROS) by the photoexcited drugs may be considered as a possible mechanism of their action.

Anti-Bacterial Agents↗

Effect of UVB radiation on human erythrocytes in vitro.

In order to evaluate the UVB radiation induced phototoxic effect, the human erythrocytes (RBCs) were used an alternate biological model and rate of photohaemolysis was assessed in vitro at various intensities of UVB radiation (0-2.0 mW/cm2) for an exposure period of 0-240 min. The alterations of biochemical activities in RBC membrane (ghosts), caused by its exposure under an average incident intensity of UVB radiation (0.5 mW/cm2) in sunlight at earth surface, were also determined to understand the possible mechanism of photohaemolysis. We observed UVB dose dependent lysis of erythrocytes by recording haemoglobin and methemoglobin (oxidized form of haemoglobin) in photohaemolysate. We also observed significant inhibition in ATPase, acetylcholinesterase, glucose-6-phosphate dehydrogenase activites and an increased amount of thiobarbituric acid-reactive substance (TBA-RS) in RBC ghosts exposed to UVB radiation (0.5 mW/cm2) for a period of 0-100 min (doses: 0, 0.33, 0.66, 1.0, 1.5 and 3.0 J). The changes were found UVB dose dependent. A decrease of glutathione content in RBC ghosts at low dose level of UVB exposure (0.33 J) was found to be recovered at higher dose levels (0.66-1.5 J). These observations suggested, UVB dose dependent toxicity to human erythrocytes in vitro. Thus the erythrocytes can be used for an assessment of UVB induced biological effects and to understand possible mechanism of the phototoxicity.

Animal Testing Alternatives↗

Morphological and metabolic alterations in duckweed (Spirodela polyrhiza) on long-term low-level chronic UV-B exposure.

Laboratory grown duckweed (Spirodela polyrhiza) plants were exposed to 0.72 and 1.44J of UV-B radiation daily for 7 days at 0.4mW/cm(2) intensity. Chlorosis and necrosis were observed along with depletion in protein, pigments (chlorophyll, pheophytin, carotenoids, phycoerythrin, phycocyanin, and flavoxanthin), biomass, root length, and frond size in UV-B-exposed plants. The study confirms morphological and metabolic alterations leading to reduction in the productivity of duckweed following long-term exposure to UV-B radiation.

Araceae↗

Tubifex: a sensitive model for UV-B-induced phototoxicity.

The natural increase of UV-B radiation levels due to depletion of the ozone layer in the atmosphere may impose additional stress for the survival of zooplanktons which serve as a major constituent of the aquatic food chain. To study the adverse effects of UV-B radiation on the aquatic biomass, studies were conducted using the aquatic organism Tubifex as a model, as UV-B radiation is known to penetrate into the natural waters. UV-B radiation induced mortality in tubifex and the production of activated oxygen species by these organisms. Alterations in DNA, RNA, protein, glutathione (GSH), hydrogen peroxide H(2)O(2), thiobarbituric acid-reactive substance (TBA-RS), ATPase, AChE, GST, and LDH activities in Tubifex at various doses (0-2.0 J) of UV-B radiation were found. LC(50) value for UV-B-induced mortality of Tubifex was 0.80+/-0.15 J and the threshold dose was 0.35+/-0.05 J; mortality began within 3h postirradiation. UV-B dose-dependent production of singlet oxygen, superoxide anion, and hydroxyl radicals by Tubifex was observed. DNA, RNA, protein, and GSH contents were found to decrease significantly (P<0.001) while H(2)O(2) and TBA-RS increased (P<0.01) under the influence of UV-B radiation. The activities of ATpase, AChE, and GST enzymes were inhibited (P<0.01) and LDH activity was significantly increased (P<0.001) in Tubifex exposed to UV-B radiation. The results suggest that an increase in UV-B radiation alters several biochemical processes, leading to the mortality of the organism. Tubifex could be useful as a sensitive alternate model for studying UV-B-induced phototoxicity and possible mechanisms of action.

Animals↗

Effect of UV-B radiation on some common antibiotics.

Some of the commonly used antibiotics such as cephaloridine, cephalexin, cephradine, nystatin and nafcillin were tested for generation of singlet oxygen (1O(2)) under UV-B (290-320 nm) exposure and the order for 1O(2) generation was obtained: cephaloridine>cephalexin>nystatin>cephradine>nafcillin. In vitro study with deoxyguanosine (dGuo) showed that 1O(2) was responsible for drug-sensitized photodegradation of the guanine base of DNA and RNA. Sodium azide (NaN(3)) and 1,4-diazabicyclo [2.2.2] octane (DABCO) accorded significant inhibition (76-98%) in the production of (1)O(2) and photo-oxidation of dGuo. The combined effect of drug and UV-B irradiation is of paramount importance in view of cell-damaging reactions by 1O(2). Our findings are important because of increasing UV-B radiation on the earth's surface due to depletion of the stratospheric ozone layer. The selected drugs are used routinely for the treatment of various diseases and their combined action may cause undesirable phototoxic responses. Our study suggests that exposure to sunlight should be avoided after the intake of the photosensitive drugs.

Anti-Bacterial Agents↗

Identification of new photoreduction products of pentachlorophenol.

Pentachlorophenol (PCP), a fungicide and insecticide, leaves behind considerable residue in the environment in the form of unreacted molecule, metabolites and photoreduction products. Most of the previously reported photoproducts have resulted from dechlorination of the parent molecule. We have shown that photoreduction of PCP also proceeds by photoreduction of the parent molecule at carbons 2 and 4. These products were identified and characterized as 2-dehydro-2,3,4,5,6-pentachlorocyclohexanone (II) and 2,3,4,5,6-pentachlorocyclohexanone (IV). Both of them display keto-enol tautomerism. Identification and characterization of new photoproducts of PCP is significant for determining its overall environmental impact in the ecosystem.

Environmental Monitoring↗

Evaluation of UV-radiation induced singlet oxygen generation potential of selected drugs.

Photosensitization reaction of drugs leading to the formation of reactive oxygen species under ultraviolet radiation (UVR) can cause tissue injury, resulting in damage to various cellular macromolecules. The aim of this study was to determine the singlet oxygen generation potential of some commonly used antibiotics so that due precautions can be exercised to minimize their photosensitizing action and oxidative stress potential. The selected antibiotics were examined for their ability to produce singlet oxygen (1O2) under artificial UVA (320-400 nm). Singlet oxygen generation of various screened antibiotics under UVA is of the following order: Nalidixic acid > Amphotericin-B > Cephradine > Cefazolin > Nafcillin > Cephalothin > Ampicillin > Cephalexin > Puromycin > Kanamycin > Lincomycin > Tetracycline > Nystatin > Gentamicin sulphate. Nalidixic acid, the most potent generator of 1O2 among the screened antibiotics, was selected to carry out further studies. Certain specific quenchers of 1O2 such as beta-carotene, 1,4-diazabicyclo[2.2.2] octane (DABCO), and sodium azide (NaN3) accorded significant inhibition in the production of 1O2. The results suggest that precautions are necessary to avoid ultraviolet radiation after the intake of photoreactive drugs, especially in tropical countries such as India. These findings are significant because UVB radiation is reportedly increasing on earth surface in part due to depletion of stratospheric ozone layer. The selected drugs are commonly used for the treatment of various diseases. Thus, the synergistic action of both can lead to undesirable phototoxic responses.

Anti-Bacterial Agents↗

Evaluation of UV-induced superoxide radical generation potential of some common antibiotics.

Photosensitization reaction of drugs leading to the formation of reactive oxygen species (ROS) cause tissue injury causing damage to various cellular macromolecules. The aim of this study was to determine the superoxide anion (O2-) generation potential of commonly used antibiotics so that due precaution could be exercised to minimize their photosensitizing action and oxidative stress potential. The selected antibiotics were examined for their ability to produce (O2-) under sunlight and artificial UVA (320-400 nm) and UVB (290-320 nm). Lincomycin, cephalothin and erythromycin generated significant amount of O2- under various irradiation conditions. Superoxide dismutase (SOD), an enzymatic quencher of O2- inhibited O2- production in all drugs tested. The results suggest that due precaution are necessary to avoid ultraviolet radiation (UVR) after the intake of photoreactive drugs, especially in tropical and sub tropical countries.

Anti-Bacterial Agents↗

Sensitivity of duckweed (Lemna major) to ultraviolet-B radiation.

The sensitivity of an important aquatic macrophyte, duckweed (Lemna major), to UV-B radiation was studied under experimental conditions at three different doses designated as no, mild, and severe injury dose by observing visible injury symptoms and estimating levels of chlorophyll, pheophytin, carotenoids, protein, starch, free sugar, and peroxidase activity. Laboratory-grown duckweed plants were exposed to UV-B radiation at 0.4 mW/cm(2) intensity for different time periods. Mild and severe injury were developed at 6.48 and 8.64 J, respectively. Peroxidase activity increased at all the exposure levels. Dose-dependent decrease in chlorophyll and starch with drastic depletion in protein and free sugar content were observed. Pheophytin and carotenoids content increased at no injury level, but decreased at higher exposure level. The results indicate that ambient UV-B radiation at the indicated level acts as a physiological stress in Lemna major.

Carotenoids↗

Ultraviolet radiation-induced production of superoxide radicals by selected antibiotics.

The ability of certain drugs and chemicals to induce cutaneous phototoxicity and DNA damage has been attributed to free radical formation during photolysis. In this context we have observed that the synergistic action of commonly used antibiotics and ultraviolet radiation (UVR) exhibited strong superoxide radical (O2-) generation potential in the following order: benzylpenicillin > amphotericin > ampicillin > nystatin > spectinomycin > gentamicin. Commercially available penicillin, nystatin, ampicillin and gentamicin also generated O2- under similar conditions. The results suggest that due precaution are necessary to avoid UVR after the intake of photoreactive drugs.

Anti-Bacterial Agents↗

Protection of UV-radiation induced skin toxicity by reactive oxygen scavengers.

Although, photoaddition reactions of psoralens with DNA and membrane lipid are regarded as the major photochemical events responsible for skin-photosensitization and photochemotherapeutic properties, their O2-dependent reactive oxygen specie (ROS) generating potential is also responsible for biologic photooxidation reactions and cutaneous phototoxicity. We have investigated the skin-sensitization reactions of psoralen in presence of selected free radical scavengers. The results confirm that sodium azide, DABCO and beta-carotene inhibited considerably the 1O2 generation reactions in a chemical system (determined by monitoring the bleaching of N,N-dimethyl-p-nitrosoaniline in the presence of histidine used as a selective acceptor of 1O2) as well as skin sensitization in vivo (epilated guinea pig skin). These observation suggest that the O2-dependent photodynamic action of psoralen contributes significantly to the development of cutaneous toxicity which can be inhibited by selective scavengers of 1O2.

Animals↗

Hyperkinesis and food additives: testing the Feingold hypothesis.

Teacher ratings, objective classroom and laboratory observational data, attention-concentration, and other psychological measures obtained on 36 school-age, hyperactive boys under experimental and control diet conditions yielded no support for the Feingold hypothesis. Parental ratings revealed positive behavioral changes for the experimental diet; however, they seemed primarily attributable to one diet sequence. Parents' behavioral ratings on ten hyperactive, preschool boys indicated a positive response to the experimental diet; again, laboratory observations showed no diet effect.

Child↗

Mefanamic acid blood and urine levels in the horse determined by derivative gas-liquid chromatography-electron capture.

Mefenamic acid is extracted from biological fluids and is acylated with pentafluoropropionic anhydride to form a derivative possessing high electron affinity. The derivative is analyzed by gas-liquid chromatography with an electron capture detector. The method is particularly valuable for determining drug levels in blood where small sample and/or drug concentrations are available.

Animals↗