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Biomedical subjects

P C Joshi

Publications and source records attributed to P C Joshi.

At least 37 records · Page 2Linked to original sources
PubMed1995

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↗
PubMed1995

Photophysical and photobiological properties of 3-carbethoxypsoralen.

3-Carbethoxypsoralen (3-CP), a linear tricyclic psoralen, known for its photoreaction with DNA to form monofunctional cyclobutane adducts with pyrimidine bases, was found to produce a highly reactive cytotoxic species, singlet oxygen (1O2) to a greater extent than several other linear psoralens such as psoralen, 8-MOP, 5-MOP or angular psoralens (angelicin). 3-CP also produced superoxide radicals (O2-.) at a rate slower than psoralens in the following order:psoralen > angelicin > 3-CP > 8-MOP > 5-MOP. 1O2 produced by photoactivated 3-CP was found to oxidize tyrosine and Dopa to Dopachrome, and subsequently their conversion to melanin. It also induced photooxidation of 2'-deoxyguanosine. Reactive oxygen species produced by 3-CP also induced lipid peroxidation. The rate of dopachrome formation to promote its conversion to melanin and lipid peroxidation by 3-CP and other linear and angular psoralens and hematoporphyrin derivatives may be related to their skin photosensitizing ability and the rate of 1O2 production. Topically applied 3-CP on hairless mice exposed to UVA radiation was found to be a nonphotocarcinogenic agent in contrast to 8-MOP, which under similar conditions produced a 70% tumour yield (squamous cell carcinoma) in 65 weeks. 3-CP was observed to be a photolabile compound and was converted to a dihydro-form as previously reported by other investigators. The photoconversion of 3-CP to 4',5'-dihydro-3-CP was enhanced under N2, whereas, under O2 atmosphere, lesser degree of photoconversion was observed, thus, indicating that reduction takes place via an anoxic or Type I mechanism. The significance of these observations are discussed in relation to the skin photosensitizing, nonphotocarcinogenic, and photochemotherapeutic potential of 3-CP.

Animals↗
PubMed1994

The role of reactive oxygen species in the degradation of lindane and DDT.

We have studied the photodegradation reactions of lindane and DDT under sunlight (72 hr) or a solar simulator (2 hr) either directly or in presence of selected photodynamic sensitizers. Direct photolysis did not cause noticeable degradation of the pesticides (below 1% in both the cases). However, addition of benzophenone or rose bengal to the irradiation solution of lindane resulted in 88% and 47% degradation, respectively, under sunlight. Similar experiments carried out with DDT resulted in 89%, 50% and 32% degradation with benzophenone, rose bengal and methylene blue, respectively. All the photosensitizers used for the study have been shown to induce photooxidation reactions by generation of reactive oxygen species. These studies suggest that by employing certain naturally occurring photosensitizers with reactive oxygen generation potential under sunlight, an effective method for safe removal of pesticides and other environmentally persistent agents from the surface of earth can be developed.

Anthracenes↗
PubMed1992

Tryptophan as an endogenous photosensitizer to elicit harmful effects of ultraviolet B.

Owing to stratospheric ozone depletion (SOD) the natural flux of ultraviolet B (UVB) radiation (290-320 nm) is likely to increase on the earth surface. In our efforts to identify endogenous chromophores which may absorb significantly in the UVB range and subsequently induce phototoxic reactions, we have observed that tryptophan (Trp) was quite photoreactive under UVB. It enhanced considerably the oxygen-dependent photooxidation of tyrosine (Tyr) to dopachrome, a precursor of melanin. Our data suggest that UVB-sensitized Trp produces singlet oxygen (1O2) and superoxide radicals (O2-.), and these reactive forms of oxygen may contribute to membrane-, cytoplasm- and DNA-damaging effects. In the event of an increasing SOD level, other UVB chromophores may also exhibit similar phototoxic properties to lead to a definitive imbalance between cell life, injury and death.

Dihydroxyphenylalanine↗
PubMed1991

Adenine photodimerization in deoxyadenylate sequences: elucidation of the mechanism through structural studies of a major d(ApA) photoproduct.

The mechanism of the photodimerization of adjacent adenine bases on the same strand of DNA has been elucidated by determining the structure of one of the two major photoproducts that are formed by UV irradiation of the deoxydinucleoside monophosphate d(ApA). The photoproduct, denoted d(ApA)*, corresponds to a species of adenine photodimer first described by Pörschke (Pörschke, D. (1973) J.Am.Chem.Soc. 95, 8440-8446). From a detailed examination of its chemical and spectroscopic properties, including comparisons with the model compound N-cyano-N1-(1-methylimidazol-5-yl)formamidine, it is deduced that d(ApA)* contains a deoxyadenosine unit covalently linked through its C(8) position to C(4) of an imidazole N(1) deoxyribonucleoside moiety bearing an N-cyanoformamidino substituent at C(5). On treatment with acid, d(ApA)* is degraded with high specificity to 8-(5-amino-imidazol-4-yl)adenine whose identity has been confirmed by independent chemical synthesis. It is concluded that the primary event in adenine photodimerization entails photoaddition of the N(7)-C(8) double bond of the 5'-adenine across the C(6) and C(5) positions of the 3'-adenine. The azetidine species thus generated acts as a common precursor to both types of d(ApA) photoproduct which are formed from it by competing modes of azetidine ring fission.

Adenine↗
PubMed1991

Human interleukin 7 is a B cell growth factor for activated B cells.

We investigated the capacity of human interleukin (IL)7 to induce proliferation of B cells. Purified tonsillar B cells were cultured in the presence of IL7 with Staphylococcus aureus Cowan I (SAC) or anti-mu beads as co-mitogens. IL7 supported a dose-dependent proliferation of anti-mu-activated B cells but did not significantly support proliferation of SAC-activated B cells. When B cells were separated on Percoll gradient into small (60%-80%) and large (50%-60%) B cells and then cultured with anti-mu beads, IL7 acted on both cell populations equally well. IL7 and BCGF (low molecular weight) were synergistic in their proliferative action on anti-mu-activated B cells in a 5-day culture. On the other hand, synergistic effect of IL7 on activated B cells was not evident in the presence of any other factor recombinant [(r)IL1 beta, rIL2, rIL3, rIL4, rIL5, rIL6, recombinant tumor necrosis factor-alpha, recombinant lymphotoxin, recombinant granulocyte-monocyte colony-stimulating factor and recombinant interferon-gamma] we tested. IL7 did not induce IgG secretion by activated B cells.

Antibodies, Anti-Idiotypic↗
PubMed1991

Membrane damaging potential of photosensitized riboflavin.

Riboflavin upon exposure to UV and visible radiations has been shown to produce active oxygen species. The present work deals with erythrocyte membrane as model system to study the damaging potential of photosensitized riboflavin. Membrane preparations (2.5 mg protein/ml) following exposure to sunlight in presence of riboflavin for different time intervals revealed significant inhibition of ATPases, p-nitrophenyl phosphatase and acetylcholinesterase. Considerable increase in lipid peroxidation was caused by the photosensitized riboflavin. Quenching studies using specific scavengers indicated remarkable inhibition. The production and identification of reactive oxygen species by photosensitized riboflavin and their possible involvement in membrane damaging effect has been discussed.

Erythrocyte Membrane↗
PubMed1990

Photosensitizing potential of benzanthrone.

In skin-photosensitization studies on guinea-pigs benzanthrone induced significant erythema and oedema, depending upon the doses both of benzanthrone and of sunlight or artificially simulated UVA radiation. Maximum sensitization and delayed tanning response on the guinea-pig skin were observed 24-36 hr after irradiation. Photosensitized benzanthrone was found to produce significant amounts of singlet oxygen in vitro, as assessed by the bleaching of N,N-dimethyl-p-nitrosoaniline. As with haematoporphyrin and rose bengal, both of which are potent generators of singlet oxygen, the production of singlet oxygen by benzanthrone was dependent on both the concentration of the test chemical and the dose of solar radiation. Benzanthrone also produced a significant yield of superoxide anion radicals on exposure to simulated solar radiation or sunlight. Photosensitized benzanthrone induced photohaemolysis of rat erythrocytes and lipid peroxidation of erythrocyte ghosts, in vitro, probably largely through involvement of singlet oxygen (1O2). The rate of lipid peroxidation by photosensitized benzanthrone was inhibited by 64-80% with 1,4-diazabicyclo(2,2,2)octane and sodium azide, 15% with superoxide dismutase but was not affected by mannitol and sodium benzoate. Equimolar concentrations of haematoporphyrin and rose bengal also produced considerable photohaemolysis of erythrocytes and lipid peroxidation in erythrocyte ghosts; in both cases rose bengal was the most active and benzanthrone the least active of the three compounds.

Animals↗
PubMed1989

Ultraviolet radiation-induced photodegradation and 1O2, O2-. production by riboflavin, lumichrome and lumiflavin.

Although UVA (320-400 nm) is considered less harmful to skin as compared to UVB (290-320 nm) and UVC (200-290 nm) radiation, certain endogenous chromophores may enhance UVA-induced cutaneous reactions by largely O2-dependent photodynamic reactions. Photodegradation pattern and singlet oxygen (1O2), superoxide anion radical (O2-.) producing capacity of riboflavin (RF), lumiflavin (LF) and lumichrome (LC) were examined to assess their phototoxic potential under UVA. Photolysis of RF upon exposure to UVA, UVB or UVC revealed considerable degradation to LF and LC with a near identical spectral pattern of photodegradation between 250-500 nm. Both LF and LC were stable to UVA (3 J/cm2) and UVB (400 mJ/cm2), whereas RF was photodegraded by 30 and 20%, respectively, under similar irradiation conditions. UVA-sensitized LF and LC respectively, produced nearly 15% higher and 60% lower yield of 1O2 in comparison to RF, whereas, O2-. was generated predominently by RF. Both RF and LF thus appeared to be potential chromophores for evoking deleterious effects of UVA in normal human skin.

Flavins↗
PubMed1987

Membrane phospholipid organization in calcium-loaded human erythrocytes.

Intracellular Ca2+ levels in human erythrocytes were increased by incubating them with variable concentrations of Ca2+ in the presence of ionophore A23187. Experiments were done to confirm that the Ca2+ loading did induce changes in the cell shape and membrane protein composition. The effect of the increased cytoplasmic Ca2+ levels on the membrane phospholipid organization was analysed using bee venom and pancreatic phospholipases A2, Merocyanine 540 and fluorescamine as the external membrane probes. About 20% phosphatidylethanolamine (PE) and 0% phosphatidylserine (PS) were hydrolysed by the phospholipases in intact control cells, whereas in identical conditions these enzymes readily degraded, 20-30% PE and 7-30% PS, in Ca2+-loaded erythrocytes, depending on the cytoplasmic Ca2+ concentration. Also, Merocyanine 540 failed to stain the fresh or control erythrocytes, but it labeled the cells loaded with Ca2+. Furthermore, fluorescamine labeled approx. 20% PE in fresh or control erythrocytes while in identical conditions, significantly higher amounts of PE were modified in intact Ca2+-loaded cells. These results demonstrate that Ca2+ loading in human erythrocytes leads to loss of the transbilayer phospholipid asymmetry, and suggest that, together with spectrin, polypeptides 2.1 and 4.1 may also play an important role in maintaining the asymmetric distribution of various phospholipids across the erythrocyte membrane bilayer.

Bee Venoms↗
PubMed1987

Involvement of reactive oxygen species in the oxidation of tyrosine and dopa to melanin and in skin tanning.

The role of reactive oxygen (1O2 and O2-.) in skin photosensitization and tanning reaction has been examined. Riboflavin (RF), hematoporphyrin (HP), 3-carbethoxypsoralen (3-CP), and 8-methoxypsoralen (8-MOP), upon photoexcitation under aerobic conditions, produced singlet O2 (1O2). RF, 3-CP, and 8-MOP also produced superoxide anion (O2-.). Reactive O2 produced by photosensitized RF, 3-CP, and 8-MOP was found to oxidize tyrosine and dopa to dopachrome and subsequently their conversion to melanin. HP did not oxidize tyrosine to dopachrome, and 3-CP and RF revealed substantial oxidation of tyrosine. Dopa was oxidized to dopachrome and subsequently to melanin by all photosensitizers tested at a variable rate as follows: RF greater than 3-CP greater than HPD greater than 8-MOP. UVA alone and to a lesser extent UVB also produced 1O2 which induced the oxidation of tyrosine and dopa to dopachrome and subsequently to melanin. The production of dopachrome was higher with dopa compared to tyrosine under all irradiation conditions. These observations appear to have relevance to the O2-requiring immediate tanning reaction of the skin stimulated by solar radiation and in the induction of skin photosensitization.

Dihydroxyphenylalanine↗
PubMed1986

Evaluation of chemically-induced phototoxicity to aquatic organism using Paramecium as a model.

Phototoxicity evaluation using Paramecium aurelia as a model revealed that 4 out of 21 pesticides produced lethal toxicity to cells. Four commonly used synthetic dyes (bromophenol blue, rose bengal, benzanthrone and methylene blue) also exhibited toxicity. Well known phototoxic agents like hematoporphyrin, riboflavin, and anthracene produced positive phototoxic response. Psoralen, a DNA cross-linking agent, also produced phototoxicity to the cells. The results clearly demonstrate that the synergistic action of chemical agents and sunlight produce lethal effects to aquatic organism.

Animals↗
PubMed1985

Comparison of the DNA-damaging property of photosensitised riboflavin via singlet oxygen (1O2) and superoxide radical O2-. mechanisms.

Riboflavin was found to generate singlet oxygen (1O2) and superoxide anion radicals O2-. on exposure to UV-A (320-400 nm) and UV-B (290-320 nm) light. Studies with deoxyguanosine (dGuo) showed that 1O2 was largely responsible for riboflavin-sensitised photodegradation of the guanine base of DNA and RNA. Azide ions (N-3) and 1,4 diazabicyclo-[2.2.2]-octane (DABCO) produced over 90% inhibition of dGuo photo oxidation, whereas superoxide dismutase did not show any noticeable quenching effect under similar conditions. Photo oxidation of dGuo by riboflavin and UV radiation is of significant importance from the point of view of cell-damaging reactions by activated oxygen species produced by the synergistic action of sunlight and chemical agents. It is now known that activated oxygen species are responsible for skin photosensitisation, tumor promotion and carcinogenic properties.

DNA↗
PubMed1984

Production of active oxygen species (1O2 and O2-.) by psoralens and ultraviolet radiation (320-400 nm).

Furocoumarins (psoralens) are potent skin photosensitizing agents that are used in combination with long-wavelength ultraviolet radiation (320-400 nm) in the treatment of psoriasis and other skin diseases. Twelve linear and angular psoralens, capable of forming monofunctional and bifunctional adducts with DNA, were examined with a view to elucidate the role of 1O2 and O2-. in evoking skin photosensitization reactions and skin carcinogenesis. The results showed that both linear psoralens (capable of forming interstrand cross-links) and isopsoralens (angular, monofunctional type) and 3-carbethoxypsoralen (a linear and monofunctional type) produced 1O2 and O2-., although at varying degrees. Psoralen and 3-carbethoxypsoralen produced 1O2 greater than isopsoralens (angelicins). However, nonphotosensitizing angelicin, 5-methylangelicin, and 4,8-dimethyl-5'-carboxypsoralen produced 1O2 greater than 8-methoxypsoralen and 5-methoxypsoralen. The three monofunctional angelicin derivatives (isopsoralens) produced more O2-. than 8-methoxypsoralen, 5-methoxypsoralen, and 3,4'-dimethyl-8-methoxypsoralen. 3-Carbethoxypsoralen, a potent generator of 1O2 and a moderate producer of O2-., was highly photolabile. Until recently, skin photosensitization reactions (erythema, edema, damage to DNA or the membrane of cutaneous cells, the inhibition of scheduled DNA synthesis and skin carcinogenesis, etc.) were believed to involve photocyclo-addition of psoralens to DNA mediated by a type-I or anoxic reaction (a sensitizer-substrate interaction through the transfer of hydrogen atoms or electrons, but no direct involvement of molecular oxygen). Oxygen-dependent sensitized photodynamic reactions of type-II, involving the production of reactive oxygen (1O2 and O2-.), were believed not to mediate psoralen photosensitization reactions. We suggest that 1O2 and O2-. may also participate in skin photosensitization and cell membrane-damaging reactions. The fact that certain monofunctional isopsoralens produce 1O2 and O2-. at rates comparable to or better than bifunctional psoralens suggests that these reactive moieties of oxygen could play a major role in explaining their recently observed carcinogenic property and cell membrane-damaging reactions (e.g., edema or inflammation, etc.).

Animals↗
PubMed1984

The role of active oxygen (1O2 and O(2)) induced by crude coal tar and its ingredients used in photochemotherapy of skin diseases.

Crude coal tar (CCT) and certain photoreactive ingredients of CCT are photosensitizing agents used in the treatment of skin diseases (psoriasis, atopic eczema, etc.). Limited information is available in elucidating the mode of action of CCT in clearing psoriasis or causing skin photosensitization reactions. The production of singlet oxygen (1O2) and superoxide radicals (O(2) or HO2), the formation of interstrand cross-links (ICL) in DNA, and the skin photosensitization reaction caused by CCT or the ingredients present in tar preparations have been examined. Both type I (oxygen-independent) and type II (sensitized reactions requiring molecular oxygen) reactions are induced by CCT. Our data show that CCT and some of the photoreactive ingredients present in CCT produce 1O2, O(2), and ICL in DNA upon exposure to UVA radiation. Based on the equivalent concentration, the efficiency of various agents to produce 1O2 was of the following order: hematoporphyrin greater than phenanthridine greater than acridine greater than methylene blue greater than CCT greater than fluoranthrene greater than anthracene greater than pyrene greater than 8-methoxypsoralen greater than anthralin greater than chloroquine greater than anthralin dimer. The O(2) formation with CCT and its ingredients was also of the same order except for anthracene which was found to be a strong producer of O(2). The therapeutic effectiveness of CCT appears to be due to: (a) its cytotoxic effects, and (b) the production of 1O2, O(2), and ICL by CCT and its photoreactive ingredients. The skin photosensitizing (smarting, edema, and erythema responses) and carcinogenic properties of CCT may also be related to the production of 1O2 and O(2) and the formation of ICL which appear to be responsible for inducing the damage to the DNA and cell membrane.

Animals↗
PubMed1983

Production of singlet oxygen and superoxide radicals by psoralens and their biological significance.

We have investigated a series of linear and angular furocoumarins, capable of forming either the monofunctional adducts (single strand) or bifunctional adducts (interstrand cross-links) with DNA with a view to examine the relationship of their skin photosensitizing potency, their ability to produce singlet oxygen (1O2) or superoxide radicals (O-.2 or HO.2), and their carcinogenic activity. The significance of photochemical interactions of psoralens and DNA is well known in skin photosensitization and skin carcinogenesis. Our data suggest that both monofunctional and bifunctional psoralens produce 1O2 and O-.2, and these reactive forms of oxygen may contribute to the development of skin cancer and membrane-damaging effects of these furocoumarins.

Cross-Linking Reagents↗