Biomedical subjects

T P Devasagayam

Publications and source records attributed to T P Devasagayam.

At least 37 records · Page 2Linked to original sources

PubMed1997

Photodynamic effects induced by meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin using rat hepatic microsomes as model membranes.

Porphyrins, in combination with light, offer an alternate approach to the treatment of cancer, in the form of photodynamic therapy (PDT). With a view to locate new porphyrins for use in PDT, we evaluated the ability of a novel water-soluble porphyrin, meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP) to induce photodamage in membranes, using rat hepatic microsomes as a model system. Hepatic microsomes treated with T4CPP and exposed to visible light showed significant lipid peroxidation, as assessed by the formation of conjugated dienes, lipid hydroperoxides, and thiobarbituric acid-reactive substances. The peroxidation induced was both time- and concentration-dependent. T4CPP plus light also resulted in the destruction of the microsomal enzymes adenosine triphosphatase and glucose-6-phosphatase. Analysis of the products of peroxidation and selective inhibition by specific inhibitors showed that the oxidative damage induced was mainly due to singlet oxygen and partly due to hydroxyl radical. The porphyrin T4CPP was efficiently labeled with 99mTc. When this 99mTc-labeled porphyrin was injected into a mammary-tumor-bearing rat, it accumulated in the tumor. Our studies suggest that T4CPP, due to its potential to localize in tumors and to induce membrane damage as exemplified by alteration in rat liver microsomes, may have possible applications in this new modality of cancer treatment.

Animals↗

PubMed1997

Effect of Maharishi AK-4 on H2O2-induced oxidative stress in isolated rat hearts.

Oxidative damage to crucial biomolecules due to excess generation of reactive oxygen species has been implicated as a major cause of organ damage and hence compounds capable of negating such damage have potential benefits. Using hydrogen peroxide (H2O2) as a model pro-oxidant to induce oxidative stress, we have examined the ability of natural food supplement Maharishi Amrit Kalash (MAK-4) to decrease oxidative damage in potassium-arrested isolated rat hearts. The protocol was that hearts isolated from male Sprague-Dawley rats were retrograde-perfused with Krebs-Henseleit (K-H) solution for 30 min for equilibration. After this period, the hearts were subjected to cardioplegia with high potassium (26-30 mM), followed by reperfusion with K-H solution in the presence or absence of 200 microM H2O2. As expected, H2O2 treatment following cardioplegia induced a high degree of oxidative stress as assessed by release of lactate dehydrogenase (LDH, a marker of plasma membrane damage) and total glutathione (GSH + GSSG). H2O2 also impaired the ability of heart to regain developed tension during the testing period. However, addition of MAK-4 in the perfusate containing H2O2 decreased oxidative stress in terms of release of LDH and glutathione. In parallel with these biochemical studies, in a few experiments the cardiac function was assessed by measuring developed contractile tension. These preliminary studies also showed that in the presence of MAK-4 the H2O2-treated hearts were able to regain better developed tension. Further in vitro studies to examine the possible mechanisms of MAK-4 action reveal that this formulation contains H2O2 binding activity which resulted in the decreased availability of H2O2 itself. Our studies hence reveal that the ayurvedic food supplement MAK-4 may have potential benefits in reducing oxidative stress.

Animals↗

PubMed1997

Photocleavage of plasmid DNA by the prophyrin meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin.

meso-Tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (H2T4CPP) cleaves pBR322 plasmid DNA to single strand breaks in the presence of molecular oxygen and visible light. The above photocleavage was much more efficient in D2O buffer of sodium phosphate (pD = 7.4) than H2O buffer of sodium phosphate (pH = 7.4). In addition this photocleavage of plasmid DNA was inhibited in the presence of sodium azide, lipoic acid, tert-butanol or mannitol suggesting the involvement of 1O2 and.OH in the photocleavage of plasmid DNA. The photocleavage was observed to be more efficient in the presence of H2T4CPP than in the presence of H2CPP [meso-tetrakis (4-carboxy-phenyl)porphyrin]. Our spectral studies using UV-visible, fluorescence and circular dichroism techniques suggest that H2T4CPP binds to DNA while H2CPP does not. Thus, the difference in photocleavage may be caused by the nonbinding of H2CPP and by the binding of H2T4CPP to calf thymus (CT) DNA.

Circular Dichroism↗

PubMed1997

Lipid peroxidation induced by a novel porphyrin plus light in isolated mitochondria: possible implications in photodynamic therapy.

With a view to locate porphyrins for use in photodynamic therapy (PDT), the new modality of cancer treatment we have evaluated the ability of a novel water soluble porphyrin meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP) to induce damage to mitochondria during photosensitization. T4CPP, when exposed to visible light, induced lipid peroxidation in rat liver mitochondria as assessed by the formation of thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LOOH). The effect on mitochondrial function was assessed by estimating the activity of succinate dehydrogenase (SDH). The peroxidation induced was observed to be time- and concentration- dependent. Analysis of product formation and selective inhibition by scavengers of reactive oxygen species showed that the oxidative damage observed was mainly due to singlet oxygen ((1)O2) and partly due to other reactive species. T4CPP plus light also caused significant lipid peroxidation in Sarcoma 180 ascites tumour mitochondria. Our studies indicate that T4CPP has the potential to photoinduce damage in hepatic and ascites mitochondria, a crucial site of damage in PDT.

Animals↗

PubMed1997

Tocotrienols from palm oil as effective inhibitors of protein oxidation and lipid peroxidation in rat liver microsomes.

Tocotrienols from palm oil showed significant ability to inhibit oxidative damage induced by ascorbate-Fe2+ and photosensitization, involving different mechanisms, in rat liver microsomes. The tocotrienol-rich fraction from palm oil (TRF), being tried as a more economical and efficient substitute for alpha-tocopherol, showed time- and concentration-dependent inhibition of protein oxidation as well as lipid peroxidation. It was more effective against protein oxidation. The extent of inhibition by TRF varied with different peroxidation products such as conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS). Among the constituents of TRF, gamma-tocotrienol was the most effective followed by its alpha- and delta-isomers. In general, at a low concentration of 5 microM, TRF was able to prevent oxidative damage to significant extent (37% inhibition of protein oxidation and 27-30% of lipid peroxidation at 1 h of incubation). The protective ability of TRF (30.1% at 5 microM with TBARS formation) was significantly higher than that of the dominant form of vitamin E, alpha-tocopherol (16.5% under same conditions). Hence our studies indicate that this fraction from palm oil can be considered as an effective natural antioxidant supplement capable of protecting cellular membranes against oxidative damage.

Animals↗

PubMed1996

Caffeine as an antioxidant: inhibition of lipid peroxidation induced by reactive oxygen species.

Caffeine (1,3,7-trimethyl xanthine), an ingredient of coffee, has been investigated for its potential antioxidant activity against oxidative damage to rat liver microsomes. Such damage was induced by three reactive oxygen species of cardinal importance in causing membrane damage in vivo namely hydroxyl radical (.OH), peroxyl radical (ROO.) and singlet oxygen (1O2). The results obtained showed that caffeine was an effective inhibitor of lipid peroxidation, at millimolar concentrations, against all the three reactive species. The extent of inhibition was high against peroxidation induced by .OH, medium against 1O2 and low against ROO. In general, the antioxidant ability of caffeine was similar to that of the established biological antioxidant glutathione and significantly higher than ascorbic acid. Investigations into the possible mechanisms involved in the observed antioxidant effect reveal that the quenching of these reactive species by caffeine may be one of the possible factor responsible. The rate constant of caffeine with .OH was 7.3 x 10(9) M-1 s-1 and with 1O2 it was 2.9 x 10(7) M-1 s-1. Considering their potential for damage, half-life estimates and generation in biological systems, the ability of caffeine to inhibit oxidative damage induced by these reactive species in membranes suggest one more positive attribute of caffeine, whose daily intake as coffee may be considerable in most populations.

Animals↗

PubMed1996

Methylene blue plus light-induced lipid peroxidation in rat liver microsomes: inhibition by nicotinamide (vitamin B3) and other antioxidants.

Methylene blue plus visible light, in the presence of oxygen, induced lipid peroxidation in rat liver microsomes, as assessed by the formation of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides and the loss of membrane-bound enzymes. Peroxidation was enhanced by deuteration of the buffer and inhibited by scavengers of singlet oxygen (1O2) and superoxide (O2.-). The damage induced seemed to be mainly due to Type II involving 1O2 and to a lesser extent Type I reactions with O2.- and hydroxyl radical (.OH) as intermediates. Nicotinamide or vitamin B3, an endogenous metabolite occurring at high concentrations in tissues, had a relatively high rate constant of 1.8 x 108 M-1 s-1 with 102 and had a significant inhibitory effect on lipid peroxidation induced by photosensitization. This effect was both time- and concentration-dependent, high inhibition being associated with millimolar concentrations. Chemically related endogenous compounds like tryptophan and isonicotinic acid also had significant inhibitory properties. Similar protective effects were observed with natural antioxidants such as beta-carotene, canthaxanthin, lipoic acid, glutathione, alpha-tocopherol and to a lesser extent ascorbic acid. Nicotinamide was a more effective antioxidant than ascorbic acid. It also showed a similar inhibitory effect against NADPH-ADP-FE3(+)-induced lipid peroxidation. Our results suggest that nicotinamide had significant ability to protect against photosensitization-induced cytotoxicity and cell damage and that it may do so by its ability to react with 102 and other reactive oxygen species.

Adenosine Triphosphatases↗

PubMed1996

Mechanisms of protection by buthionine sulphoximine against gamma-ray-induced micronuclei in polychromatic erythrocytes of mouse bone marrow.

The effect of pretreatment with buthionine sulphoximine (BSO) on the radiosensitivity of mouse bone marrow cells was studied using the in vivo micronucleus test. Varying concentrations of BSO were injected into mice by intraperitoneal injection 2 h before irradiation, and the frequency of micronuclei in polychromatic erythrocytes (MnPCEs) of bone marrow were scored. Treatment with BSO resulted in a significant reduction (41% at 20 mg/kg body weight) in the frequency of micronuclei induced by 1 Gy gamma-rays. Reduction was observed in cells sampled at 24, 30 and 48 h postirradiation with no apparent effect on the ratio of poly- to normo-chromatic erythrocytes in BSO-treated versus control groups. Glutathione levels in the bone marrow of BSO-treated animals 2 h after a single injection were found to be unaltered. The protective effect of BSO was not observed if it was given either immediately or 2 h after irradiation. Based on these and earlier findings it seemed as if BSO molecules may be involved in physicochemical reactions with reactive species generated in the system by irradiation. BSO showed relatively high reaction rate constants with hydroxyl radical (.OH, 2.5 x 10(9) dm3 mol-1s1, calculated on the basis of competition kinetics) and with singlet oxygen (1O2, 4.3 x 10(7) dm3 mol-1s-1 but a lower rate constant with hydrated electrons (< or = 5.0 x 10(6) dm3 mol-1s1). Based on half-life estimates, transients formed and potential for damage to biomolecules, .OH and 1O2 seemed to be the possible species responsible. In vitro studies reveal that BSO has significant abilities to protect DNA against single-strand breaks and lipid peroxidation induced by 1O2 in microsomal membranes. This supports our hypothesis that BSO may be involved in scavenging the reactive species generated and that besides .OH, 1O2 may also be a major player in radiation damage.

Animals↗

PubMed1996

Radioprotective and antioxidant action of caffeine: mechanistic considerations.

Caffeine, a major constituent of coffee and other beverages has significant abilities to scavenge highly reactive free radicals and excited states of oxygen and to protect crucial biological molecules against these species. This is one of the possible reasons why caffeine acts as a radioprotector against oxygen-dependent ('oxic') pathway of radiation damage and as an antimutagen/anticarcinogen under certain conditions. The possible physicochemical and molecular mechanisms of caffeine action are briefly reviewed in the light of the recent findings.

Animals↗

PubMed1995

Tocotrienols from palm oil as potent inhibitors of lipid peroxidation and protein oxidation in rat brain mitochondria.

The tocotrienol-rich-fraction (TRF) from palm oil, being tried as a more economical and efficient substitute for alpha-tocopherol, significantly inhibited oxidative damage in vitro to both lipids and proteins in rat brain mitochondria induced by ascorbate-Fe2+, the free radical initiator azobis(2-amidopropane)dihydrochloride (AAPH) and photosensitisation. The observed inhibitory effect was both time- and concentration-dependent. At a low concentration of 5 microM, TRF can significantly inhibit oxidative damage to both lipids and proteins. The inhibitory effect of TRF seems to be mainly due to gamma-tocotrienol and to a lesser extent alpha- and delta-tocotrienols. TRF was significantly more effective than alpha-tocopherol. This fraction from palm oil can be considered a natural antioxidant supplement capable of protecting the brain against oxidative damage and thereby from the ensuing adverse alterations.

Animals↗

PubMed1995

Protection of plasmid pBR322 DNA by flavonoids against single-stranded breaks induced by singlet molecular oxygen.

Flavonoids, the dominant colouring pigments of plants, as well as the related polyphenol tannic acid significantly inhibit single-strand breaks in plasmid pBR322 DNA induced by singlet molecular oxygen ((1)O2). This reactive species of oxygen was generated in an aqueous buffer system by the thermal dissociation of the endoperoxide of 3,3'-(1,4-naphthylene)dipropionate. Among the antioxidants examined, myricetin showed the highest protective ability, followed by tannic acid, (+)catechin, rutin, fisetin, luteolin and apigenin, when the inhibitory abilities were compared at 90 min after incubation. The protective abilities of these compounds were both time and concentration dependent. At equimolar concentrations (100 microM) the antioxidant effect of myricetin was better than that of other known antioxidants such as lipoate, alpha-tocopherol and beta-carotene. Data, when analysed in relation to the structures of various compounds, showed a rough correlation with protective abilities. Owing to the abundance of these compounds in our normal diet, they may play significant roles in preventing oxidative damage resulting from potentially deleterious (1)O2.

Antioxidants↗

PubMed1995

Variation in the modulation of superoxide-induced single-strand breaks in plasmid pBR322 DNA by biological antioxidants.

Superoxide radical (O2-.), generated by the xanthine-xanthine oxidase system, induces significant amount (20%) of single-strand breaks in plasmid pBR322 DNA. This is almost completely inhibited by its specific scavenger, superoxide dismutase. The biological antioxidants, at near physiological concentrations show great variation in their modulation of DNA damage induced by O2-.. The thiols glutathione, cysteine and dithiothreitol do not protect DNA, instead they greatly enhance the strand-breaking activity of this free radical. However, the lipid soluble antioxidants tannic acid, butein, canthaxanthin, beta-carotene and lipoate offered significant protection to plasmid DNA against O2-.. Since O2-. is the most abundant reactive oxygen species generated, the above mentioned modulating abilities of biological antioxidants may have significant biological implications.

Antioxidants↗

PubMed1994

Diminution of singlet oxygen-induced DNA damage by curcumin and related antioxidants.

Curcumin, the natural antioxidant from turmeric, an Indian spice, and its derivatives have significant abilities to protect plasmid pBR322 DNA against single-strand breaks induced by singlet oxygen (1O2), a reactive oxygen species with potential genotoxic/mutagenic properties. 1O2 was generated at 37 degrees C in an aqueous buffer system by the thermal dissociation of the endoperoxide of 3,3'-(1,4-naphthylene)dipropionate (NDPO2). Among the compounds tested, curcumin was the most effective inhibitor of DNA damage followed by desmethoxycurcumin, bisdesmethoxycurcumin and other derivatives. The observed antioxidant activity was both time- and concentration-dependent. The protective ability of curcumin was higher than that of the well-known biological antioxidants lipoate, alpha-tocopherol and beta-carotene. However, the highest protective ability with saturating concentrations of curcumin did not exceed 50%. The ability of curcumin and its derivatives to protect DNA against 1O2 seems to be related to their structures and may at least partly explain the therapeutic and other beneficial effects of these compounds including anticarcinogenic and antimutagenic properties.

Antimutagenic Agents↗

PubMed1994

Developmental changes in the peroxidation potential of rat brain homogenate and mitochondria.

Lipid peroxidation, one of the most common expressions of oxidative stress, may be altered during normal physiological states including development. We have examined the changes in lipid peroxidation in rat brain, a tissue highly susceptible to oxidative damage, during this physiological state. In vivo lipid peroxidation was moderate in the foetal and neonatal period and increased during the postnatal development. Lipid peroxidation potential in brain homogenate and mitochondria, in Tris-HCl buffer or with exogenous cofactors, such as ascorbate-Fe2+, NADPH ADP-Fe3+ and cumene hydroperoxide, showed significant changes during pre- and postnatal development. In general, brain as well as liver (used as a standard tissue for comparison) seem to have low peroxidation potential in the foetal and neonatal period which then increases at different rates during development to reach adult values at different days. The low peroxidation potential corresponds to the rapid phase of cell proliferation. These results taken together with similar earlier finding in other systems may indicate a possible occurrence of a 'permissible period' during which the low levels of lipid peroxidation may be able to yield only low amounts of cytostatic aldehydes and peroxides as byproducts, thereby allowing rapid proliferation of cells.

Animals↗

PubMed1993

Gestation confers temporary resistance to peroxidation in the maternal rat brain.

Lipid peroxidation, as assessed by the formation of thiobarbituric acid substances on incubation with ascorbate-Fe2+, NADPH-ADP-Fe3+ and cumene hydroperoxide in brain homogenate and mitochondria, was significantly decreased during gestation and restored to respective control levels post partum. The decrease observed with the brain homogenate on Day 10 of pregnancy was 42% with ascorbate-Fe2+ and 70% with NADPH-ADP-Fe3+. This temporary decrease in peroxidation potential seems to be due to lesser availability of substrate in the form of unsaturated fatty acids besides increase in the cholesterol:phospholipid ratio and glutathione. Progesterone, the gestational steroid elaborated during pregnancy, inhibited lipid peroxidation in brain mitochondria in a dose-dependent manner. The observed temporary decrease in peroxidation potential may be a special adaptation to protect membranes in the brain against oxidant stress during pregnancy.

Adenosine Diphosphate↗

PubMed1993

Prevention of singlet oxygen-induced DNA damage by lipoate.

Among the several biologically and pharmacologically active sulfur compounds examined, only lipoic acid and dihydrolipoic acid provided protection to plasmid DNA against singlet molecular oxygen (1O2). 1O2 was generated in phosphate buffer by the thermal dissociation of the endoperoxide of 3,3'-(1,4-naphthylidene) dipropionate (NDPO2). The protecting effect of lipoic acid was time- and pH-dependent and significant protection was seen even at 50 microM. The antioxidant effect was adversely affected by temperatures above 45 degrees C. Superoxide dismutase and catalase marginally enhanced this effect. Metal chelation with EDTA decreased the protection by lipoate, indicating that metal ions may be involved. The protective effect was diminished when the disulfide was added after single-strand breaks were induced by 1O2. The formation of 8-oxoguanosine from guanosine upon exposure to NDPO2 was not altered by lipoate.

Catalase↗

PubMed1993

Influence of palm oil or its tocotrienol-rich fraction on the lipid peroxidation potential of rat liver mitochondria and microsomes.

The effect of palm oil, a widely used vegetable oil, rich in tocotrienols, on peroxidation potential of rat liver was examined. Long-term feeding of rats with palm oil as one of the dietary components significantly reduced the peroxidation potential of hepatic mitochondria and microsomes. As compared to hepatic mitochondria isolated from rats fed control or corn oil-rich diet, those from palm oil-fed group showed significantly less susceptibility to peroxidation induced by ascorbate and NADPH. However, in microsomes, only NADPH-induced lipid peroxidation was significantly reduced in rats fed palm oil rich-diet. Though the accumulation of thiobarbituric acid reactive substances during ascorbate-induced lipid peroxidation in mitochondria from rats fed corn oil-rich diet supplemented with tocotrienol-rich fraction (TRF) of palm oil was similar to that of control rats, the initial rate of peroxidation was much slower than those from control or corn oil fed diets. Our in vitro studies as well as analyses of co-factors related to peroxidation potential indicated that the observed decrease in palm oil-fed rats may be due to increased amount of antioxidants in terms of tocotrienol as well as decrease in the availability of substrates for peroxidation.

Animals↗

PubMed1992

Synthetic carotenoids, novel polyene polyketones and new capsorubin isomers as efficient quenchers of singlet molecular oxygen.

Novel synthetic polyene polyketones and new synthetic capsorubin isomers were examined for their ability to quench singlet molecular oxygen (1O2) generated by the thermodissociation of the endoperoxide of 3,3'-(1,4-naphthylene) dipropionate (NDPO2). C28-polyene-tetrone (1) exhibits the highest physical quenching rate constant with 1O2 (kq = 16 x 10(9) M-1 s-1). For comparison, the rate constant for the most efficient biological carotenoid, lycopene (3) is kq = 9 x 10(9) M-1 s-1 and that of beta-carotene (5) kq = 5 x 10(9) M-1 s-1. The presence of two oxalyl chromophores at the ends of the polyene chain seems to enhance the 1O2 quenching ability in the C28-polyene-tetrone (1). C28-polyene-tetrone-diacetal (2) (kq = 9 x 10(9) M-1 s-1) and C40-epiisocapsorubin (4) (kq = 8 x 10(9) M-1 s-1) also have high 1O2 quenching abilities. Two carotenoids from plants, phytoene and phytofluene, were much less efficient, kq values being below 10(7) M-1 s-1. Due to the very high singlet oxygen quenching abilities, C28-polyene-tetrone (1), C28-polyene-tetrone-diacetal (2) and C40-epiisocapsorubin (4) may have potential use in preventing 1O2-induced damage in biological and non-biological systems.

Carotenoids↗