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T P Devasagayam

Publications and source records attributed to T P Devasagayam.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Formation of 8-hydroxy(deoxy)guanosine and generation of strand breaks at guanine residues in DNA by singlet oxygen.

Singlet molecular oxygen (1O2) was generated in aqueous solution (H2O or D2O) at 37 degrees C by the thermal dissociation of the endoperoxide of 3,3'-(1,4-naphthylidene) dipropionate (NDPO2). Guanosine and deoxyguanosine quench 1O2 with overall quenching rate constants of 6.2 X 10(6) M-1 s-1 and 5.2 X 10(6) M-1 s-1, respectively. Reaction with 1O2 results in the formation of 8-hydroxyguanosine (8-OH-Guo) and 8-hydroxydeoxyguanosine (8-OH-dGuo), respectively, with a yield of 1.5% at 1 mM substrate with an NDPO2 concentration of 40 mM; a corresponding 8-hydroxy derivative is not formed from deoxyadenosine. In D2O the yield of 8-OH-Guo is 1.5-fold that in H2O. Sodium azide suppresses 8-OH-Guo and 8-OH-dGuo production. In contrast, the hydroxyl radical scavengers, tert-butanol, 2-propanol, or sodium formate, do not decrease the production of the 8-OH derivatives. The formation of 8-OH derivatives is significantly increased (2-5-fold) by thiols such as dithiothreitol, glutathione, cysteine, and cysteamine. With use of a plasmid containing a fragment of the mouse metallothionein I promoter (pMTP3') and a novel end-labeling technique, the position of 1O2-induced single-strand breaks in DNA was examined. Strand breaks occur selectively at dGuo; no major differences (hot spots) were observed between individual guanines.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1991

Singlet oxygen induced single-strand breaks in plasmid pBR322 DNA: the enhancing effect of thiols.

The biologically occurring thiols, glutathione, cysteamine and cysteine, significantly enhance the single-strand breaks in plasmid pBR322 DNA induced by singlet molecular oxygen (1O2) generated by the thermodissociation of the endoperoxide of 3,3'-(1,4-naphthylidene)dipropionate. The enhancing effect was also observed with chemically related sulfhydryl compounds but not by disulfides. In contrast, dihydrolipoate and its disulfide lipoate protected the plasmid DNA. Metal chelators as well as superoxide dismutase or catalase had no effect, whereas mannitol or sodium azide, decreased the thiol-1O2-induced strand breaks. It is concluded that the observed effects are mediated by reactive oxidation products arising from the 1O2-oxidation of thiols.

Chelating Agents↗
PubMed1991

Activity of thiols as singlet molecular oxygen quenchers.

Singlet molecular oxygen O2(1 delta g) arising from the thermodissociation of the endoperoxide of 3,3'-(1,4-naphthylidene) dipropionate (NDPO2) was used to assess the quenching ability of various thiols and related compounds in sodium phosphate buffer in D2O at 37 degrees C. The overall quenching ability decreases in the sequence ergothioneine, methionine, cysteine, beta,beta-dimethyl cysteine (penicillamine), mercaptopropionylglycine, mesna, glutathione (GSH), dithiothreitol, N-acetyl cysteine and captopril. Cystine, glutathione disulphide, dimesna, methionine sulphone and methionine sulphoxide have no quenching effect. Comparison of the rate constants for physical (kq) with chemical (kr) quenching by thiols indicates that chemical reactivity accounts fully for their ability to quench O2(1 delta g), and pD dependence indicates that the thiolate anion reacts with O2(1 delta g). Loss of thiol groups, as exemplified by GSH, is not affected by the free radical scavengers superoxide dismutase and mannitol. However, sodium azide, a scavenger of O2(1 delta g), completely prevents NDPO2-induced thiol depletion. Depletion of GSH by NDPO2 is accompanied by the formation of its disulphide, sulphinate, sulphonate, sulphoxide and other products.

Glutathione↗
PubMed1990

Carotenoids, tocopherols and thiols as biological singlet molecular oxygen quenchers.

Singlet molecular oxygen (1O2) has been shown to be generated in biological systems and is capable of damaging proteins, lipids and DNA. The ability of some biological antioxidants to quench 1O2 was studied by using singlet oxygen generated by the thermodissociation of the endoperoxide of 3,3'-(1,4-naphthylidene) dipropionate (NDPO2). The carotenoid lycopene was the most efficient 1O2 quencher (kq + kr = 31 x 10(9) M-1 s-1). Tocopherols and thiols were less effective. The singlet oxygen quenching ability decreased in the following order: lycopene, gamma-carotene, astaxanthin, canthaxanthin, alpha-carotene, beta-carotene, bixin, zeaxanthin, lutein, bilirubin, biliverdin, tocopherols and thiols. However, the compounds with low quenching rate constants occur at higher levels in biological tissues. Thus, carotenoids and tocopherols may contribute almost equally to the protection of tissues against the deleterious effects of 1O2. The quenching abilities of carotenoids and tocopherols were mainly due to physical quenching. In case of some thiols chemical quenching also plays a significant role. Carotenoids and tocopherols have been reported to exert a protective action against some types of cancer.

Animals↗
PubMed1990

Modulation of lipid peroxidation in human spermatozoa and human prostate by prostatic inhibin.

Loss of sperm motility as a result of the production of hydrogen peroxide by lipid peroxidation is regulated by as yet unidentified prostatic factor(s). Inhibinlike peptide of prostatic origin isolated from human seminal plasma, with a molecular size of about 10,400 daltons, was studied for its effect on ascorbate-induced lipid peroxidation in human spermatozoa. Dose-related suppression of lipid peroxidation was observed at dose levels of 0.25, 0.5, and 1.0 micrograms. The data suggest that inhibinlike peptide could be one of the factors involved in the regulation of lipid peroxidation and thereby of sperm motility. Inhibinlike peptide also exhibited local action in both normal and benign hyperplastic human prostate tissue by enhancing the rate of lipid peroxidation. These findings have implications in the pathophysiology of the prostate.

Dose-Response Relationship, Drug↗
PubMed1990

Lipid peroxidation in the rat uterus during deciduoma induced cell differentiation.

The influence of deciduoma-induced differentiation on the lipid peroxidation in the rat uterus was investigated. The wet weight of uterus and its protein content increased during deciduoma progression. Content of the thiobarbituric acid reactive substances (TBARS) as well as lipid peroxidation induced by ascorbate and cumene hydroperoxide showed significant decreases during deciduoma growth. Restoration of normalcy was observed during regression. The activity of superoxide dismutase, an inhibitor of lipid peroxidation showed an opposite pattern namely increase during deciduoma development and decline during the regressive phase. We conclude that cell differentiation during deciduoma induction is accompanied by a temporary and reversible decrease in the peroxidative potential of the rat uterus.

Animals↗
PubMed1989

Decreased peroxidative potential in rat brain microsomal fractions during ageing.

Rough and smooth microsomes of brain in senescent rats showed less sensitivity to ascorbate-, NADPH- and cumene hydroperoxide-induced peroxidative damage compared with those of young adults. The observed decrease in peroxidative potential in senescent rats seemed to be due to decrease in the substrate for peroxidation in the form of phospholipids and increase in the level of antioxidants such as reduced glutathione and superoxide dismutase.

Aging↗
PubMed1989

Suppression of lipid peroxidation in human spermatozoa by prostatic inhibin.

Loss of sperm motility owing to the production of hydrogen peroxide by lipid peroxidation is regulated by yet unidentified prostatic factor(s). Inhibinlike peptide (HSPI) of prostatic origin isolated from human seminal plasma and having a molecular weight of about 10,400 daltons was studied for its effect on ascorbate-induced lipid peroxidation in human spermatozoa. Dose-related suppression of lipid peroxidation occurred at a dose level of 0.25, 0.5, and 1.0 micrograms. HSPI may be one of the factors involved in the regulation of lipid peroxidation and therefore sperm motility.

Humans↗
PubMed1988

Pregnancy-associated decrease in lipid peroxidation in rat liver.

A significant decrease in the hepatic malonaldehyde content and lipid peroxidation, induced by ascorbate, NADPH and cumene hydroperoxide, was observed during gestation in the rat. Lipid peroxidation tends to reach normal levels 3 days post partum. While a significant decrease in the lipid peroxidation of hepatic mitochondria was observed with ascorbate and NADPH, that of microsomes was affected by ascorbate and cumene hydroperoxide. The observed decrease in lipid peroxidation during pregnancy seems to be due to lesser phospholipid content, a lower degree of unsaturation in lipids, and an increase in the level of antioxidants.

Animals↗
PubMed1987

Decreased lipid peroxidation in the rat kidney during gestation.

Renal malonaldehyde content and lipid peroxidation, induced by ascorbate, NADPH and cumene hydroperoxide, are significantly decreased during gestation in rats. Lipid peroxidation tends to reach normal levels in the kidney post partum. In the renal mitochondria lipid peroxidation without co-factors and that induced by cumene hydroperoxide, ascorbate and NADPH is decreased during pregnancy. However, in the microsomes, only lipid peroxidation induced by NADPH and cumene hydroperoxide is affected. The observed decrease in lipid peroxidation during gestation is reflected by low levels of total lipid and phospholipid. Endogenous inhibitors of lipid peroxidation also increase during pregnancy.

Animals↗
PubMed1986

Senescence-associated decrease of NADPH-induced lipid peroxidation in rat liver microsomes.

Senescence is associated with decrease in the NADPH-induced lipid peroxidation in liver homogenate as well as rough and smooth microsomes of female rats. In the microsomal fractions, sensitivity to NADPH-induced lipid peroxidation is high in young adults (3-month-old), decreases in middle aged (12-month-old) and reaches lowest levels in senescent (30-month-old) rats. Increasing the concentration of co-factors or time of incubation does not alter this resistance observed in the senescent rats. Major factors responsible for this resistance in senescent rats seem to be low levels of substrate in the c reductase, cytochrome P-450 and high cholesterol:phospholipid ratios besides enhanced levels of superoxide dismutase, alpha-tocopherol and reduced glutathione.

Age Factors↗
PubMed1986

Lipid peroxidation in rat uterus.

Lipid peroxidation in rat uterus has been studied using NADPH- and ascorbate-induced systems. Lipid peroxidation in rat uterus is low as compared to rat liver. Uterus is more sensitive to ascorbate-induced lipid peroxidation than that induced by NADPH. Uterus contains lower amounts of phospholipids and has a lesser degree of unsaturation in lipids. Co-factor studies show that Fe2+ is more important for ascorbate-induced lipid peroxidation. Endometrium is more sensitive to ascorbate-induced lipid peroxidation than myometrium. It also contains more total lipids and phospholipids besides having a higher degree of unsaturation in the lipids as compared to myometrium. Among the subcellular fractions, mitochondria are more prone to ascorbate-induced lipid peroxidation, whereas microsomes are more sensitive to NADPH-induced lipid peroxidation. Uteri from old rats (24 months) and pregnant rats are more resistant to lipid peroxidation than those from 3-month-old control rats. Uterus of pregnant rats contains more factors which inhibit lipid peroxidation and also has a lesser degree of unsaturation in lipids compared with uterus of control rats. The possible consequences of the resistance of uterus to lipid peroxidation, especially during pregnancy and senescence, are discussed.

Animals↗
PubMed1986

Low level of lipid peroxidation in newborn rats. Possible factors for resistance in hepatic microsomes.

Hepatic rough and smooth microsomes of newborn rats show less sensitivity to ascorbate- and NADPH-induced lipid peroxidation as compared to those of adult rats. Though optimum concentrations of Fe2+, ascorbate and Fe3+ significantly increase lipid peroxidation in both age groups, the lipid peroxidation observed in newborns is much less compared with that of adults. Microsomal fractions from newborn rats contain significantly lower amounts of phospholipid, NADPH cytochrome c reductase, cytochrome P-450 and a lower degree of unsaturation in lipids. These fractions also exhibit high cholesterol:phospholipid ratios. The resistance to lipid peroxidation observed in the newborns appears to be due to the low availability of substrate and high cholesterol:phospholipid ratio.

Aging↗
PubMed1986

Changes in ascorbate-induced lipid peroxidation of hepatic rough and smooth microsomes during postnatal development and ageing of rats.

In female Wistar rats, sensitivity to ascorbate-induced lipid peroxidation in rough and smooth microsomes increases with age, reaching a maximum in 1-year-old rats and decreases during ageing. Time course of lipid peroxidation, and lipid peroxidation with optimum concentrations of ascorbic acid, Fe2+ and protein in rough microsomes show that 1-year-old rats are the most susceptible followed by 75-day-old, 15-day-old, 2-year-old and 1-day-old rats. However, smooth microsomes show a slightly different trend with maximum sensitivity in 1-year-old rats followed by 15-day-old, 75-day-old, 2-year-old and 1-day-old rats. Smooth microsomes are more susceptible to lipid peroxidation than the rough in all age groups except 75-day-old rats. Smooth microsomes are also more sensitive to inhibitors of lipid peroxidation. Microsomal content of phospholipid increases during postnatal development and decreases during ageing, whereas that of ascorbic acid and alpha-tocopherol do not show any particular trend.

Aging↗
PubMed1985

Kinetics of NADPH-induced lipid peroxidation in rat liver microsomal fractions as a function of age.

The kinetics of NADPH-induced lipid peroxidation in hepatic rough and smooth microsomes have been studied in rats ranging in age from 1 day to 2 years. Apparent Km and Vmax for NADPH and the extent of lipid peroxidation show that lipid peroxidation potential is low at birth, increases during postnatal development, and decreases during senescence. Our results indicate that this trend may be due to changes in phospholipid content and NADPH cytochrome c reductase activity in microsomal fractions.

Aging↗