Biomedical subjects

M N Rao

Publications and source records attributed to M N Rao.

At least 37 records · Page 2Linked to original sources

PubMed1998

Physico-chemical properties and antioxidant activities of methoxy phenols.

A few structurally related phenols, dehydrozingerone (DZ), bromopentenone (BP), eugenol (EG) and isoeugenol (IEG), derived from plant products show antioxidant properties by inhibiting lipid peroxidation in membrane models. The phenoxyl radicals produced by the scavenging of free radicals during the inhibition of lipid peroxidation, were also generated by specific one-electron oxidants using pulse radiolysis. The radical lifetimes (second order rate constants for radical-radical reactions), reactivities with hydroxyl and model peroxyl radicals and the one-electron reduction potentials with respect to the standard couples were quantified. These results along with their lipophilicity data were correlated with their antioxidant activity (IC50 values).

Antioxidants↗

PubMed1998

Gastroprotective effect of 1-phenyl-3-(4-hydroxy-3,5-di-tert-butylphenyl)prop-2-en-1-one in rats.

1-Phenyl-3-(4-hydroxy-3,5-di-tert-butylphenyl)prop-2-en-1-one (PHP), an antioxidant, has been studied for gastroprotective activity in-vitro and in-vivo, more specifically for its capacity to inhibit in-vitro iron- and copper-driven oxidant damage at acidic pH values mimicking intragastric conditions in the clinical setting. Our studies showed significant inhibition of both iron- and copper-driven oxidant damage at pH 3.5 and 5.3. Intragastric and intraperitoneal administration of PHP (250 mg kg(-1)) reduced gastric mucosal haemorrhagic lesions in stress-induced and ethanol-induced rat models. The gastroprotective effect of PHP against ethanol was reversed significantly by prior treatment with a dose of indomethacin that inhibits prostaglandin biosynthesis, indicating a possible role of prostaglandins in its gastroprotective effect. Treatment of PHP replenished reduced levels of gastric mucosal non-protein sulphydryls in ethanol-treated rats, suggesting the mediation of its effect through sulphydryls. These results indicate that PHP was active at acidic pH. This is an interesting observation because highly acidic pH is known to be important in the development of gastric ulcers. Our study suggests that PHP might protect gastric mucosa by its capacity to scavenge free radicals.

Animals↗

PubMed1998

Protective effects of selenomethionine against cisplatin-induced renal toxicity in mice and rats.

The effect of selenomethionine on the toxicity of cisplatin has been studied in mice and rats. When selenomethionine (0.5-4 mg kg(-1)) was administered intraperitoneally to mice 1 h before intraperitoneal cisplatin (6 mg kg(-1)), the toxicity of cisplatin, as measured by loss of body weight and blood urea nitrogen and serum creatinine levels, was reduced significantly. The protection was dose-dependent but less when given orally. Similar results were obtained with rats. Deterioration of renal function was characterized by reduced creatinine clearance, and increased excretion of urinary protein was significantly reversed. Partial but significant protection was also observed against capsulation-induced reduction of white blood-cell count. Protective properties were further demonstrated by increased survival of mice pretreated with selenomethionine compared with the lethality observed for animals given cisplatin only. These results suggested that selenomethionine protects against cisplatin-induced renal and other toxicity. The study has many clinical implications in cancer chemotherapy and needs further investigation.

Animals↗

PubMed1997

Purification and partial characterization of a cellular carotenoid-binding protein from ferret liver.

A cellular carotenoid-binding protein was purified to homogeneity from beta-carotene-fed ferret liver utilizing the following steps: ammonium sulfate precipitation, ion exchange, gel filtration, and affinity chromatography. The final purification was 607-fold. [14C]beta-Carotene co-purified with the binding protein throughout the purification procedures. SDS-PAGE of the purified protein showed a single band with an apparent molecular mass of 67 kDa. Scatchard analysis of the specific binding of the purified protein to beta-carotene showed two classes of binding sites, a high affinity site with an apparent Kd of 56 x 10(-9) M and a low affinity site with a Kd of 32 x 10(-6) M. The Bmax for beta-carotene binding to the high affinity site was 1 mol/mol, while that for the low affinity site was 145 mol/mol. The absorption spectrum of the complex showed a 32-nm bathochromic shift in lambdamax with minor peaks at 460 and 516 nm. Except for alpha-carotene and cryptoxanthin, none of the model carotenoids or retinol competed with beta-carotene binding to the protein. Thus, a specific carotenoid-binding protein of 67 kDa has been characterized in mammalian liver with a high degree of specificity for binding only carotenoids with at least one unsubstituted beta-ionone ring.

Animals↗

PubMed1997

Protection against radiation-induced chromosome damage in mouse bone marrow by Ocimum sanctum.

The radioprotective effect of the leaf extract of Ocimum sanctum (Ocimum extract, OE) was investigated by taking chromosome aberrations as the end point. Adult Swiss mice were whole-body exposed to 1-6 Gy of gamma radiation with/without pretreatment with 10 mg/kg b.wt. of OE intraperitoneally for 5 consecutive days. Radiation was given 30 min after the last injection. Metaphase plates were prepared from femur marrow on days 1, 2, 7 and 14 post-treatment and the frequency of aberrant cells and individual aberrations were scored. OE alone did not have any significant effect on the chromosomes. Maximum percent of aberrant cells was observed at 24 h in all the exposed groups. The percent aberrant cells showed a linear quadratic increase with radiation dose, in both radiation alone (RT) and OE + RT-treated groups. Exchange (dicentrics and rings) and multiple (pulverized and severely damaged cells) aberrations also showed a similar response. However, the slopes of OE + RT was significantly shallower than RT groups (p < 0.05). A dose-modifying factor of 2.63 was obtained taking percent aberrant cells for 2 Gy as the base. Progressive decline in the percent aberrant cells as well as the number of aberrations with time after irradiation was observed in both RT and OE + RT groups. OE treatment resulted in a faster recovery compared to RT alone group. At doses below 3 Gy, OE pretreatment almost completely eliminated the exchange aberrations from the cell population by day 2. Studies on a chemical system demonstrated that OE significantly reduced the generation of hydroxyl radical; a lower dose of OE (1 mg/ml) was more effective than 5 mg/ml and this effect was more pronounced than that produced by DMSO. These results show that OE affords in vivo protection against radiation-induced cytogenetic damage. Free radical scavenging is a likely mechanism of OE protection.

Animals↗

PubMed1997

Nitric oxide scavenging by curcuminoids.

Because curcumin, a compound with anti-inflammatory and anticancer activity, inhibits induction of nitric oxide synthase in activated macrophages and has been shown to be a potent scavenger of free radicals we have investigated whether it can scavenge nitric oxide directly. Curcumin reduced the amount of nitrite formed by the reaction between oxygen and nitric oxide generated from sodium nitroprusside. Other related compounds, e.g. demethoxycurcumin, bisdemethoxycurcumin and diacetylcurcumin were as active as curcumin, indicating that the methoxy and the phenolic groups are not essential for the scavenging activity. The results indicate curcumin to be a scavenger of nitric oxide. Because this compound is implicated in inflammation and cancer, the therapeutic properties of curcumin against these conditions might be at least partly explained by its free-radical scavenging properties, including those toward nitric oxide.

Antioxidants↗

PubMed1997

Chronic ethanol downregulates Gal-beta-1,4GlcNAc alpha 2,6-sialyltransferase and Gal-beta-1,3GlcNAc alpha 2,3-sialyltransferase mRNAs in rat liver.

We have previously demonstrated that chronic ethanol specifically decreases the hepatic level and rate of synthesis of 2,6-sialyltransferase (2,6-ST). To understand its mechanism of action, effects of 8 weeks of chronic ethanol feeding on the expression of sialyltransferase (ST) genes in rat liver and kidneys were determined by Northern-blot analysis of ST mRNAs. It was found that, compared with the pair-fed control rats, the percentage decreases in ST mRNAs in the ethanol-fed group were as follows: liver-Gal-beta-1,4GlcNAc alpha 2,6-ST (2,6-ST): 59% (p < 0.001); liver-Gal-beta-1,3GlcNAc alpha 2,3-ST (2,3-ST): 32% (p < 0.01); and kidneys-2,6-ST: 5% (NS). In contrast, glyceral-dehyde-3-phosphate dehydrogenase mRNA in both liver and kidneys was unaffected by the same ethanol treatment. Taken together, these results demonstrate that chronic ethanol downregulates the expression of 2,6-ST and 2,3-ST genes in rat liver.

Alcoholism↗

PubMed1996

Regulated nuclear polyadenylation of Xenopus albumin pre-mRNA.

Cytoplasmic regulation of the length of poly(A) on mRNA is a well-characterized process involved in translational control during development. In contrast, there is no direct in vivo evidence for regulation of the length of poly(A) added during nuclear pre-mRNA processing in somatic cells. We previously reported that Xenopus serum albumin [Schoenberg et al. (1989) Mol. Endocrinol. 3, 805-815] and transferrin [Pastori et al. (1992) J. Steroid Biochem. Mol. Biol. 42, 649-657], mRNA have exceptionally short poly(A) tails ranging from 12 to 17 residues, whereas vitellogenin mRNA has long poly(A). An RT-PCR protocol was adapted to determine the length of poly(A) added onto pre-mRNA, defined here as that species bearing the terminal intron. Using this assay we show that vitellogenin pre-mRNA has the same long poly(A) tail as mature vitellogenin mRNA. In contrast, albumin pre-mRNA has the same short poly(A) as found on fully-processed albumin mRNA. These results indicate that the short poly(A) tail on albumin mRNA results from regulation of poly(A) addition during nuclear 3' processing.

Animals↗

PubMed1996

Role of lysine, tryptophan and calcium in the beta-elimination activity of a low-molecular-mass pectate lyase from Fusarium moniliformae.

An extracellular pectate lyase from Fusarium moniliformae was purified to homogeneity by affinity chromatography followed by gel filtration, with a yield of 76.5%. Laser desorption MS of the enzyme gave a molecular mass of 12,133.5 +/- 2.5 Da. The pectate lyase was a glycoprotein with a 5% carbohydrate content and had a pl value of 9.1. Atomic-emission spectrometry showed that Ca2+ was a part of the holoenzyme held by carboxy groups of the protein. These results support the hypothesis of a putative Ca2+ site suggested by Yodder, Keen and Jurnak [(1993) Science 260, 1503-1507] in the crystal structure of pectate lyase C of Erwinia chrysanthemi. Loss of Ca2+ was observed by treatment with EGTA or carboxy-modifying Woodward's reagent K, with subsequent loss of enzyme activity. Tryptophan fluorescence quenching showed that Ca2+ does not affect binding of substrate to enzyme. Chemical-modification and substrate-protection studies showed the presence of lysine and tryptophan at or near the active site of the pectate lyase. Chemically modified enzyme showed no major structural changes as determined by CD. Amino acid analyses of native, trinitrobenzenesulphonate (TBNS)-treated and substrate-protected TNBS-treated enzyme showed that a single essential residue of lysine is present at or near the active-site. Substrate-affinity studies showed that tryptophan could be essential for substrate binding, whereas lysine could be involved in the catalysis. Fluorescence quenching further confirmed the involvement of tryptophan in substrate binding. The reaction mechanism involving beta-elimination by this enzyme is discussed.

Amino Acids↗

PubMed1996

Implication of tryptophan and histidine in the active site of endo-polygalacturonase from Aspergillus ustus: elucidation of the reaction mechanism.

The mechanism of action for the hydrolysis of polygalacturonic acid by the enzyme endo-polygalacturonase (poly(1,4-alpha-D-galacturonide) glycanohydrolase, EC 3.2.1.15) was investigated. The enzyme from Aspergillus ustus was purified to homogeneity and used for the study. The endo-polygalacturonase had a molecular weight of 36,000 daltons, a pI of 8.3, specific activity of 785 units/mg, Km of 0.82 mg/ml, and Vmax of 976 micromoles of product min-1 mg-1. Amino acids involved in the catalysis were identified by chemical modification and the active site characterized. Inhibition by hydroxynitrobenzyl bromide and diethylpyrocarbonate, followed by substrate protection studies showed that tryptophan and histidine were involved at or near the active site. Kinetic constants of partially inhibited enzyme, suggest the involvement of tryptophan in substrate binding and histidine in catalysis. Quenching of tryptophan fluorescence of the enzyme in the presence of polygalacturonic acid substantiated the conclusion that tryptophan was involved in substrate binding. An isotope effect of 1.8 was observed with deuterated water on the Vmax of the endo-polygalacturonase, with the proton inventory giving a linear relationship. The proposed mechanism involves a single proton transfer from the histidine residue of the enzyme to the glycosidic oxygen and hydrolysis by the addition of a water molecule.

Aspergillus↗

PubMed1996

Purification and characterization of a 5' to 3' exoribonuclease from rabbit reticulocytes that degrades capped and uncapped RNAs.

The cytoplasm of mammalian cells of undoubtedly contain a number of different ribonuclease activities, few if any of which have been well characterized. We describe the purification of an exoribonuclease from rabbit reticulocytes which is able to degrade capped RNAs in a 5' to 3' manner. The purified enzyme contains polypeptides of 62 and 58 kDa and may contain an additional polypeptide of 54 kDa. It behaves as a complex of 150 kDa when analyzed by HPLC gel retardation on Superdex 200HR. It is heat-labile, dependent upon divalent cations (Mg2+) for activity, resistant to placental ribonuclease inhibitor, and active over a broad range (10-200 mM) of monovalent cation (K+) concentrations. The enzyme requires a polynucleotide chain of at least 10 bases for activity and cleaves oligonucleotides, up to an octamer long, from the 5' end of an appropriate substrate. In the case of a capped RNA substrate, product analysis by TLC and PAGE indicates that a capped trinucleotide or tetranucleotide or both is produced. Examination of the kinetics of the enzyme with capped and triphosphate-terminated substrates shows that that the cap structure inhibits the action of the enzyme. Furthermore, the data suggest that the rate-limiting step involves the positioning of the enzyme at the 5' end of the substrate and/or cleavage of the first internucleotide bond.

Animals↗

PubMed1996

Free radical scavenging activity of curcuminoids.

Three natural curcuminoids (curcumin (CAS 458-37-7), demethoxycurcumin, bisdemethoxycurcumin) and acetylcurcumin were compared for their ability to scavenge superoxide radicals and to interact with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radicals. The results showed that curcumin is the most potent scavenger of superoxide radicals followed by demethoxycurcumin and bisdemethoxycurcumin. Acetylcurcumin was inactive. Interaction with DPPH showed a similar activity profile. The study indicates that the phenolic group is essential for the free radical scavenging activity and presence of methoxy group further increases the activity.

Bepridil↗

PubMed1995

Anticancer and antioxidant activity of synthetic chalcones and related compounds.

Nineteen synthetic chalcones and ten structurally related compounds were investigated for their cytotoxic, tumour reducing and antioxidant activities. Methyl and hydroxy substituted chalcones were found to be cytotoxic in vitro whereas only hydroxy substituted chalcones could reduce ascites tumour in animals. Although most of the compounds analysed showed antioxidant activity, hydroxy and methyl substituted compounds were found to be the most potent antioxidants.

Animals↗

PubMed1995

Curcumin inhibits nitrogen dioxide induced oxidation of hemoglobin.

Curcumin protects hemoglobin from nitrogen dioxide induced oxidation. Curcumin was also found to scavenge nitrogen dioxide in a concentration dependent way. The study also explains the ability of curcumin to protect hemoglobin from nitrite induced oxidation, where nitrogen dioxide is a key intermediate.

Curcumin↗

PubMed1995

Synthesis and antiinflammatory, analgesic, and antipyretic testing of 4-[1-oxo-(3-substituted aryl)-2-propenyl]-3-phenylsydnones and of 3-[4-[3-(substituted aryl)-1-oxo-2-propenyl]phenyl]sydnones.

Two series of styrylcarbonyl 3-phenylsydnone derivatives, 4-[1-oxo-(3-substituted aryl)-2-propenyl]-3-phenylsydnones (series 1, 1-21) and 3-[4-[3-(substituted aryl)-1-oxo-2-propenyl]phenyl]sydnones (series II, 22-40), were synthesized and evaluated pharmacologically at a dose of 100 mg/kg po. Eleven compounds in series I plus one in series II and six in series I plus seven in series II were active in the carrageenan-induced edema and acetic acid-induced writhing assays, respectively. Compound 35 in the latter assay showed activity somewhat similar to that of the positive control drug, aspirin, administered at the same dosage. Compounds 11, 17, and 23 showed activity in both assays, and 23 also was active in the adjuvant-induced arthritis assay.

Acetates↗

PubMed1995

Cranial sonography in pyogenic meningitis in neonates and infants.

Cranial sonography was performed in 34 infants with proven meningitis and with clinical suspicion of its complications, utilizing the patent anterior fontanelle. Twenty-five patients showed various sonographic findings which included ventriculomegaly, echogenic sulci, subdural effusion, ventriculitis, infarction/cerebritis, cerebral oedema, porencephalic cyst, etc. Sonography is safe and cost-effective in diagnosis of complications, and management of pyogenic meningitis in infants.

Brain Diseases↗

PubMed1995

Scavenging of free-radicals and inhibition of lipid peroxidation by 3-phenylsydnone.

The antioxidant properties of 3-phenylsydnone were studied in various models in-vitro. 3-Phenylsydnone scavenged the stable free radical, 1,1-diphenyl-2-picrylhydrazyl, and inhibited the degradation of deoxyribose mediated by hydroxyl radicals, although, to a lesser extent than trolox, a water soluble analogue of vitamin E. Many antioxidants possess pro-oxidant properties due to their ability to reduce ferric ions; however, 3-phenylsydnone was free from pro-oxidant properties, and also inhibited the lipid peroxidation induced by iron, in rat brain homogenates.

Animals↗

PubMed1995

Antioxidant properties of phenyl styryl ketones.

Phenolic and non phenolic derivatives of phenyl styryl ketones were synthesized and evaluated as in vitro inhibitors of iron and cumene hydroperoxide dependent lipid peroxidation in rat brain homogenates. The compounds were also tested for antioxidant activity in phosphatidylcholine liposomes. Phenyl 3,5-di-tert-butyl-4-hydroxystyryl ketone was found to be the most potent inhibitor of peroxidation among all the compounds tested. It was found to be more active than vitamin E. It also reduced the stable free radical 1,1-diphenyl-2-picrylhydrazyl to an appreciable extent.

Animals↗