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1.
Plants (Basel) ; 11(24)2022 Dec 12.
Article in English | MEDLINE | ID: mdl-36559587

ABSTRACT

Myelosuppression is a major adverse effect of chemotherapy. With the increasing number of cancer patients worldwide, there is a growing interest in therapeutic approaches that reduce the adverse effects of chemotherapy. Angelica gigas Nakai (AGN) roots have been widely used in oriental medicine to treat blood-related diseases, including cancer. However, the effects of AGN on myelosuppression have not been studied. Here, we investigated the effects of AGN ethanol extract (AGNEX) on cyclophosphamide-induced myelosuppression. AGNEX treatment significantly decreased white blood cell levels while increasing red blood cell and platelet levels in the peripheral blood. It inhibited thymus and spleen atrophy. It also enhanced serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. qRT-PCR results showed that AGNEX decreased the expression of IL-1b and stem cell factor (SCF) in the bone marrow (BM) while increasing the mRNA expression of IL-3 and IL-6 in the spleen. Although AGNEX did not significantly decrease apoptosis and cell cycle arrest in the BM and splenocytes, AGNEX plays a positive role in cyclophosphamide-induced myelosuppression. AGNEX administration increased BM cells in the femur while decreasing apoptotic BM cells. These findings suggest that AGNEX could be used to treat myelosuppression and as a combination therapy in cancer patients.

2.
Article in English | MEDLINE | ID: mdl-31978742

ABSTRACT

Vardenafil, a remedy for erectile dysfunction, is easily modified, facilitating the creation of analogues that have been illegally added to functional foods and counterfeit medications. However, the medical profile of these analogues, including their safety, efficacy, safe drug combinations, metabolism and excretion, has not been completely evaluated, which could cause serious health problems. In this study, two representative vardenafil analogues, pseudovardenafil and hydroxyvardenafil, were metabolized with in-vitro model (human liver microsome) and in-vivo model (rats). The metabolized samples were extracted and characterized, using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS). Some imprecise interpretations were evaluated with tandem mass spectrometry (LC-Q-TOF-MS/MS) for mass fragmentation analysis. A total of 11 metabolites of pseudovardenafil and 13 metabolites of hydroxyvardenafil that were identified have never been reported. These new metabolites could be usefully applied to forensic science and other metabolic fields. Furthermore, they could serve as principal references for the toxicity, danger, and side effects of unlawful vardenafil counterfeits.


Subject(s)
Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Vardenafil Dihydrochloride , Animals , Humans , Male , Microsomes, Liver/metabolism , Rats , Rats, Sprague-Dawley , Vardenafil Dihydrochloride/analogs & derivatives , Vardenafil Dihydrochloride/analysis , Vardenafil Dihydrochloride/metabolism
3.
Forensic Sci Int ; 302: 109846, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31255840

ABSTRACT

Pyrethroids, organic compounds similar to natural pyrethrums, constitute the majority of insecticides. Pyrethroids are widely used around the world owing to their excellent selective toxicity to certain insects. In addition, they are easily found in daily life, accounting for most household pesticides. Owing to the easy access to pyrethroid insecticides, pyrethroid-related accidents and suicides have occurred yearly. For the first time, nine pyrethroids commonly used in South Korea and their seven major metabolites were simultaneously analyzed and validated in human plasma using liquid chromatography triple quadrupole mass spectrometry. Plasmas spiked with these pyrethroids and their metabolites were prepared and deproteinized via the addition of acetonitrile. This deproteinized supernatant was filtered and directly injected to ascertain the liquid chromatography-tandem mass spectrometry. For a sensitive and reproducible analysis, all the pyrethroid and metabolite analysis conditions for the multiple reaction monitoring mode were optimized in advance and employed. The validation parameters of the method, including the specificity, linearity, limit of detection, limit of quantification, accuracy, precision, recovery, matrix effect, and stability were also evaluated. The R2 value of linearity was greater than 0.997 for all the analytes, the accuracy ranged from 81.8% to 112.3%, the precision from 0% to 10.1%, and the recovery from 90.9% to 112.4%, depending on the analyte. The stability was 97.0% to 107.0% in fresh plasma and 97.6% to 107.7% in corrupt plasma. The results were satisfactory for all the validation parameters. Furthermore, authentic pyrethroid-poisoned samples were analyzed using this validation method, to determine the suitability; deltamethrin and its metabolites, cis-DBCA and 3-PBA, were successfully analyzed.


Subject(s)
Forensic Toxicology/methods , Insecticides/blood , Pyrethrins/blood , Chromatography, Liquid , Drug Stability , Humans , Limit of Detection , Specimen Handling , Tandem Mass Spectrometry
4.
Korean J Physiol Pharmacol ; 21(1): 27-36, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28066138

ABSTRACT

Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of GABAA-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and 0.1 µg/ml) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase (GAD65/67) and GABAA receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of GABAA-ergic systems, and can be useful in the treatment of insomnia.

5.
Neuroreport ; 25(16): 1243-9, 2014 Nov 12.
Article in English | MEDLINE | ID: mdl-25171200

ABSTRACT

Epilepsy is a neurological disorder with recurrent unprovoked seizures as the main symptom. Of the coumarin derivatives in Angelica gigas, decursin, a major coumarin component, was reported to exhibit significant protective activity against glutamate-induced neurotoxicity when added to primary cultures of rat cortical cells. This study served to investigate the effects of decursin on a kainic acid (KA)-induced status epilepticus model. Thirty minutes after intraperitoneal injections of decursin (20 mg/kg) in male 7-week-old C57BL/6 mice, the animals were treated with KA (30 mg/kg, intraperitoneally) and then examined for behavioral seizure score, electroencephalogram, seizure-related expressed protein levels, neuronal cell loss, neurodegeneration, and astrogliosis. KA injections significantly enhanced neurodegenerative conditions but treatment with decursin 30 min before KA injection reduced the detrimental effects of KA in mice. The decursin-treated KA-injected group showed significantly decreased behavioral seizure activity and remarkably attenuated intense and high-frequency seizure discharges in the parietal cortex for 2 h compared with the group treated only with KA. Furthermore, in-vivo results indicated that decursin strongly inhibits selective neuronal death, astrogliosis, and oxidative stress induced by KA administration. Therefore decursin is able to attenuate KA-induced seizures and could have potential as an antiepileptic drug.


Subject(s)
Benzopyrans/pharmacology , Butyrates/pharmacology , Seizures/prevention & control , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/physiopathology , Electroencephalography , Excitatory Amino Acid Agonists/toxicity , Gliosis/prevention & control , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Kainic Acid/toxicity , Male , Mice , Mice, Inbred C57BL , Proto-Oncogene Proteins c-fos/metabolism , Seizures/chemically induced
6.
Antimicrob Agents Chemother ; 58(9): 5036-46, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24890600

ABSTRACT

Macrolactin A (MA) and 7-O-succinyl macrolactin A (SMA), polyene macrolides containing a 24-membered lactone ring, show antibiotic effects superior to those of teicoplanin against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. MA and SMA are currently being evaluated as antitumor agents in preclinical studies in Korea. We evaluated the potential of MA and SMA for the inhibition or induction of human liver cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs) in vitro to assess their safety as new molecular entities. We demonstrated that MA and SMA are potent competitive inhibitors of CYP2C9, with Ki values of 4.06 µM and 10.6 µM, respectively. MA and SMA also weakly inhibited UGT1A1 activity, with Ki values of 40.1 µM and 65.3 µM, respectively. However, these macrolactins showed no time-dependent inactivation of the nine CYPs studied. In addition, MA and SMA did not induce CYP1A2, CYP2B6, or CYP3A4/5. On the basis of an in vitro-in vivo extrapolation, our data strongly suggested that MA and SMA are unlikely to cause clinically significant drug-drug interactions mediated via inhibition or induction of most of the CYPs involved in drug metabolism in vivo, except for the inhibition of CYP2C9 by MA. Similarly, MA and SMA are unlikely to inhibit the activity of UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 enzymes in vivo. Although further investigations will be required to clarify the in vivo interactions of MA with CYP2C9-targeted drugs, our findings offer a clearer understanding and prediction of drug-drug interactions for the safe use of MA and SMA in clinical practice.


Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Glucuronosyltransferase/antagonists & inhibitors , Macrolides/metabolism , Macrolides/pharmacology , Cytochrome P-450 Enzyme Inhibitors/metabolism , Cytochrome P-450 Enzyme Inhibitors/pharmacology , Drug Interactions , Humans , Microsomes, Liver/enzymology , Microsomes, Liver/metabolism
7.
Biomed Chromatogr ; 27(3): 273-9, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22829119

ABSTRACT

A simple, sensitive and reproducible isocratic reversed-phase (C(18) ) high-performance liquid chromatography (HPLC) method was developed to determine 7-O-succinyl macrolactin A (SMA) in rat plasma and urine samples using UV detector set at 230 nm. Lamotrigine was used as internal standards (IS) to ensure the precision and accuracy of the method. The retention times of SMA and IS for the plasma sample were 9.2 and 4.4 min, respectively, and those for the urine samples were 7.9 and 4.3 min, respectively. The intra- and inter-day variations of the analytical responses, expressed in terms of relative standard deviation, were less than 14.9%. The accuracy, in terms of average analytical recovery, ranged from 90.4 to 119%. The lower limits of quantification of SMA in rat plasma and urine samples were 0.02 and 0.1 µg/mL, respectively. This method is applicable for the pharmacokinetic studies of SMA in rats.


Subject(s)
Chromatography, High Pressure Liquid/methods , Macrolides/blood , Macrolides/urine , Animals , Drug Stability , Lamotrigine , Linear Models , Macrolides/chemistry , Macrolides/pharmacokinetics , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity , Triazines/blood , Triazines/chemistry , Triazines/urine
8.
Int J Mol Med ; 31(2): 477-83, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23232935

ABSTRACT

Decursin, a coumarin compound, was originally isolated from the roots of Angelica gigas almost four decades ago, and it was found to exhibit cytotoxicity against various types of human cancer cells and anti-amnesic activity in vivo through the inhibition of AChE activity. However, the anti-skin photoaging effects of decursin have not been reported to date. In the present study, we investigated the inhibitory effects of decursin on the expression of matrix metalloproteinase (MMP)-1 and MMP-3 in human dermal fibroblast (HDF) cells. Western blot analysis and real-time PCR revealed that decursin inhibited the ultraviolet (UV)B-induced expression of MMP-1 and MMP-3 in a dose-dependent manner. Decursin significantly blocked the UVB-induced activation of nuclear factor-κB (NF-κB). However, decursin showed no effect on MAPK or AP-1 activity. In this study, decursin prevented the UVB-induced expression of MMPs via the inhibition of NF-κB activation. In conclusion, decursin may be a potential agent for the prevention and treatment of skin photoaging.


Subject(s)
Benzopyrans/pharmacology , Butyrates/pharmacology , Dermis/cytology , Fibroblasts/drug effects , Fibroblasts/radiation effects , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 3/genetics , NF-kappa B/metabolism , Angelica/chemistry , Benzopyrans/isolation & purification , Butyrates/isolation & purification , Cells, Cultured , DNA/metabolism , Dermis/drug effects , Dermis/metabolism , Dermis/radiation effects , Fibroblasts/metabolism , Gene Expression Regulation/drug effects , Gene Expression Regulation/radiation effects , Humans , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 3/metabolism , Signal Transduction/drug effects , Signal Transduction/radiation effects , Transcription Factor AP-1/metabolism , Ultraviolet Rays
9.
Arch Pharm Res ; 34(1): 147-52, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21468926

ABSTRACT

The principal objective of this study was to evaluate the antibacterial activities of macrolactin A (MA) and 7-O-succinyl macrolactin A (SMA) generated from Bacillus polyfermenticus KJS-2 against vancomycin-resistant enterococci (VREs) and methicillin-resistant Staphylococcus aureus. The minimal inhibitory concentrations (MICs) of MA and SMA against VREs were 16 and 2∼1 µg/mL, respectively, and the MICs of MA and SMA against methicillin-resistant Staphylococcus aureus were 2 and < 0.25 µg/mL, respectively. Their MIC values were comparable or superior to those of teicoplanin. In evaluating the inhibitory effects of intestinal VRE colonization in mice, the oral MA and SMA effected a rapid inhibition of intestinal VRE colonization in mice, and the intraperitoneal SMA also inhibited VRE colonization, whereas intraperitoneal MA did not.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacillus/metabolism , Macrolides/pharmacology , Animals , Anti-Bacterial Agents/isolation & purification , Enterococcus/drug effects , Female , Intestines/microbiology , Macrolides/isolation & purification , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Mice, Inbred ICR , Microbial Sensitivity Tests , Teicoplanin/pharmacology , Vancomycin Resistance
10.
Arch Pharm Res ; 34(2): 289-98, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21380813

ABSTRACT

One of the strains of the Bacillus mojavensis group, Bacillus mojavensis KJS-3 (B. mojavensis KJS-3), which has been demonstrated to play a role in protecting plants against diseases as a bacterial endophyte and in reducing the accumulation of mycotoxins generated by an endophytic fungus, was recently discovered in food waste. In this study, the identification and characterization of B. mojavensis KJS-3 was performed via TEM analysis, API-zym test, API 50 CHB test, assays of catalase and oxidase activity, lactic acid production, stability under various conditions, antibiotic susceptibility, and cellular fatty acid composition. The overall results of this study demonstrate that B. mojavensis KJS-3 may have great potential as a probiotic product, as this bacterium is quite stable in somewhat harsh environments. B. mojavensis KJS-3 was positive on oxidase and catalase tests, and the conversion rate of glucose to lactic acid was 58.9%. Finally, anteiso-C(15:0) (43.10%) was identified as the major fatty acid.


Subject(s)
Bacillus/physiology , Probiotics , Bacillus/chemistry , Bacillus/cytology , Bacillus/isolation & purification , Catalase/metabolism , Drug Stability , Electron Microscope Tomography , Fatty Acids/analysis , Lactic Acid/biosynthesis , Microbial Sensitivity Tests , Oxidoreductases/metabolism , Probiotics/isolation & purification
11.
J Control Release ; 143(2): 251-7, 2010 Apr 19.
Article in English | MEDLINE | ID: mdl-20026364

ABSTRACT

Even though salmon calcitonin (sCT) has been known as a potent hypocalcemic agent, only injection or nasal spray products are available on the market. In order to develop oral delivery system of the agent, a novel sCT-sodium tripolyphosphate (STPP) ionic complex was fabricated and also characterized. For the optimization of the ionic complexation, the effect of incubation time and molar ratio between sCT and STPP was evaluated. Particle size of the ionic complex in aqueous media, SEM images, DSC, FT-IR, in vitro release test, stability within the simulated intestinal fluid, and hypocalcemic effect were evaluated. The optimal molar complexation ratio of sCT to STPP was ranged from 1:5 to 1:10 and the complexation efficiency was about 95%. The SEM image has shown that the freeze dried ionic complex has rough morphology in their surface and the particle size in PBS (pH 7.4) was about 220nm. The DSC and FT-IR results provided evidences for ionic interaction between -NH(2) groups and -P horizontal lineO groups of sCT and STPP, respectively. The sCT ionic complex has shown sustained sCT releasing characteristics for 3weeks. The sCT-STPP ionic complex was protective to enzymatic attack and in vivo animal data revealed that the present ionic complex would show continuous hypocalcemic effect. Conclusively, the present sCT-STPP ionic complex formulation thought to be a novel oral delivery candidate for the treatment of osteoporosis.


Subject(s)
Calcitonin/administration & dosage , Calcitonin/chemistry , Hypocalcemia/chemically induced , Polyphosphates/chemistry , Administration, Oral , Animals , Calcitonin/pharmacology , Calorimetry, Differential Scanning , Drug Stability , Ions/chemistry , Male , Particle Size , Rats , Rats, Sprague-Dawley , Spectroscopy, Fourier Transform Infrared
12.
J Microbiol Biotechnol ; 19(9): 1013-8, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19809260

ABSTRACT

The identification and characterization of Bacillus polyfermenticus KJS-2 (B. polyfermenticus KJS-2) was conducted using TEM, an API 50CHB kit, 16S rDNA sequencing, a phylogenetic tree, and catalase and oxidase testing. The conversion rate of glucose to lactic acid by B. polyfermenticus KJS-2 was found to be 60.71+/-4.9%. In addition, treatment of B. polyfermenticus KJS-2 with artificial gastric juice (pH 2.0) and bile acid (pH 6.5) for 4 h resulted in a final viability of 140+/-7.9% and 108+/-3.5%, respectively. Finally, the results of adhesion experiments using Caco-2 cells revealed that the adherence of B. polyfermenticus KJS-2 to Caco-2 cells was approximately 65+/-0.6%.


Subject(s)
Bacillus/physiology , Probiotics/chemistry , Bacillus/drug effects , Bacillus/ultrastructure , Bacterial Adhesion , Bile Acids and Salts/pharmacology , Caco-2 Cells/microbiology , Fermentation , Gastric Juice , Humans , Hydrogen-Ion Concentration , Monosaccharides/metabolism , Spores, Bacterial/physiology , Spores, Bacterial/ultrastructure , Substrate Specificity
13.
Arch Pharm Res ; 32(5): 711-5, 2009 May.
Article in English | MEDLINE | ID: mdl-19471885

ABSTRACT

Bacillus polyfermenticus KJS-2 (BP-KJS-2) was used to produce a lipopeptide-type surfactin. To accomplish this, a surfactin-producing BP-KJS-2 was fermented by soybeans. The surfactin was then purified by a procedure including ethanol treatment and preparative chromatography. Next, the biochemical structure of the purified surfactin was analyzed by electrospray ionization mass spectrometry (ESI-MS) and high-resolution ESI Q-Tof mass spectrometry (Q-Tof MS). In addition, the masses of the four peaks were determined to be 1007, 1021, 1035, and 1049 m/z revealing that the compound was mixture with quasi-molecular ions. Taken together, these findings indicated that the lipopeptide had a cyclic structure and amino acid composition of Gln-Leu-Leu-Leu-Val-Asp-Leu-Leu, and that the major lipopeptide product of BP-KJS-2 is the surfactin isoform. In addition, this lipopeptide showed strong antimicrobial activity against bacteria at the level of 0.05 mg/mL.


Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Bacillus/metabolism , Fermentation , Glycine max , Lipopeptides/chemistry , Lipopeptides/isolation & purification , Peptides, Cyclic/chemistry , Peptides, Cyclic/isolation & purification , Anti-Infective Agents/metabolism , Chromatography, High Pressure Liquid , Disk Diffusion Antimicrobial Tests , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/growth & development , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/growth & development , Lipopeptides/metabolism , Molecular Structure , Peptides, Cyclic/metabolism , Spectrometry, Mass, Electrospray Ionization
14.
J Microbiol Biotechnol ; 19(12): 1569-72, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20075620

ABSTRACT

The pharmacokinetics of decursin and decursinol angelate (D/DA) was investigated in male SD rats following oral and intravenous administration. D/DA and metabolites obtained from in vitro samples were evaluated by LC/MS. The level of D/DA and metabolized decursinol in the blood following oral and intravenous administration declined according to first-order kinetics, with T1/2 values of 56.67, 58.01 and 57.22 h, respectively, being observed after administration of a dose of 2 mg/kg body weight. The large intestine was the major site of disposition following oral administration. These data indicate that D/DA is rapidly absorbed from the gastrointestinal tract. In in vitro experiment utilizing liver microsomal protein, the major metabolic reaction of D/DA occurred to change decursinol. The cumulative biliary, urinary, and fecal excretion of D/DA in bile duct-cannulated rats was 36.10+/-2.9, 25.35+/-3.8, and 34.20+/-3.2%, respectively, at 72 h after administration. These results indicate that the absorption of D/DA is almost complete, and that its metabolites are primarily excreted into feces through the bile. These results indicate that D/DA is subject to enterohepatic circulation.


Subject(s)
Angelica/chemistry , Benzopyrans/pharmacokinetics , Butyrates/pharmacokinetics , Absorption , Administration, Oral , Animals , Benzopyrans/administration & dosage , Benzopyrans/chemistry , Benzopyrans/metabolism , Biological Availability , Butyrates/administration & dosage , Butyrates/chemistry , Butyrates/metabolism , Enterohepatic Circulation , Feces/chemistry , Injections, Intravenous , Intestine, Large/metabolism , Male , Metabolic Clearance Rate , Rats , Rats, Sprague-Dawley , Time Factors , Tissue Distribution
15.
Arch Pharm Res ; 31(5): 622-7, 2008 May.
Article in English | MEDLINE | ID: mdl-18481019

ABSTRACT

The aim of this study was to elucidate the antioxidant properties of fucoidan extracts (FE) against CCl(4)-induced oxidative stress by monitoring the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Female, Sparague-Dowley rats were administered with FE (100 mg/kg daily) for 14 days and CCl(4) on the 15'th day, 12 h before they were sacrificed. The levels of GOT, GPT, ALP and LDH in serum of rats, as well as the levels of MDA, SOD, CAT and GPx in total liver homogenate were analyzed. CCl(4)-treatment was found to increase the levels of GOT, GPT, ALP, LDH and MDA, as well as decrease levels of SOD, CAT and GPx significantly. The pre-treatment of rats with FE, however, suppressed the increment of levels of GOT, GPT, ALP, LDH and MDA, as well as recovered the levels of SOD, CAT and GPx in CCl(4)-treated rats. Moreover there was a significant decrease in incidences of necrosis and cirrhosis in the liver tissue of FE-treated rats. These results implied that FE possessed antioxidant properties against CCl(4)-induced oxidative stress.


Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Laminaria , Polysaccharides/pharmacology , Undaria , Animals , Antioxidants/metabolism , Carbon Tetrachloride Poisoning/metabolism , Carbon Tetrachloride Poisoning/pathology , Carbon Tetrachloride Poisoning/prevention & control , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Female , Lipid Peroxidation/drug effects , Liver/enzymology , Liver/pathology , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley
16.
Arch Microbiol ; 189(5): 463-73, 2008 May.
Article in English | MEDLINE | ID: mdl-18080113

ABSTRACT

The four overlapping cosmids from the rubradirin producer, Streptomyces achromogenes var rubradiris NRRL 3061, have 58 ORFs within a 105.6 kb fragment. These ORFs harbored essential genes responsible for the formation and attachment of four distinct moieties, along with the genes associated with regulatory, resistance, and transport functions. The PKS (rubA) and glycosyltransferase (rubG2) genes were disrupted in order to demonstrate a complete elimination of rubradirin production. The rubradirin biosynthetic pathway was proposed based on the putative functions of the gene products, the functional identification of sugar genes, and the mutant strains.


Subject(s)
Anti-Bacterial Agents/biosynthesis , Streptomyces/genetics , Streptomyces/metabolism , Aminobenzoates/metabolism , Base Sequence , Cosmids , DNA, Bacterial/analysis , Fermentation , Gene Silencing , Glycosides/biosynthesis , Hydroxybenzoates , Molecular Sequence Data , Multigene Family , Naphthoquinones/metabolism , Open Reading Frames , Sequence Analysis, DNA
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