Xin-sheng Deng - Academia.edu (original) (raw)

Papers by Xin-sheng Deng

Research paper thumbnail of Nitric Oxide And Propofol

The Internet Journal of Pharmacology, 2004

Research paper thumbnail of Fine mapping of a major QTL for alcohol sensitivity in the AT and ANT rats

Alcoholism Clinical and Experimental Research

Research paper thumbnail of Adult aortic valve interstitial cells have greater responses to toll-like receptor 4 stimulation

The Annals of thoracic surgery, 2015

Aortic valve interstitial cells (AVICs) have been implicated in the pathogenesis of calcific aort... more Aortic valve interstitial cells (AVICs) have been implicated in the pathogenesis of calcific aortic valve disease. Signal transducer and activator of transcription 3 (Stat3) possesses antiinflammatory effects. Given that calcification occurs in adult valves, we hypothesized that AVICs from adult valves more likely undergo a proosteogenic phenotypic change than those from pediatric valves and that may be related to different Stat3 activation in the response of those two age groups to toll-like receptor 4 (TLR4). AVICs from healthy human aortic valve tissues were treated with TLR4 agonist lipopolysaccharide. Cellular levels of TLR4, intercellular adhesion molecule 1, bone morphogenetic protein 2, and alkaline phosphatase, as well as phosphorylation of p-38 mitogen-activated protein kinase (MAPK), nuclear factor-κβ (NF-κβ), and Stat3, were analyzed. Toll-like receptor 4 protein levels were comparable between adult and pediatric AVICs. Adult cells produce markedly higher levels of the a...

Research paper thumbnail of Formation of ethyl nitrite in vivo after ethanol administration

Alcohol (Fayetteville, N.Y.)

The purpose of the current study was to ascertain whether ethyl nitrite could be detected in vitr... more The purpose of the current study was to ascertain whether ethyl nitrite could be detected in vitro from the reaction of ethanol with peroxynitrite, as well as after administration of ethanol to mice. Ethyl nitrite analyte was determined by using gas chromatography--mass spectrometry with headspace analysis with the use of a solid-phase microextraction device. Peroxynitrite was allowed to react with ethanol under a variety of conditions in vitro. Ethyl nitrite was generated when peroxynitrite was allowed to react with ethanol. Male, inbred short-sleep mice were injected intraperitoneally with either ethanol [5.2 g/kg; 15.0% (weight/volume) ethanol in saline] or a 50:50 mixture of deuterium-labeled ethanol (D5-ethanol) and ethanol. Blood samples, as well as whole brain and liver sections, were obtained from mice 30 min later for determination of ethanol, D5-ethanol, ethyl nitrite, and deuterium-labeled ethyl nitrite (D5-ethyl nitrite). Time courses for the appearance of ethyl nitrite ...

Research paper thumbnail of Detection of anabolic steroids in head hair

Journal of forensic sciences, 1999

We developed a gas chromatography/mass spectrometry method for detection and quantitation of anab... more We developed a gas chromatography/mass spectrometry method for detection and quantitation of anabolic steroids in head hair. Following alkaline digestion and solid-phase extraction, the MO-TMS derivatives gave a specific fragmentation pattern with EI ionization. For stanozolol, the TMS-HFBA derivative showed several diagnostic ions. For androstanolone, mestanolone (methylandrostanolone), and oxymetholone two chromatographic peaks for cis and trans isomers of derivatives were seen. Recoveries were 35 to 45% for androstanolone, oxymetholone, chlorotestosterone-acetate, dehydromethyltestosterone, dehydrotestosterone, fluoxymesterone, mestanolone, methyltestosterone, and nandrolone; 52% for mesterolone, trenbolone; 65% for bolasterone; 24% for methenolone and 17% for stanozolol. Limits of detection were 0.002 to 0.05 ng/mg and of quantitation were 0.02 to 0.1 ng/mg. Seven white male steroid abusers provided head hair samples (10 to 63 mg) and urine. In the hair samples, methyltestostero...

Research paper thumbnail of P XVII B.45 - P XVII B.45 Prevention of oxidative DNA damage by Brussels sprouts in rats

E. col i IB I02 and E. coli IBI03. Th is means that antimutagenic activity of the extracts was no... more E. col i IB I02 and E. coli IBI03. Th is means that antimutagenic activity of the extracts was not due 10the interference with the postreplicationmismatch repair system. Further, we tested the extracts with excision repair proficient E. coli WPl and it's excis ion repair deficient derivative WP2uvrA. All the extracts reduced the number of UV induced revertants in both strains, but the reduction was significantly more efficient in the repair proficient strain, This means, that the observed bic-antimutagenic activity can be at least partly attributed to the promotion of DNA excision repair system in E. coli WP2 strain by some components of the extracts. Similar results were obtained by Shimoi et .1. (Shimoi , et al ., (1986) Mutat, Res., 113, 239) for several natural pyrogallol related compounds.

Research paper thumbnail of Cancer Stem Cell Phenotype Is Supported by Secretory Phospholipase A2 in Human Lung Cancer Cells

The Annals of Thoracic Surgery, 2014

Research paper thumbnail of Confirmation of quantitative trait loci for ethanol sensitivity and neurotensin receptor density in crosses derived from the inbred High and Low Alcohol Sensitive selectively bred rat lines

Psychopharmacology, 2006

Rationale Genetically influenced alcohol sensitivity is thought to be an important risk factor fo... more Rationale Genetically influenced alcohol sensitivity is thought to be an important risk factor for the development of alcoholism. An effective first step for identifying genes that mediate variation in alcohol sensitivity is through quantitative trait loci (QTL) mapping in model organisms.

Research paper thumbnail of 2-Nitropropane-induced DNA damage in rat bone marrow

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 1997

Research paper thumbnail of Determination of volatile anesthetics isoflurane and enflurane in mouse brain tissues using gas chromatography-mass spectrometry

Journal of Pharmacological and Toxicological Methods, 2004

Introduction: A method for determination of the volatile anesthetics, isoflurane, and enflurane i... more Introduction: A method for determination of the volatile anesthetics, isoflurane, and enflurane in mouse brain tissues using headspace gas chromatography-mass spectrometry (GC-MS) is described. Methods: Halothane was used as internal standard (I.S.). Brain samples were completely homogenized in ice-cold water and isoflurane, enflurane, and I.S. were extracted with headspace. One milliliter of headspace gas was injected onto the GC-MS and separation was achieved by using porous layer open tubular (PLOT) capillary column with a solid stationary phase (GSC). As a result, isoflurane, enflurane, and halothane were cleanly separated. Results: The method demonstrated satisfactory recovery (72% and 76% for isoflurane and enflurane, respectively) and linear calibration ranges of 0.015 -2.20 and 0.0152 -3.94 Ag/sample for isoflurane and enflurane, respectively. Reproducibility calculated as CV% was 3.3 -3.9% for all intraday and interday determinations. The procedure was applied for quantitation of isoflurane and enflurane in about 300 mouse brain samples for genetic behavioral study. Discussion: The method was achieved and shown to be effective. D

Research paper thumbnail of Gas chromatographic–mass spectrometric determination of etomidate in mouse brain

Journal of Pharmacological and Toxicological Methods, 2000

A simple, rapid and reliable method was developed to determine the concentration of etomidate [et... more A simple, rapid and reliable method was developed to determine the concentration of etomidate [ethyl-1-(1-phenylethyl)-1 H-imidazole-5-carboxylate] in mouse brain tissue by gas chromatography–mass spectrometry (GC–MS). Ethyl 5-amino-1-phenyl-4-pyrazolecarboxylate was used as internal standard (IS) and liquid–liquid extraction using ethyl ether as the solvent. The method demonstrated excellent recovery (93%) and a linear calibration range of 50–2500 ng/0.2 g. Intra-day accuracy and

Research paper thumbnail of Gas chromatographic–mass spectrometric determination of polycyclic aromatic hydrocarbons formed during the pyrolysis of phenylalanine

Journal of Chromatography A, 2004

Research paper thumbnail of A major QTL for acute ethanol sensitivity in the alcohol tolerant and non-tolerant selected rat lines

Genes, Brain and Behavior, 2009

The Alcohol Tolerant and Alcohol Non-Tolerant rats (AT, ANT) were selectively bred for ethanol-in... more The Alcohol Tolerant and Alcohol Non-Tolerant rats (AT, ANT) were selectively bred for ethanol-induced ataxia as measured on the inclined plane. Here we report on a quantitative trait locus (QTL) study in an F 2 intercross population derived from inbred AT and ANT (IAT, IANT) and a follow-up study of congenics that were bred to examine one of the mapped QTLs. Over 1200 F 2 offspring were tested for inclined plane sensitivity, acute tolerance on the inclined plane, duration of the loss of righting reflex (LORR), and blood ethanol at regain of the righting reflex (BECRR). F 2 rats that were in the upper and lower 20% for inclined plane sensitivity were genotyped with 78 SSLP markers. Significant QTLs for inclined plane sensitivity were mapped on chromosomes 8 and 20; suggestive QTLs were mapped on chromosomes 1, 2, and 3. Highly significant QTLs for LORR duration (LOD=12.4) and BECRR (LOD=5.7) were mapped to the same locus on chromosome 1. Breeding and testing of reciprocal congenic lines confirmed the chromosome 1 LORR/BECRR QTL. A series of recombinant congenic sub-lines were bred to fine-map this QTL. Current results have narrowed the QTL to an interval of between 5 and 20 Mb. We expect to be able to narrow the interval to less than 5 Mb with additional genotyping and continued breeding of recombinant sub-congenic lines.

Research paper thumbnail of Dexamethasone ameliorates oxidative DNA damage induced by benzene and LPS in mouse bone marrow

Free Radical Research, 1999

Research paper thumbnail of Experimental study of oxidative DNA damage

Free Radical Research, 1998

Animal experiments allow the study of oxidative DNA damage in target organs and the elucidation o... more Animal experiments allow the study of oxidative DNA damage in target organs and the elucidation of doseresponse relationships of carcinogenic and other harmful chemicals and conditions as well as the study of interactions of several factors. So far the effects of more than 50 different chemical compounds have been studied in animal experiments mainly in rats and mice, and generally with measurement of 8-oxodG with HPLC-EC. A large number of well-known carcinogens induce 8-oxodG formation in liver and/or kidneys. Moreover several animal studies have shown a close relationship between induction of dative DNA damage and tumour formation.

Research paper thumbnail of Effects of a Brussels sprouts extract on oxidative DNA damage and metabolising enzymes in rat liver

Food and Chemical Toxicology, 2001

The apparent anticarcinogenic eect of cruciferous vegetables found in numerous epidemiological an... more The apparent anticarcinogenic eect of cruciferous vegetables found in numerous epidemiological and experimental studies has been associated with their in¯uence on phase I and phase II metabolising enzymes as well as on the antioxidant status. In the present study we investigated the eect of administration of a Brussels sprouts extract on the expression at the mRNA level and/or catalytic activity in rat liver of three phase I enzymes [cytochrome P450-1A2 (CYP1A2),-2B1/2 (CYP2B1/2) and-2E1 (CYP2E1)] and two phase II enzyme [NADPH:quinone reductase (QR) and glutathione S-transferase pi 7 (GSTp)], all previously suggested to be induced by vegetables. We also examined the activity and/or expression of several important antioxidant enzymes: glutathione peroxidase (GPx), catalase and g-glutamyl-cysteine synthetase (GCS) and the activity of the repair enzyme 8-oxoguanine DNA glycosylase (OGG1). QR, GPx and catalase activity was also assessed in the kidneys. In order to examine a possible eect of the Brussels sprouts related to oxidative stress, we measured oxidative DNA damage in terms of 7-hydro-8-oxo-2 H -deoxyguanosine (8-oxodG) and lipid peroxidation in terms of malondialdehyde (MDA) formation in the liver. Oral administration of an aqueous Brussels sprouts extract for 4 days was found to induce the expression of GST 1.3-fold (P<0.05) and the activity of QR 2.6-fold in rat liver (P<0.05). No signi®cant dierences were seen in the expression of the phase I enzymes. No dierences in antioxidant enzyme activity/expression or OGG1 activity were observed. In a second experiment, administration of the Brussels sprouts extract for 3 or 7 days was found to increase the level of 8-oxodG in rat liver from 0.75 to 0.97 per 10 5 dG and from 0.81 to 0.97 per 10 5 dG, respectively (P<0.05). No eects on MDA levels were found. The present results support the data obtained in several studies that consumption of cruciferous vegetables is capable of inducing various phase II enzyme systems. However, the observed increase in oxidative DNA damage raises the question of whether greatly increased ingestion of cruciferous vegetables is bene®cial. #

Research paper thumbnail of Prevention of oxidative DNA damage by Brussels sprouts in rats

European Journal of Cancer Prevention, 1997

ABSTRACT The alleged cancer preventive effects of cruciferous vegetables could be related to prot... more ABSTRACT The alleged cancer preventive effects of cruciferous vegetables could be related to protection from mutagenic oxidative DNA damage. We have studied the effects of Brussels sprouts, some non-cruciferous vegetables and isolated glucosinolates on spontaneous and induced oxidative DNA damage in terms of 8-oxo-7,8-dihydro-2&#39;-deoxyguanosine (8-oxodG) in groups of 6-8 male Wistar rats. Excess oxidative DNA damage was induced by 2-nitropropane (2-NP 100 mg/kg). Four days oral administration of 3 g of cooked Brussels sprouts homogenate reduced the spontaneous urinary 8-oxodG excretion by 31% (p&lt;0.05) whereas raw sprouts, beans and endive (1:1), isolated indolyl glucosinolates and breakdown products had no significant effect. An aqueous extract of cooked Brussels sprouts (corresponding to 6.7 g vegetable per day for 4 days) decreased the spontaneous 8-oxodG excretion from 92 +/- 12 to 52 +/- 15 pmol/24 h (p&lt;0.05). After 2-NP administration the 8-oxodG excretion was increased to 132 +/- 26 pmol/24 h (p&lt;0.05) whereas pretreatment with the sprouts extract reduced this to 102 +/- 30 pmol/24 h (p&lt;0.05). The spontaneous level of 8-oxodG in nuclear DNA from liver and bone marrow was not significantly affected by the sprouts extract whereas the level decreased by 27% in the kidney (p&lt;0.05). In the liver 2-NP increased the 8-oxodG levels in nuclear DNA 8.7 and 3.8 times (p&lt;0.05) 6 and 24 h after dose, respectively. The sprouts extract reduced this increase by 57% (p&lt;0.05) at 6 h whereas there was no significant effect at 24 h. In the kidneys 2-NP increased the 8-oxodG levels 2.2 and 1.2 times (p&lt;0.05) 6 and 24 h after dose, respectively. Pretreatment with the sprouts extract abolished these increases (p&lt;0.05). Similarly, in the bone marrow the extract protected completely (p&lt;0.05) against a 4.9-fold 2-NP induced increase (p&lt;0.05) in the 8-oxodG level. These findings demonstrate that cooked Brussels sprouts contain bioactive substance(s) with a potential for reducing the physiological as well as oxidative stress induced oxidative DNA damage in rats. This could explain the suggested cancer preventive effect of cruciferous vegetables. The correspondence between the urinary excretion and 8-oxodG levels in 2-NP target organs supports its being the main repair product that reflects the rate of guanine oxidation in DNA.

Research paper thumbnail of Putative Role of Brain Acetaldehyde in Ethanol Addiction

Current Drug Abuse Reviewse, 2008

The putative contribution of brain acetaldehyde (AcH) to ethanol (EtOH) tolerance and dependence ... more The putative contribution of brain acetaldehyde (AcH) to ethanol (EtOH) tolerance and dependence (addiction) is reviewed. Although the role of AcH in EtOH addiction has been controversial, there are data showing a relationship. AcH can be formed in the brain tissues through the peroxidatic activity of catalase and by oxidation via other oxidizing enzymes such as cytochrome P-4502E1. Significant formation of AcH occurs in vitro in brain tissue at concentrations of EtOH that can be achieved by voluntary consumption of EtOH by rodents. AcH itself possesses reinforcing properties, which suggests that some of the behavioral pharmacological effects attributed to EtOH may be a result of the formation of AcH, and supports the involvement of AcH in EtOH addiction. Modulation of aldehyde dehydrogenase (ALDH) and brain catalase activity can change EtOH-related addictive behaviors presumably by changing AcH levels. Moreover, some condensation reaction products of AcH may promote some actions of EtOH and its consumption. On the basis of the findings, it can be concluded that AcH may mediate some of the CNS actions of EtOH including tolerance and dependence, although further exploration the involvement of AcH in EtOH addiction is warranted.

Research paper thumbnail of Ethanol Metabolism and Effects: Nitric Oxide and its Interaction

Current Clinical Pharmacology, 2007

in alcoholic beverages is consumed by a large number of individuals and its elimination is primar... more in alcoholic beverages is consumed by a large number of individuals and its elimination is primarily by oxidation. The role of nitric oxide (NO) in EtOH's effects is important since NO is one of the most prominent biological factors in mammals. NO is constantly formed endogenously from L-arginine. Dose and length of EtOH exposure, and cell type are the main factors affecting EtOH effects on NO production. Either acute or chronic EtOH ingestion affects inducible NO synthase (iNOS) activity. However it seems that EtOH suppresses induced-NO production by inhibition of iNOS in different cells. On the other hand, it is clear that acute low doses of EtOH increase both the release of NO and endothelial NOS (eNOS) expression, and augment endothelium-mediated vasodilatation, whereas higher doses impair endothelial functions. EtOH selectively affects neuronal NOS (nNOS) activity in different brain cells, which may relate to various behavioral interactions. Therefore, there is an excellent chance for EtOH and NO to react with each other. Effects of EtOH on NO production and NOS activity may be important to EtOH modification of cell or organ function. Nitrosated compounds (alkyl nitrites) are often found as the interaction products, which might be one of the minor pathways of EtOH metabolism. NO also inhibits EtOH metabolizing enzymes. Furthermore, NO is involved in EtOH induced liver damage and has a role in fetal development during EtOH exposure in pregnancy. The mechanisms underlying these effects are only partially understood. Hence, the current discussion of the interaction of EtOH and NO is presented.

Research paper thumbnail of Metformin targets Stat3 to inhibit cell growth and induce apoptosis in triple-negative breast cancers

Cell Cycle, 2012

Key words: triple-negative breast cancer, metformin, Stat3, mTOR transition (EMT), stimulation of... more Key words: triple-negative breast cancer, metformin, Stat3, mTOR transition (EMT), stimulation of the Janus tyrosine kinases (JAK/Stat) pathway and transcriptional regulation of Stat 3-specific target genes that may block apoptosis and induce cell proliferation, angiogenesis, cell migration and metastasis. 9-15 Stat3 activation can also result from serine phosphorylation, which has more significant effects on cytoplasmic/mitochondrial activity, including Ras-associated oncogenesis 16,17 and functioning of the electron transport chain (ETC) via binding to complexes I and II. 18 Non-phosphorylated Stat3s have also been shown to play important roles in cellular function, for example, via binding nuclear factor κB (NFκB) to mediate its nuclear import. In summary, aberrant Stat3 expression is frequently observed in TN breast cancers. It likely plays a critical role in the pathogenesis of this highly aggressive cancer subtype.

Research paper thumbnail of Nitric Oxide And Propofol

The Internet Journal of Pharmacology, 2004

Research paper thumbnail of Fine mapping of a major QTL for alcohol sensitivity in the AT and ANT rats

Alcoholism Clinical and Experimental Research

Research paper thumbnail of Adult aortic valve interstitial cells have greater responses to toll-like receptor 4 stimulation

The Annals of thoracic surgery, 2015

Aortic valve interstitial cells (AVICs) have been implicated in the pathogenesis of calcific aort... more Aortic valve interstitial cells (AVICs) have been implicated in the pathogenesis of calcific aortic valve disease. Signal transducer and activator of transcription 3 (Stat3) possesses antiinflammatory effects. Given that calcification occurs in adult valves, we hypothesized that AVICs from adult valves more likely undergo a proosteogenic phenotypic change than those from pediatric valves and that may be related to different Stat3 activation in the response of those two age groups to toll-like receptor 4 (TLR4). AVICs from healthy human aortic valve tissues were treated with TLR4 agonist lipopolysaccharide. Cellular levels of TLR4, intercellular adhesion molecule 1, bone morphogenetic protein 2, and alkaline phosphatase, as well as phosphorylation of p-38 mitogen-activated protein kinase (MAPK), nuclear factor-κβ (NF-κβ), and Stat3, were analyzed. Toll-like receptor 4 protein levels were comparable between adult and pediatric AVICs. Adult cells produce markedly higher levels of the a...

Research paper thumbnail of Formation of ethyl nitrite in vivo after ethanol administration

Alcohol (Fayetteville, N.Y.)

The purpose of the current study was to ascertain whether ethyl nitrite could be detected in vitr... more The purpose of the current study was to ascertain whether ethyl nitrite could be detected in vitro from the reaction of ethanol with peroxynitrite, as well as after administration of ethanol to mice. Ethyl nitrite analyte was determined by using gas chromatography--mass spectrometry with headspace analysis with the use of a solid-phase microextraction device. Peroxynitrite was allowed to react with ethanol under a variety of conditions in vitro. Ethyl nitrite was generated when peroxynitrite was allowed to react with ethanol. Male, inbred short-sleep mice were injected intraperitoneally with either ethanol [5.2 g/kg; 15.0% (weight/volume) ethanol in saline] or a 50:50 mixture of deuterium-labeled ethanol (D5-ethanol) and ethanol. Blood samples, as well as whole brain and liver sections, were obtained from mice 30 min later for determination of ethanol, D5-ethanol, ethyl nitrite, and deuterium-labeled ethyl nitrite (D5-ethyl nitrite). Time courses for the appearance of ethyl nitrite ...

Research paper thumbnail of Detection of anabolic steroids in head hair

Journal of forensic sciences, 1999

We developed a gas chromatography/mass spectrometry method for detection and quantitation of anab... more We developed a gas chromatography/mass spectrometry method for detection and quantitation of anabolic steroids in head hair. Following alkaline digestion and solid-phase extraction, the MO-TMS derivatives gave a specific fragmentation pattern with EI ionization. For stanozolol, the TMS-HFBA derivative showed several diagnostic ions. For androstanolone, mestanolone (methylandrostanolone), and oxymetholone two chromatographic peaks for cis and trans isomers of derivatives were seen. Recoveries were 35 to 45% for androstanolone, oxymetholone, chlorotestosterone-acetate, dehydromethyltestosterone, dehydrotestosterone, fluoxymesterone, mestanolone, methyltestosterone, and nandrolone; 52% for mesterolone, trenbolone; 65% for bolasterone; 24% for methenolone and 17% for stanozolol. Limits of detection were 0.002 to 0.05 ng/mg and of quantitation were 0.02 to 0.1 ng/mg. Seven white male steroid abusers provided head hair samples (10 to 63 mg) and urine. In the hair samples, methyltestostero...

Research paper thumbnail of P XVII B.45 - P XVII B.45 Prevention of oxidative DNA damage by Brussels sprouts in rats

E. col i IB I02 and E. coli IBI03. Th is means that antimutagenic activity of the extracts was no... more E. col i IB I02 and E. coli IBI03. Th is means that antimutagenic activity of the extracts was not due 10the interference with the postreplicationmismatch repair system. Further, we tested the extracts with excision repair proficient E. coli WPl and it's excis ion repair deficient derivative WP2uvrA. All the extracts reduced the number of UV induced revertants in both strains, but the reduction was significantly more efficient in the repair proficient strain, This means, that the observed bic-antimutagenic activity can be at least partly attributed to the promotion of DNA excision repair system in E. coli WP2 strain by some components of the extracts. Similar results were obtained by Shimoi et .1. (Shimoi , et al ., (1986) Mutat, Res., 113, 239) for several natural pyrogallol related compounds.

Research paper thumbnail of Cancer Stem Cell Phenotype Is Supported by Secretory Phospholipase A2 in Human Lung Cancer Cells

The Annals of Thoracic Surgery, 2014

Research paper thumbnail of Confirmation of quantitative trait loci for ethanol sensitivity and neurotensin receptor density in crosses derived from the inbred High and Low Alcohol Sensitive selectively bred rat lines

Psychopharmacology, 2006

Rationale Genetically influenced alcohol sensitivity is thought to be an important risk factor fo... more Rationale Genetically influenced alcohol sensitivity is thought to be an important risk factor for the development of alcoholism. An effective first step for identifying genes that mediate variation in alcohol sensitivity is through quantitative trait loci (QTL) mapping in model organisms.

Research paper thumbnail of 2-Nitropropane-induced DNA damage in rat bone marrow

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 1997

Research paper thumbnail of Determination of volatile anesthetics isoflurane and enflurane in mouse brain tissues using gas chromatography-mass spectrometry

Journal of Pharmacological and Toxicological Methods, 2004

Introduction: A method for determination of the volatile anesthetics, isoflurane, and enflurane i... more Introduction: A method for determination of the volatile anesthetics, isoflurane, and enflurane in mouse brain tissues using headspace gas chromatography-mass spectrometry (GC-MS) is described. Methods: Halothane was used as internal standard (I.S.). Brain samples were completely homogenized in ice-cold water and isoflurane, enflurane, and I.S. were extracted with headspace. One milliliter of headspace gas was injected onto the GC-MS and separation was achieved by using porous layer open tubular (PLOT) capillary column with a solid stationary phase (GSC). As a result, isoflurane, enflurane, and halothane were cleanly separated. Results: The method demonstrated satisfactory recovery (72% and 76% for isoflurane and enflurane, respectively) and linear calibration ranges of 0.015 -2.20 and 0.0152 -3.94 Ag/sample for isoflurane and enflurane, respectively. Reproducibility calculated as CV% was 3.3 -3.9% for all intraday and interday determinations. The procedure was applied for quantitation of isoflurane and enflurane in about 300 mouse brain samples for genetic behavioral study. Discussion: The method was achieved and shown to be effective. D

Research paper thumbnail of Gas chromatographic–mass spectrometric determination of etomidate in mouse brain

Journal of Pharmacological and Toxicological Methods, 2000

A simple, rapid and reliable method was developed to determine the concentration of etomidate [et... more A simple, rapid and reliable method was developed to determine the concentration of etomidate [ethyl-1-(1-phenylethyl)-1 H-imidazole-5-carboxylate] in mouse brain tissue by gas chromatography–mass spectrometry (GC–MS). Ethyl 5-amino-1-phenyl-4-pyrazolecarboxylate was used as internal standard (IS) and liquid–liquid extraction using ethyl ether as the solvent. The method demonstrated excellent recovery (93%) and a linear calibration range of 50–2500 ng/0.2 g. Intra-day accuracy and

Research paper thumbnail of Gas chromatographic–mass spectrometric determination of polycyclic aromatic hydrocarbons formed during the pyrolysis of phenylalanine

Journal of Chromatography A, 2004

Research paper thumbnail of A major QTL for acute ethanol sensitivity in the alcohol tolerant and non-tolerant selected rat lines

Genes, Brain and Behavior, 2009

The Alcohol Tolerant and Alcohol Non-Tolerant rats (AT, ANT) were selectively bred for ethanol-in... more The Alcohol Tolerant and Alcohol Non-Tolerant rats (AT, ANT) were selectively bred for ethanol-induced ataxia as measured on the inclined plane. Here we report on a quantitative trait locus (QTL) study in an F 2 intercross population derived from inbred AT and ANT (IAT, IANT) and a follow-up study of congenics that were bred to examine one of the mapped QTLs. Over 1200 F 2 offspring were tested for inclined plane sensitivity, acute tolerance on the inclined plane, duration of the loss of righting reflex (LORR), and blood ethanol at regain of the righting reflex (BECRR). F 2 rats that were in the upper and lower 20% for inclined plane sensitivity were genotyped with 78 SSLP markers. Significant QTLs for inclined plane sensitivity were mapped on chromosomes 8 and 20; suggestive QTLs were mapped on chromosomes 1, 2, and 3. Highly significant QTLs for LORR duration (LOD=12.4) and BECRR (LOD=5.7) were mapped to the same locus on chromosome 1. Breeding and testing of reciprocal congenic lines confirmed the chromosome 1 LORR/BECRR QTL. A series of recombinant congenic sub-lines were bred to fine-map this QTL. Current results have narrowed the QTL to an interval of between 5 and 20 Mb. We expect to be able to narrow the interval to less than 5 Mb with additional genotyping and continued breeding of recombinant sub-congenic lines.

Research paper thumbnail of Dexamethasone ameliorates oxidative DNA damage induced by benzene and LPS in mouse bone marrow

Free Radical Research, 1999

Research paper thumbnail of Experimental study of oxidative DNA damage

Free Radical Research, 1998

Animal experiments allow the study of oxidative DNA damage in target organs and the elucidation o... more Animal experiments allow the study of oxidative DNA damage in target organs and the elucidation of doseresponse relationships of carcinogenic and other harmful chemicals and conditions as well as the study of interactions of several factors. So far the effects of more than 50 different chemical compounds have been studied in animal experiments mainly in rats and mice, and generally with measurement of 8-oxodG with HPLC-EC. A large number of well-known carcinogens induce 8-oxodG formation in liver and/or kidneys. Moreover several animal studies have shown a close relationship between induction of dative DNA damage and tumour formation.

Research paper thumbnail of Effects of a Brussels sprouts extract on oxidative DNA damage and metabolising enzymes in rat liver

Food and Chemical Toxicology, 2001

The apparent anticarcinogenic eect of cruciferous vegetables found in numerous epidemiological an... more The apparent anticarcinogenic eect of cruciferous vegetables found in numerous epidemiological and experimental studies has been associated with their in¯uence on phase I and phase II metabolising enzymes as well as on the antioxidant status. In the present study we investigated the eect of administration of a Brussels sprouts extract on the expression at the mRNA level and/or catalytic activity in rat liver of three phase I enzymes [cytochrome P450-1A2 (CYP1A2),-2B1/2 (CYP2B1/2) and-2E1 (CYP2E1)] and two phase II enzyme [NADPH:quinone reductase (QR) and glutathione S-transferase pi 7 (GSTp)], all previously suggested to be induced by vegetables. We also examined the activity and/or expression of several important antioxidant enzymes: glutathione peroxidase (GPx), catalase and g-glutamyl-cysteine synthetase (GCS) and the activity of the repair enzyme 8-oxoguanine DNA glycosylase (OGG1). QR, GPx and catalase activity was also assessed in the kidneys. In order to examine a possible eect of the Brussels sprouts related to oxidative stress, we measured oxidative DNA damage in terms of 7-hydro-8-oxo-2 H -deoxyguanosine (8-oxodG) and lipid peroxidation in terms of malondialdehyde (MDA) formation in the liver. Oral administration of an aqueous Brussels sprouts extract for 4 days was found to induce the expression of GST 1.3-fold (P<0.05) and the activity of QR 2.6-fold in rat liver (P<0.05). No signi®cant dierences were seen in the expression of the phase I enzymes. No dierences in antioxidant enzyme activity/expression or OGG1 activity were observed. In a second experiment, administration of the Brussels sprouts extract for 3 or 7 days was found to increase the level of 8-oxodG in rat liver from 0.75 to 0.97 per 10 5 dG and from 0.81 to 0.97 per 10 5 dG, respectively (P<0.05). No eects on MDA levels were found. The present results support the data obtained in several studies that consumption of cruciferous vegetables is capable of inducing various phase II enzyme systems. However, the observed increase in oxidative DNA damage raises the question of whether greatly increased ingestion of cruciferous vegetables is bene®cial. #

Research paper thumbnail of Prevention of oxidative DNA damage by Brussels sprouts in rats

European Journal of Cancer Prevention, 1997

ABSTRACT The alleged cancer preventive effects of cruciferous vegetables could be related to prot... more ABSTRACT The alleged cancer preventive effects of cruciferous vegetables could be related to protection from mutagenic oxidative DNA damage. We have studied the effects of Brussels sprouts, some non-cruciferous vegetables and isolated glucosinolates on spontaneous and induced oxidative DNA damage in terms of 8-oxo-7,8-dihydro-2&#39;-deoxyguanosine (8-oxodG) in groups of 6-8 male Wistar rats. Excess oxidative DNA damage was induced by 2-nitropropane (2-NP 100 mg/kg). Four days oral administration of 3 g of cooked Brussels sprouts homogenate reduced the spontaneous urinary 8-oxodG excretion by 31% (p&lt;0.05) whereas raw sprouts, beans and endive (1:1), isolated indolyl glucosinolates and breakdown products had no significant effect. An aqueous extract of cooked Brussels sprouts (corresponding to 6.7 g vegetable per day for 4 days) decreased the spontaneous 8-oxodG excretion from 92 +/- 12 to 52 +/- 15 pmol/24 h (p&lt;0.05). After 2-NP administration the 8-oxodG excretion was increased to 132 +/- 26 pmol/24 h (p&lt;0.05) whereas pretreatment with the sprouts extract reduced this to 102 +/- 30 pmol/24 h (p&lt;0.05). The spontaneous level of 8-oxodG in nuclear DNA from liver and bone marrow was not significantly affected by the sprouts extract whereas the level decreased by 27% in the kidney (p&lt;0.05). In the liver 2-NP increased the 8-oxodG levels in nuclear DNA 8.7 and 3.8 times (p&lt;0.05) 6 and 24 h after dose, respectively. The sprouts extract reduced this increase by 57% (p&lt;0.05) at 6 h whereas there was no significant effect at 24 h. In the kidneys 2-NP increased the 8-oxodG levels 2.2 and 1.2 times (p&lt;0.05) 6 and 24 h after dose, respectively. Pretreatment with the sprouts extract abolished these increases (p&lt;0.05). Similarly, in the bone marrow the extract protected completely (p&lt;0.05) against a 4.9-fold 2-NP induced increase (p&lt;0.05) in the 8-oxodG level. These findings demonstrate that cooked Brussels sprouts contain bioactive substance(s) with a potential for reducing the physiological as well as oxidative stress induced oxidative DNA damage in rats. This could explain the suggested cancer preventive effect of cruciferous vegetables. The correspondence between the urinary excretion and 8-oxodG levels in 2-NP target organs supports its being the main repair product that reflects the rate of guanine oxidation in DNA.

Research paper thumbnail of Putative Role of Brain Acetaldehyde in Ethanol Addiction

Current Drug Abuse Reviewse, 2008

The putative contribution of brain acetaldehyde (AcH) to ethanol (EtOH) tolerance and dependence ... more The putative contribution of brain acetaldehyde (AcH) to ethanol (EtOH) tolerance and dependence (addiction) is reviewed. Although the role of AcH in EtOH addiction has been controversial, there are data showing a relationship. AcH can be formed in the brain tissues through the peroxidatic activity of catalase and by oxidation via other oxidizing enzymes such as cytochrome P-4502E1. Significant formation of AcH occurs in vitro in brain tissue at concentrations of EtOH that can be achieved by voluntary consumption of EtOH by rodents. AcH itself possesses reinforcing properties, which suggests that some of the behavioral pharmacological effects attributed to EtOH may be a result of the formation of AcH, and supports the involvement of AcH in EtOH addiction. Modulation of aldehyde dehydrogenase (ALDH) and brain catalase activity can change EtOH-related addictive behaviors presumably by changing AcH levels. Moreover, some condensation reaction products of AcH may promote some actions of EtOH and its consumption. On the basis of the findings, it can be concluded that AcH may mediate some of the CNS actions of EtOH including tolerance and dependence, although further exploration the involvement of AcH in EtOH addiction is warranted.

Research paper thumbnail of Ethanol Metabolism and Effects: Nitric Oxide and its Interaction

Current Clinical Pharmacology, 2007

in alcoholic beverages is consumed by a large number of individuals and its elimination is primar... more in alcoholic beverages is consumed by a large number of individuals and its elimination is primarily by oxidation. The role of nitric oxide (NO) in EtOH's effects is important since NO is one of the most prominent biological factors in mammals. NO is constantly formed endogenously from L-arginine. Dose and length of EtOH exposure, and cell type are the main factors affecting EtOH effects on NO production. Either acute or chronic EtOH ingestion affects inducible NO synthase (iNOS) activity. However it seems that EtOH suppresses induced-NO production by inhibition of iNOS in different cells. On the other hand, it is clear that acute low doses of EtOH increase both the release of NO and endothelial NOS (eNOS) expression, and augment endothelium-mediated vasodilatation, whereas higher doses impair endothelial functions. EtOH selectively affects neuronal NOS (nNOS) activity in different brain cells, which may relate to various behavioral interactions. Therefore, there is an excellent chance for EtOH and NO to react with each other. Effects of EtOH on NO production and NOS activity may be important to EtOH modification of cell or organ function. Nitrosated compounds (alkyl nitrites) are often found as the interaction products, which might be one of the minor pathways of EtOH metabolism. NO also inhibits EtOH metabolizing enzymes. Furthermore, NO is involved in EtOH induced liver damage and has a role in fetal development during EtOH exposure in pregnancy. The mechanisms underlying these effects are only partially understood. Hence, the current discussion of the interaction of EtOH and NO is presented.

Research paper thumbnail of Metformin targets Stat3 to inhibit cell growth and induce apoptosis in triple-negative breast cancers

Cell Cycle, 2012

Key words: triple-negative breast cancer, metformin, Stat3, mTOR transition (EMT), stimulation of... more Key words: triple-negative breast cancer, metformin, Stat3, mTOR transition (EMT), stimulation of the Janus tyrosine kinases (JAK/Stat) pathway and transcriptional regulation of Stat 3-specific target genes that may block apoptosis and induce cell proliferation, angiogenesis, cell migration and metastasis. 9-15 Stat3 activation can also result from serine phosphorylation, which has more significant effects on cytoplasmic/mitochondrial activity, including Ras-associated oncogenesis 16,17 and functioning of the electron transport chain (ETC) via binding to complexes I and II. 18 Non-phosphorylated Stat3s have also been shown to play important roles in cellular function, for example, via binding nuclear factor κB (NFκB) to mediate its nuclear import. In summary, aberrant Stat3 expression is frequently observed in TN breast cancers. It likely plays a critical role in the pathogenesis of this highly aggressive cancer subtype.