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D Zhou

Publications and source records attributed to D Zhou.

At least 55 records · Page 3Linked to original sources
PubMed2001

Down-regulation of promoter 1.3 activity of the human aromatase gene in breast tissue by zinc-finger protein, snail (SnaH).

Aromatase (estrogen synthetase) is expressed in breast cancer tissue, and in situ expression of the enzyme stimulates breast cancer growth. Promoter I.3 is one of the major promoters that control the expression of aromatase in breast cancer tissue. Using the yeast one-hybrid approach to screen a human breast tissue hybrid cDNA expression library, we found that the zinc-finger transcriptional factor Snail (SnaH) interacted with a regulatory region near promoter I.3 of the human aromatase gene. DNA mobility shift assays and mutation analyses using recombinant SnaH protein expressed in Escherichia coli have revealed that this protein interacts with a segment, 5'-CTGATGAAGT-3', which is between 66 and 76 bp upstream from the transcriptional start site of promoter I.3. Using mammalian cell transfection experiments, SnaH was found to act as a repressor of promoter I.3 activity. Site-directed mutagenesis experiments have revealed that the NH2-terminal SNAG domain is important for the repressor activity of SnaH. To demonstrate the inhibitory activity against aromatase expression, a stable SnaH-expressing MDA-MB-231 breast cancer cell line was generated, and the aromatase RNA messages in the SnaH-transfected cell line were found to be 30% of those in the vector-transfected cell line. Reverse transcription-PCR analysis on RNAs isolated from 12 cell lines has confirmed that SnaH is expressed at a higher level in normal breast epithelial cell and stromal fibroblast cell lines than in breast cancer cell lines. In addition, SnaH mRNA was detected in only 16 of 55 breast cancer specimens. On the other hand, aromatase mRNA was detected in 54 of the 55 specimens. Our results indicate that SnaH acts as a repressor that down-regulates the expression of aromatase in normal breast tissue by suppressing the function of promoter I.3. A reduction of the expression of SnaH in breast cancer tissue further suggests a cancer-protective role for this protein in normal breast tissue.

Amino Acid Sequence↗
PubMed2001

[Combination treatment for craniopharyngiomas with stereotactic intracavitary irradiation and gamma knife surgery].

OBJECTIVE: To evaluate the effectiveness of the combination treatment for craniopharygiomas with stereotactic intracavitary irradiation and gamma knife surgery. METHODS: Combination treatment of stereotactic instillation of radioisotopes and gamma knife surgery was performed in 46 patients with craniopharyngioma between October 1996 and June 1999. There were 24 men and 22 women, with age ranging from 3 to 60 years (average 38.6 years). There were 13 solid tumors and 33 mixed solid and cystic tumors. Twenty-eight patients had undergone prior caraniotomies with total or partial resection of tumors, with or without followed external beam radiation therapy. Gamma knife surgery was done in solid tumors and the combination treatment was done in mixed tumors: the cyst being treated with stereotactic intracavitary radiation and the solid part with Gamma knife. RESULTS: Thirty-eight patients (10 solid and 28 mixed) were followed up from 6 months to two years (averaged 16 months). The tumor control rate (disappeared, decreased and unchanged) was 90% in solid tumor, 85.7% in mixed tumors, and 92.1% in solid segment and the total control rate was 89.5%. CONCLUSION: The combination treatment is a simple, safe and effective method for craniopharyngiomas, especially for the recurrent mixed solid and cystic tumors. Gamma knife surgery plays an important role in the treatment of solid component of the craniopharyngiomas.

Adolescent↗
PubMed2001

A comparative study on cockroach and ovalbumin sensitizations and challenge responses in Hartley guinea-pigs.

The role of allergens in asthmatic inflammation is not clearly understood. To elucidate the mechanism of cockroach allergen (CRa)-induced airway disease, we studied three groups of Hartley guinea-pigs sensitized to control, ovalbumin (OA) or CRa. Parameters measured were anaphylactic antibodies by allergy skin test (AST), PCA assay and Western blot, changes in specific airway resistance (SRaw), analysis of bronchoalveolar lavage (BAL) and contracture responses of tracheal muscle (TSM) to non-specific and specific stimuli, in vitro. Both OA and CRa animals showed a similar allergic sensitization (AST and PCA), while Western blot identified several reaginic bands in CRa group compared to a single band in OA group. SRaw illustrated that CRa induce dual-asthmatic responses (4/6) in the CRa group, whereas OA induce only an early asthmatic response (3/6) in the OA group (P<0.01). The average total leukocytes in BALF of the CRa were 27.0x10(6), mostly neutrophils and eosinophils, while those of the OA showed 3.5x10(6), mostly eosinophils, respectively (P<0.0001). TSM responses to non-specific stimuli were similar in both groups (P>0.1), while the antigen-specific TSM contractions were more brisk in the OA group than those of CRa group (P<0.001). Thus, the study indicates that both CRa and OA sensitize guinea-pigs, yet CRa induces more severe and persistent late-phase inflammation than OA. This appears to be related to an influx of neutrophils rather than anaphylactic bronchospasm.

Airway Obstruction↗
PubMed2001

Topiramate on ictal seizure semiology: a quantitative, randomized, low and medium dose-controlled study.

OBJECTIVE: Intensive and quantitative evaluation of the severity and frequency of seizures and ictal signs during topiramate (TPM) treatment. METHODS: Twenty patients with refractory partial seizures undergoing presurgical evaluation were randomized into a low dosage (100 mg daily) and a parallel medium dosage (200 mg daily) group of TPM add-on medication. Study phases included a 3-day baseline video-EEG phase, a 10-day TPM titration phase without video-EEG and a 3-day TPM dose maintenance phase with video-EEG. During the baseline and the dose maintenance phase seizures were recorded using video-EEG monitoring and the following parameters were measured: duration (lasting seconds of each seizure and ictal sign), intensity (on a 0-3 scale), N/24 h (numbers of attacks per 24 h), D/24 h (duration per 24 h) of both seizures and defined ictal signs. RESULTS: A total of 399 seizures during the baseline phase and the dose maintenance phase were intensively analyzed. Intergroup comparison suggested that duration, N/24 h and D/24 h of all seizures decreased more in the medium dosage group computing the reduction from baseline to the dose maintenance phase (P<0.05). There were statistically more significant reductions in the duration, intensity and N/24 h of ictal signs like hypermotoric movements, fumbling and vocalization in the medium dosage group (P<0.05). CONCLUSION: Topiramate has an early dose-dependent effect on ictal seizures. SHORT COMMUNICATION: The present study intensively analyzed the duration, intensity, N/24 h and D/24 h of ictal seizure manifestations. The quantitative data suggested that topiramate had an early effect on ictal phenomena like ictal hypermotoric movements, fumbling and vocalization (P<0.05); effects were more prominent in the medium dosage group (200 mg daily) than the low dosage group (100 mg daily).

Adolescent↗
PubMed2001

Modulation of aromatase expression in human breast tissue.

Aromatase plays an important role in breast cancer development through its role in the synthesis of estrogen. Aromatase expression in breast tissue can be regulated by several mechanisms. The major promoter usage for aromatase expression in breast tumors (i.e. cAMP-stimulated promoters I.3 and II) is different from that in normal breast tissue (i.e. glucocorticoid-stimulated promoter I.4). Recent characterization of transcription factors that interact with the two important regulatory elements near promoters I.3 and II, i.e. S1 and CREaro, helps us better understand the mechanism of the switch of promoter usage between normal breast tissue and cancer tissue. It is thought that in normal breast tissue, the function of promoters I.3 and II is suppressed through the binding of EAR-2, COUP-TFI, and EARgamma to S1, and through the binding of Snail/Slug proteins to their binding site that quenchs the CREaro activity. In cancer tissue, the expression levels of EAR-2, COUP-TFI, EARgamma, Snail, and Slug decrease, and aromatase expression is then up regulated through the binding of ERRalpha-1 to S1 and the binding of CREB or related factors to CREaro. Results from this and other laboratories reveal that aromatase activity in aromatase expressing cells can also be modified by treatment with aromatase inhibitors and the antiestrogen ICI 182, 780. While aromatase inhibitors are used to treat breast cancer, the treatment has been found to increase the level of aromatase in the breast tissue of some patients. The enhancement of aromatase activity by aromatase inhibitors is thought to be due to a decrease of aromatase protein degradation by enzyme-inhibitor complex formation, up-regulation of the aromatase gene transcription through a cAMP-mediated mechanism, and an induction of aromatase expression by gonadtropins that are released from the pituitary in response to a reduction of estrogen levels in circulation in premenopausal women. Antiestrogen ICI 182, 780 has been found to suppress aromatase expression, but the mechanism has not yet been determined. In addition, aromatase activity and expression can be affected by environmental chemicals. A detailed structure-function study has revealed that flavones, but not isoflavones, are inhibitors of aromatase. It was found that flavones bind to the active site of aromatase in an orientation in which their rings-A and -C mimic rings-D and -C of the androgen substrate. The modulation of aromatase expression by endocrine disrupting chemicals is exemplified by two organochlorine pesticides (i.e. toxaphene and chlordane) that have been found to be antagonists of ERRalpha-1 orphan receptor. These compounds reduce ERRalpha-1 activity, resulting in a suppression of aromatase expression.

Aromatase↗
PubMed2001

Investigation of cosmic rays and their secondaries at aircraft altitudes.

A very extensive study of the radiation field at aircraft altitudes has been carried out over the last few years. These investigations formed part of a European wide collaboration involving several laboratories with extensive experience in cosmic ray research and/or dosimetry. Among the main topics investigated were the charge spectra, LET spectra, anisotropy and dose values. The measurements were performed on subsonic and supersonic flights covering a wide range of altitudes and latitudes. Several active and passive instruments were employed in these studies and some results obtained with nuclear track detectors are described here. Comparisons are made with the results of other experiments and theoretical estimates using computer codes.

Aircraft↗
PubMed2001

Synthesis of structured triacylglycerols containing caproic acid by lipase-catalyzed acidolysis: optimization by response surface methodology.

Production in a batch reactor with a solvent-free system of structured triacylglycerols containing short-chain fatty acids by Lipozyme RM IM-catalyzed acidolysis between rapeseed oil and caproic acid was optimized using response surface methodology (RSM). Reaction time (t(r)), substrate ratio (S(r)), enzyme load (E(l), based on substrate), water content (W(c), based on enzyme), and reaction temperature (T(e)), the five most important parameters for the reaction, were chosen for the optimization. The range of each parameter was selected as follows: t(r) = 5-17 h; E(l) = 6-14 wt %; T(e) = 45-65 degrees C; S(r) = 2-6 mol/mol; and W(c) = 2-12 wt %. The biocatalyst was Lipozyme RM IM, in which Rhizomucor miehei lipase is immobilized on a resin. The incorporation of caproic acid into rapeseed oil was the main monitoring response. In addition, the contents of mono-incorporated structured triacylglycerols and di-incorporated structured triacylglycerols were also evaluated. The optimal reaction conditions for the incorporation of caproic acid and the content of di-incorporated structured triacylglycerols were as follows: t(r) = 17 h; S(r) = 5; E(l) = 14 wt %; W(c) = 10 wt %; T(e) = 65 degrees C. At these conditions, products with 55 mol % incorporation of caproic acid and 55 mol % di-incorporated structured triacylglycerols were obtained.

Brassica↗
PubMed2001

Therapeutic intensive seizure analysis (TISA) in presurgical evaluation of Losigamone.

OBJECTIVE: The new method TISA was used to evaluate Losigamone efficacy. METHODS: Sixteen patients with pharmacoresistant partial seizures undergoing presurgical evaluation were randomized in this double-blind, placebo-controlled, parallel-group Losigamone monotherapy study under continuous video-EEG monitoring. Duration (in s, of each seizure and each ictal sign), intensity (grade zero to three), N/24h (number of seizures and ictal signs per 24 h), D/24h (seconds per 24 h covered by seizures and ictal signs) and seizure free intervals were recorded. RESULTS: A total of 246 seizures were intensively analyzed. The duration and intensity of all seizures improved more in the active treatment group than in the placebo group. There was a statistically significant superiority in the duration of the seizure free interval in the Losigamone group. Ictal signs such as oro-alimentary automatisms and fumbling were improved during Losigamone treatment. CONCLUSION: Losigamone has a preferred inhibitory effect on propagated epileptic activity. TISA is a sensitive method for evaluation of the selective effects of AEDs.

Adult↗
PubMed2001

A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization.

A central feature of Salmonella pathogenicity is the bacterium's ability to enter into non-phagocytic cells. Bacterial internalization is the consequence of cellular responses characterized by Cdc42- and Rac-dependent actin cytoskeleton rearrangements. These responses are triggered by the co-ordinated function of bacterial proteins delivered into the host cell by a specialized protein secretion system termed type III. We report here that SopB, a Salmonella inositol polyphosphatase delivered to the host cell by this secretion system, mediates actin cytoskeleton rearrangements and bacterial entry in a Cdc42-dependent manner. SopB exhibits overlapping functions with two other effectors of bacterial entry, the Rho family GTPase exchange factors SopE and SopE2. Thus, Salmonella strains deficient in any one of these proteins can enter into cells at high efficiency, whereas a strain lacking all three effectors is completely defective for entry. Consistent with an important role for inositol phosphate metabolism in Salmonella-induced cellular responses, a catalytically defective mutant of SopB failed to stimulate actin cytoskeleton rearrangements and bacterial entry. Furthermore, bacterial infection of intestinal cells resulted in a marked increase in Ins(1,4,5,6)P4, a consumption of InsP5 and the activation of phospholipase C. In agreement with the in vivo findings, purified SopB specifically dephosphorylated InsP5 to Ins(1,4,5,6)P4 in vitro. Surprisingly, the inositol phosphate fluxes induced by Salmonella were not caused exclusively by SopB. We show that the SopB-independent inositol phosphate fluxes are the consequence of the SopE-dependent activation of an endogenous inositol phosphatase. The ability of Salmonella to stimulate Rho GTPases signalling and inositol phosphate metabolism through alternative mechanisms is an example of the remarkable ability of this bacterial pathogen to manipulate host cellular functions.

Actins↗
PubMed2001

Microencapsulated bovine chromaffin cell xenografts into hemiparkinsonian rats: a drug-induced rotational behavior and histological changes analysis.

Bovine chromaffin cells were microencapsulated within alginate-polylysine-alginate (APA) membranes. Microencapsulated bovine chromaffin cells as well as unencapsulated cells and empty microcapsules were grafted into the brain of hemiparkinsonian rats with 6-hydroxydopamine (6-OHDA) lesions. Apomorphine-induced rotational behavior of the host animals and the survival of the grafted chromaffin cells were examined after transplantation. The animals receiving microencapsulated bovine chromaffin cells showed a significant decrease (17.6--35.6%) in apomorphine-induced rotation 1 week postimplantation that remained stable for the 10 month test period. Fluorescent histochemistry further revealed that microencapsulation increased the chromaffin cell survival with only a minimum host reaction for up to 10 months posttransplantation while the survival of free, unencapsulated chromaffin cells was only modest and was accompanied by a large inflammatory response. The reduction of apomorphine-induced rotations was correlated with the survival of bovine chromaffin cells in the host brain. The data indicate that encapsulation of bovine chromaffin cells in APA membranes reduces the host immune response to the xenograft and prolongs the viability of the grafted cells.

Animals↗
PubMed2001

Effects of NF-kappaB1 (p50) targeted gene disruption on ionizing radiation-induced NF-kappaB activation and TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression in vivo.

PURPOSE: To investigate the role of the NF-kappaB1 (p50) gene in ionizing radiation (IR)-induced NF-kappaB activation and TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression in vivo. MATERIALS AND METHODS: NF-kappaB activation was analysed by the gel shift/supershift assay and the levels of TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA were measured using RNase protection assay (RPA). Various tissues from BALB/c, B6,129P-Nfkb1 (NF-kappaB1 or p50 gene knockout, p50(-/-)) and B6,129PF2 (wild-type, p50(+/+)) mice were analysed before or after exposure to a lethal dose (8.5 Gy) of total-body gamma-irradiation. RESULTS: Exposure of BALB/c mice to total-body IR selectively activated NF-kappaB in the spleen, mesenteric lymph nodes (LN) and bone marrow (BM). Gel supershift assay using polyclonal antibodies against NF-kappaB p50, p65 or c-Rel protein revealed that the NF-kappaB p50 subunit is a critical component of the NF-kappaB complexes activated by IR in vivo. Discretely augmented TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression was found in the spleen, LN and BM after BALB/c mice received IR. However, mice lacking the p50 gene (p50(-/-)) showed a significant reduction in IR-induced activation of NF-kappaB and increases in TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression, as compared with that of wild-type mice (p50(+/+)). CONCLUSIONS: The NF-kappaB p50 subunit is a critical component of the NF-kappaB complexes activated by IR and it plays an important role in mediating IR-induced TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression in vivo.

Animals↗
PubMed2001

In vivo T-lymphocyte activation and transient reduction of viral replication in macaques infected with simian immunodeficiency virus.

While it is well established that cellular activation can increase human immunodeficiency virus (HIV) replication in T lymphocytes, it is also clear that both activated CD8+ and CD4+ T lymphocytes mediate anti-HIV activity. To assess the relative importance of these contrary effects on HIV replication in vivo, we evaluated the consequences of Mycobacterium bovis BCG and staphylococcal enterotoxin B (SEB) inoculation in vivo in rhesus monkeys chronically infected with simian immunodeficiency virus of macaques (SIVmac). BCG inoculation induced as much as a 2.5-log reduction of plasma and intracellular SIV RNA in SIVmac-infected monkeys. This down-regulation of virus replication persisted as long as 4 weeks after BCG inoculation. Similarly, SEB injection resulted in up to a 3-log decrease in plasma and intracellular SIV RNA in SIVmac-infected macaques. Interestingly, the short-term reduction of viremia in these monkeys correlated with the peak in vivo production of SEB- and BCG-induced cytokine responses. However, no long-term clinical benefit was observed in the SIVmac-infected macaques. These studies provide in vivo evidence that potent T-cell stimulation driven by antigens other than the virus itself can, under some circumstances, mediate short-term reduction of viremia in AIDS virus-infected individuals.

Animals↗
PubMed2001

Antiretroviral agents restore Mycobacterium-specific T-cell immune responses and facilitate controlling a fatal tuberculosis-like disease in Macaques coinfected with simian immunodeficiency virus and Mycobacterium bovis BCG.

The contribution of immune reconstitution following antiretroviral treatment to the prevention or treatment of human immunodeficiency virus-related primary or reactivation tuberculosis remains unknown. Macaque models of simian immunodeficiency virus-Mycobacterium bovis BCG (SIV/BCG) coinfection were employed to determine the extent to which anti-Mycobacterium tuberculosis immunity can be restored by antiretroviral therapy. Both SIV-infected macaques with active BCG reinfection and naive animals with simultaneous SIV/BCG coinfection were evaluated. The suppression of SIV replication by antiretroviral treatment resulted in control of the active BCG infection and blocked development of the fatal SIV-related tuberculosis-like disease. The resolution of this disease coincided with the restoration of BCG purified protein derivative (PPD)-specific T-cell immune responses. In contrast, macaques similarly coinfected with SIV/BCG but not receiving antiretroviral therapy had depressed PPD-specific primary and memory T-cell immune responses and died from tuberculosis-like disease. These results provide in vivo evidence that the restoration of anti-mycobacterial immunity by antiretroviral agents can improve the clinical outcome of an AIDS virus-related tuberculosis-like disease.

Adenine↗
PubMed2001

Synthesis and characterization of nanocrystalline silver coating of fly ash cenosphere particles by electroless process.

Electroless nanocrystalline Ag coating of fly ash cenosphere particles utilizing a Sn-Pd catalyst system is demonstrated in this article. The deposition of pure metallic nanocrystalline Ag on the fly ash cenosphere particle surface is confirmed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) analysis. Under the described conditions of electroless coating, average nanocrystalline Ag-coating thickness is observed to be approximately 220 nm, using a focused ion beam technique, which is less than that observed by transmission electron microscopy (TEM) (260-360 nm). TEM observation further reveals that the Ag-coating is made up of 50 nm Ag nanocrystallites, which is comparable with the size of approximately 37 nm obtained from the XRD data. The mechanism of the electroless Ag-coating process is discussed. Ag-coated fly ash particles find applications in manufacturing conducting polymers for electromagnetic interference shielding applications.

Carbon↗
PubMed2001

[Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in the Han and Li nationalities in Hainan, China and identification of a new mutation in human G6PD gene].

OBJECTIVE: To elucidate the molecular basis of G6PD deficiency in the Han and Li nationalities in Hainan, China. METHODS: Polymerase chain reaction and restriction enzyme digestion were used to screen the mutations 1388G-->A, 1360C-->T, 1024C-->T, 592C-->T, 517T-->C, 493A-->G, 487G-->A, 392G-->T and 95A-->G. Single strand conformation polymorphism analysis was used to screen the other mutations followed by DNA sequencing to characterize the mutations of the samples with abnormal SSCP bands. RESULTS: Of the fifty-nine Han cases with G6PD deficiency, fourteen with 1388G-->A (23.7%), three with 871G-->A(5.1%), one with 835A-->T(1.7%), one with 517T-->C (1.7%), three with 392G-->T(5.1%), and four with 95A-->G(6.8%) were found. Of the thirty-two Li cases with G6PD deficiency, six with 1388G-->A(18.8%), three with 871G-->A(9.4%), and two with 95A-->G(6.3%) were found. A new mutation 835A-->G which causes the substitution of Ala for Thr at 279 in a Han case was identified and named as G6PD Haikou. The enzyme activity of the variant is about 10% of the normal and lower than the activity of the variant 835A-->T with about 40% of the normal. Analysis of the 3D model of human G6PD has revealed that the hydroxyl group of Thr at 279 is a group in maintaining the interaction of the G6PD subunits. CONCLUSION: The most common mutations of G6PD deficiency in Han and Li nationalities in Hainan are similar. Compared with the mutation spectrum of G6PD gene in the populations in other regions of China, the results indicate that some G6PD gene mutations are widespread in the populations of different regions in the southern part of China. The hydroxyl group of the Thr at 279 of human G6PD may be a necessary group for maintaining the interaction of the G6PD subunits and the enzyme activity.

Child↗
PubMed2001

[Effect of cholesterol deficiency on the membrane fluidity of Jurkat T lymphocytes].

The mechanism of cholesterol deficiency on inhibiting the proliferation of T lymphocytes was investigated on cell membrane fluidity by using fluorescence polarization measurement, 3H-TdR incorporation test and flow cytometer analysis in Jurkat cells, in order to clarify the importance of cholesterol in maintaining the normal function of lymphocytes. The results showed that cell membrane fluidity was increased, cell proliferation was inhibited and blocked on G0/G1 phase in Jurkat cells after being cultured with lovastatin (an inhibitor of rate limiting enzyme for cholesterol synthesis) for 3 days. When the cells were treated with LDL. The changes could be partially buffered. These results suggest that the change of membrane fluidity may be caused by cholesterol deficiency on the proliferation of Jurkat cells.

Anticholesteremic Agents↗
PubMed2001

D609 inhibits ionizing radiation-induced oxidative damage by acting as a potent antioxidant.

Tricyclodecan-9-yl-xanthogenate (D609) has been extensively studied in biological systems and exhibits a variety of biological functions, including antiviral, antitumor, and anti-inflammatory activities. Most of these activities have been largely attributed to the inhibitory effect of D609 on phosphatidylcholine-specific phospholipase C. However, as a xanthate derivative, D609 is a strong electrolyte and readily dissociates to xanthate anions and cations of alkali metals in solution. Xanthate anions and protonated xanthic acid contain a free thiol moiety and are highly reductive. This implies that D609 and other xanthate derivatives may function as potent antioxidants. Indeed, we found that D609 inhibited the Fenton reaction-induced oxidation of dihydrorhodamine 123 in a dose-dependent manner similar to that of pyrrolidinedithiocarbamate, a well known antioxidant. In addition, D609 inhibited the formation of the alpha-phenyl-tert-butylnitrone-free radical spin adducts and lipid peroxidation of synaptosomal membranes by the Fenton reagents. Furthermore, preincubation of lymphocytes with D609 resulted in a significant diminution of ionizing radiation (IR)-induced 1) production of reactive oxygen species; 2) decrease in intracellular reduced glutathione; 3) oxidative damage to proteins and lipids; and 4) activation of nuclear factor-kappaB. Moreover, when D609 (50 mg/kg i.v.) was administered to mice 10 min prior to total body IR (6.5 and 8.5 Gy), it protected the mice from IR-induced lethality. Thus, these results indicate that D609 is a potent antioxidant and has the ability to inhibit IR-induced cellular oxidative stress.

Animals↗