UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis of diastereoisomeric [1,2-bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes, DL-3-PtCl2 and meso-3-PtCl2, and their evaluation on the hormone-independent, human MDA-MB231 breast cancer cell line, on the cisplatin-sensitive and -resistant L1210 leukemia cell line, on the cisplatin-resistant human NIH:OVCAR 3 ovarian cancer cell line, on the P-388 leukemia of the mouse and on the cisplatin-sensitive and -resistant Ehrlich ascites tumor of the mouse are described. On all tumor models DL-3-PtCl2 produces a marked inhibitory effect. The diastereoisomer meso-3-PtCl2 is less active and more toxic. It is striking that DL-3-PtCl2 leads to a pronounced inhibition of all cisplatin-resistant tumors. At non-toxic concentrations DL-3-PtCl2 produces cytocidal effects on the NIH:OV-CAR 3 cell line. Therefore DL-3-PtCl2 is of interest for further evaluation for the therapy of ovarian cancer.
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PMID:[DL-1,2-bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II), a new compound for the therapy of ovarian cancer. 237 Feb 48

To study oxidative mechanisms in cyanide toxicity, cyanide-induced generation of intracellular oxidant species was determined by microfluorescence in cerebellar granule cells loaded with the oxidant-sensitive fluorescence dye 2,7-dichlorofluorescin. KCN produced a concentration-dependent (25-200 microM) generation of intracellular oxidant species that was blocked by N-methyl-D-aspartate receptor antagonists (MK-801 or AP5) or by removal of extracellular Ca++ from the incubation medium. To determine the relative contribution of NO and reactive oxygen species (ROS) to the increase of cellular fluorescence after KCN, a selective inhibitor of nitric oxide synthase, a NO scavenger and enzymes that metabolize ROS were added to the incubation medium. Interference with the nitric oxide system (reduced hemoglobin as a NO scavenger or [N(G)-nitro-L-arginine methyl ester [L-NAME] reduced fluorescence by 50%). Addition of enzymes that metabolize peroxide (catalase or superoxide dismutase [SOD]) also reduced fluorescence by nearly 50%. Combination of SOD with hemoglobin or L-NAME provided additional attenuation of the fluorescence and it was concluded that both NO and ROS are generated concurrently after KCN. Furthermore a correlation was observed between NO and ROS formation and levels of malonaldehyde (MDA), a marker of lipid peroxidation. Pretreatment with MK-801 blocked KCN-induced MDA formation, whereas L-NAME partially diminished MDA production. Treatment with a combination of SOD/catalase and L-NAME blocked the KCN-induced lipid peroxidation. In cytotoxicity studies cyanide-induced cell death was blocked by MK-801, whereas partial attenuation was produced by L-NAME; SOD/catalase treatments did not protect the cells. However, significant protection from cyanide-induced cytotoxicity was observed when L-NAME was combined with SOD/catalase. It is concluded that cyanide activates N-methyl-D-aspartate receptors to simultaneously generate both NO and ROS, which may lead to formation of the cytotoxic peroxynitrite anion.
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PMID:Cyanide-induced neurotoxicity involves nitric oxide and reactive oxygen species generation after N-methyl-D-aspartate receptor activation. 861 12

We investigated the effects of NG-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on bone metastasis of human breast cancer, MDA-231 cells. Tumor cells (2 x 10(5) cells in 0.2 ml of phosphate-buffered saline; PBS) were injected through the diaphragm into the left ventricle of the heart of laparotomized nude mice (male 5-week-old ICR-nu/nu). L-NAME (2 mg/mouse/injection in 0.1 ml of PBS) was given intraperitoneally to mice 6 h and 3 h before and immediately, 3 h, 6 h, 18 h and 21 h after the intracardiac injection of tumor cells. As a control, 0.1 ml of PBS was injected instead of L-NAME. The effect of NG-nitro-D-arginine-methyl ester (D-NAME; 2 mg/mouse/injection), an inactive analogue of L-NAME, was also investigated to evaluate the specificity of L-NAME action. Radiographical examination 31 days after the tumor-cell injection showed that the incidence and number of osteolytic bone metastases and the number of bones with metastasis in L-NAME-treated mice were significantly reduced compared with those in PBS-treated mice (P < 0.05). The differences between PBS-treated and D-NAME-treated mice were not significant. Our findings suggest that specific and appropriate NOS inhibitors may represent a new pharmacological approach to therapy for cancer patients at risk of developing osteolytic bone metastases.
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PMID:NG-nitro-L-arginine methyl ester inhibits bone metastasis after modified intracardiac injection of human breast cancer cells in a nude mouse model. 936 34

Erythrocyte deformability is one of the most important charactheristics of erythrocytes for an effective microcirculatory function and is affected from a number of factors, including the oxidative-damage-induced by nitric oxide (NO). This study was performed to investigate the effects of in vitro melatonin incubation on the antioxidant status and deformability of erythrocytes in sodium nitroprusside (SNP), a nitric oxide donor, induced oxidative stress. 40 blood samples taken from the adult healthy people were divided into 4 groups randomly and incubated with saline, SNP (1 mM), melatonin (MEL, 1 mM), MEL + SNP and SNP + L-NAME (5 mM) respectively. Relative filtration rate (RFR), relative filtration time (RFT) and relative resistance (Rrel) were determined as the indexes of erythrocyte filterability. In addition, malondialdehyde (MDA, as an index of lipid peroxidation) and the antioxidant activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) were also determined in the red blood cells of all groups revealing the oxidant-antioxidant activity. RFT and the Rrel of the erythrocytes incubated with SNP increased significantly (p<0.05) whereas the RFR of the erythrocytes decreased (p<0.05) in comparison to all groups. This reduction in RFR was prevented with both L-NAME or MEL incubation. Furthermore, MEL was found to be significantly efficient in preventing the erythrocytes from lipid peroxidation in these groups. In addition, GSH-Px and SOD activities were elevated with SNP incubation reflecting the oxidative stress in erythrocytes, whereas the CAT activity remained unchanged. Melatonin has no significant effect on the GSH-Px and CAT activity but, it caused a significant decrease in SOD activity (p<0.05). These results reveal that, melatonin can protect the erythrocytes from impaired deformability in SNP-induced oxidative stress due to antioxidant effects as revealed by lipid peroxidation and antioxidant enzyme activities.
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PMID:In vitro effects of melatonin on the filtrability of erythrocytes in SNP-induced oxidative stress. 1525 61

Reactive oxygen species avidly reacts with nitric oxide (NO) producing cytotoxic reactive nitrogen species capable of nitrating proteins and damaging other molecules which leads to the reduction of erythrocyte deformability. The aim of this investigation was to assess the importance of alpha-tocopherol (Vit-E) in the total antioxidant status of the erythrocytes in sodium nitroprusside (SNP), a nitric oxide donor, induced oxidative stress and its relation to erythrocyte deformability. Male Swiss Albino rats were used in 4 groups, comprising of 10 animals in each group. The first group was the control, and the other groups were administered SNP (10 mg/kg, i.p.), Vit-E (10 mg/kg, i.p.) + SNP, and SNP + L-NAME (10 mg/kg, i.p.), respectively. Relative filtration rate (RFR), relative filtration time (RFT) and relative resistance (Rrel) were determined as the indexes of erythrocyte deformability. In addition, malondialdehyde (MDA, as an index of lipid peroxidation) and nitric oxide levels and the antioxidant activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) were also determined in the red blood cells of all groups revealing the oxidant-antioxidant activity. RFT and the Rrel of the erythrocytes of the SNP-treated rats increased significantly (p<0.05) whereas the RFR of the erythrocytes decreased (p<0.05) in comparison to all groups reflecting the impaired deformability. This reduction in RFR was prevented with both L-NAME or Vit-E incubation. Vit-E has also reduced the Rrel of the erythrocyte which reveals that it has improved the erythrocyte deformability. Lipid peroxidation was suppressed by Vit-E and L-NAME significantly, where the red blood cell deformability was improved. Furthermore, SOD and CAT activities were significantly stimulated with SNP treatment (p<0.05), where as GSH-Px remained unchanged. In the contrary, GSH-Px activity was triggered significantly by Vit-E administration, whereas the SOD and CAT activities were reduced (p<0.05). As a result, these data reveal that Vit-E improves the erythrocyte deformability in SNP-induced oxidative stress by its antioxidant effects on the lipid peroxidation and antioxidant enzyme activities.
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PMID:The in vivo antioxidant effectiveness of alpha-tocopherol in oxidative stress induced by sodium nitroprusside in rat red blood cells. 1525 62

The aim of this study is to evaluate histopathological findings induced by Nomega-nitro-L-arginine methyl ester (L-NAME) and molsidomine (MOL) on the kidney of bile duct ligated rats. Forty Sprague-Dawley rats, each weighing 125 to 140 g, were included in the study. Extent of histological glomerular injury scores (GIS), arterial injury scores (AIS), and tubulointerstitial injury scores (TIS) in each animal were graded. Alpha-smooth muscle actin (alpha-SMA), tenascin, lectin (Ulex europaeus agglutinin-1), and vimentin were used to determine extent of the injury. The cholestasis was evidenced by a significant increase in the levels of serum total bilirubin in BDL rats (p < 0.01). Malondialdeyde MDA levels increased by the bile duct ligation (BDL) to 12.10 +/- 0.45. This value was significantly higher than the other groups (p < 0.01). Changes in the BDL kidney were marked at 7 days after surgery. GIS were observed to have the highest score, especially at juxtamedullary region in BDL/L-NAME rats, and AIS were also the highest score in this region. These observations were lower in BDL/MOL rats. There is a correlation between GIS and AIS scores (r = .2, p < .01). TIS revealed that BDL/L-NAME rats were significantly more damage than rats in the other groups (p<.001). MOL-treated rats showed considerably fewer lesions in the tubules and interstitium (p < .001). The tubular injuries observed in BDL and BDL/L-NAME rats were significantly attenuated by MOL treatment. Lectin was more and extensively stained in tubular epithelia of the BDL/L-NAME group than in the other (p <.05). Expression of tenascin in tubular epithelia was significantly higher in BDL and BDL/L-NAME as compared with controls (p < .01). Fibrous tissue was only observed in the BDL and BDL/L-NAME group. These areas were weakly stained with vimentin. alpha-SMA staining was more reduced in the L-NAME-treated arterioles than in BDL/MOL (p < .05). In conclusion, the analysis of cell injury based on a histological grading system in the model of BDL kidney allows the quantification of the degree of injury.
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PMID:Does the analysis based on a histological and immunohistochemical grading system in the model of BDL kidney allow the quantification of the degree of injury? 1552 6

Intragastric administration of L-carnosine suspension to Wistar-Kyoto rats 3 days before and after 7-day course of intraperitoneal injections of ototoxic aminoglycoside antibiotic kanamycin compensated expenditures of tissue antioxidant systems and significantly eliminated kanamycin-induced intensification of MDA production in tissues of the membrane part of the cochlea and in the auditory cortex of the temporal lobe. L-NAME (competitive NO synthase inhibitor) also inhibited LPO, increased total antioxidant activity, and decreased ototoxicity of kanamycin, which confirms the contribution of NO into LPO intensification under conditions of aminoglycoside treatment. Inhibition of pathological intensification of LPO processes and increase in total antioxidant activity under conditions of induced acute aminoglycoside ototoxicity characterizes L-carnosine as a highly effective otoprotector.
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PMID:Natural antioxidant L-carnosine inhibits LPO intensification in structures of the auditory analyzer under conditions of chronic exposure to aminoglycoside antibiotics. 1566 45

Losartan, an angiotensin II type-1 receptor (AT1) antagonist, was used to investigate whether it can offer protection against the sustained hypertension, cardiac hypertrophy, and renal damage induced by chronic inhibition of nitric oxide (NO) by Nomega-nitro-L-arginine methyl ester (L-NAME). We studied the involvement of both NO metabolism and oxidative stress in L-NAME-induced hypertension, and how AT1 receptor antagonism may interact. Male Wistar albino rats were subjected to NO synthesis inhibition by the use of L-NAME (60 mg/kg/day), and the effects of losartan (10 mg/kg/day) in drinking water for six weeks were observed. After six weeks, animals were subjected to the measurements for systolic, mean, and diastolic blood pressure (BPs, BPm, and BPd, respectively). Under light ether anesthesia blood was withdrawn for ACE activity, NOx and creatinine determinations. Heart and kidneys were weighed, and organ indices were calculated comparing to their body weights. These tissues were immediately preserved for GSH, MDA, NOx estimations. Chronic L-NAME treatment raised BPs, BPm, and BPd, respectively, above the normal. Treatment also increased NOx in plasma, significantly decreased it in the heart, and tended to increase it in kidney. L-NAME caused GSH depletion in the heart and kidney tissues with a concomitant increase in MDA contents in both the tissues. Plasma creatinine doubled in L-NAME-treated animals. Plasma ACE activity showed a nonsignificant decrease below control. Concurrent treatment with losartan almost completely inhibited any rise in blood pressure. Losartan replenished the partly depleted cardiac and renal antioxidant GSH and ameliorated the increase of oxidative stress damage index, MDA. However, losartan alone did not change appreciably the plasma level or cardiac and renal contents of NO,. Losartan plus L-NAME treatment caused an increase in plasma ACE activity above control. Furthermore, losartan ameliorated the L-NAME induced increase in creatinine back to value nonsignificantly different from control.
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PMID:Effects of losartan on blood pressure, oxidative stress, and nitrate/nitrite levels in the nitric oxide deficient hypertensive rats. 1598 79

In the present study, we attempted to clarify the role of nitric oxide (NO) and its release during the ischemia-reperfusion rat testis. Eight-week-old male Sprague-Dawley rats were divided into seven groups: age-matched control rats, ischemia (30 minutes)-reperfusion (30 minutes) rats without NG-nitro-L-arginine methyl ester (L-NAME) and L-arginine (L-Arg) treatment, ischemia (30 minutes)-reperfusion (30 minutes) rats treated with L-NAME (10, 30, and 100 mg/kg), ischemia-reperfusion rats treated with L-Arg (10 and 30 mg/kg). Sixty minutes prior to induction of ischemia, L-NAME or L-Arg was administrated intraperitoneally. Real-time monitoring of blood flow and NO release were measured simultaneously with a laser Doppler flowmeter and an NO-selective electrode, respectively. NO2-NO3 and malonaldehyde (MDA) concentrations were measured in the experimental testes. Furthermore, we investigated possible morphological changes in the testis. Clamping of the testicular artery decreased blood flow to 5-20% of the basal level measured before clamping. Immediately following clipping of the artery, NO release rapidly increased. After removing the clip, NO release gradually returned to the basal level. This phenomenon was enhanced by treatment with L-Arg and inhibited by treatment with L-NAME. NO2-NO3 concentrations were increased by treatment with L-Arg and decreased by treatment with L-NAME, while MDA concentrations were increased by treatment with L-NAME and were decreased by treatment with L-Arg. In histological studies, the ischemia-reperfusion caused infiltration of leukocytes and a rupture of microvessels in the testis. Our data suggest that NO has cytoprotective effects on ischemia-reperfusion injury in the rat testis.
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PMID:Real-time monitoring of nitric oxide and blood flow during ischemia-reperfusion in the rat testis. 1649 12

The inducible nitric oxide synthase (iNOS) is abundantly expressed by smooth muscle cells and macrophages in atherosclerotic lesions. Apolipoprotein E-deficient (apoE(-/-)) mice develop early and advanced atherosclerotic lesions. The role of iNOS in both early and advanced atherosclerotic formation was determined in apoE(-/-) mice. Mice were fed chow or a Western diet containing 42% fat, 0.15% cholesterol, and 19.5% casein. At 12 weeks of age on chow diet, iNOS(-/-)/apoE(-/-) mice developed comparable sizes of early atherosclerotic lesions in the aortic root as did iNOS(+/+)/apoE(-/-) mice (30,993+/-4746 vs. 26,648+/-6815 microm(2)/section; P=0.608). After being fed the Western diet for 12 weeks, iNOS(-/-)/apoE(-/-) mice developed significantly smaller advanced lesions than iNOS(+/+)/apoE(-/-) mice (458,734+/-14,942 vs. 519,570+/-22,098 microm(2)/section; P=0.029). This reduction in lesion formation could not be explained by differences in plasma lipid levels. To examine whether iNOS contributed to LDL oxidation, smooth muscle cells were isolated from the aorta, activated with TNF-alpha, and then incubated with native LDL in the absence or presence of N-Omega-nitro-L-arginine methyl ester (L-NAME), a specific NOS inhibitor. L-NAME significantly inhibited LDL oxidation by smooth muscle cells from iNOS(+/+)/apoE(-/-) mice (P=0.048), but it had no effect on LDL oxidation by cells from iNOS(-/-)/apoE(-/-) mice. iNOS(-/-)/apoE(-/-) mice had a significantly lower plasma lipoperoxide level on the Western diet (2.74+/-0.23 vs. 3.89+/-0.41 microM MDA; P=0.021) but not on chow diet (1.02+/-0.07 vs. 1.51+/-0.29 microM MDA; P=0.11). Thus, the absence of iNOS-mediated LDL oxidation may contribute to the reduction in advanced lesion formation of iNOS(-/-)/apoE(-/-) mice.
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PMID:Deficiency of inducible NO synthase reduces advanced but not early atherosclerosis in apolipoprotein E-deficient mice. 1651 41

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