Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149958 (complex partial seizures)
 2,563 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human breast tumor cells MCF-7 were grown during 5 days in the presence of Adriamycin and the IC50 was 50 nM with the highest sublethal concentration 0.1 microM. At this latter concentration Adriamycin produced a complete inhibition of cell division and a partial reversion to a normal breast epithelial appearance. Similar effects of Adriamycin were observed in cells cultured in the presence of 10% FBS and in a chemically defined medium, with Se-glutathione peroxidase activities of 3.8 and 1.3 U/mg of protein, respectively. Cell size and cell oxygen uptake were increased by 41% and by 50%, respectively, in Adriamycin-treated cells. The spontaneous chemiluminescence of monolayers of intact MCF-7 cells (81 +/- 9 cps/mg protein) was increased by 48% in the Adriamycin-treated cultures (120 +/- 11 cps/mg of protein) in agreement with a 91% higher concentration of malondialdehyde in the same cultures. Adriamycin treatment produced a 71% increase in the steady state concentration of H2O2, which was estimated assuming diffusion equilibrium with the external medium, from 1.38 microM in the control cells to 2.38 microM in the treated cells. Cyanide-insensitive respiration was also higher in the cells exposed to the drug than in the control cells. Adriamycin did not affect the activity of the antioxidant enzymes, Cu-Zn and Mn-superoxide dismutase, Se and non-Se-glutathione peroxidase, and catalase. These results contribute to the current hypothesis that oxygen free radicals produced by Adriamycin redox cycling are responsible for at least part of the cytotoxic effects due to this drug.
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PMID:Adriamycin effects on hydroperoxide metabolism and growth of human breast tumor cells. 209 92

The pathophysiological roles of superoxide (O2.-) at the site of infection of facultative intracellular bacteria were examined in this study. To evaluate the actual in vivo generation of the superoxide, an ex vivo chemiluminescence assay was newly developed. When ICR mice were infected with a sublethal dose (8 x 10(4) CFU) of Salmonella typhimurium, the number of bacteria in the liver reached its peak at 5 days after infection (10(5.05) CFU/g of liver) and decreased thereafter. At 21 days after infection, the bacteria became undetectable. On the other hand, phorbol myristate 13-acetate-stimulated O2.- generation reached a maximum at 7 days after infection (mean photon count, 1,249 cps versus 28.8 cps before infection; n = 4) and decreased thereafter to a level similar to that before infection at 21 days after infection (28.8 cps). Histological examinations revealed that the total area of the lesions reached a peak at 7 days after infection (7.2 x 10(4) microns 2/10 visual fields). In the early phase, a microabscess with infiltration of polymorphonuclear cells was noted, and then, in the late stage, the lesion was replaced by granulation with mononuclear cell infiltration. When microscopic lesions were measured histologically, a significant correlation between the area of the lesions and phorbol myristate 13-acetate-stimulated O2.- generation was observed, which suggested that superoxide was responsible for the generation of the lesions. Modified superoxide dismutase, i.e., alpha-4-([6-(N-maleimido)hexanoyloxymethyl] cumyl)half-butyl-esterified poly(stylrene-co-malelic acid)-conjugated superoxide dismutase (SM-SOD), was then applied. When SM-SOD was administered to suppress the O2.- generation in vivo, the number of bacteria increased (10(6.1) CFU). However, the lesion formation was inhibited (total lesion area, 0.3 x 10(4) microns 2). These results suggest that the establishment of the microabscess and granuloma formation after S. typhimurium infection is not due to the bacteria per se but rather to the O2.- from the host's phagocytes. Two aspects of the O2.-, i.e., the bactericidal role and the tissue-injurious effect, were clearly demonstrated in this study. Therefore, the information obtained from these results is useful in designing treatment strategy for similar kinds of infection.
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PMID:Granulation in livers of mice infected with Salmonella typhimurium is caused by superoxide released from host phagocytes. 759 Oct 77

In 8 trained subjects (T) and 9 untrained subjects (UT), lipid peroxidation (LPO), total antioxidant capacity (TRAP), superoxide dismutase, catalase, and glutathione peroxidase (GPx) activities were measured in the blood before and after three different intensities of exercise on the treadmill, determined from ventilatory threshold and maximal oxygen uptake data, obtained from a maximal aerobic power test. In plasma, LPO decreased from 3589 +/- 193 to 3274 +/- 223 cps x mg Hb(-1) (p < 0.05), and TRAP increased from 304 +/- 45 to 384 +/- 57 micromol x L(-1) trolox (p < 0.05) after high intensity exercise in T. GPx activity increased in the T group as compared to the UT group, after exercise in moderate (25.90 +/- 3.79 to 15.05 +/- 3.23 nM x min(-1) x mg protein(-1)) and high (21.75 +/- 4.91 to 12.1 +/- 2.46 nM x min(-1) x mg protein(-1)) intensities (p < 0.05). Superoxide dismutase activity increased after exercise at low (8.35 +/- 0.85 to 9.23 +/- 1.03 U SOD x mg protein(-1)) and moderate (8.89 +/- 0.98 to 10.44 +/- 0.86 U SOD x mg protein(-1)) intensity in UT (p < 0.05). There were no changes in catalase activity. These findings indicate that exercise in this model did not increase lipid peroxidation, probably because of the alterations in TRAP and enzymatic antioxidants.
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PMID:Oxidative stress after three different intensities of running. 1648 22

Myocardial activity and gene expression of antioxidant defenses and oxidative damage were examined in an experimental model of pressure overload hypertrophy. Male Wistar rats were divided into abdominal aortic-banded or sham-operated groups. After 30 days, arterial pressure and heart rate were measured. Heart, lung, and liver were extracted and weighted to evaluate cardiac hypertrophy and pulmonary and hepatic congestion. Heart homogenates were prepared to quantify lipid peroxidation (LPO); the activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR); and Cu-Zn SOD and GST concentrations. Total glutathione (GSH) myocardial content was also measured. Arterial pressure (142 +/- 17 mmHg) and cardiac hypertrophy index (3.4 +/- 0.45 mg/g) were significantly increased (by 38% and 22%, respectively, p<0.0001) in the aortic-banded group. LPO was enhanced by 55% in the aortic-banded group (11891 +/- 766 cps/mg protein, p<0.001) compared with that in the controls. SOD activity and concentration were higher (40% and 38%, 15.15 +/- 1.03 U/mg protein, 49.187 pixels, respectively, p<0.05) in the aortic-banded group than in the controls. Aortic-banding induced a decrease by 28% in GST (48 +/- 10 pmol/min/mg protein, p<0.005), by 36% in GPx (38.2 +/- 9.5 nmol/min/mg protein, p<0.005), by 31% in GR activities (1.55 +/- 0.23 nmol/mg protein, p<0.0005), and by 43% in GSH content (0.13 +/- 0.02 nmol/mg protein, p<0.005). In conclusion, in this model it was observed that myocardial oxidative stress induces alterations in antioxidant enzyme activities and protein expression. The follow up of these parameters could afford an early therapeutical window to avoid heart failure progression.
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PMID:Aortic-banding induces myocardial oxidative stress and changes in concentration and activity of antioxidants in male Wistar rats. 1695 25