Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:001372 (ESR)
 7,313 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolated hepatocytes and liver microsomes incubated with monomethyl-1,1 dimethyl- and 1,2 dimethyl-hydrazines produced free radical intermediates which were detected by ESR spectroscopy by using 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) as spin trapping agent. The spectral features of the spin adducts derived from all three hydrazine derivatives corresponded to the values reported for the methyl free radical adduct of 4-POBN. In the microsomal preparations inhibitors of the mixed function oxidase system and the destruction of cytochrome P450 by pretreating the rats with CoCl2 all decreased the free radical formation. Methimazole, an inhibitor of FAD-containing monoxygenase system, similarly decreased the activation of 1,1 dimethyl-hydrazine, but not that of monomethyl- and 1,2 dimethyl-hydrazines. The addition to liver microsomes of physiological concentrations of glutathione (GSH) lowered by approx. 80% the intensities of the ESR signals. Consistently, incubation of isolated hepatocytes with methyl-hydrazines decreased the intracellular GSH content, suggesting that GSH can effectively scavenge the methyl free radicals. The results obtained suggest that methyl free radicals could be the alkylating species responsible for the toxic and/or carcinogenic effect of methyl-hydrazines.
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PMID:Free radical activation of monomethyl and dimethyl hydrazines in isolated hepatocytes and liver microsomes. 253 41

By the use of spin trapping agents phenyl-t-butyl nitrone (PBN) and 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) free radical species were detected in isolated hepatocytes incubated with either isoniazid, iproniazid and their respective metabolites acetyl-hydrazine and isopropyl-hydrazine. The addition of bis-nitrophenyl phosphate, an inhibitor of the acylamidase enzymes, to isolated hepatocytes decreased the free radical activation of isoniazid and iproniazid, but not that of acetyl- and isopropyl-hydrazine, confirming that the radical species were originating from the biotransformation of these latter compounds. The ESR spectra were ascribed to the trapping of, respectively, acetyl and isopropyl free radicals on the basis of the analogies of the spectral feature with those of chemically-prepared spin adducts. Comparable ESR spectra were also observed during the metabolism of acetyl- and isopropyl-hydrazines by liver microsomes and their formation was inhibited by the omission of NADP+, anaerobic incubation and enzyme denaturation. In the microsomal preparations inhibitors of the mixed function oxidase system decreased to various extents the free radical formation and a similar effect was also observed following the destruction of cytochrome P-450 induced by pretreating the rats with CoCl2. The addition of reduced glutathione also decreased the radical trapping indicating that GSH can effectively compete with the spin traps for the reaction with the free radicals. The incubation of isolated hepatocytes with isoniazid or acetyl-hydrazine reduced by 20-25% the intracellular GSH content, while a 50% decrease in GSH was present in the cells exposed to iproniazid and isopropyl-hydrazine. In the same hepatocyte preparations stimulation of lipid peroxidation and leakage of LDH were also observed during cell incubation with iproniazid and isopropyl-hydrazine, but not with isoniazid or acetyl-hydrazine and the extent of both phenomena correlated with the susceptibility of the above compounds to the free radical activation.
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PMID:Spin trapping of free radical intermediates produced during the metabolism of isoniazid and iproniazid in isolated hepatocytes. 282 Apr 25

Effect of potassium permanganate, cobalt chloride and vitamin B complex on the haematological parameters of common carp Cyprinus carpio were markedly influenced by a treatment of 2.5 mg/l Cd in the laboratory for 96 hours. Hb% and ESR values were increased but the RBC and PCV values were reduced. Treatment of KMnO4 (1 mg/l) or CoCl2 (2 mg/l) induced a further reduction of RBC of the Cd treated fish. But parameters like PCV, MCV and MCH of Cd treated fish were not affected by the treatment of KMnO4 and CoCl2. Intramuscular injection of vitamin B complex did not produce any impact on ESR and MCV values of the Cd treated exposed fish but most of the other parameters of such fish were found comparable to control indicating that vitamin B complex could counteract Cd to reduce its ill effect.
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PMID:Effect of potassium permanganate, cobalt chloride and vitamin B complex on the haematological parameters of cadmium treated common carp, Cyprinus carpio. 858 May 24

Dopamine dose-dependently reduced the viable cell number of both human salivary gland tumor HSG and oral squamous cell carcinoma HSC-2, HSC-4, and NA cells. CoCl2 significantly reduced both the cytotoxic activity and radical intensity of dopamine (determined by ESR spectroscopy). Dopamine produced DNA fragments (demonstrated by TUNEL method) and induced degradation of cytokeratin by activated caspase in HSG cells (detected by an immunocytochemical method, using a specific M30 monoclonal antibody). FACS analysis demonstrated that dopamine induced DNA fragmentation, a biochemical hallmark of apoptosis, in human promyelocytic leukemia HL-60 cells. The addition of catalase did not prevent the apoptosis-inducing activity of dopamine, reducing the possibility of the involvement of H2O2 for dopamine-induced apoptosis. Dopamine transiently induced p38 mitogen-activated protein kinase (MAP kinase) phosphorylation. However, an inhibitor of p38 MAP kinase phosphorylation, SB203680, failed to inhibit the dopamine-induced apoptosis. These data suggest that p38 phosphorylation at an early stage may not be a causative event for apoptosis.
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PMID:Induction of apoptosis by dopamine in human oral tumor cell lines. 1076 62

The effect of CoCl2 on the cytotoxic activity of various antioxidants against human oral tumor cell lines (HSC-2, HSG) and normal human gingival fibroblasts (HGF) was investigated. Noncytotoxic concentrations of CoCl2 significantly reduced the cytotoxic activity of sodium ascorbate, gallic acid, epigallocatechin gallate (EGCG), curcumin and dopamine, but not that of sodium 5,6-benzylidene-L-ascorbate (SBA) and benzaldehyde. Among these compounds, benzaldehyde showed the most prominent tumor-specific cytotoxic action. ESR spectroscopy showed that these antioxidants produced radicals under alkaline condition and that their radical intensity was transiently enhanced and finally disappeared by addition of CoCl2. Antioxidants which are sensitive to CoCl2 generally had higher cytotoxic activity and oxidation potential (measured by NO monitor) and addition of CoCl2 significantly reduced their oxidation potential. The present study suggests that cobalt ion stimulates the oxidation of antioxidants to their inactive products.
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PMID:Effect of cobalt ion on radical intensity and cytotoxic activity of antioxidants. 1106 35

Millimolar concentrations of chlorogenic acid (CGA) showed higher cytotoxic activity against human oral squamous cell carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines, as compared with that against human gingival fibroblast (HGF). The cytotoxic activity of CGA was significantly reduced by catalase or CoCl2, but not affected by FeCl3 or CuCl2. ESR spectroscopy showed that higher (millimolar) concentrations of CGA produced radicals under alkaline conditions, acting as a prooxidant, whereas lower concentrations of CGA scavenged superoxide and hydroxyl radical. CGA produced large DNA fragments (as identified by slightly faster migrating band of DNA on agarose gel electrophoresis) and nuclear condensation (as demonstrated by Hoechst (No. 33258) staining) in tumor cell lines. Activation of caspase was demonstrated by staining with M30 monoclonal antibody, which reacts with degradation products of cytokeratin 18. Contact with CGA for at least 6 h was necessary for irreversible cytotoxicity induction. Pretreatment of the cells with caspase 3 inhibitor partially inhibited the cytotoxic action of CGA. These date suggest that CGA induces cytotoxicity in oral tumor cell lines, possibly by hydrogen peroxide-mediated oxidation mechanism.
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PMID:Induction of cytotoxicity by chlorogenic acid in human oral tumor cell lines. 1119 77

Chlorogenic acid (CGA) induced apoptotic cell death in human oral squamous cell carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines. CGA exhibited oxidation potential in the culture medium, as demonstrated by NO monitor. Both cytotoxic activity and oxidation potential were significantly reduced by the addition of CoCl2. ESR spectroscopy showed that CGA produced seven peaks of radicals under alkaline condition, while addition of CoCl2 altered the spectral pattern and diminished the radical intensity of CGA. CoCl2 accelerated the CGA-induced coloration of the culture medium and modified the difference spectrum at around 325 nm, an absorption maximum characteristic of CGA. These data suggest that CoCl2 induced conformational changes in the CGA molecule.
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PMID:Inhibition of chlorogenic acid-induced cytotoxicity by CoCl2. 1184 93

We have recently found that millimolar concentrations of sodium fluoride (NaF) induced apoptotic cell death, characterized by caspase activation and DNA fragmentation, in tumor cell lines. This finding paved the way to investigating the interaction between NaF and the oral environment. As an initial step, we investigated redox compounds, metals and saliva, which may modify the cytotoxic activity of NaF against a human oral squamous cell carcinoma cell line (HSC-2). The minimum exposure time to NaF required for cytotoxicity induction was 8 hours. Noncytotoxic concentrations of antioxidants (sodium ascorbate, gallic acid, epigallocatechin gallate, chlorogenic acid, curcumin, superoxide dismutase, catalase), oxidants (hydrogen peroxide, sodium hypochlorite), metals (CuCl, CuCl2, FeCl2, FeCl3, CoCl2) or saliva neither protected against, nor enhanced the cytotoxic activity of NaF. Cytotoxic concentrations of these compounds produced somewhat additive, but not synergistic, effects on the cytotoxicity of NaF. ESR analysis demonstrated that NaF did not apparently change the radical intensity of sodium ascorbate and gallic acid, measured under alkaline conditions. During the cell death induction in human promyelocytic leukemia HL-60 cells by NaF, the consumption of glucose rapidly declined, followed by a decline in the consumption of major amino acids. The present study suggests that the cytotoxic activity of NaF is not regulated by the redox mechanism, but rather linked to the rapid decline in glucose consumption at early stage.
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PMID:Effect of antioxidants, oxidants, metals and saliva on cytotoxicity induction by sodium fluoride. 1466 69