Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial dysfunction and oxidative stress are often linked to various neurodegenerative disorders including ischemic stroke and Huntington's disease (HD). S-Nitrosoglutathione (GSNO) is an endogenous nitric oxide carrier recently identified as a potent antioxidant capable of neutralizing oxidative stress. In the present study, we explore the neuroprotective effects of GSNO against metabolic insults induced by 3-nitropropionic acid (3-NP), a mitochondrial complex II inhibitor commonly used as a pharmacological model for HD, in primary culture of fetal rat cortical and striatal neurons. Application of GSNO (1-5 microM) substantially reduced neuronal loss caused by 3-NP (1-5 mM) exposure based on MTT reduction, lactate dehydrogenase (LDH) release, and Hoechst staining assays. The protective effect of GSNO appeared to be more potent than N-acetyl-l-cysteine (NAC), a glutathione precursor, at the same concentrations. These results suggest that manipulation of GSNO metabolism may exert protective effects against mitochondrial dysfunction often observed in neurodegenerative disorders.
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PMID:Protective effects of S-nitrosoglutathione against neurotoxicity of 3-nitropropionic acid in rat. 1515 20

Respiration of fossil fuel-derived airborne particulate matter (PM) has been linked to various pulmonary disorders. Transition metals contained in such PM, such as zinc, iron and vanadium, have been suggested as the primary culprits in PM-induced pulmonary distress by rat instillation studies. In this study, the cytotoxicity of zinc, iron, and vanadium on confluent monolayers of rat alveolar epithelial cells was evaluated as the inhibition of cellular succinate dehydrogenase metabolic activity as quantified via the MTT assay. In addition, the effect of culture medium serum concentration on the toxicities of these three metals was investigated. Of the three metals tested, zinc was the most toxic, with an EC50 of 0.6 mM in culture medium with 10% serum; vanadium and iron had EC50's of 3 and 4 mM, respectively. Serum in culture medium was found to substantially reduce the apparent toxicity of zinc: EC50's for zinc ranged from 0.6 mM in 10% serum to 0.1 mM in serum-free medium. Zinc toxicity analyses in various culture medium conditions demonstrated that the toxicity-reducing effect of serum was due largely and perhaps entirely, to serum albumin. Some, but not all of the effect of serum and albumin on zinc toxicity is apparently due to zinc-albumin binding.
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PMID:In vitro alveolar cytotoxicity of soluble components of airborne particulate matter: effects of serum on toxicity of transition metals. 1525 Nov 86

This study aimed to evaluate the cytotoxicity of substances leached by pseudowollastonite (CaSiO(3)). It has been previously shown that calcium (Ca(2+)) and silicate (SiO(3)(-)) ions are released from pseudowollastonite into biological solutions. Both of these ions are known to influence the biological metabolism of osteoblastic cells essential in the mineralization process and bone-bonding mechanism. The indirect toxicity evaluation was performed by extraction method, according to International Standard Organization (ISO). Pseudowollastonite pellets obtained by solid-state reaction were incubated, in culture medium, during 24, 48, 72 or 168 h at different concentrations (5, 10, 15, 50, 100, 200 mg/ml). The cytotoxicity of each extract in presence of human osteoblastic cell line (SaOS-2) was quantitatively assessed by measuring the viability (succinate dehydrogenase activity, MTT), the membrane integrity (the uptake of the neutral red by viable cells, NR) as well as the cell necrosis by measuring the lactate dehydrogenase (LDH) released in the culture medium. No significant alteration of membrane integrity or cell suffering was detectable. However, increased cell metabolism was observed for cells exposed to pseudowollastonite extract with longest extraction time (168 h). In conclusion, mineral elements leached by pseudowollastonite do not significantly affect the metabolism of osteoblastic cells.
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PMID:Indirect cytotoxicity evaluation of pseudowollastonite. 1534 36

Oxidative stress has been implicated in neuronal death caused by cerebral ischemia or some neurologic disorders. Chemical hypoxia (term defining the simulation by using respiratory inhibitors) chosen as in vitro ischemic model, was induced in primary cultures of rat cerebellar granule neurons by inhibitors of mitochondrial electron transport such as rotenone or paraquat (complex I), 3-nitropropionic acid (3-NPA, complex II), antimycin A (complex III), or sodium azide (complex IV). All compounds caused neuronal death determined by trypan blue staining and MTT-test. On the other hand, neurotoxicity of rotenone and paraquat but not of 3-NPA, antimycin or azide was significantly abolished by menadione (vitamin K3, 2-methyl-1,4-naphthoquinone). This neuroprotective effect of menadione was associated with a decrease of rotenone-induced free radical production.
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PMID:Menadione reduces rotenone-induced cell death in cerebellar granule neurons. 1537 39

Sodium butyrate (NaBu), a potent histone deacetylase inhibitor, modulates the expression of a large number of genes. The purpose of this study was to determine whether this dietary agent could induce apoptosis in MCF-7 cells, a breast cancer cell line that lacks caspase-3 activity, and to identify the mechanisms that underlie NaBu toxicity in these cells. Cell viability assessed by the activity of mitochondrial succinate dehydrogenase (MTT assay) revealed a dose-dependent reduction of MCF-7 cellular growth in response to NaBu treatment. Restoring caspase-3 function by transfection did not modify NaBu toxicity in these cells. Following a 24-h exposure, NaBu-induced cell growth arrest in G2/M phase in a dose-dependent fashion in association with stable expression of CDC25A, a G1-specific regulator of the cell cycle. The anti-proliferative effects of NaBu were accompanied by diminished expression of p53. Similarly, mRNA encoding c-Myc, a well-known regulator of p53, was decreased in NaBu-treated cells, while p21(Waf1/Cip1) mRNA was increased. Furthermore, bax mRNA level was up-regulated whereas a decline in Bcl-2 both protein and mRNA levels were detected in NaBu-treated cells. Apoptosis was observed following a treatment with 2 mM NaBu, reflected by Annexin-V staining and by the cleavage of poly(ADP-ribose) polymerase, whereas DNA laddering was absent. Apoptosis was associated with a pronounced depletion of intracellular glutathione levels. Finally, NaBu treatment significantly increased the activities of several antioxidant enzymes, including glutathione reductase, glutathione peroxidase, and catalase. Together, these data suggest that the pro-apoptotic effects of NaBu observed in MCF-7 cells are associated with oxidative stress.
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PMID:The histone deacetylase inhibitor sodium butyrate induces breast cancer cell apoptosis through diverse cytotoxic actions including glutathione depletion and oxidative stress. 1554 8

Acrylic resin dentures may have cytotoxic effects on oral soft tissues. However, there is sparse data about the cytotoxic effect of fibre-reinforced acrylic resin denture base materials. The purpose of this in vitro study was to determine the effect of two fibre impregnation methods on the cytotoxicity of a glass and carbon fibre-reinforced heat-polymerized acrylic resin denture base material on oral epithelial cells and fibroblasts. One hundred acrylic resin discs were assigned to five experimental groups (n = 20). One of the groups did not include any fibre. Two groups consisted of silane and monomer treated glass fibres (Vetrolex) impregnated into acrylic resin (QC-20) discs. The other two groups consisted of silane and monomer treated carbon fibres (Type Tenox J, HTA). Untreated cell culture was used as positive control. The human oral epithelial cell line and buccal fibroblast cultures were exposed to test specimens. The cytotoxicity of the test materials was determined by succinic dehydrogenase activity (MTT method) after 24 and 72 h exposures. Data were analysed with a statistical software program (SPSSFW, 9.0). A one-way analysis of variance (anova) test and Bonferroni test were used for the comparisons between the groups. All statistical tests were performed at the 0.95 confidence level (P < 0.05). After 24 and 72 h incubation, cell viability percentages of all experimental groups showed significant decrease according to the positive control cell culture. Fibroblastic cell viability percentages of silane and monomer treated fibre-reinforced groups were lower than the unreinforced group. Cell viability of monomer-treated groups displayed the lowest percentages. Elapsed incubation time decreased epithelial cell viability in silane-treated groups. Fibroblastic cell viability was not influenced by elapsed time except the unreinforced group.
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PMID:The effect of two fibre impregnation methods on the cytotoxicity of a glass and carbon fibre-reinforced acrylic resin denture base material on oral epithelial cells and fibroblasts. 1692 40

We assessed the biological response to several novel titanium alloys that have promising physical properties for biomedical applications. Four commercial titanium alloys [Super-TIX(R) 800, Super-TIX(R) 51AF, TIMETAL(R) 21SRx, and Ti-6Al-4V (ASTM grade 5)] and three experimental titanium alloys [Ti-13Cr-3Cu, Ti-1.5Si and Ti-1.5Si-5Cu] were tested. Specimens (n = 6; 5.0 x 5.0 x 3.0 mm(3)) were cast in a centrifugal casting machine using a MgO-based investment and polished to 600 grit, removing 250 mum from each surface. Commercially pure titanium (CP Ti: ASTM grade 2) and Teflon (polytetrafluoroethylene) were used as positive controls. The specimens were cleaned and disinfected, and then each cleaned specimen was placed in direct contact with Balb/c 3T3 fibroblasts for 72 h. The cytotoxicity [succinic dehydrogenase (SDH) activity] of the extracts was assessed using the MTT method. Cytotoxicity of the metals tested was not statistically different compared to the CP Ti and Teflon controls (p > 0.05). These novel titanium alloys pose cytotoxic risks no greater than many other commonly used alloys, including commercially pure titanium. The promising short-term biocompatibility of these Ti alloys is probably due to their excellent corrosion resistance under static conditions, even in biological environments.
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PMID:Initial cytotoxicity of novel titanium alloys. 1738 27

The prenylated flavanone 2'-4'-dihidroxy-5'-(1" '-dimethylallyl)-6-prenylpinocembrin) (6PP), isolated from the roots of Dalea elegans, shows antimicrobial activity. The aim of this study was to evaluate mitochondrial toxicity and antioxidant properties of 6PP. Addition of micromolar concentrations of 6PP to rat liver mitochondria, stimulated O2 uptake in state 4 and inhibited it in state 3 when malate-glutamate was the respiratory substrate, and inhibited O2 uptake in state 3 when succinate was the substrate. Highest concentration of 6PP also inhibited O2 uptake in state 4 in the latter case; in both conditions, respiratory control index values were decreased. This flavanone collapsed the mitochondrial membrane potential in a concentration-dependent manner. 6PP also inhibited F0F1-ATPase activity in coupled mitochondria and in submitochondrial particles. In the latter, this compound also inhibited NADH oxidase and succinate dehydrogenase activities. HEp-2 cells were incubated for 24 h with 6PP in presence or absence of 0.5% albumin. As measured by reduction of the mitochondrial-related probe MTT, in the albumin-free condition, 6PP was cytotoxic in a concentration-dependent manner; on the other hand, albumin decreased 6PP effect. In addition, in rat liver microsomes 6PP: (1) inhibited the enzymatic lipid peroxidation, (2) exhibited significant scavenging activity, measured by DPPH reduction assay and (3) demonstrated significant antioxidant activity by decreasing the reduction of Mo(VI) to Mo(V). We suggest that 6PP impairs the hepatic energy metabolism by acting as mitochondrial uncoupler and by inhibiting enzymatic activities linked to the respiratory chain. 6PP also exerts both antioxidant and antiradical activities. Due to its cytotoxicity, this molecule, and its future structure developments, can be considered as a potentially promising therapeutic agent, for instance in cancer chemotherapy.
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PMID:Mitochondrial toxicity and antioxidant activity of a prenylated flavonoid isolated from Dalea elegans. 1807 19

Repeated low-dose exposure to carbofuran exerts its neurotoxic effects by non-cholinergic mechanisms. Emerging evidence indicates that oxidative stress plays an important role in carbofuran neurotoxicity after sub-chronic exposure. The purpose of the present study is to evaluate the role of mitochondrial oxidative stress and dysfunction as a primary event responsible for neurotoxic effects observed after sub-chronic carbofuran exposure. Carbofuran was administered to rats at a dose of 1 mg/kg orally for a period of 28 days. There was a significant inhibition in the activity of acetylcholinesterase (66.6%) in brain samples after 28 days of carbofuran exposure. Mitochondrial respiratory chain functions were assessed in terms of MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) reduction and activity of succinate dehydrogenase in isolated mitochondria. It was observed that carbofuran exposure significantly inhibited MTT reduction (31%) and succinate dehydrogenase activity (57%). This was accompanied by decrease in low-molecular weight thiols (66.6%) and total thiols (37.4%) and an increase in lipid peroxidation (43.7%) in the mitochondria isolated from carbofuran-exposed rat brain. The changes in mitochondrial oxidative stress and functions were associated with impaired cognitive and motor functions in the animals exposed to carbofuran as compared to the control animals. Based on these results, it is clear that carbofuran exerts its neurotoxicity by impairing mitochondrial functions leading to oxidative stress and neurobehavioral deficits.
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PMID:Mitochondrial oxidative stress and dysfunction in rat brain induced by carbofuran exposure. 1834 May 26

The in vitro cytotoxic potential of yangambin was evaluated. Yangambin is a pharmacologically active furofuran lignan obtained from the leaves of Ocotea duckei. It is the major compound from the lignoids fraction. Yangambin presented low cytotoxicity in all in vitro models analyzed. Its cytotoxicity to murine macrophages was measured by the Trypan blue dye exclusion test and MTT reduction assay, resulting in high CC50 values of 187.0 microg/mL (383.3 microM) and 246.7 microg/mL (504.3 microM), respectively. The difference obtained in the inhibitory concentrations aforementioned can be explained, at least in part, by the different principles of the methods. While the MTT reduction assay evaluates the ability of yangambin to inhibit the activity of the mitochondrial enzyme succinate dehydrogenase, the Trypan blue dye exclusion test evaluates possible damages to the integrity of the cytoplasmic membrane which result in cell death. The capacity of yangambin to inhibit the sea urchin embryonic development showed that it has low antimitotic and teratogenic potential, once continued exposure of embryos to concentrations up to 500 microg/mL (1.025 microM) did not result in an inhibitory effect on the first egg cleavages. Such low in vitro cytotoxicity is correlated with the low acute toxicity previously studied. All these data, together with the various therapeutic properties of yangambin, make this lignan a promising one for a new drug.
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PMID:Yangambin cytotoxicity: a pharmacologically active lignan obtained from Ocotea duckei vattimo (Lauraceae). 1904 Jan 7


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