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:1.1.1.27 (lactate dehydrogenase)
29,211 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used the neutral red test, MTT assay and lactate dehydrogenase (LDH) release to compare the potential cytotoxicity of six surfactants belonging to different classes--three non-ionic surfactants (Triton x100, octylphenoxypolyethoxy alcohol, from Orion; Tween 60, polyoxyethylene (20) sorbitan monostearate, from ICI Speciality Chemicals; Tween 80, polyoxyethylene (20) sorbitan monolaurate, from Labosi), two anionic surfactants (Texapon K1298, sodium lauryl sulphate, from Henkel; Texapon N40, sodium laurylether sulphate, from Henkel) and one cationic surfactant (benzethonium chloride, from Siber Hegner)--on human fibroblast cultures. According to the LC50 (microg ml(-1)), the tested surfactants can be classified in the following order of increasing cytotoxicity: Tween 80 < Texapon N40 < Tween 60 < Texapon K1298 < Triton x100 < benzethonium chloride.
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PMID:Comparison of cytotoxicity of various surfactants tested on normal human fibroblast cultures using the neutral red test, MTT assay and LDH release. 1036 66

Vitamin Ds have been reported to have diverse effects on cell homeostasis, leading to suggestions that they have therapeutic applications extending beyond their traditional actions on the Ca2+/parathyroid/bone axis. As some of these potential indications carry an inherent risk of acute renal failure (ARF; eg, cancer chemotherapy and organ transplantation), the goal of this study was to assess whether vitamin Ds directly affect renal tubule injury responses. Cultured human proximal tubular (HK-2) cells were exposed to physiological or pharmacological doses of either calcitriol (D3) or a synthetic vitamin D2 analogue (19-nor) for 3 to 48 hours. Their impact on cell integrity (percent lactate dehydrogenase (LDH) release and tetrazolium dye MTT uptake) under basal conditions and during superimposed injuries (ATP depletion/Ca2+ ionophore or iron-mediated oxidant stress) were determined. As vitamin Ds can be anti-proliferative, cell outgrowth ([3H]thymidine uptake and crystal violet staining) was also tested. Finally, the action of D3 on in vivo ARF (glycerol-induced myoglobinuria) and isolated proximal tubule injury responses were assessed. D3 induced a rapid, dose-dependent increase in HK-2 susceptibility to both ATP-depletion/Ca2+-ionophore- and Fe-mediated attack without independently affecting cell integrity or proliferative responses. In contrast, D2 negatively affected only Fe toxicity and only after relatively prolonged exposure (48 hours). D3 dramatically potentiated in vivo ARF (two- to threefold increase in azotemia), suggesting potential in vivo relevance of the above HK-2 cell results. Proximal tubules, isolated from these glycerol-exposed mice, suggested that D3 can worsen tubule injury despite a parodoxic suppression of H2O2 production. In contrast, D3 had a mild negative impact on cellular energetics (depressed ATP/ADP ratios), and it accentuated plasma membrane phospholipid breakdown. The latter was observed in both glycerol-treated and control tubules, suggesting a primary role in the injury- potentiation effect of D3. Vitamins D(s) may directly, and differentially, increase proximal tubule cell susceptibility to superimposed attack. This property should be considered as new uses for these agents are defined.
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PMID:Calcitriol directly sensitizes renal tubular cells to ATP-depletion- and iron-mediated attack. 1036 17

Human adenocarcinoma cells of the line WiDr have been treated with 2 mM 5-aminolaevulinic acid (5-ALA) in the presence of 10% foetal calf serum. The treatment induces a linear accumulation of protoporphyrin IX (PpIX) for at least 7.5 h. After 7.5 h of incubation about 45% of the PpIX accumulated is cell-bound, while the rest is found in the medium (25%) or lost from the cells during washing with phosphate-buffered saline (30%). Exposure to white light at an intensity of 30 W/m2 for 18 min results in 95% reduction of clonogenicity in cells treated with 2 mM 5-ALA for 3.5 h. The enzymatic activities of enzymes located in cytosol (glyceraldehyde 3-phosphate dehydrogenase and lactate dehydrogenase) and lysosomes (acid phosphatase and beta-glucuronidase) are not influenced by a 5-ALA and light treatment inactivating about 35% of the cells. The MTT assay, which reflects mitochondrial dehydrogenase activity, but not succinate dehydrogenase, is partly inhibited by the same treatment. Treatment with 5-ALA in the absence of light increases O2 consumption by a factor of two, while the O2 consumption is inhibited when 5-ALA treatment is combined with exposure to light. In addition, 5-ALA and light exposure enhance accumulation of rhodamine 123 by 40% and reduce the intracellular ATP level by 25%. Confocal laser scanning microscopical analysis indicates granular perinuclear localization of the PpIX formed by 5-ALA treatment. In conclusion, photodynamic treatment using 5-ALA as a prodrug induces damage to mitochondrial function without inhibiting lysosomal and cytosolic marker enzymes.
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PMID:Photodynamically induced effects in colon carcinoma cells (WiDr) by endogenous photosensitizers generated by incubation with 5-aminolaevulinic acid. 1039 65

Extracellular iron, which is predominantly bound by transferrin, is present in low concentrations within alveolar structures, and concentrations are increased in various pulmonary disorders. Iron accumulation by cells can promote oxidative injury. However, the synthesis of ferritin stimulated by metal exposure for intracellular iron storage is normally protective. The cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta may alter iron metabolism by alveolar cells. In this study, we assessed the effects of TNF-alpha and IL-1beta on iron metabolism with a cell line with properties of type 2 alveolar epithelial cells (A549) exposed to non-transferrin-bound (NTBI; FeSO(4)) or transferrin-bound (TBI) iron. In addition, we assessed the cytotoxicity of these exposures by measuring the cell accumulation of malondialdehyde (MDA), a product of lipid peroxidation, and cell death (MTT assay and lactate dehydrogenase release). A549 cells treated with NTBI or TBI in concentrations up to 40 microM accumulated iron and synthesized predominantly L-type ferritin without accumulation of MDA or cell death. Treatment of A549 cells with TNF-alpha (20 ng) or IL-1beta (20 ng) decreased cell transferrin-receptor expression and induced synthesis of H-type ferritin. TNF-alpha and IL-1beta decreased the uptake of TBI; however, the uptake of NTBI was increased. Both cytokines enhanced total ferritin synthesis (H plus L types) in response to iron treatments due to enhanced synthesis of H-type ferritin. Coexposure to TNF-alpha and NTBI, but not to TBI, induced MDA accumulation and greater cytotoxicity (MTT and lactate dehydrogenase release) than TNF-alpha alone. These findings indicate that TNF-alpha and IL-1beta modulate iron uptake by A549 cells, with differing effects on TBI and NTBI, as well as on H-ferritin synthesis. Enhanced iron uptake induced by TNF-alpha and NTBI was also associated with increased cytotoxicity to A549 cells.
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PMID:Effects of TNF-alpha and IL-1beta on iron metabolism by A549 cells and influence on cytotoxicity. 1044 19

Hydrogen peroxide was cytotoxic to the small intestine epithelial cell line, IEC-6, as judged from an MTT assay and the release of lactate dehydrogenase. The glutathione S-transferase and thioredoxin reductase activities and SH content decreased dose-dependently with H2O2, but thioredoxin activity increased at low H2O2 concentrations. In addition, the increase in thioredoxin activity was time-dependent during the initial stages of oxidative stress. A reverse transcription-polymerase chain reaction (RT-PCR) amplification also showed that the mRNA content in IEC-6 cells increased time-dependently at 0.25 mM H2O2. These results indicate that cellular oxidative shock causes an increase in the activity of thioredoxin, which is involved in the defense mechanism against oxidative stress.
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PMID:Increase in thioredoxin activity of intestinal epithelial cells mediated by oxidative stress. 1051 9

The effect of (-)-(S)-2-[3,5-bis(1, 1-dimethylethyl)-4-hydroxyphenyl]-3-[3-[N-methyl-N-[2-(3, 4-methylenedioxyphenoxy)ethyl]amino]propyl]-1,3-thiazolidin- 4-one hydrogen fumarate (CP-060S), a novel Ca(2+) channel blocker, on hydrogen peroxide (H(2)O(2))-induced cytotoxicity was studied in cultured rat cardiac myocytes. The CP-060S effect was compared with that of CP-060R, an optical isomer of CP-060S with a less potent Ca(2+) channel blocking action than CP-060S. H(2)O(2) increased the release of lactate dehydrogenase from cardiac myocytes and decreased the formation of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) (MTT) formazan in cardiac myocytes (i.e., cytotoxic action). Both CP-060S (1 microM) and CP-060R (1 microM) attenuated to a similar extent the foregoing alterations induced by H(2)O(2). On the other hand, 1,3-dimethyl-2-thiourea (10 mM), a scavenger of both H(2)O(2) and hydroxyl radical, also attenuated the H(2)O(2)-induced cytotoxicity whereas diltiazem (10 microM) did not. In an experiment using electron spin resonance (ESR) with 5, 5-dimethyl-1-pyrroline N-oxide (DMPO), a spin-trapping agent, both CP-060S and CP-060R decreased the intensity of DMPO-hydroxyl radical signal concentration dependently. These results suggest that CP-060S protects cardiac myocytes from oxidative stress through its radical scavenging action.
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PMID:Effects of CP-060S, a novel Ca(2+) channel blocker, on oxidative stress in cultured cardiac myocytes. 1059 47

o-Hydroxyphenylacetaldehyde (o-HPA), the product of coumarin 3, 4-epoxide, was synthesized and its contribution to the hepatotoxic effects of coumarin in the rat was determined. The relative toxicity of coumarin and o-HPA were initially assessed in Chinese hamster ovary K1 (CHO K1) cells, a cell line that does not contain cytochrome P450. In CHO K1 cells, o-HPA-mediated toxicity greatly exceeded that of coumarin. CHO K1 cell viability, determined via the reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT), was decreased by 95 and 6% in cultures containing o-HPA and coumarin (4 mM), respectively. Coumarin and o-HPA were then incubated in metabolically competent primary rat hepatocyte cultures. Cell viability was determined via the reduction of MTT, and lactic dehydrogenase (LDH) release was used as a measure of cytotoxicity. Concentration-dependent decreases in cell viability and increased LDH release were observed using 0.2 to 0.8 mM o-HPA and coumarin, with coumarin being consistently less toxic than o-HPA. Cell viability was decreased by 11 and 50% at 0.5 mM coumarin or o-HPA, respectively. Hepatocyte LDH release increased 5-fold after a 6-h exposure to 0.8 mM o-HPA, corresponding to a greater than 90% loss of cell viability in these cultures. In contrast, 0.8 mM coumarin decreased cell viability by 60%, an effect likely due to the conversion of coumarin to coumarin epoxide and o-HPA. Furthermore, 3-hydroxycoumarin (0.8 mM), which is not a product of coumarin epoxidation, had no effect on cell viability or hepatocellular LDH release. These studies demonstrate that metabolically active rat hepatocytes convert coumarin into toxic metabolites, and strongly suggest that o-HPA and coumarin 3, 4-epoxide mediate the toxicity of coumarin in rodents in vivo.
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PMID:o-hydroxyphenylacetaldehyde is a hepatotoxic metabolite of coumarin. 1064 May 21

On the basis of reports that astrocytes play an important role in the neurotoxicity of trimethyltin (TMT), we investigated the sensitivity of astrocytes to TMT and compared it to triethyltin (TET), a neurotoxic analog with a different in vivo specificity. The gliotoxicity of these two compounds was further compared to that of tributyltin (TBT) and triphenyltin (TPT), two purportedly nonneurotoxic organotin compounds. The time and concentration components of organotin toxicity were determined by measuring lactate dehydrogenase (LDH) release and formazan production from dimethylthiazolyldiphenyltetrazolium bromide (MTT). A TMT concentration of 100 micromol/L did not elevate extracellular LDH until 48 h after exposure, while signs of toxicity were not seen at 72 h for concentrations less than 10 micromol/L. Extracellular LDH activity increased 24 h after exposure to concentrations of TET, TBT, and TPT as low as 2.5 micromol/L. TMT was the only organotin to produce a delayed cytotoxicity, requiring both higher concentrations and more time to produce discernible toxicity. In contrast with TBT and TPT, the toxicity of the two neurotoxic organotins (TMT and TET) produced an early increase in MTT reduction. The distinct pattern of toxicity for TMT does not explain its selective in vivo toxicity, but the lack of sensitivity of astrocytes to this organotin also does not rule out more subtle changes in these cells that could disrupt normal glial/neuronal interactions.
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PMID:Differential gliotoxicity of organotins. 1069 25

Neuronal apoptosis induced in cortical cultures by exposure to serum deprivation, staurosporine, nifedipine, or C2-ceramide was assayed by lactate dehydrogenase (LDH) release or inhibition of 3-(4, 5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) reduction. The protective effects of neurotrophin-4, Z-Val-Ala-Asp-fluoromethylketone (ZVAD), and cycloheximide against each insult were also assayed. The level of injury for each insult was similar whether determined by LDH release or inhibition of MTT reduction, but effects of anti-apoptotic agents were assay dependent. ZVAD and cycloheximide protected neurons from nifedipine-induced death, when assayed by LDH release, but not MTT reduction. In contrast, only cycloheximide attenuated C2-ceramide-induced LDH release, while ZVAD and cycloheximide actually enhanced the C2-ceramide induced inhibition of MTT reduction. Counting of trypan blue positive cells provided results consistent with values obtained using the LDH assay. These results indicate that both LDH release and MTT reduction accurately determine apoptotic death of neurons. However, the MTT assay does not always correctly quantify neuroprotective effects, this likely reflects differences in the point of the death pathway that the neuroprotective agents act. Therefore, while the MTT assay is of limited value in assessing the efficacy of neuroprotective strategies, it may provide information regarding whether specific anti-apoptotic agents act up or downstream of mitochondrial dysfunction.
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PMID:Comparison of the LDH and MTT assays for quantifying cell death: validity for neuronal apoptosis? 1072 Jun 79

The potential cytotoxic effects of the compounds 8-quinolinol, chloramine-T and natamycin have been studied in isolated pig hepatocytes. The relative cytotoxicity of these compounds was evaluated on the basis of the leakage of cytosolic lactate dehydrogenase (LDH), 3-(4,5 dimethyl)thiazol-2-yl,-2,5-diphenyl tetrazolium bromide (MTT) reduction by mitochondrial dehydrogenases, uptake of neutral red (NR) by cytosolic lysosomes, glutathion (GSH) depletion and oxidized glutathion (GSSG) efflux after 24 h exposure. Evaluation of the 20%, 50% and 80% reduced absorbance data obtained from the parameters NR20, NR50, and NR80, and MTT20, MTT50 and MTT80 enabled us to rank these compounds in decreasing order of cytotoxicity: 8-quinolinol > natamycin > chloramine-T. Also for the parameters LDH and GSH, chloramine-T appears to be less cytotoxic than natamycin and 8-quinolinol. Our study demonstrated that pig hepatocytes may be a useful model for examining cytotoxic events of drugs to be used in pigs, therefore avoiding possible extrapolation problems due to species differences.
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PMID:Cytotoxicity in pig hepatocytes induced by 8-quinolinol, chloramine-T and natamycin. 1074 41


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