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PubMed1990

[In vitro chemosensitivity test: succinate dehydrogenase inhibition (SDI) test].

The succinate dehydrogenase inhibition (SDI) test was used for determining chemosensitivity of various human tumors. This test was based on the correlation between the cellular succinate dehydrogenase activity as determined by 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT), and cell viability. The chemosensitivity varied in the tissue. Some factors are involved in the chemosensitivity, that is origin of a tumor, tissue differentiation and tissue DNA synthetic activity. This test is a convenient method for clinical use and provides important information about chemosensitivity.

Drug Screening Assays, Antitumor↗
PubMed1990

Effect in vitro of benthiocarb on rat brain succinate dehydrogenase.

Kinetic study of succinate dehydrogenase (SDH) was studied in the brain of albino rat to elucidate the interaction of benthiocarb, an organocarbamate with oxidative metabolism. The significant decrease in maximal velocity (Vmax) without appreciable change in Michaelis-Menten constant (Km) indicates that benthiocarb did not affect or interfere with succinate oriented sites on the enzyme and the inhibition is of a classical non-competitive type.

Animals↗
PubMedDate not supplied

Chemosensitivity testing of human lung cancer tissues using the succinate dehydrogenase inhibition test.

We examined the chemosensitivity of 57 primary lung cancer specimens to 9 antitumor drugs, using the succinate dehydrogenase inhibition (SDI) test. Average succinate dehydrogenase (SD) activity was reduced to less than 50% by cis-diaminedichloroplatinum (II) (DDP), cyclophosphamide (CPA), carboquone (CQ), mitomycin C (MMC) and adriamycin (ADM). The lung cancer cells were relatively resistant to pepleomycin (PEP), 5-fluorouracil (5 FU), vincristine (VCR) and vindesine (VDS). Small cell lung cancers, or early stage lung cancers, tended to be more sensitive to these antitumor drugs. However, differences in sensitivity with respect to either histology, staging or degree of differentiation were not statistically significant. Correlation of SD activity between 2 drugs was high among those which inhibit DNA synthesis (DDP, CPA, CQ or MMC), or between VCR and VDS (inhibitor of mitosis), however, the correlation between VDS and CPA, CQ or DDP was weak. The SDI test is a simple in vitro method readily available to aid in selecting drugs to treat patients with lung cancer.

Adult↗
PubMed1989

[Hyperthermo-chemo-radiotherapy of patients with carcinoma of the esophagus and prediction of the clinical remedial value using the in vitro succinate dehydrogenase inhibition test].

Hyperthermia combined with irradiation and chemotherapy was prescribed for patients with resectable (n = 88) and unresectable (n = 36) carcinoma of the esophagus. The histopathological effectiveness, and the long term results were compared between two groups of patients treated with hyperthermo-chemo-radiotherapy (HCR therapy) and those treated with chemoradiotherapy (CR therapy). A correlation between the hyperthermia sensitivity test, using the in vitro succinate dehydrogenase inhibition test, and the clinical remedial value was also examined in malignant tissues from 47 patients with esophageal cancer, and treated with HCR therapy. In the resected cases, preoperative HCR therapy resulted in a significantly higher histopathological effectiveness rate (69%) compared with that in cases treated by CR therapy (48%) (P less than 0.05). The long term results of patients with both resectable and unresectable carcinoma, given HCR therapy were significantly better than those given CR therapy (P less than 0.05). On the other hand, the clinical remedial value, determined radiographically showed a correlation rate of 77% to the hyperthermia sensitivity test. Thus, the HCR therapy resulted in not only a higher histopathological effectiveness rate but also a significantly longer survival without severe side effects, and this hyperthermia sensitivity test using the succinate dehydrogenase inhibition test facilitates prediction of the outcome of the HCR therapy.

Antineoplastic Agents↗
PubMed1989

[5-Alkyl(C19-C25) resorcinols as regulators of succinate and NAD-dependent substrate oxidation by mitochondria].

The effect of 5-n-alkyl(C19-C25) resorcinols isolated from Azotobacter chroococcum on the oxidation of succinate and NAD-dependent substrates (glutamate, alpha-ketoglutarate, malate, pyruvate) by rat liver mitochondria was studied, using the polarographic technique. With succinate, the above resorcinol lipids activated to some extent the 2,4-dinitrophenol-decoupled mitochondrial respiration, but markedly suppressed it (up to 95%) in the presence of NAD-dependent substrates. The activating and inhibiting effects correlated with the resorcinol lipid/mitochondrial proteins ratio and were observed, when the lipid concentration in the incubation mixture ranged from 2.4.10(-4) to 6.0.10(-4) M. The most striking inhibiting effect was observed with alpha-ketoglutarate as substrate. The results obtained suggest that 5-n-alkyl(C19-C25) resorcinols should be regarded as rotenone type regulators of cell respiration.

Animals↗
PubMed1989

The development of activity of succinate dehydrogenase (EC.1.3.99.1) in the areas of the nigro-striatal pathway during the ontogenesis of a pig.

The development of activity of succinate dehydrogenase was investigated by histochemical methods under the light and electron microscopes and also by biochemical methods. The studies were carried out in the areas of the nigro-striatal pathways of 7 foetal groups, two day-old piglets, three week-old piglets and adult pigs. It was demonstrated that the activity of succinate dehydrogenase appeared first in foetuses of about 86 days (180 mm). The highest activity in prenatal development appeared just before birth in about 112 days old (260 mm) foetuses. After birth in 2 day-old piglets the activity of the examined enzyme decreases, while in 3 week-old it increases however not reaching the activity level observed in adult pigs.

Aging↗
PubMed1989

Enzymes of carbohydrate metabolism in fast-growing Rhizobium grown on hexoses or succinate.

Enzymatic evidence supports that succinate mediates repression of hexose-catabolising enzymes in fast-growing Rhizobium sp. (Cicer arietinum). Enzymes of the Embden-Myerhof-Parnas, Entner-Doudoroff and pentose phosphate pathways were found present in hexose-grown cells but not in succinate-grown cells. These however could be induced by the presence of hexoses.

Carbohydrate Metabolism↗
PubMed1989

Comparison of the subrenal capsule assay and succinate dehydrogenase inhibition test.

Fresh surgical explants of solid tumors obtained from 50 patients were tested against the same chemotherapeutic agents in both the in vivo subrenal capsule (SRC) assay and the in vitro succinate dehydrogenase inhibition (SDI) test. Control growth adequate to meet evaluable assay criteria was obtained in 36 of 50 tumors tested in the SRC assay (72.0%). In the SDI test, 46 of 50 tumors were evaluable (92.0%). Correlations between the two test systems were dependent upon the activity criteria established for each system. With activity criteria set at current drug screening levels as a change of less than or equal to -2.0 in modified PAPAN score (S) for the SRC and an inhibition of greater than or equal to 50.0% in succinate dehydrogenase activity (SD) for the SDI, 12.5% of the drugs tested were active in the SRC and 22.3% were active in the SDI. Correlations of tumor response between the two test systems were 31.7% for sensitive (13/41) and 95.1% for resistant (98/103).

Antineoplastic Agents↗
PubMed1988

Cytochemical examinations of Ca, cytochrome oxidase and succinate dehydrogenase enzymes in endometrium carcinomatous tissue after high dose progestogen treatment.

Authors investigated the effect of high dose progestogen in endometrium carcinomatous tissue on the distribution of calcium depots, as well as on the chemically detectable activity of cytochrome oxidase and succinate dehydrogenase. By means of electron microscopy no characteristic destructive effect could unequivocally be demonstrated; cytochemical examinations showed a very significant activity of cytochrome oxidase, and in the activity of succinate dehydrogenase a considerable decrease was observed. They found distributional alterations in plasma membranes, in mitochondria and in the ground cytoplasm. Changes between Ca depots are thought to have an effect on tumour cells also in a protective way, and can be regarded as compensatory phenomena.

Antineoplastic Agents↗
PubMed1985

Electron paramagnetic resonance studies of mammalian succinate dehydrogenase. Detection of the tetranuclear cluster S2.

Electron paramagnetic resonance studies of Complex II from the mitochondrial respiratory chain and soluble preparations of succinate dehydrogenase have, for the first time, identified a signal arising from a [4Fe-4S]1+ cluster, S2, in dithionite-reduced samples. Redox titrations, monitored by electron paramagnetic resonance spectroscopy demonstrate that this signal appears at the same midpoint potential as the enhancement of the spin relaxation properties of the [2Fe-2S]1+ center, S1, in both Complex II and reconstitutively active soluble enzyme. The results complement recent magnetic circular dichroism studies of succinate dehydrogenase (Johnson, M. K., Morningstar, J. E., Bennett, D. E., Ackrell, B. A. C., and Kearney, E. B. (1985) J. Biol. Chem. 260, 7368-7378) which assigned cluster S2 as a [4Fe-4S]2+,1+ center and provide evidence for spin interaction between the paramagnetic reduced forms of centers S1 and S2.

Animals↗
PubMedDate not supplied

[The activity of alpha-ketoglutarate dehydrogenase and succinate dehydrogenase in the liver of the developing chick embryo. The relation to the rate of the tricarboxylic acid cycle].

Succinate dehydrogenase and alpha-ketoglutarate dehydrogenase activities were determined in the liver of chick embryos and one and two day old chickens. The succinate dehydrogenase activity remained unchanged throughout development. The alpha-ketoglutarate dehydrogenase activity decreased by the end of embryogenesis and increased after hatching. The alpha-ketoglutarate dehydrogenase activity as an index of rate of the tricarboxylic acid cycle is discussed.

Animals↗
PubMed1987

Malic enzyme, malate dehydrogenase, fumarate reductase and succinate dehydrogenase in the larvae of Taenia crassiceps (Zeder, 1800).

Malate dehydrogenase, malic enzyme, succinate dehydrogenase, and fumarate reductase activities have been studied in the cytoplasm and mitochondria of Taenia crassiceps larvae. The results show that these larvae contain enzymes for anaerobic acquisition of energy with terminal fumarate reductase, but some facts, as the high ratio of succinate dehydrogenase activity to fumarate reductase activity and the low proportion of fumarate reductase in the whole NADH oxidase activity in mitochondria, suggest that aerobic processes are also involved in the energy acquisition in this parasite.

Aerobiosis↗
PubMed1987

[Effect of short-term exposure to ash from electric power plants on histochemical reactions of succinate dehydrogenase and lactate dehydrogenase in the lungs of experimental animals].

Histochemical studies of the activity of succinic dehydrogenase (SDH) and lactic dehydrogenase (LDH) in the pulmonary tissue of experimental animals which were given four coal ashes issued from different thermal-electric power stations: group VII--from the thermal-electric power station Siekierki (Warsaw), group VIII--from Wrocław, group IX--from Leg (Cracow) and group XI--from Lódź, were carried out. In particular ash samples the content of trace elements and free silica was determined. The studies yield the following conclusions: 1. The activity of succinic dehydrogenase (SDH) and lactic dehydrogenase (LDH) was changed in the respiratory tract and pulmonary alveoli as a result of the electroenergetic ashes applied. 2. Changes in cytoenzymatic reactions of SDH and LDH vary with the type of ash applied. The greatest changes were found in group XI where the ashes contained almost doubled amount of such elements as Mn, Zn, Pb, Cu. 3. SDH exhibited a greater sensitivity to the effects of electroenergetic ashes, as compared to LDH. 4. Changes in the activity of the test SDH and LDH enzymes indicate disorders in oxydoreductory processes of cells.

Aerosols↗
PubMedDate not supplied

[The role of succinic acid in neuron reaction to synaptic activation].

It has been shown on Retzius neuron of the leech that after preintroduction of sodium succinate the reaction to synaptic stimulation expressed in increased frequency of the impulse activity proceeds more intensively than in the norm. In connection with the fact that against the background of succinate effect reaction to acetylcholine increases it is suggested that this very mediator is responsible for slower decrease of the impulse activity frequency at synaptic activation.

Acetylcholine↗
PubMed1985

Radioimmunoassay for phorbol esters using rabbit antisera against phorbol succinate.

The phorbol nucleus was succinylated and then conjugated to bovine albumin using dicyclohexylcarbodiimide. Rabbits given injections of the conjugate developed antibodies which rose in titer progressively with repeated immunization. By the ninth bleeding, the binding of one antiserum, diluted 1:15,000, was saturated with about 10 nM [3H]phorbol-12,13-dibutyrate [( 3H]-PDBU) and had an average association constant, Ka, of 2.6 X 10(8) M-1. The serological specificity of the antisera was characterized by examining the inhibition of the [3H]PDBU-anti-phorbol succinate immune system by 18 phorbol-related compounds. The specificities of antibodies from two rabbits tested in detail were qualitatively similar. The rank order of inhibitory activity for certain phorbol-related compounds was PDBU [concentration of inhibitor required to give 50% inhibition of PDBU binding (IC50) = 7.6 nM] = phorbol-13-acetate [IC50 = 8.2 nM] greater than phorbol-12,13-dibenzoate greater than 4-beta-phorbol [IC50 = 124 nM] greater than or equal to phorbol-12,13-diacetate greater than or equal to phorbol-12-myristate-13-acetate [IC50 = 184 nM] greater than phorbol-13,20-diacetate greater than phorbol-12-acetate [IC50 = 2300 nM]. The following compounds showed no detectable serological activity: mezerein, 4-0-methylphorbol-12-myristate-13-acetate, ingenol, 4-alpha-phorbol, teleocidin B, and dihydroteleocidin B. These and other results indicated that the 4-beta-phorbol nucleus was required for serological activity, that esterification of the C-13 position with benzoate, acetate, or butyrate enhanced the immunoreactivity of 4-beta-phorbol, and that among the phorbol-related compounds examined there was no direct relationship between serological activity and biological potency as tumor promoters. Using the [3H]PDBU-anti-phorbol succinate immune system, we measured the concentrations of immunoreactive phorbol-related material in crude mixtures such as croton oil and performed pharmacokinetic studies in rats given PDBU s.c.

Animals↗
PubMed1985

Changes in succinic dehydrogenase activity in the central nervous system of mice during morphine dependence development, withdrawal and naloxone treatment.

The possible role of succinic dehydrogenase (SD) in producing physical dependence to morphine by affecting tissue respiration was investigated in Swiss albino mice during the development of morphine tolerance through a period of addiction and naloxone withdrawal therapy. Tolerance and physical dependence were induced by injecting the mice with morphine sulfate subcutaneously at 8-hour intervals, increasing the dose from 10 mg/kg BW every 24 h for 15 days. The animals were considered to be addicted when they were able to tolerate an otherwise lethal dose of 150 mg/kg 3 times a day. Results indicated that succinic dehydrogenase was inhibited throughout the 15-day period of morphine administration and that this effect was greatest in tolerant animals. Increasing the dose and duration of treatment did not cause further decreases in enzyme activity; instead, after 15 days levels of enzyme activity increased in addicted animals compared with tolerant mice. Furthermore, morphine abstinence for 2 days, markedly increased the levels of SD activity, while 6 days of abstinence had little effect. Naloxone withdrawal at each stage was associated with increased SD activity, but the increase was significant only in tolerant mice.

Animals↗
PubMed1977

Induction of tumors in mice with the herbicide succinic acid 2,2-dimethylhydrazide.

A solution of 2% succinic acid 2,2-dimethylhydrazide was given continuously in the drinking water of 6-week-old randomly bred albino mice for the remainder of their lives. The treatment gave rise to tumors of blood vessels, lungs, and kidneys. The tumor incidences in these tissues in the controls were 6, 18, and 0%, whereas in the treated groups the corresponding tumor incidences were 73, 73, and 5%. Light microscopic examination revealed typical angiomas and angiosarcomas of blood vessels, adenomas and adenocarcinomas of lungs, and adenomas of kidneys. The study thus demonstrates the tumorigenicity of the herbicide, succinic acid 2,2-dimethylhydrazide. Since the residues of this chemical occur in fruit, the human population is exposed to it. The environmental implication of this finding and the fact that the hydrazines as a class have tumorigenic properties are discussed.

Adenocarcinoma↗