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PubMed1957

An integrated morphological and biochemical study of a purified preparation of the succinate and DPNH oxidase system.

Electron micrographs of a purified succinate and DPNH oxidase system prepared from heart muscle reveal that it has a vesicular appearance and is membranous in nature. In keeping with its vesicular appearance is the fact that light scattering by this preparation shows marked changes as the molarity of the suspending medium is altered. Treatment of this preparation with 0.5 per cent deoxycholate solutions removes a large part of the lipide material, which comprises almost half of the dry weight of the preparation. The residue, which still contains the "core" of the cytochrome electron transmitter system, as shown by spectroscopic and enzymatic experiments, is still structured and is membranous in morphological appearance. It is concluded that the enzyme preparation is largely composed of fragmented mitochondrial membranes, and some of the consequences of the localization of the succinate and DPNH oxidase systems in or on these membranes are discussed.

Cytochromes↗
PubMed1993

Inhibition of membrane-bound succinate dehydrogenase by fluorescamine.

Fluorescamine rapidly inactivated membrane-bound succinate dehydrogenase. The inhibition of the enzyme by this reagent was prevented by succinate and malonate, suggesting that the group modified by fluorescamine was located at the active site. The modification of the active site sulfhydryl group by 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) did not alter the inhibitory action of fluorescamine. However, the protective effect of malonate against fluorescamine inhibition was abolished in the enzyme modified at the thiol.

Animals↗
PubMed1986

Rapid redox equilibrium between the mitochondrial Q pool and cytochrome b during triphasic reduction of cytochrome b by succinate.

The reliability of monitoring the redox reactions of cytochrome b using the different wavelengths employed by different authors has been reexamined. It was found that 562-575 nm is suitable in succinate: cytochrome c reductase but not in mitochondria, in which case 562-540 nm is a better pair. Direct optical measurements of the redox reaction kinetics of the mitochondrial Q pool using a commercial dual-wavelength spectrophotometer are possible when succinate is used as the electron donor. Using the correct wavelength pair, and with malonate to slow down the electron input, the reduction course of cytochrome b was still triphasic but a plateau or a turn replaced the oxidation phase previously reported by several authors. At the same time, the reduction course of the Q pool was also triphasic, and in perfect match with that of cytochrome b. Destruction of the Rieske iron-sulfur cluster by British anti-Lewisite (BAL) + O2 treatment or prereduction of the high-potential components made the reduction of both Q and b monophasic. The plot of log (Q/QH2) against log (b3+/b2+) gave a straight line with an n value of 1.7 for cytochrome b at pH 7.4. This n value rose to 2.0 at pH 6.5 and dropped to 1.4 at pH 8.5. On the other hand, the mid-point potential of cytochrome b relative to that of the Q pool remained essentially unchanged between pH 6.5 and 8.4. BAL treatment had a small effect on the midpoint potential of cytochrome b relative to that of the Q pool and had no effect on the n value. Addition of quinone homologues and analogues extended the plateau phase in the reduction of cytochrome b, but exogenous quinones did not equilibrate rapidly with cytochrome b. It was concluded that the appearance of the plateau between the two reduction phases of Q and b is caused by the rapid delivery of electrons to the high-potential components of the respiratory chain as envisaged in the Q cycle; the unexpected n value for cytochrome b suggests a concerted reduction by QH2 of two species of cytochromes b-562.

Animals↗
PubMed1964

COENZYME Q: REVERSAL OF INHIBITION OF SUCCINATE CYTOCHROME C REDUCTASE BY LIPOPHILIC COMPOUNDS.

The activity of a particulate succinate cytochrome c reductase is inhibited by antimycin, 2-heptyl-4-hydroxyquinoline-N-oxide, 2-(9-cyclohexyl-n-nonyl)-3-hydroxy-1,4naphthoquinone and thenoyltrifluoroacetone. The ratio of antimycin A (required for complete inhibition) to the molar content of the cytochrome b of the reductase is approximately 0.5 in contrast to the reported value of 1.0 or higher for succinate oxidase preparations. However, the degreeof inhibition by antimycin is dependent on the exogenous coenzyme Q (ubiquinone) present. Indeed, the inhibition from any of these compounds is competitively reversed by exogenous coenzyme Q in the system.

Antimycin A↗
PubMed1982

Succinate dehydrogenase mutant of Rhizobium meliloti.

A succinate dehydrogenase mutant strain of Rhizobium meliloti was isolated after nitrosoguanidine mutagenesis. It failed to grow on succinate, glutamate, acetate, pyruvate, or arabinose but grew on glucose, sucrose, fructose, and other carbohydrates. The mutant strain showed delayed nodulation of lucerne plants, and the nodules were white and ineffective. A spontaneous revertant strain of normal growth phenotype induced red and effective nodules.

Carbohydrate Metabolism↗
PubMed1986

Cortisol succinate is slowly hydrolysed in organ cultures of porcine articular tissues and is not equivalent to cortisol.

The pro-drug cortisol succinate is frequently used as a substitute for cortisol in organ cultures. We found, however, that in Dulbecco's modified Eagle's medium the time taken for the ester to undergo 50 per cent hydrolysis (t1/2) to cortisol was 75 h. When 15 per cent heat-inactivated normal rabbit serum was present t1/2 decreased to 47 h, but the rate of hydrolysis was not further increased in the presence of porcine articular cartilage or minced synovial tissue. When frozen and thawed synovium was present t1/2 decreased to 33 h, presumably due to the release of carboxyl-esterases from the disrupted cells. The level of tetrahydrocortisol was low in all of the cultures. The slow hydrolysis of cortisol succinate resulted in the exposure of the tissues to undesirable fluctuations in the concentration of active hormone, which decreased to low levels at each medium change. Thus, in co-cultures of porcine synovium and articular cartilage, cortisol had a greater inhibitory effect than cortisol succinate on the breakdown of cartilage matrix caused by synovial tissue.

Animals↗
PubMed1976

A double-blind comparison of loxapine succinate and trifluoperazine in newly admitted schizophrenic patients.

A study was conducted evaluating the efficacy of loxapine succinate in newly admitted schizophrenic patients through a four-week double-blind comparison with trifluoperazine. Twenty-four patients received between 40 and 80 mg loxapine succinate daily and 19 patients received between 20 and 50 mg trifluoperazine daily. The two groups showed comparable significant improvement on the BPRS and CGI. The discharge and termination rates of the two groups were not significantly different and the incidence and severity of side effects, most frequently extrapyramidal signs, were similar in both groups. Loxapine succinate was judged to be an effective treatment for newly admitted schizophrenic patients.

Adolescent↗
PubMed1978

Ditheophylline succinate: transfer of theophylline across everted rat intestinal sacs.

The cumulative theophylline transfer rate across 10-cm everted rat intestinal sacs incubated at 37 degrees in pH 7.4 Krebs phosphate buffer was determined. A suspension of ditheophylline succinate ( a potential prodrug of theophylline) and a solution of theophylline at equimolar concentration were evaluated to determine the magnitude of the difference between the cumulative theophylline transfer rates from the two preparations. A linear concentration dependency for the rate across the intestinal wall was evidenced. The theophylline formation rate from ditheophylline succinate suspended in pH 7.4 Krebs buffer at 37 degrees followed apparent zero-order kinetics. The observed difference (fourfold) between the cumulative transfer rates estimated for the theophylline solution and the ditheophylline succinate suspention was attributed to the prevailing theophylline concentration in the mucosal solutions. The biopharmaceutical implication of these observations are discussed.

Animals↗
PubMed1982

Ontogeny and distribution of specific succinic semialdehyde reductase apoenzyme in the rat brain.

The ontogeny and distribution in rat brain of specific succinic semialdehyde reductase is described. This enzyme is probably responsible for the synthesis of gamma-hydroxybutyrate in brain. The highest activities and levels of apoenzyme are found in cerebellum, olfactory bulb, septum and median hypothalamus. During neonatal development, the enzyme activity remains stable at least until 63 days of age. As the levels of other enzymes of the GABA shunt pathway increase during this same period, this result indicates that there is a relative decrease in the reductive pathway of succinic semialdehyde catabolism during development leading to gamma-hydroxybutyrate synthesis, compared to the oxidative pathway leading to succinate.

Animals↗
PubMed1985

Inhibitory effects of intravenous chloramphenicol sodium succinate on the disposition of phenylbutazone in horses.

The effects of i.v. chloramphenicol sodium succinate on the pharmacokinetics of i.v. phenylbutazone in six healthy adult horses were investigated. Administration of chloramphenicol sodium succinate to mares reduced mean (+/- SD) phenylbutazone clearance from 0.600 +/- 0.222 to 0.339 +/- 0.123 ml/min per kg and increased mean (+/- SD) half life from 244 +/- 59.8 to 371 +/- 80.8 min and mean residence time from 333 +/- 86.2 to 533 +/- 124 min. The mean steady-state volume of distribution of phenylbutazone was unchanged, with mean (+/- SD) values of 187 +/- 28.9 ml/kg in control animals and 170 +/- 32.4 ml/kg after chloramphenicol sodium succinate.

Animals↗
PubMed2006

Effect of beta-blocker therapy on left atrial function in patients with heart failure: comparison of metoprolol succinate with carvedilol.

OBJECTIVE: We aimed to compare the effects of carvedilol and metoprolol succinate on left atrial (LA) function in patients with chronic heart failure. METHODS: Thirty three patients (6 females, 27 males) who had not received beta blocker treatment previously and whose left ventricular ejection fraction was below 40% were included in this study. LA volumes were measured echocardiographically just before the time of mitral valve opening (V (max)), onset of atrial systole (p-wave at the electrocardiography = V (p)) and mitral valve closure (V (min)) according to the biplane area length method at baseline and in the 3rd month after the administration of beta blockers. NT-proBNP level was measured at the beginning and in the third month of beta blocker treatment. The first group was given carvedilol 6.25 mg/day, the second group was given 12.5 mg/day metoprolol succinate and it was increased to the tolerable maximal dose. RESULTS: LA diameter and LA V (max), V (p), V (min) decreased significantly both in carvedilol group and metoprolol group after beta blocker theraphy (P < 0.01, : P < 0.01, : P < 0.05, : P < 0.05: for metoprolol, P < 0.001, P < 0.01, P < 0.01, P < 0.01 for carvedilol). But it was increased in conduit volume (P < 0.05 for two groups). LA-passive emptying fraction, LA-active emptying fraction and reservoir fraction were no significant differences both in carvedilol group and metoprolol group after beta blocker theraphy. NT-proBNP levels were found to decrease significantly in both groups after beta blocker treatment (P < 0.001).: CONCLUSION: Our findings indicate that beta blocker treatment leads to a decrease in LA diameters and volumes, and metoprolol succinate and carvedilol had similar effects on this decrease.

Adrenergic beta-Antagonists↗
PubMed1988

Effect of alpha tocopheryl succinate on cyclic AMP-dependent protein kinase activity in murine B-16 melanoma cells in culture.

d-Alpha tocopheryl succinate (vitamin E succinate), which inhibited growth and survival, and induced differentiation in murine B-16 melanoma cells in culture, increased adenosine 3',5'cyclic monophosphate-(cAMP)-dependent protein kinase (PK) activity without increasing the cellular cAMP level. Prostaglandin (PG)A2, which produced changes in melanoma cells similar to those produced by vitamin E succinate, also increased cAMP-dependent PK activity without changing the intracellular level of cAMP.

Animals↗
PubMed1978

The effect of estriol succinate therapy on plasma renin activity and urinary aldosterone in postmenopausal women.

The effects of estriol succinate (Synapause, 2 mg daily) on the renin-aldosterone system and blood pressure (RR) were studied in 14 postmenopausal women after bilateral oophorectomy. Plasma renin activity (PRA) and daily urinary aldosterone excretion (dU-Ald) were determined 1 mth after the operation and before estrogen treatment, at the end of 2 mth therapy, and, for the third time, 2 mth after the termination of treatment with the drug. No changes in PRA, dU-Ald or RR were found in normotensive women, or in 3 women with hypertension in this group. Another group of 11 postmenopausal women was investigated after long-term estriol succinate therapy, which had lasted for 5-8 yr after oophorectomy. PRA, dU-Ald and RR were measured during treatment and 2 mth after terminating the therapy. No changes were found either in hormone differences in the mean levels of PRA or dU-Ald. The results suggest that estriol succinate is devoid of general harmful effects on the renin-aldosterone system during postmenopausal therapy for climacteric symptoms.

Aldosterone↗
PubMed1978

Serum oestrone, oestradiol and oestriol concentrations during oral oestradiol valerate and oestriol succinate therapy in ovariectomized women.

Serum oestrone, oestradiol and oestriol concentrations were investigated during oral treatment with oestradiol valerate and oestriol succinate in ovariectomized women. The dosages used were 1 mg oestradiol valerate in the morning and 2 mg oestriol succinate in the evening of the first day and 2 mg oestradiol valerate in the morning of the second day of treatment. The other group of patients received the same therapy in reverse order. The variation in the serum oestrone and oestradiol concentrations with a daily dose of 1 or 2 mg of oestradiol valerate were considerable. 2 mg oestriol succinate caused a fairly small elevation of serum oestriol concentration. In both treatment groups the quotient E3/(E2 + E1) was similar to that found at the 6-7th day and in the middle of the normal menstrual cycle, the quotient E1/(E2 + E3) was somewhat higher than during normal cycle.

Castration↗
PubMed1991

Effect of vitamin E succinate and a cAMP-stimulating agent on the expression of c-myc and N-myc and H-ras in murine neuroblastoma cells.

D-Alpha-tocopheryl succinate (vitamin E succinate) at a concentration of 11.3 microM inhibited growth and reduced the expression of c-myc, N-myc and H-ras specific mRNAs in murine neuroblastoma cells (NBP2) in culture. R020-1724 [4-(3-butoxy-4-methoxybenzyl)-2- imidazolidinone], an inhibitor of cyclic AMP phosphodiesterase, also inhibited growth and reduced the expression of these oncogenes. Vitamin E succinate treatment caused the formation of two c-myc related transcript of 1.9 and 3.7 kb; however, R020-1724 treatment did not. These results suggest that the inhibition of growth is sufficient to reduce the expression of c-myc, N-myc and H-ras in NB cells in culture, but it is not sufficient to produce two c-myc related transcripts.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Biokinetics in humans of RRR-alpha-tocopherol: the free phenol, acetate ester, and succinate ester forms of vitamin E.

The bioavailability of RRR-alpha-tocopherol from the oral administration of RRR-alpha-tocopherol itself and its acetate and succinate esters was determined in healthy human subjects. Venous blood samples were withdrawn periodically over a 51-h period following oral administration of a gelatin capsule containing an equimolar mixture of RRR-alpha-tocopherol and RRR-alpha-tocopheryl acetate. In a second study, subjects received a capsule containing an equimolar mixture of RRR-alpha-tocopheryl acetate and RRR-alpha-tocopheryl succinate. In Study 1, RRR-alpha-tocopherol was absorbed at similar rates from both the free phenol, and the acetate ester and maximum plasma levels occurred at 12 h in most subjects. The extent of absorption of RRR-alpha-tocopherol varied considerably between subjects in absolute terms, but the relative absorption from the two forms was remarkably consistent, and a ratio of 1.0 was found for parameters of relative bioavailability in plasma. The concentration of RRR-alpha-tocopherol from each form was maximal at approximately 27 h in red blood cells and, as seen with the plasma data, there was a large interindividual variability. In Study 2, there was no significant difference in the extent of absorption of RRR-alpha-tocopherol from the acetate ester and the succinate ester, although there was an apparently higher initial rate of absorption from the acetate ester.

Administration, Oral↗
PubMed2006

Intravitreal prednisolone sodium succinate reduces diabetic macular edema without intraocular pressure rise.

PURPOSE: To evaluate the six-month results of patients treated with intravitreal prednisolone sodium succinate injections for persistent diabetic macular edema. DESIGN: Retrospective, noncontrolled, clinical case series. METHODS: Nineteen eyes had intravitreal injections with prednisolone sodium succinate. Need for retreatment was based on fluorescein angiographic or optical coherence tomography evidence of persisting macular edema. RESULTS: Mean visual acuity at six weeks, three months, and six months after injection was significantly better than the mean preoperative visual acuity (P = .015, P = .004, and P = .031, respectively). In none of the studied eyes intraocular pressure exceeded 22 mm Hg. No other adverse events, such as endophthalmitis or retinal detachment, occurred. CONCLUSIONS: In this small pilot study, mean visual acuity improvement was statistically significant up to six months postoperatively. Current results suggest that intravitreal injection of the solution of prednisolone sodium succinate may be a safe and good alternative in eyes with macular edema.

Aged↗
PubMed1984

Purification and properties of succinic oxidase factor, an extracellular product of Staphylococcus aureus.

Mitochondrial respiration can be inhibited in vitro by a complex of exotoxins elaborated by Staphylococcus aureus. This complex, designated Succinic Oxidase Factor, consists of two components, one of which (A) has a molecular weight of 75,000, is heat-stable, and interferes with cytochrome c oxidase and the other (B) has a molecular weight of 42,000, is heat-labile, and interferes with succinate-cytochrome c reductase. Each component can be separated by Sephadex G200 chromatography and purified by isoelectric focussing. Component A focussed at pH 3.4 and component B focussed at pH 4.5. Antibody prepared in rabbits to Succinic Oxidase Factor could neutralise the biological activities of each component separately or the whole complex and could react serologically with each component in an agar precipitation test.

Animals↗