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PubMed1993

Inhibition of human oral squamous carcinoma cell (SCC-25) proliferation by prostaglandin E2 and vitamin E succinate.

The primary objective of this investigation was to study the effect of D-alpha-tocopherol acid succinate (vitamin E succinate) and prostaglandin E2 (PGE2), individually and in combination, on the proliferation of human tongue squamous carcinoma cells (SCC-25) in vitro. Test compounds in varying concentrations were incubated with cells in serum-free Dulbecco's Modified Eagle's Medium-Ham's F-12 Medium (50:50), supplemented with 0.1% albumin for sixteen hours. Cell proliferation was measured by the incorporation of [3H] thymidine in acid-insoluble material (i.e. DNA). Prostaglandin E2 and vitamin E succinate, individually at 10(-9)-10(-6) M, caused significant dose-dependent inhibition in DNA synthesis. A combined dose of each compound at 10(-5) M resulted in significant additive inhibition which averaged 43.53% (p < 0.005). Addition of indomethacin (INDO) to cell cultures induced significant dose-dependent stimulation in DNA synthesis. Hence, we might suggest that the overall potential of vitamin E in controlling malignant cell proliferation in vivo could be due to its own effect combined with that of endogenous PGs which are normally produced in excessive amounts by malignant cells.

Carcinoma, Squamous Cell↗
PubMed2004

Intensive swimming exercise-induced oxidative stress and reproductive dysfunction in male wistar rats: protective role of alpha-tocopherol succinate.

In the present study, 30 male rats (age 3 mos, Wt 128.6 +/- 3.7 g) were randomly divided into Control group (CG), Experimental group (EG), and Supplemented group (SG), 10 per group. An exercise protocol (3 hrs swimming per day, 5 days a week for 4 weeks) was followed in EG and SG, with no exercise in CG. In SG, alpha-tocopherol succinate was injected sub-cutaneously at a dose of 50 mg x kg(- 1) per body weight per day. After 4 weeks of exercise, significant diminutions (p < 0.05) were noted in somatic indices of testes and accessory sex organs; seminiferous tubuler diameter (STD); testicular (delta (5), 3 beta-hydroxysteroid dehydrogenase delta(5), 3 beta-HSD), 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activities; plasma levels of testosterone (T), luteinizing hormone (LH); preleptotine spermatocytes (pLSc), mid-pachytene spermatocytes (mPSc), and Stage 7 spermatids (7 Sd); testicular alpha-tocopherol and glutathione (GSH) content; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione-s-transferase (GST) activities in EG when compared to CG. Moreover, a significant elevation (p < 0.05) in malondialdehyde (MDA) was found in testes of EG compared to CG. No significant alteration was noted in body weight among the groups. Co-administration of alpha-tocopherol succinate restored the above parameters. Intensive swimming exercise-induced oxidative stress causes dysfunction in the male reproductive system, which can be protected by alpha-tocopherol succinate.

Animals↗
PubMed1987

Hydrolysis of prednisolone succinate by esterase in rabbit ocular tissue.

Prednisolone concentrations in serum after both subconjunctival and intravenous injections of prednisolone sodium succinate at a 1 mg/kg equivalent dose of prednisolone in rabbits were analyzed by regularly phased high-performance liquid chromatography. The systemic availability after subconjunctival injection was determined to be almost 1.0 by comparing areas under the serum concentration-time curves for both administration routes. The initial hydrolytic rate of prednisolone succinate ester was dependent on the amount of total protein in ocular tissue homogenates and fluids as well as that in serum. The rate followed Michaelis-Menten kinetics, with an almost consistent Michaelis constant. Although the maximum hydrolytic rate per unit amount of tissue protein was the highest in conjunctival tissue, followed by corneal tissue and serum, the esterase activity corrected by total protein in the whole rabbit body should be the highest in serum, followed by conjunctival tissue. These results indicate that prednisolone sodium succinate administered subconjunctivally is hydrolyzed rapidly by esterase and absorbed almost completely into the systemic circulation.

Animals↗
PubMed1984

Succinic semialdehyde dehydrogenase deficiency.

A coupled assay using [14C]4-aminobutyric acid and a direct assay using [14C]succinic semialdehyde have been designed to assay te activity of succinic semialdehyde dehydrogenase in a patient with 4-hydroxybutyric aciduria and family members. In the coupled assay less than 3% of control succinic semialdehyde dehydrogenase activity was found in lysates of lymphocytes isolated from whole blood of the patient. In the direct assay there was no detectable activity of the enzyme in lysates of isolated lymphocytes or cultured lymphoblasts. Results indicated the parents to be heterozygous carriers carriers of the abnormal gene, consistent with an autosomal recessive inheritance.

Adult↗
PubMed1984

dl-alpha-Tocopheryl succinate enhances the effect of gamma-irradiation on neuroblastoma cells in culture.

The effect of dl-alpha-tocopheryl (vitamin E) succinate in modifying the radiation response of mouse neuroblastoma (NBP2) and mouse fibroblast (L-cells) cells in culture was studied on the criterion of growth inhibition (due to cell death and inhibition of cell division). Results show that vitamin E succinate markedly enhanced the effect of 60CO-gamma-irradiation on NB cells, but it did not significantly modify the effect of irradiation on mouse fibroblasts. Sodium succinate plus ethanol (0.25% final concentration) did not modify the radiation response of NB cells or fibroblasts. Butylated hydroxyanisole, a lipid soluble antioxidant, also enhanced the effect of irradiation on NB cells, indicating that the effect of vitamin E in modifying the radiation response may be mediated, in part, by antioxidation mechanisms.

Animals↗
PubMed2001

Inhibitory effects of RRR-alpha-tocopheryl succinate on benzo(a)pyrene (B(a)P)-induced forestomach carcinogenesis in female mice.

AIM: To study the inhibitory effects of VES (RRR-alpha-tocopheryl Succinate, VES),a derivative of natural Vitamin E, on benzo(a)pyrene(B(a)P)-induced forestomach tumor in female mice. METHODS: The model of B(a)P-induced forestomach tumor was established according to the methods of Wattenberg with slight modify-cations. One hundred and eighty female mice (6 weeks old) were divided into six groups equally; negative control (Succinic acid), vehicle control (Succinate+B(a)P),positive control(B(a)P), high VES(2.5 g/kg.b.w+B(a)P), low VES(1.25 g/kg.b.w+B(a)P)ig as well as VES by ip (20 mg/kg.b.w+B(a)P). Except the negative control group, the mice were administrated with B(a)P ig. and corresponding treatments for 4 weeks to study the anti-carcinogenetic effect of VES during the initiation period. The experiment lasted 29 weeks, in which the inhibitory effects of VES both on tumor incidence and tumor size were tested. RESULTS: The models of B(a)P-induced forestomach tumor in female mice were established successfully. Some were cauliflower-like, others looked like papilla, even a few were formed into the ulcer cavities. VES at 1.25 g/kg.b.w, 2.5 g/kg.b.w. by ig and 20 mg/kg.b.w. via ip could decrease the number of tumors per mouse (1.7 plus minus 0.41, 1.6 plus minus 0.34 and 1.1 +/- 0.43), being lower than that of B(a)P group (5.4 +/- 0.32, P<0.05). The tumor incidence was inhibited by 18.2%, 23.1% and 50.0%. VES at 1.25 g/kg.b.w., 2.5 g/kg.b.w. by ig and 20 mg/kg.b.w. via ip reduced the total volume of tumors per mouse (54.8 +/- 8.84, 28.4 8 +/- 8.32 and 23.9 8 +/- 16.05), being significantly lower than that of B(a)P group (150.2 8 +/- 20.93, P < 0.01). The inhibitory rates were 63.5%, 81.1% and 84.1%, respectively. CONCLUSION: VES has inhibitory effects on B(a)P-induced forestomach carcinogenesis in female mice, especially by ip and it may be a potential anti-cancer agent in vivo.

Animals↗
PubMed2002

Acute pancreatitis and acute renal failure complicating doxylamine succinate intoxication.

Doxylamine succinate is an antihistaminic drugwith additional hypnotic, anticholinergic and local anesthetic effects first described in 1948. In Korea and many other countries, it is a common-over-the counter medication frequently involved in overdoses. Clinical symtomatology of doxylamine succinate overdose includes somnolence, coma, seizures, mydriasis, tachycardia, psychosis, and rhabdomyolysis. A serious complication may be rhabdomyolysis with subsequent impairment of renal function and acute renal failure. We report a case of acute renal failure and acute pancreatitis complicating a doxylamine succinate intoxication.

Acute Disease↗
PubMed1990

[Tocopherol Succinate Reference Standard (Control 881) of National Institute of Hygienic Sciences].

Tocopherol succinate was tested for the preparation of "Tocopherol Succinate Reference Standard (Control 881)". Analytical data obtained were as follows: infrared spectrum, same as Tocopherol Succinate Reference Standard (Control 851); absorbance, E1cm1% (286 nm) = 40.5; thin-layer chromatography, contaminants were not detected until 50 micrograms; high-performance liquid chromatography, three contaminants were detected; loss on drying, 0.09%; assay, 100.0%. On the basis of the above results, this material was authorized as the Japanese Pharmacopoeia Standard (Control 881).

Chromatography, High Pressure Liquid↗
PubMed2004

[Structural basis of alpha-tocopherol succinate as an antineoplastic agent].

Alpha-tocopherol succinate is a redox-silent analog of alpha-tocopherol which is the major component of vitamin E. Recently, the research findings showed that, as a kind of pro-vitamin E, alpha-tocopherol succinate possesses antineoplastic activity which alpha-tocopherol lacks of. In this review paper, the link between the structure and antineoplastic activity of alpha-tocopherol succinate was focused.

Antineoplastic Agents↗
PubMed1987

Experimental evaluation of amylose succinate absorbable hemostat in a canine model.

Using a semiquantitative animal model of standardized injuries to parenchymatous organs resulting in a range of degrees of hemorrhage, we compared freeze-dried amylose succinate topical hemostat to the most widely used commercially available products. Hemostatic efficacy parameters included bleeding time, blood loss, incidence of rebleeding, and amount of material used. Although no material was consistently superior in all parameters, in general amylose succinate and microcrystalline collagen performed equally well and both were significantly more effective than oxidized regenerated cellulose. Both amylose succinate and oxidized regenerated cellulose were superior to microcrystalline collagen, however, in biodegradation time, inflammatory response and adhesion-forming potential. Details of the animal model and an adhesion grading scheme are presented.

Absorption↗
PubMed1985

Pharmacokinetics of prednisolone sodium succinate and its metabolites in normovolemic and hypovolemic dogs.

Tritium-labeled prednisolone sodium succinate was administered IV to 4 healthy, awake, nonsplenectomized dogs. The concentration of prednisolone and its metabolites in the plasma were measured for 10 hours. Forty-one percent of the blood volume of these dogs was removed, and plasma prednisolone was measured again. The data before and after hemorrhage were fitted to a 2-compartment open model. From plasma profiles, a rapid distributional phase, followed by a slower phase, was observed in control and shock groups. Volume of the central compartment of prednisolone before and after hemorrhage was 165 ml/kg of body weight and 110 ml/kg, respectively; and the difference was significant (P less than 0.05). The rate of total body clearance of prednisolone before and after hemorrhage was 3.96 ml/min/kg and 2.53 ml/min/kg, respectively; the difference was significant. The mean plasma half-lives for prednisolone sodium succinate and its metabolites, before and after hemorrhage, were 166 and 197 minutes, respectively; the difference was not significant. The mean half-life data indicated that prednisolone sodium succinate may be repeated in a patient 2.5 to 3 hours after onset of treatment if signs of hypovolemic shock reappear.

Animals↗
PubMed1978

Reduction of experimental myocardial infarct size by combined treatment with methylprednisolone sodium succinate and betahistine hydrochloride.

This laboratory and others have shown that methylprednisolone sodium succinate and betahistine hydrochloride can each reduce the size of experimental myocardial infarct in dogs at six hours. In light of the fact that these two agents probably act via different mechanisms, a study was carried out to determine if there would be cumulative effects of using these two agents together. Using a left anterior descending coronary artery ligation model to create an experimental myocardial infarction and an intracellular lactic dehydrogenase (LDH) stain to measure the infarct size, 66 dogs were studied. Nineteen dogs served as controls with no therapy; 20 received a continuous intravenous infusion of betahistine hydrochloride (0.24 mg/kg/min) for six hours following ligation; 10 dogs received methylprednisolone sodium succinate intravenously 30 mg/kg at one hour postligation; and 17 other dogs received betahistine hydrochloride intravenously (0.24 mg/kg/min) over six hours following ligation, plus methylprednisolone sodium succinate intravenously (30 mg/kg) at one hour postligation. At six hours, the combined treatment demonstrated no significant improvement over betahistine HCl alone (control, 16.0%; betahistine HCl, 11.4%; combined, 11.2% P less than 0.05). At 24 hours, only the combined treatment group demonstrated a significant infarct size reduction (control, 15.5%; methylprednisolone, 13.1%; betahistine--HCl, 14.2%; combined, 9.7%; P less than 0.0025). Other parameters that were evaluated and analyzed include mean aortic pressure, left atrial pressure, cardiac index, total peripheral resistance, arterial and coronary sinus pH, pCO2, pO2, hematocrit, O2 consumption, O2 content difference, and coronary sinus lactate and creatine phosphokinase (CPK). These results suggest a significant cumulative effect in reducing infarct size over that achieved with one agent alone; however, further studies are needed to determine the appropriate dosage and temporal factors.

Animals↗
PubMed1981

Phenytoin, methylprednisolone sodium succinate and graft survival.

A laboratory study was undertaken to explore the possible interference of phenytoin with the immunosuppressive effect of methylprednisolone sodium succinate on skin graft survival in mice. Full thickness skin allografts were performed on five groups of 10 mice. Each group received various combinations of phenytoin and/or methylprednisolone sodium succinate or no treatment at all (control). In vitro stimulation of lymphocytes from these mice with phytohemagglutinin was carried out to corroborate the immune status of the recipients. All mice demonstrated prolonged graft survival as compared to the control group regardless of what agents were used. Our results indicate that the concomitant administration of phenytoin and methylprednisolone sodium succinate does not accelerate skin homograft rejection in the murine model.

Animals↗
PubMed1981

Stability of methylprednisolone sodium succinate in small volumes of 5% dextrose and 0.9% sodium chloride injections.

The stability of methylprednisolone sodium succinate in small volumes of 5% dextrose and 0.9% sodium chloride injections was studied. Vials of methylprednisolone sodium succinate (125-3000 mg) were reconstituted and added to 50- and 100-ml volumes of the two diluents. These piggyback solutions were visually inspected for the development of haze over a 24-hour period. A nephelometer was used to quantitate the development of turbidity with time. The effect of pH on haze formation was investigated, and infrared spectroscopy was used to identify the haze. Nephelometer readings were found to correlate well with visual inspections. The haze was identified as being formed by the precipitation of free methylprednisolone. The rate of change of turbidity was directly related to the pH. A 1.4-3.2 percentage-point increase in the free methylprednisolone concentration secondary to hydrolysis over the 24-hour period was noted. The duration of stability was variable among the investigated lots and concentrations. Nineteen of the 24 admixtures stored at room temperature remained stable and free of visible haze for at least 12 hours after preparation. For all dosage strengths of methylprednisolone sodium succinate studied, these data indicate that solutions can be made stable for at least 12 hours by selecting the appropriate volume of diluent.

Drug Packaging↗
PubMed1981

Chloramphenicol succinate pharmacokinetics in Macaca nemestrina: dose dependency study.

Chloramphenicol succinate ester in doses equivalent to 25, 100 and 250 mg/kg of chloramphenicol were administered by rapid i.v. infusion in a randomized crossover fashion to five adolescent ((18-36 month) male Macaca nemestrina monkeys. Thirteen serum samples and all voided urine were collected over a 5- to 6-hr period. Urinary excretion of unhydrolyzed ester was independent of dose and averaged 26.3 +/- 6.2% of the administered dose. Dose dependency was observed for the elimination rate constant, total body clearance and metabolic clearance of chloramphenicol succinate. Dose dependency was also observed for the apparent volume of distribution, total body clearance, metabolic clearance and time to peak concentration of chloramphenicol. Although significant dose dependency of various pharmacokinetic parameters ws demonstrated, the peak chloramphenicol concentration and the elimination rate constant of chloramphenicol after administration of chloramphenicol succinate showed no significant dose-dependent changes. Therefore, peak chloramphenicol concentrations would be expected to reflect changes in dose in a linear or proportional manner.

Animals↗
PubMed1993

[Bioenergetic mechanisms of the antihypoxic action of mexidol, the succinate-containing derivative of 3-hydroxypyridine].

The mechanism of antihypoxic action of succinate-containing derivative of 3-hydroxypiridine (mexidol) on hypoxic isolated contractive heart was investigated. By means of inhibitory analysis it was shown that the mechanism is connected with oxidation of succinate in mitochondrial respiratory chain. Activation of succinate oxidase pathway in that situation may be regarded as a immediate compensatory mechanism entering in action at limitation of NADH-oxidase pathway and promoting increase of tissue resistance at oxygen deficiency. Thus, mexidol is antihypoxant of energizing action.

Animals↗
PubMed1976

A two year trial of loxapine succinate in chronic psychotic patients.

Thirty-one chronic psychotic patients were treated with loxapine succinate, 20 for two years and eleven for one year, in order to evaluate its long-term efficacy and safety. Results presented here indicate that loxapine succinate is an effective treatment for chronic schizophrenia over a period of at least two years. Improvement, which occurred during the first six months of treatment (mostly during the first month), was maintained over the following year and a half. Unwanted effects were most frequent inthe early months of treatment and decreased as the two year trial progressed. No specifically long-term side effects were observed. The most frequent side effects were mild to moderate extrapyramidal signs. Blood pressure decreased and pulse rate increased, while remaining within normal limits, and returned to normal or near normal levels during the second year of treatment. Weight increased steadily during the two years and dropped markedly during the four week post-drug period. No drug-related abnormal laboratory findings were observed. It may be concluded that loxapine succinate is a safe and effective maintenance treatment for chronic schizophrenia.

Adult↗
PubMed1976

Effect of castration and long-term oral oestrogen therapy with oestriol succinate on serum lipids.

The effects of continuous oestriol succinate therapy (2 mg/day) of three years' duration on serum cholesterol, triglycerides and phospholipids were investigated on 50 women with a mean age of 48 years. In addition, the effects of castration only were investigated in 10 women with a similar mean age. One month after castration the serum cholesterol, triglyceride and phospholipid levels were significantly raised (p less than 0.05). During oestriol succinate therapy the cholesterol level tended to decrease. In the control group without hormone therapy, the cholesterol level showed a tendency to rise during the three years. The serum triglyceride and phospholipid levels remained almost unchanged during the oestriol succinate therapy and differed not from corresponding values of the control group.

Administration, Oral↗