Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1835664 (TOC)
 2,763 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic administration of amiodarone (AMIO), widely used by clinicians for the treatment of therapy-resistant cardiac arrhythmias, is frequently associated with serious side-effects. AMIO and its main metabolite desethylamiodarone (DEA) are known to induce phospholipidosis in vivo and in cultured cells presumably by inhibition of lysosomal phospholipid degradation. D-alpha-Tocopherol = vitamin E (alpha-TOC) was able to reduce AMIO and DEA toxicity in cell cultures. Results from the present study showed that alpha-TOC reduced phospholipidosis in cultured human skin fibroblasts chronically exposed to micromolar concentrations of AMIO and DEA and inhibited cumulative uptake of the drugs in a dose-dependent manner. A linear correlation was observed between cellular AMIO levels and phospholipid accumulation suggesting a stoichiometric relationship. alpha-TOC was also effective in clearing previously accumulated phospholipids after discontinuation of the drug treatment. The results can best be explained by an interference of alpha-TOC (a) with drug-phospholipid complex formation responsible for both phospholipid storage and drug accumulation, and (b) with pre-existing drug-phospholipid complexes, accelerating their dissociation and rendering phospholipids to substrates for lysosomal phospholipases. The finding raises hope that side-effects of AMIO and DEA can be prevented or made reversible by the administration of alpha-TOC. It must, however, be proven that the antiarrhythmic drug will still be effective.
 ...
PMID:Vitamin E reduces accumulation of amiodarone and desethylamiodarone and inhibits phospholipidosis in cultured human cells. 759 36

The effect of d-alpha-tocopherol on the progression of renal dysfunction was investigated in rats injected with adriamycin (ADR), a model of progressive glomerulosclerosis associated with the nephrotic syndrome. Treatment with d-alpha-tocopherol was started 1 day before or 1 day after ADR injections (BE-TOC or AF-TOC rats). When compared to rats without d-alpha-tocopherol treatment (ADR-CON rats), the serum total cholesterol and triglyceride levels were significantly lower in the BE-TOC and AF-TOC groups. In week 16, the LDL cholesterol level and the atherogenic index were both significantly lower in BE-TOC and AF-TOC rats than in ADR-CON rats. The urinary protein, serum creatinine, blood urea nitrogen, malondialdehyde, and systolic blood pressure levels as well as the glomerulosclerosis score were high in ADR-CON rats, and reduced in BE-TOC or AF-TOC rats. There were no significant differences in body weight and serum albumin between the three groups in week 16. It is concluded that d-alpha-tocopherol can improve hyperlipidemia and ameliorate glomerulosclerosis in rats with ADR-induced progressive renal failure. Thus, d-alpha-tocopherol may have the potential for clinical application to treat focal glomerulosclerosis.
 ...
PMID:Alpha tocopherol improves focal glomerulosclerosis in rats with adriamycin-induced progressive renal failure. 783 58

An experiment was conducted to compare the efficacy of two dietary sources and an injectable form of vitamin E (VE) to improve the VE status of poults. Six of the treatments consisted of a factorial arrangement of three concentrations and two sources of dietary VE. Turkeys in these treatments received 12, 80, or 150 IU of either dl-alpha-tocopheryl acetate or d-alpha-tocopherol (d-alpha-TOC)/kg of diet. The seventh treatment consisted of a single subcutaneous injection of d-alpha-TOC at 1 d of age. Poults in this treatment were subcutaneously injected in the dorsal area of the neck with 25 IU of d-alpha-TOC, this amount being approximately equivalent to the amount poults would consume if their diet was supplemented with 150 IU of VE/kg during their 1st wk of life. Concentration, source, or route of VE administration did not affect growth parameters, plasma creatine kinase, plasma triglycerides, or liver lipid peroxidation as measured by the thiobarbituric acid reactive substances assay (TBARS). Plasma, red blood cells (RBC), and liver alpha-TOC decreased from hatching to 14 d of age in poults fed either source of VE. The use of 80 or 150 IU of dietary VE (either source) reduced (P < 0.05) the extent of depletion of alpha-TOC at all ages and also reduced the susceptibility of RBC to hemolysis. There was no effect of source of dietary VE on concentration of alpha-TOC in plasma, RBC, or liver, or on RBC hemolysis. Subcutaneous injection of 25 IU of d-alpha-TOC at Day 1 increased (P < 0.05) alpha-TOC concentration until 7 d of age. Also, d-alpha-TOC injection reduced (P < 0.05) RBC susceptibility to hemolysis through 21 d of age. Data showed that one single subcutaneous injection of 25 IU of d-alpha-TOC at 1 d of age was as effective as 80 IU or more of dietary VE through 21 d to improve the alpha-TOC status of poults.
 ...
PMID:Efficacy of dietary and injected vitamin E for poults. 893 93

A critical analysis of the changes in fatty acid patterns and their metabolism elicited by vitamin E deficiency leads to the proposal that a major role of dietary RRR-alpha-tocopherol (alpha-TOC) is as an enzymatic precursor of alpha-tocopherolquinone (alpha-TQ) whose semiquinone radical functions as an essential enzyme cofactor for the fatty acid desaturases of the recently elucidated carnitine-dependent, channeled, mitochondrial desaturation-elongation pathway; a detailed mechanism for its function is proposed. Pathophysiological states produced by vitamin E deficiency and alpha-TOC transfer protein defects, such as ataxia, myopathy, retinopathy, and sterility are proposed to develop from the effects of impaired alpha-TQ-dependent desaturases and the resulting deficiency of their polyenoic fatty acid products.
 ...
PMID:A function for the vitamin E metabolite alpha-tocopherol quinone as an essential enzyme cofactor for the mitochondrial fatty acid desaturases. 1010 Jun 2

An experiment was conducted to investigate the effect of dietary antioxidants and storage on fatty acid profile, oxidative stability, and vitamin E concentration of n-3 fatty acid-enriched eggs. Eggs (384, 48/diet) were collected from ISA Brown layers fed diets containing corn-soy (control) with 100 g/kg of flax seed and 2 types of antioxidants [alpha-tocopherols (alpha-TOC) and butylated hydroxytoluene (BHT)] at 0, 50, 100, or 150 IU or mg/kg. Eggs were stored at 4 degrees C. On d 0, 20, 40, and 60 of storage, 2 eggs were selected randomly from each replicate (totaling 12 eggs per treatment) and analyzed. Eggs from hens fed flax had increased alpha-linolenic (18:3n-3), eicosapentaenoic (20:5n-3), and docosahexaenoic acids (DHA, 22:6n-3) and decreased arachidonic acid (20:4n-6) and total n-6:n-3 ratio when compared with control eggs (P<0.05). The n-6:n-3 fatty acid ratio was lowest in the flax+50 IU of alpha-TOC, flax+100 IU of alpha-TOC, and flax+BHT supplemented group when compared with the flax group (P<0.05). With the exception of flax+100 mg of BHT, addition of antioxidants led to a reduction in palmitic acid in fresh eggs (P<0.05). During the first 20 d of storage, over a 17% reduction in total n-3 fatty acids was observed in eggs from flax+50 mg of BHT supplemented groups (P<0.05). Docosahexaenoic acid was the predominant long-chain n-3 fatty acid in egg and was stable during storage in the control, flax, flax+100 IU of alpha-TOC, flax+150 IU of alpha-TOC, and flax+150 mg of BHT groups. However, antioxidant supplementation had no effect on DHA upon storage in flax+50 IU of alpha-TOC and flax+50 mg of BHT eggs where over 13 to 17% reduction in DHA content was observed during 20 to 60 d of storage (P<0.05). Inclusion of alpha-TOC led to over 4.5- to 12-fold increases in alpha-TOC in eggs. Egg storage for 40 d or longer led to over 50% reduction in egg alpha-TOC (P<0.05). Feeding flax seeds led to an increase in TBA reactive substances in eggs (P<0.05). alpha-Tocopherol was better in preventing lipid oxidation than BHT at d 0 of storage. However, neither had a significant effect on egg TBA reactive substances upon 60 d of storage (P>0.05). These studies demonstrate that the level and type of antioxidants and duration of egg storage significantly affected the fatty acid profile, alpha-TOC status, and oxidative stability of chicken eggs.
 ...
PMID:Oxidative stability and lipid components of eggs from flax-fed hens: effect of dietary antioxidants and storage. 2046 Jun 75