Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042875 (vitamin E deficiency)
 916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipid peroxidation of rat liver microsomal fractions was monitored by its low-level chemiluminescence in preparations from controls and vitamin-E-deficient animals. Measurements were made (a) of the duration of the lag phase tau0 after initiation with NADPH/iron-ADP and (b) of the slope of the chemiluminescence increase. In microsomes with normal vitamin E (alpha-tocopherol) level the lag phase tau0 was substantially increased by ascorbate; in contrast, even an enhanced peroxidation was observed with ascorbate in vitamin-E-deficient microsomes. Therefore, the ascorbate-mediated protection of microsomal membranes against lipid peroxidation is dependent on vitamin E in the membrane. In vitamin E deficiency the pro-oxidant effect of ascorbate was abolished when glutathione (GSH) was present. Likewise, GSH does not prolong the lag phase tau0 in vitamin E deficiency. However, GSH (but not cysteine) exerts an antioxidant effect both in controls and in vitamin E deficiency by decreasing the slope of the chemiluminescence increase during lipid peroxidation. The involvement of GSH in an enzyme-dependent mechanism is suggested.
 ...
PMID:The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin E. 338 50

The effect of vitamin E deficiency on levels of proteinase inhibitors in sex glands of male rats was studied. Inhibitor levels against cysteine proteinases, such as ficin and cathepsin H, and against serine proteinase such as trypsin were examined. Vitamin E deficiency for 4 mo after weaning induced a fivefold increase in cysteine proteinase inhibitor level in testis, a two- to fourfold increase in prostate and epididymis and no change in seminal vesicle. No appreciable change was observed in trypsin inhibitor level in testis, epididymis or seminal vesicle. Therefore, vitamin E deficiency was reflected most sensitively by the cysteine proteinase inhibitor level in testis. These observations agree with our previous findings that alpha-cysteine proteinase inhibitors in serum increased greatly whereas trypsin inhibitor in serum did not change in vitamin E-deficient rats. Major histological changes were observed in the testes of rats fed a vitamin E-deficient diet for 4 mo, although testis weight was not significantly affected by vitamin E deficiency.
 ...
PMID:Enhancement of testicular cysteine proteinase inhibitor level in vitamin E-deficient rats. 349 20

Mitochondria clearly play a central role in the pathogenesis of Friedreich's Ataxia. The most common genetic abnormality results in the deficiency of the protein frataxin, which is targeted to the mitochondrion. Research since this discovery has indicated that mitochondrial respiratory chain dysfunction, mitochondrial iron accumulation and oxidative damage are important components of the disease mechanism. While the role of frataxin is not known, evidence is currently pointing to a role in either mitochondrial iron handling or iron sulphur centre synthesis. These advances in our understanding of the disease mechanisms are enabling therapeutic avenues to be explored, in particular the use of established drugs such as antioxidants and enhancers of respiratory chain function. Vitamin E therapy has been shown to be beneficial in patients with ataxia with vitamin E deficiency, and CoQ10 therapy was effective in some patients with ataxia associated with CoQ10 deficiency. A combined therapy involving long term treatment with high doses of vitamin E and coenzyme Q10 has jointly targeted two of the major features of Friedreich's Ataxia; decreased mitochondrial respiratory chain function and increased oxidative stress. This therapy clearly showed a rapid and sustained increase in the energy generated by the FRDA heart muscle, nearly returning to normal levels. The improvements in skeletal muscle energy generation parallel those of the heart but to a lower level. While this therapy appeared to slow the predicted progression of some clinical symptoms a larger placebo controlled study is required to confirm these observations. Other antioxidant strategies have involved the use of Idebenone, selenium and N acetyl cysteine but only the use of Idebenone has involved structured trials with relatively large patient numbers. Idebenone clearly had an impact upon the cardiac hypertrophy in the majority of patients, although there have not been any other significant benefits reported to date.
 ...
PMID:Friedreich's Ataxia: disease mechanisms, antioxidant and Coenzyme Q10 therapy. 1469 32