Luca Barella

α-Tocopherol Affects Androgen Metabolism in Male Rat

Abstract: The Alpha‐Tocopherol Beta‐Carotene Cancer Prevention Study has provided the first evidence implicating vitamin E in hormone synthesis. The effect of vitamin E on stereoidogenesis in testes and adrenal glands was assessed in growing rats using Affymetrix gene‐chip technology. Dietary supplementation of rats with vitamin E (60 mg/kg feed) for a period of 429 days caused a significant repression of genes encoding for proteins centrally involved in the uptake (low‐density lipoprotein receptor) and de novo synthesis (for example, 7‐dehydrocholesterol reductase, 3‐hydroxy‐3‐methylglutaryl coenzyme A synthase, 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase, isopentenyl‐diphosphate delta‐isomerase, and farnesyl pyrophosphate synthetase) of cholesterol, the precursor of all steroid hormones. The present investigation indicates that dietary vitamin E may induce changes in stereoidogenesis by affecting cholesterol homeostasis.

Cortical Gene Expression in the Vitamin E-Deficient Rat: Possible Mechanisms for the Electrophysiological Abnormalities of Visual and Neural Function

In mammals, severe and chronic deficiency of vitamin E (α-tocopherol) is associated with a characteristic neurological syndrome. Previously, we have shown that this syndrome is accompanied by electrophysiological abnormalities of neural and visual function. To investigate the molecular basis of the observed abnormalities, we used microarrays to monitor the expression of ∼14,000 genes in the cerebral cortex from rats which had received diets containing 0, 1.25 and 5.0 mg/kg diet of all-rac-α-tocopheryl acetate for 14 months. Compared to the groups receiving 1.25 and 5.0 mg/kg α-tocopheryl acetate, a total of 11 genes were statistically significantly upregulated (≧1.3-fold) and 34 downregulated (≤1.3-fold) in the vitamin E-deficient group. Increased expression was observed for the genes encoding the antioxidant enzyme catalase and the axon guidance molecule tenascin-R, while decreased expression was detected for genes encoding protein components of myelin and determinants of neuronal signal propagation. Thus our observations suggest that vitamin E deficiency results in transcriptional alterations in the cerebral cortex of the rat which are consistent with the observed neurological and electrophysiological alterations.

The Natural Compound Ascorbigen Modulates NADPH-Quinone Oxidoreductase (NQO1) mRNA and Enzyme Activity Levels in Cultured Liver Cells and in Laboratory Rats

Ascorbigen (ABG) is a natural compound that represents a breakdown product of the glucosinolates that are present in Brassica vegetables. It is postulated that ABG may have anticarcinogenic activity; however, the underlying molecular and cellular mechanisms are largely unknown. In the present study we investigated the effect of ABG on the mRNA and enzyme activity levels of NADPH-quinone oxidoreductase (NQO1), which is centrally involved in the detoxification of xenobiotics, in cultured liver cells and in rats. The mRNA levels of NQO1 showed an increase of up to 100% in cultured liver cells (HepG2) following incubation with different concentrations of ABG (3–100 µmol/l) compared to control cells. Furthermore, NQO1 activity was elevated (up to 20%) by ABG treatment. The in vitro results were confirmed in rats who received either 5 mg/day ABG or vehicle for 7 days. Significantly higher mRNA (a 90% increase) and enzyme activity levels (a 40% increase) of NQO1 were detected in the liver of ABG-treated rats as compared to control animals. Current data indicate that ABG is a moderate inducer of the phase II enzyme NQO1, both in cultured hepatocytes and in vivo.