Does long term supplementation of vitamin E cause detrimental effects on the central nervous system? Morphological and histological study in experimental male Wistar rats.

AIM: Aging is attributed to neuronal loss associated with increased oxidative stress. Vitamin E, and in particular, tocotrienol are potent antioxidants, which have been shown to be neuroprotective. The main aim of the present study was to observe the effect of long term intake of vitamin E in the form of tocotrienol rich fraction (TRF) and refined, bleached, deodorized palm olein (RBDPO) on the brain of experimental rats. MATERIALS AND METHODS: Thirty male Wistar rats aged 3 months were either supplemented with TRF (dose of 200 mg/kg body weight), RBDPO (dose of 1 ml/kg body weight) or distilled water, continuously for 8 months. The animals were then examined in vivo for clinical magnetic resonance imaging (MRI) studies before being sacrificed. The brain was extracted, measured and studied for histological changes. RESULTS: The magnetic resonance imaging (MRI) scan of the lateral ventricle, cortical thickness of cingulate gyrus and hippocampus size did not show any significant changes in all three groups. The brain weight, length and width as well as histological sections of the brain showed no significant changes between the groups. CONCLUSION: It is thereby concluded that chronic consumption of vitamin E was not detrimental to the central nervous system.

Predominance of G to A codon 12 mutation K-ras gene in Dukes' B colorectal cancer.

INTRODUCTION: K-ras gene mutations in codons 12 and 13 are one of the earliest events in colon carcinogenesis. METHODS: DNA was extracted from 25 mg of tumour tissue (n = 70) that were taken from tumour mass and pairs with normal epithelial tissue distant from the tumour of colorectal cancer patients. Exon 1 and exon 2 of the K-ras gene were amplified. Hotspot mutations were detected using polymerase chain reaction-based single-strand conformation polymorphism method and confirmed by direct DNA sequencing analysis. RESULTS: Mutations were identified in 14 out of the 70 (20%) colorectal carcinoma tissues. Single-base transition from GGT to GAT (glycine to aspartate) in codon 12 was detected in nine samples, while three samples presented with GGC to GAC transition in codon 13. Patients with large adenoma had a 12-fold higher likelihood of K-ras mutations (odds ratios [OR] 12.31; 95% confidence intervals [CI] 1.81-83.76). Tumours located at the left colon were more likely to present with K-ras mutations (OR 4.54; 95% CI 0.96-21.54). CONCLUSION: Our study showed a high frequency of G to A transition of codon 12 mutation of the K-ras gene, with significant correlation with tumour size and tumour location.

Effect of ovariectomy and sex hormones replacement on tumour marker enzymes under administration of chemical carcinogens in the rat.

The effect of ovariectomy and sex hormone/s replacement in female rats was investigated by the determination of the tumour marker enzymes gamma-glutamyltranspeptidase (GGT) and alkaline phosphatase (ALP). This was compared to ovariectomized rats receiving sex hormone replacement and treated with carcinogen. Ovariectomy significantly increased the activity of plasma GGT. Plasma and microsomal ALP and microsomal GGT were unchanged. When replacements of estrogen (E), or progesterone (Prog), or combinations of both estrogen and progesterone were given to ovariectomized rats, the activity of plasma GGT was brought to the level of normal intact females. Treatment with carcinogen increased the PGGT activities in intact rats. In ovariectomized rats receiving carcinogen, the PGGT activities were significantly lower than in intact females and rats receiving both hormone replacement and carcinogen (p < 0.01). Carcinogen treatment in case of estrogen or progesterone replacement, either individually or in combination, showed GGT activities comparable to intact females receiving carcinogen. Both plasma and microsomal ALP were not affected by carcinogen administration. These results showed that ovariectomy reduced the severity of hepatocarcinogenesis while sex hormone replacement worsened the process.