Abnormal lipid metabolism in collagen-induced arthritis rat model: In vitro, high resolution NMR spectroscopy based analysis.

Collagen-induced arthritis (CIA) was induced in female Wistar rats by intradermal injection of porcine immunization grade native collagen type II (Chondrex). Development and progression of CIA was monitored by studying histopathological, radiographical and biochemical features of arthritic manifestations in the knee joints, hind limb and blood plasma. In addition, oxidative stress status of arthritic animals was determined by measuring lipid peroxidation and the antioxidant enzymes: catalase, superoxide dismutase and glutathione peroxidase. High resolution proton NMR spectroscopy was employed for the analysis of lipid components in the lipid extracts of the joint tissue and plasma of collagen-induced arthritic and control rats. Triglyceride levels showed significant decreases in plasma (1.7 times) but were unchanged in the joint tissue of CIA rats as compared to control. One-dimensional proton NMR spectra showed a 6.2 times reduction in the quantity of choline-containing phospholipids in the plasma of CIA as compared to control rats. There was a 1.6 times elevation of choline-containing phospholipids in the joint tissue of CIA rats as compared to controls. Induction of arthritis showed a 4.0 times reduction in the level of total cholesterol in the plasma and 1.6 times elevation in the joint tissue of CIA rats as compared to controls. The ratio of saturated fatty acids to unsaturated fatty acids was 1.5 times significantly higher in joint tissue and 2.1 times significantly higher in plasma of CIA rats as compared to controls. The results demonstrated significantly altered lipid patterns in the joint tissue and plasma of collagen-induced arthritic rats as detected by one- and two-dimensional NMR spectroscopy compared with controls.

Insights into the mechanism of action of benzoyl peroxide as a tumor promoter.

A comparison of the mechanism of action of benzoyl peroxide, a tumor promoter was studied in three different cell lines i.e. NIH 3T3, HDCS and A431. Benzoyl peroxide was found to mediate its effect by inducing poly ADP-ribosylation in all the three cell types studied but to different extents, with histone H1 serving as a common acceptor for poly ADP-ribose. It also stimulated the activities of the antioxidant enzymes CuZn superoxide dismutase and catalase in NIH 3T3 and HDCS cells, but not in A431. Alterations in the expression of c-jun and c-fos were observed in NIH 3T3 and A431 cells. Benzoyl Peroxide appeared to mediate its effect via genetic and epigenetic mechanisms.

Poly ADP ribosylation as a possible mechanism of microwave--biointeraction.

Electromagnetic fields (EMFs) affect the metabolism of the body including the nervous, endocrine, cardiovascular, hematological as well as the reproductive system. EMFs are environmental pollutants, thus posing a health hazard which can cause steric changes in the molecule located at the cell surface. Microwaves are known to cause chromosomal abberations and act as tumor promoters. The process involves a stream of signals from cell membrane to nucleus and other organelles. The present investigations aim to understand the mechanism of biological effects of microwaves (2.45 GHz). The effect was studied on poly ADP-ribosylation, which is a post translational modification of chromatin protein catalysed by the enzyme poly ADPR polymerase using NAD+ as the substrate. Poly ADP-ribosylation has been shown to be involved in several aspects of chromatin structure and function. Twenty-three days old rats weighing 42-48 gms were exposed at a microwave dose level of 1.0 mW/cm2. After exposure for sixty days the animals were sacrificed and an estimation of poly ADPR polymerase activity was undertaken in different organs of these animals. There was an increase of 20% in its activity in liver, 35% in testis, whereas brain showed a 53% decrease in diencephalon and 20% decrease in the cortex in the exposed animals as compared to their respective controls. There was no change in enzyme activity in spleen and kidney. This was accompanied by concomitant changes in NAD+ levels. The above results may be cited as important events in carcinogenesis and tumor promotion related to microwave exposure and the signal transduction mechanism involved. The goal is to shed light on complex ecogenetic interactions leading to cancer modulation of gene expression by epigenetic mechanism.