Browsing by Author "Kumar, BP"
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Item Alterations in collagen metabolism and increased fibroproliferation in the heart in cerium-treated rats - Implications for the pathogenesis of endomyocardial fibrosis(BIOLOGICAL TRACE ELEMENT RESEARCH, 1998) Kumar, BP; Shivakumar, KCerium (Ce), a rare earth element, has been postulated to play a role in the pathogenesis of tropical endomyocardial fibrosis (EMF). Investigations carried out recently in pursuance of the postulation furnished histological evidence of EMF and increased cardiac collagen content in rats on prolonged administration of Ce. The present study was undertaken to understand the molecular basis of myocardial injury and fibrosis produced by the element. This article presents evidence of increased lipid peroxidation and elevated rates of fibroblast proliferation and collagen deposition in the heart in Ce-treated rats. It is suggested that the element may trigger a wound-healing response in the cardiac tissue leading to cardiac fibrosis.Item Cerium stimulates protein biosynthesis in rat heart in vivo(BIOLOGICAL TRACE ELEMENT RESEARCH, 1995)The aim of the study was to ascertain whether Ce, a lanthanide that has been implicated in the pathogenesis of tropical endomyocardial fibrosis, interferes with the biosynthetic repertoire of the cardiac muscle in vivo. Female Sprague-Dawley rats received Ce chloride iv at 1.3 mg/kg body wt.; controls received an equal volume of physiological saline. Rates of protein synthesis and transcription in cardiac muscle, measured in terms of incorporation of (H-3)-phenylalanine and (H-3)-uridine, respectively, into trichloroacetic acid-insoluble material were found to be significantly higher in Ce-treated animals. As low levels of Ce were earlier shown to stimulate collagen as well as noncollagen protein synthesis in cardiac fibroblasts in vitro, the stimulatory effect of the element in vivo reported here supports the speculation that it may influence the expression of proteins Like collagen in the heart and contribute to their accumulation as in endomyocardial fibrosis.Item Depressed antioxidant defense in rat heart in experimental magnesium deficiency - Implications for the pathogenesis of myocardial lesions(BIOLOGICAL TRACE ELEMENT RESEARCH, 1997)Magnesium (Mg) deficiency has been shown to produce myocardial lesions in different experimental models. Based on several lines of evidence, it has been proposed that oxidative injury to the cardiac muscle may explain the pathobiology of such lesions. In pursuance of this postulation, the present study examined the effect of dietary deficiency of Mg on the activity of the antioxidant enzymes, superoxide dismutase (SOD) and catalase, in rat heart. This article reports a significant lowering of the activity of both these enzymes in the cardiac tissue in Mg-deficient rats. Since depressed antioxidant defense in the heart may enhance myocardial susceptibility to oxidative injury, the observation is of possible relevance to the pathogenesis of cardiac lesions in Mg deficiency.Item Magnesium deficiency and cerium promote fibrogenesis in rat heart(BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY, 1996)Cerium is a biologically active lanthanide and a major constituent of monazite. The observation that inhalation of particles of cerium causes pneumoconiosis had generated considerable interest in the toxicology of the element (Venugopal and Luckey 1978; Vocatura et al 1983). Cerium tartrate was found to produce cardiac injury and polycythaemia in small animals (Venugopal and Luckey 1978). More recently, tropical endomyocardial fibrosis (EMF), a restrictive cardiomyopathy, was postulated to be the cardiac expression of cerium toxicity in combination with magnesium deficiency (Valiathan et al 1989; Valiathan and Kartha 1990). The postulation was based upon the observation of elevated levels of cerium and depressed levels of magnesium in the cardiac tissue of patients with EMF (Valiathan et al 1989; Valiathan and Kartha 1990). Studies carried out in pursuance of the hypothesis showed that tissue levels of cerium are enhanced in magnesium deficiency (Eapen et al 1996) and that cerium and magnesium deficiency have a synergistic effect on cardiac metabolism (Gunther 1990; Shivakumar and Renuka Nair 1991). Importantly, recent observations on the mode of action of cerium at the molecular level suggested that the element may influence expression of matrix proteins like collagen in the heart and produce fibrosis (Prakash et al 1995; Shivakumar et al 1992). A sequel to these earlier investigations, the present study examined whether chronic ingestion of low doses of cerium would produce cardiac fibrosis in experimental animals. This communication presents evidence that cerium per se or in combination with magnesium deficiency produces subendocardial fibrosis and increase in interstitial cellularity and collagen content in rat heart. It also confirms the earlier observation from this laboratory that magnesium deficiency promotes accumulation of cerium in the cardiac tissue (Eapen el al 1996).Item Magnesium deficiency enhances oxidative stress and collagen synthesis in vivo in the aorta of rats(INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 1997)Magnesium deficiency has been shown to produce vascular lesions in experimental animals, but the underlying mechanisms of vascular injury are not clear. It has been reported that in rodents, magnesium deficiency enhances circulating levels of factors that promote free radical generation and are mitogenic, In pursuance of these observations, the present study tested the hypothesis that magnesium deficiency may enhance oxidative stress and trigger an accelerated growth response in vivo in the aorta of rats. Oxidative stress mas evaluated in terms of levels of thiobarbituric acid-reactive substances in the serum and aorta and activity of superoxide dismutase and catalase in the aorta; fractional rates of collagen synthesis were assessed using [H-3]-proline. Serum and tissue levels of magnesium and calcium were determined by atomic absorption spectrophotometry, The present study demonstrated for the first time that magnesium deficiency significantly (P < 0.001) increases levels of thiobarbituric acid-reactive substances in the aorta of rats, Other changes in the aorta of animals on the Mg-deficient diet included a significant reduction (54%, P < 0.001) in the activity of superoxide dismutase and catalase (37%, P < 0.01) and a 19% increase in net fractional rates of collagen synthesis (P < 0.05), While serum magnesium was significantly reduced in these animals (P < 0.001), aortic tissue levels of magnesium in these animals remained unaltered throughout the duration of the study, suggesting the existence of other control mechanisms, apart from reduced tissue levels of magnesium, mediating the observed effects. These findings suggest that magnesium deficiency may trigger a wound healing response, involving oxidative injury and growth stimulation, in the vascular system. (C) 1997 Elsevier Science Ltd. All rights reserved.Item Magnesium deficiency-related changes in lipid peroxidation and collagen metabolism in vivo in rat heart(INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 1997)Magnesium deficiency is known to produce a cardiomyopathy, characterised by myocardial necrosis and fibrosis. As part of the ongoing investigations in this laboratory to establish the biochemical correlates of these histological changes, the present study probed the extent of lipid peroxidation and alterations in collagen metabolism in the heart in rats fed a magnesium-deficient diet for 28, 60 or 80 days. While lipid peroxidation was measured by the thiobarbituric acid reaction, collagen turnover rates and fibroblast proliferation were assessed using [H-3]-proline and [H-3]-thymidine, respectively. Tissue levels of magnesium and calcium were determined by atomic absorption spectrophotometry. A 39% increase in the cardiac tissue level of thiobarbituric acid reactive substances was observed on day 60 of deficiency (p < 0.001). A marked drop in collagen deposition rate (59%, p < 0.001%) on day 28 but a significant rise in fractional synthesis rate (12%, p < 0.001) and collagen deposition rate (24%, p < 0.001) on day 60 were observed. A fibroproliferative response in the heart was evident on day 80 but not at earlier time-points. Thus, the present study provides evidence of increased lipid peroxidation and net deposition of collagen in the myocardium in response to dietary deficiency of magnesium. These changes were, however, not directly related to alterations in the tissue levels of Mg. It is suggested that the increase in cardiac collagen synthesis and fibroplasia associated with Mg deficiency may represent reparative fibrogenesis, upon oxidative damage to the cardiac muscle, and is mediated by a mechanism independent of changes in cardiac tissue levels of Mg. (C) 1997 Elsevier Science Ltd.