Magnesium deficiency and cerium promote fibrogenesis in rat heart

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).