Animal models for the study of trace metal requirements.

Abstract

In this paper six of the trace elements which are essential for optimum human health will be considered. These are copper, zinc, manganese, molybdenum, chromium and selenium. For each element the realization that it may be essential for man was preceded by the demonstration of a similar dependence either in experimental animals or in livestock inadvertently deprived of the micronutrient. This account will review the value of animal models in identifying possible human requirements for a trace metal and while it is not reliable to extrapolate from such studies to man in determining human quantitative requirements the important contribution which animal studies have made in identifying factors which modify quantitative requirements for these elements will also be outlined. Early this century the ubiquity of trace amounts of certain metals in biological material stimulated efforts to investigate their possible biological function (Underwood, 1977). Cu was reported to be essential for growth and haemoglobin synthesis in rats in 1928 (Hart et al. 1928) and soon afterwards endemic nutritional Cu deficiency was recognized in cattle. Hart and his colleagues feeding rats purified diets then succeeded in demonstrating that Mn and Zn were essential micronutrients, and subsequently these dependencies have been shown in all species studied (Underwood, 1977). Further investigations using purified diets have enabled the identification of Mo, Cr and Se as essential dietary components in animals. More recently, the use of plastic isolators fitted with filters and airlocks to exclude atmospheric dust (Smith & Schwarz, 1967) and create ‘trace element sterile environments’ has provided evidence that tin, nickel, silicon, vanadium, arsenic, lead and cadmium may be essential. None of these elements have been shown to be essential for man. Extension of experience with animals to man has been slow. The possibility that Zn deficiency may contribute to the features of human vitamin deficiency states was considered soon after the original studies with Zn deficient animal studies (Eggleton, 1939) but it was not until the 1960s, in Iran and Egypt, that human Zn deficiency syndromes were identified (Prasad, 1978). These patients exhibited some features of Zn deficiency in common with the earlier description in animals. They had growth retardation with delayed skeletal maturation, icthyosis and hypogonadism. An associated anaemia responded to Fe supplements but the other manifestations only resolved after oral Zn supplements had been given. The more florid features of Zn deficiency such as parakeratosis, eczematous dermatitis, alopecia, impaired immunity and diarrhoea were not observed in man until it was realized that the features of acrodermatitis enteropathica were those of a profound w29-6651/80/3933-4105 fo1.w 0 1980 The Nutrition Society