Manganese concentrations in rat organs: Effect after life-long manganese treatment

Abstract

Manganese is an essential trace metal in human and animals (Underwood, 1977). For normal humans, the concentrations of this metal are higher in bone, liver and kidney and lowest in muscle (Hamilton & Minski, 1972; Hamilton et al., 1972; Underwood, 1977). Depending on the species, the distribution of manganese in various organs in other mammals may differ from that in humans (Cotzias et al., 1972; Underwood, 1977; J. C. K. Lai, A. W. K. Chan, M. J. Minski & L. Lim, unpublished work). Manganese contents tend to be higher in tissues rich in mitochondria and this metal is more concentrated in mitochondria than in other organelles (see Underwood, 1977). Studies on the pathogenesis and pathophysiology of chronic manganese toxicity have largely been focused on cerebral metabolism and dysfunction since the clinical symptoms of manganese encephalopathy in man are strikingly similar to those characteristic of Parkinson's disease (Cotzias et al., 197 1). However, it is well established that in manganese toxicity in animals, organs other than the central nervous system are also affected (Witzleben et al., 1968; Underwood, 1977). For instance, acute manganese overloading gives rise to a form of experimental intrahepatic cholestasis (Witzleben et al., 1968) and chronic manganese feeding retards haemoglobin regeneration in lambs (see Underwood, 1977). Few systematic studies on the distribution of manganese in different organs in chronic manganese toxicity are presently available. We have demonstrated that with chronic MnCI, treatment for over 2 months the manganese concentrations in certain brain regions (see Lai et al., 1981) and in some peripheral tissues (A. W. K. Chan, J. C. K. Lai, M. J. Minski & L. Lim, unpublished work) are selectively increased. As an extension of these studies we have monitored the concentrations of manganese in brain, liver, lung, kidney, heart and spleen in rats that had been treated from conception onwards with MnCI, for over 2 years. We now report on the selective increases in the concentrations of this metal in certain organs as a result of such a treatment. The developmental rat model of chronic manganese toxicity was employed in these studies (see Lai et al., 1981). Female rats (24-28 month old) that had been treated with MnCI, (Lai et al., 1981) from conception onwards until they were used for experiments, and age-matched controls, were studied. Rats were decapitated and brain, liver, lung, kidney, heart and spleen from each animal were removed, put into a plastic bag, rapidly frozen on dry ice and stored at -2OOC. Each organ was freeze-dried and its content of manganese determined by instrumental neutron activation analysis. The samples were irradiated in the University of London Consort Reactor with a neutron flux of 2 x 1012ncm-2. s-l. A 15-min irradiation, 2-min decay and 5-min counting time using gamma-ray spectrometry and a