Satya V. Chandra

Possible role of regional superoxide dismutase activity and lipid peroxide levels in cadmium neurotoxicity: in vivo and in vitro studies in growing rats

Cd2+ (0.4 mg/kg) administration to growing rats (45 +/- 5 g) intraperitoneally, daily for 30 days was found to decrease the activity of superoxide dismutase (SOD) in all the brain regions, except hippocampus. The concentrations of lipid peroxides were significantly elevated in the cerebellum, cerebral cortex, corpus striatum and midbrain. A 100% inhibition in SOD activity was observed by 14 microM and 50 microM of Cd2+ in bovine blood and rat brain preparations, respectively. Cadmium-induced strong inhibitory effect on brain and purified bovine blood SOD suggested a direct effect of the metal on enzyme molecule. Furthermore, in vitro addition of a wide range of Cd2+ (1-100 microM) increased the rate of lipid peroxidation (LPO) reaction in fresh brain homogenate, however, did not affect boiled homogenate. The studies on LPO in reconstituted homogenate resulting from mixing of fresh and/or heated different subcellular fractions indicated the presence of some heat-labile Cd2+ -sensitive factor in 15000 x g pellet fraction. It is suggested that Cd2+ directly and indirectly through inhibition of SOD, increases the LPO of cell membranes and thus produces damage to the associated physiological functions leading to central nervous dysfunctions.

An Exploratory Study of Manganese Exposure to Welders

Sixty welders (20 each from Plants A, B, and C) and 20 control subjects were investigated for the possible occurrence of manganese poisoning among welders exposed to the welding fumes containing this metal. Ten, 9, and 5 welders from Plants B, C, and A, respectively, were diagnosed as suspected cases of early manganese poisoning. The diagnosis was based on the proof of overexposure to manganese by the findings of increased urinary levels of this metal, signs of early neurological involvement, and increased contents of serum calcium. These results are discussed in relation to the manganese concentration in the air around the welders breathing zones.

LEVELS OF 5-HYDROXYTRYPTAMINE, DOPAMINE AND NOREPINEPHRINE IN WHOLE BRAIN OF RABBITS IN CHRONIC MANGANESE TOXICITY

Abstract— The levels of 5‐Hydroxytryptamine (5‐HT), dopamine and norepinephrine were estimated in whole brain of rabbits inoculated intratracheally with manganese dioxide (400 mg). Twenty one and 58 per cent lowering in the concentrations of dopamine and norepinephrine, respectively, were observed as compared to that of controls, the concentration of 5‐HT was found to be unaltered.

Comparative toxicity of trivalent and hexavalent chromium: Alterations in blood and liver

The effects of trivalent and hexavalent chromium compounds on rabbits were studied with a view toward investigating the toxic potentials of two different forms of chromium to which industrial workers or miners might be exposed. While both forms of chromium altered the levels of certain important chemical constituents of blood and serum and produced significant morphological changes in the liver, the hexavalent form induced a greater effect. The accumulation of the metal was also higher in animals exposed to chromium in oxidation state 6 than in those exposed to metal in state 3.

Concentrations of Striatal Catecholamines in Rats Given Manganese Chloride Through Drinking Water

Abstract: Male albino rats were exposed to manganese through drinking solution containing MnCl2·4H2O (1 mg/ml) in water. The contents of catecholamines, homovanillic acid, manganese and the activity of monoamine oxidase (MAO) were measured in the corpus striatum at different time intervals up to a period of 360 days. The contents of tyrosine in the corpus striatum and serum were also estimated. Manganese treatment produced an initial increase in the contents of dopamine (DA), norepinephrine (NE), homovanillic acid (H VA) and tyrosine in the corpus striatum. This was followed by a period when concentrations were almost normal (dopamine from 120 to 240 days, norepinephrine at 180 and 240 days and homovanillic acid at 240 days after manganese administration). Thereafter the contents of these substrates declined significantly at 300 and 360 days of treatment. However, these alterations were not correlated with the concentrations of manganese in this region, which gradually increased up to 240 days, and thereafter remained constant until the termination of the experiment. The underlying biochemical mechanisms of manganese‐induced sequential changes in the striatal contents of catecholamines have been discussed in relation to the development of psychiatric and neurological phases of manganese poisoning.

Manganese-induced behavioral dysfunction and its neurochemical mechanism in growing mice

Abstract— Suckling mice were exposed to manganese from birth indirectly through their mothers and then directly through drinking water after weaning. The growth and development of these mice and their age‐matched controls were almost identical. Motor activity of offspring measured at 30‐day intervals showed a significant increase at 60 and 90 days in manganese‐treated mice compared to controls. Increased motor activity was associated with significant elevation in the levels of dopamine and norepinephrine in the corpus striatum of treated mice. The levels of striatal tyrosine, homovanillic acid and manganese were also significantly increased in mice after manganese exposure. Thus an animal model of early manganese poisoning has been developed with a possible role of striatal amines in the production of behavioral dysfunction in the treated mice. Implications of these findings are discussed in relation to the manifestations of the psychiatric phase of early manganese poisoning in man.

Role of iron deficiency in inducing susceptibility to manganese toxicity.

SummaryDaily intraperitoneal administration of manganese chloride (15 mg/kg) to rats, maintained on an irondeficient diet, produced marked alterations in the activity of succinic dehydrogenase, monoamine oxidase, and in the morphology of the liver. Manganese accumulation was also significantly increased in such rats than after similar treatment to normally fed rats. Iron deficiency leads to increased absorption of manganese which is responsible for increased susceptiblity to manganese toxicity in these animals.ZusammenfassungDie tägliche intraperitoneale Verabreichung von Manganchlorid (15 mg/kg) führt an Ratten, die auf eisenarmer Diät gehalten wurden, zu deutlichen Veränderungen in der Aktivität der Succinatdehydrogenase und der Monaminoxydase sowie zu morphologischen Veränderungen der Leber. Die Anreicherung von Mangan war unter diesen Bedingungen signifikant stärker als bei normal gefütterten Ratten. Der Eisenmangel bewirkt eine gesteigerte Resorption von Mangan, was für die erhöhte Mangantoxizität bei diesen Tieren verantwortlich ist.

Manganese encephalopathy in growing rats

Abstract Manganese chloride was administered orally to growing rats, and enzymatic and morphological studies in the brain were carried out at different time intervals for a period of 60 days. The activity of monoamine oxidase was significantly increased at 15 days in manganese-administered rats, and the activity further increased at 30 days and thereafter remained almost stationary until the termination of the experiment. Neuronal degeneration in the cerebral and cerebellar cortex was observed at 30 days, the intensity of the lesion increased with the duration of metal exposure, and at 60 days marked neuronal degeneration along with neuroglial proliferation was observed in the cerebral cortex and in the caudate nucleus. Thus manganese exposure produced enzymic and morphological alterations in the brain of growing animals much earlier than reported in the adult animals, even though the dose of manganese was much lower in growing rodents as compared to adults. This observation indicates that the growing brain is more susceptible to the toxic effects of the metal. Further, ingestion of manganese can also produce chemical and morphological alterations in the brain. These observations are of great significance in view of increasing environmental pollution with manganese due to its recent use in gasoline.

Neuromelanin in manganese-exposed primates

Monkeys developed muscular weakness and rigidity of the lower limbs after 18 months exposure to manganese. These are neurological signs typical of chronic manganese intoxication. Marked neuronal degeneration with depigmentation was noticed in the region of substantia nigra. Significance of depigmentation in relation to the depletion in the contents of brain dopamine in chronic manganese intoxication has been discussed.

Manganese poisoning: Clinical and biochemical observations

Abstract Clinical and biochemical studies were conducted in twelve cases of suspected manganese poisoning. On the basis of neurological observations they were divided into three grades of poisoning, mild, moderate and severe. A significant increase in serum calcium and adenosine deaminase levels was observed in cases of mild and moderate grades of poisoning, respectively. In a case of severe poisoning the increase in serum calcium was twofold and that of adenosine deaminase threefold that in normal volunteers. Serum inorganic phosphates, alkaline phosphatase and proteins were not altered. No relationship could be established between the period of exposure to manganese and severity of poisoning. The mechanism of hypercalcemia and increase in adenosine deaminase in serum has been discussed. It is suggested that serum calcium levels could be of great significance in detecting manganese poisoning in its early stages. Significant changes in adenosine deaminase levels did not appear until moderate poisoning occurred.