We have investigated the effect of lead exposure on lipid peroxidation, a deteriorative process of the membranes, in the different regions of the brain. Lead treatment (50 mg/kg b.wt. intragastrically) for a period of eight weeks to rats resulted in a significant accumulation of lead in all the regions of brain, at maximum in hippocampus. The lipid peroxidation was accentuated following lead exposure and there was a linear correlation between the increase in lipid peroxidation and increase in lead levels (r = 0.75). The antioxidant capacity of the neuronal cells in terms of the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase was diminished. Lead treatment also altered the glutathione status i.e. levels of reduced glutathione were lowered, accompanied with the accumulation of oxidized glutathione. Furthermore, the activity of glutathione reductase was significantly lowered in lead-treated animals. The activity of membrane bound enzyme acetylcholinesterase was significantly inhibited following lead exposure and there was a linear correlation between the increase in lipid peroxidation and decrease in acetylcholinesterase activity (r = -0.83). It appears from the results that lead may exert its neurotoxic effects via peroxidative damage to the membranes.

The effect of aluminium, A1(3+) (10 mg/kg body weight/day i.p.) for a period of 4 weeks was examined on the calcium homeostatic mechanisms in rat central nervous system. Incubation of synaptosomes prepared from rat brain, with aluminium in vitro had a detrimental effect on the activity of Ca2+ ATPase which could be reversed completely on exogenous addition of desferrioxamine (10 microM) and partially with glutathione (1 mM). In vivo administration also revealed a similar observation. A marked increase in the levels of intracellular calcium was observed after aluminium treatment. Concomitant to the increased levels of intracellular calcium, there was an increase in the levels of lipid peroxidation and a consequent decrease in fluidity of synaptic plasma membranes. In addition, aluminium also had an inhibitory effect on the depolarization-induced calcium uptake which was found to be of a competitive type. The biological activity of calcium regulatory proteins calmodulin and protein kinase C was considerably affected by aluminium. The results suggest that aluminium exerts its toxic effects by modification of the intracellular calcium messenger system with detrimental consequences on neuronal functioning.

1. Respiratory and circulatory effects of phenyldiguanide (PDG), sodium cyanide and lobeline have been studied in eighteen patients. 2. PDG, when injected into the main pulmonary artery, produced stimulation of breathing together with bradycardia and hypotension. A mean injection-response time of 5·2 s was close to the pulmonary artery-ear lobe circulation time in the same patients. 3. Sodium cyanide produced respiratory and circulatory effects similar to PDG and with the same injection-response time. It was concluded that both drugs act on the carotid body. 4. Lobeline sulphate produced apnoea with or without cough in twelve of the fifteen patients studied, with a mean injection-response time of 2·1 s; this was shorter than the pulmonary artery-ear lobe circulation time. This response preceded the well-known hyperpnoea. 5. The short injection-response time of lobeline is consistent with the hypothesis that lobeline stimulates pulmonary receptors before it acts on the carotid bodies, and that there are receptors in the human lung that are depolarized by chemical agents. 6. The cough response was replaced by apnoea when the dose of lobeline was decreased. 7. Whereas PDG did not produce any abnormal sensation in the body, lobeline caused a sensation of fumes or smoke in the lower throat or burning over the manubrium sterni. Neither drug produced a sensation of breathlessness.

The effects of Al on the central cholinergic system have been studied. Al, at a dose of 10 mg/kg of body weight/day for 4 weeks, had a deleterious effect on the activities of biosynthetic (choline acetyltransferase) and hydrolytic (acetylcholinesterase) enzymes of the neurotransmitter acetylcholine. The levels of acetylcholine were also significantly lowered in different brain regions at the end of the dose regimen. There was a significant decrease in high‐affinity choline uptake following Al exposure. Muscarinic acetylcholine receptor binding studies revealed a decreased number of binding sites (Bmax), with the maximum effects being manifested in the hippocampus. Exogenous addition of 10 µM desferrioxamine restored the muscarinic receptor binding completely. The impaired cholinergic functioning had severe effects on cognitive functions. Neurobehavioral deficits were manifested in terms of decreased active (52%) and passive (73.30%) avoidance tests. The results suggest that Al exerts its toxic effects by altering cholinergic transmission, which is ultimately reflected in neurobehavioral deficits.

In the present study, an attempt has been made to investigate the distribution of aluminum in different regions of brain and body organs of male albino rats, following subacute and acute aluminum exposure. Aluminum was observed to accumulate in all regions of the brain with maximum accumulation in the hippocampus. Subcellular distribution of aluminum indicated that there was maximum localization in the nucleus followed by cytosolic, microsomal, and mitochondrial deposition. Elution profile of cytosolic proteins on G-75 Sephadex column revealed a substantial amount of aluminum bound to high-mol-wt protein fraction. Aluminum was also seen to compartmentalize in almost all the tissues of the body to varying extents, and the highest accumulation was in the spleen.