Changes in selected biomarkers in freshwater teleost fish, Cyprinus carpio var. communis exposed to sublethal concentrations of chromium sulphate toxicity.

The toxicity of chromium sulphate on plasma electrolytes (Na+, K+, Cl-) level and Na+, K(+)-ATPase activity of an economically important fish, Cyprinus carpio var. communis was evaluated. During sublethal treatment, plasma sodium level was increased, whereas plasma chloride level decreased throughout the experimental period. Plasma potassium level increased upto 10th day and then declined in the rest of the study period. The Na+, K(+)-ATPase activity decreased upto 15th day of treatment and slowly recovered showing significant increase upto 25th day of treatment. The significant changes in the plasma electrolytes levels and Na+, K(+)-ATPase activity can serve as a valuable biomarker of pollutant exposure and effects.

Changes in erythrocyte contents of potassium, sodium and magnesium and Na, K-pump activity after the administration of potassium and magnesium salts.

Low potassium and magnesium status and decreased Na, K-pump activity is an endemic condition among rural Northeast Thais. The authors examined the effect of supplementing potassium and magnesium on erythrocyte potassium, sodium and magnesium content and on Na, K-pump activity. Rural Northeast Thai renal stone patients (62) were recruited, divided into four groups and supplemented for one month with potassium chloride (Group1, n = 16), potassium-sodium citrate (Group2, n = 15), chelated magnesium (Group 3, n =16) and potassium-magnesium citrate (Group 4, n =15) in order to achieve 40 mmol potassium, 10 mmol magnesium and 60 mmol citrate daily. After supplementation with potassium (Groups 1, 2 and 4), plasma potassium and Na, K-pump activity rose significantly in Groups 1, 2 and 4, but erythrocyte potassium rose only in Groups 2 and 4. When supplementing elemental magnesium (Groups 3 and 4), the chelated magnesium caused a significant increase in plasma potassium, erythrocyte potassium, sodium and magnesium without a significant increase in Na, K-pump activity. By contrast, potassium-magnesium citrate caused a significant increase in erythrocyte potassium and magnesium and Na, K-pump activity, but depressed erythrocyte sodium. These results suggest the forms of potassium and /or magnesium salts being supplemented should be considered because they affect erythrocyte potassium, sodium and magnesium content and Na, K-pump activity differently.

Membrane Na+ K+ ATPase inhibition related dyslipidemia and insulin resistance in neuropsychiatric disorders.

There are several reports in literature implicating cholesterol metabolism in the pathogenesis of neuronal degenerations, oncogenesis, functional neuropsychiatric disorders and multiple sclerosis. Biosynthesis of cholesterol takes place by the isoprenoid pathway, which also produces digoxin, an inhibitor of membrane Na(+)-K+ ATPase. Inhibition of this enzyme results in intracellular Mg++ deficiency which can influence cholesterol metabolism. Digoxin also influences transport of tryptophan and tyrosine which are precursors of various neurotransmitters. Alterations in digoxin, membrane Na(+)-K+ ATPase and also in neurotransmitters have been reported in the disorders mentioned above. In view of this, serum lipid profile, activity of plasma HMG CoA reductase (the major rate limiting step in the isoprenoid pathway), RBC membrane Na(+)-K+ ATPase activity, serum Mg++ concentration, concentration of digoxin and concentration of serum neurotransmitters were studied in some neuropsychiatric disorders. The serum serotonin level was increased while that of serum dopamine and noradrenaline was reduced. Serum digoxin levels were high and RBC membrane sodium-potasium ATPase activity and serum magnesium were reduced. There was a reduction in HDL cholesterol and increase in plasma triglycerides (pattern similar to insulin resistance and syndrome X) in most of the disorders studied. The HMG CoA reductase activity was high, the serum total cholesterol was increased while RBC membrane cholesterol was reduced in most of the cases. The significance of increased digoxin with consequent inhibition of membrane Na(+)-K+ ATPase in relation to changes in cholesterol metabolism and insulin resistance type of dyslipidemia is discussed in this paper.

Hypothalamic digoxin and neural regulation of blood pressure and vascular thrombosis.

The isoprenoid pathway produces three key metabolites--digoxin (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter/aminoacid transport), dolichol (regulates N-glycosylation of proteins) and ubiquinone (free radical scavenger). This was assessed in patients with essential hypertension, familial hypotension, acute coronary artery disease and acute thrombotic strokes. The pathway was also assessed in patients with right hemispheric, left hemispheric and bihemispheric dominance for comparison. In patients with acute coronary artery disease, acute thrombotic stroke, essential hypertension and right hemispheric dominance, there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels and low ubiquinone and high free radical levels. There was also an increase in tryptophan catabolites, reduction in tyrosine catabolites, increase in cholesterol-phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in this group of patients as well as in those with right hemispheric dominance. In patients with familial hypotension and left hemispheric dominance, the patterns were reversed. The role of a dysfunctional isoprenoid pathway and endogenous digoxin in the pathogenesis of essential hypertension and familial hypotension and in thrombotic vascular disease in relation to hemispheric dominance is discussed.

Endogenous strychnine, nicotine, and morphine--description of hypo and hyper-strychninergic, nicotinergic and morphinergic state in relation to neuropsychiatric diseases.

Previous work from this laboratory had demonstrated the presence of endogenous morphine, strychnine and nicotine in the mammalian brain and human serum samples. Morphine is synthesised from tyrosine and strychnine and nicotine from tryptophan. This study examines the role of strychnine, nicotine and morphine in neuropsychiatric disorders. The blood levels of tyrosine, tryptophan, strychnine, nicotine and morphine were studied as also RBC membrane Na(+)-K+ ATPase activity. It was found that serum tyrosine levels were reduced and tryptophan levels elevated in all neuropsychiatric disorders studied with a reduction in RBC Na(+)-K+ ATPase activity. Nicotine was present in significant amounts in serum of patients with schizophrenia, CNS glioma and syndrome X with multiple lacunar state. Morphine was present in significant amounts only in the serum of patients with multiple sclerosis and MDP. Strychnine was present in significant amounts in the serum of patients with epilepsy, Parkinson's disease and MDP. The presence of nicotine and strychnine in significant amounts could be related to elevated tryptophan levels suggesting the synthesis of these alkaloids from tryptophan. Morphine was not detected in most of the disorders owing to low tyrosine levels noted in them. Na(+)-K+ ATPase inhibition noticed in most of the disorders could be related to decreased hyperpolarising morphinergic transmission and increased depolarising nicotinergic and strychinergic transmission. The role of morphine, strychnine and nicotine in the pathogenesis of these disorders in the setting of membrane Na(+)-K+ ATPase inhibition is discussed.

Decreased sodium-potassium and calcium adenosine triphosphatase activity in asthma: modulation by inhaled and oral corticosteroids.

The activation of both the inflammation-producing cells and the airway smooth muscle in asthma is believed to be a phenomenon dependent on the intracellular calcium. The activity of Na+ K+ ATPase and Ca2+ ATPase, enzymes responsible for regulating the intracellular calcium concentrations has been reported to be decreased in asthma. An increase in plasma lysophosphatidylcholine (LPC), which is known to be a pro-inflammatory compound and has an inhibitory effect on the two ATPases has also been reported. Corticosteroids are potent antiinflammatory drugs very effective in the treatment of asthma. The effect of long-term (12 weeks) treatment with inhaled beclomethasone dipropionate (BDP) and short-term (1 week) treatment with oral prednisolone on the activity of the two ATPases and intracellular calcium in leukocytes and plasma LPC levels was investigated. Both the treatments resulted in an improvement in lung function accompanied by an increase in the activities of the ATPases and a decrease in the intracellular calcium and LPC levels. It was concluded that increase in the activities of Na+ K+ ATPase and Ca2+ ATPase and a consequent lowering of intracellular calcium, and a lowering of plasma LPC may underlie the beneficial effect of corticosteroids in asthma.

linkage of anp level to NA+,K+ -atpase, osmotic fragility under the effect of mannitol in crf patients

The present study was designed to determine the plasma level of ANP in chronic renal failure CRF patients before and after mannitol infusion in order to find whether the protective effect of mannitol is a primary action or is due to release of ANP, also, to elucidate the possible effects of mannitol on red cell membrane changes and enzyme activities in these CRF patients. To achieve this goal, 20 patients with CRF and 10 healthy controls were investigated for the following parameters: Plasma ANP level, blood urea and creatinine concentration, blood picture, blood indices, the activity of erythrocyte Na-K-ATPase and hemolysis of red cell to different concentrations of NaCl. 500 ml 20% mannitol were given to uremic patients by i.v. infusion for 5 consecutive days. All the previous parameters were reestimated on the 5th day half an hour after mannitol infusion [MI] and then 24 hours after the last mannitol infusion [6th day]. From this study, it can be concluded that the volume loading by MI can be regarded as an important physiological stimulus of ANP release. This beneficial effect obtained by MI were transient and it is suggested that it is more advantageously replaced by an infusion of doses of synthetic h-ANP to obtain more durable results. Activation of sodium-potassium ATPase of the erythrocyte ghosts accompanying the elevated level of ANP in this study was supported by the positive correlation between Na-K-ATPase and ANP after MI

Plausible involvement of a diabetic serum factor in neutrophil membrane pathology.

With a view to determining the role of diabetic serum factor (DSF) in the progression of membrane pathology, time-dependent preincubation effects of DSF on certain membrane-bound enzymes of normal polymorphonuclear leucocytes (PMNL) have been studied. DSF is found to cause significant decrements in the activities of Na+/K+ ATPase, PLC and AcE of PMNL on in vitro incubation for 60 min, while the effect on Ca2+/Mg2+ ATPase appears only on prolonged incubation with an initial hike in activity at 5 min. The implications of these results have been discussed.

Haematological and erythrocyte membrane changes induced by amiodarone, in rats.

The effect of Amiodarone (AD), a cationic amphiphilic drug, on erythrocytes and leucocytes was studied. Treatment of rats with AD showed a significant decrease in the red cell count and the level of Hemoglobin. Amiodarone altered the fluidity of the erythrocyte membrane followed by a decrease in the activities of membrane bound enzymes like (Na+, K+)-ATPase, Acetylcholine esterase and NADH dehydrogenase. A slight increase in the leucocyte count was also observed in the treated animals.

Abnormal erythrocyte Na, K-ATPase activity in a northeastern Thai population.

We studied the cellular membrane enzyme responsible for potassium transport in different Thai populations. We measured plasma and intraerythrocytic concentrations of sodium and potassium, activities of erythrocytic membrane Na, K-activated adenosine triphosphatase (Na, K-ATPase), ouabain-insensitive ATPase, total ATPase and the activity ratio of Na, K-ATPase/total ATPase in 25 healthy blood donors at Khon Kaen University Hospital, Khon Kaen (group 1), and in 32 donors at the National Blood Center, Thai Red Cross Society, Bangkok (group 2). Group 1 subjects had significantly higher concentrations of erythrocyte sodium (p < 0.001) and lower activity of Na, K-ATPase (p < 0.001) than group 2. When data of these 2 groups were combined, erythrocyte Na+ correlated inversely with Na, K-ATPase and the activity ratio of Na, K-ATPase/total ATPase. Our study suggests that there is a defect in membrane transport enzymes for sodium/potassium in certain northeast Thai populations.

Tannic acid as a marker for membrane sidedness of human red cell vesicles

Membrane sidedness of human eythrocytes was investigated in inside-out vesicles (IOV's), ghosts and intact cells by means of transmission electron microscopy (e.m.) after tannic acid fixation. No gross difference in appeearance of either membrane surface was observed when IOV's were subjected to conventional e.m. preparation. This included in addition to tannic acid, a double fixation with glutaraldehyde and osmium, followed by "en bloc" and thin section staining with uranyl acetate and lead citrate. By contrast, if IOV's were treated with a high EDTA concentration (2-5 mM) before tannic fixation, granular, electron-dense deposits were found on one of the surfaces. The presence of such a meterial was unaffected by neuraminidase treatment prior to the EDTA step. On the hand, red cells show no electron-dense deposits when exposed to EDTA (5 mM) unless they presented a light cytoplasm and an altered membrane appearance. Such a material was only observed on the inner membrane surface. Furthermore, a similar distribution of such deposits following EDTA treatment was also found in white ghosts before being induced to vesiculate. These results indicate that tannic acid can be employed as a marker for the cytoplasmic surface of the human erythrocyte membrane when used in combination with EDTA

Effect of sexual cycle on red cell membrane permeability as revealed by influx of Rubidium-86 and adenosinetriphosphatase in female rats.

Red cell membrane permeability, as revealed by influx of Rubidium-86 and ATPase activity, was studied in different phases of sexual cycle in female rats and no significant changes have been found.