Biomedical subjects

T Funakoshi

Publications and source records attributed to T Funakoshi.

At least 73 records · Page 4Linked to original sources

PubMed1996

Mechanism of mobilization of cadmium by dithiocarbamates in rat primary hepatocyte cultures.

The mechanism of mobilization of cadmium (Cd) by N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) in rat primary hepatocyte cultures was studied. Probenecid pretreatment increased Cd efflux from the hepatocytes by BGD, but did not affect Cd efflux by HBGD. p-Aminohippurate treatment had no effect on Cd efflux by the chelating agents. These results suggest that an enhancing effect of probenecid on the BGD-induced Cd mobilization is due to its inhibitory effect on the glucuronidation of BGD and not its specific action on BGD transport. Verapamil and nicardipine had no effect on the chelating agent-induced Cd mobilization. Phlorizin did not affect Cd efflux by BGD or HBGD. Phloretin and cytochalasin B inhibited Cd efflux by the chelating agents. These results seem to be evidence that BGD and HBGD may be transported by a facilitated diffusion system in the hepatocytes.

Animals↗

PubMed1996

Effects of lanthanide ions on the binding ability of annexin V to phospholipid vesicle.

The effects of lanthanide ions (Ln(3+)), La(3+), Ce(3+), Gd(3+), and Tb(3+), on the binding ability of annexin V to phospholipid vesicle were studied, and compared with that of Ca(2+). The energy transfer following excitation at 278 nm was accompanied by a small decrease (about 3%) in the fluorescence signal (310-315 nm) of the aromatic amino acid residues, followed by strong re-emission of annexin V-bound Tb(3+) at 547 nm. The results of the titration of Tb(3+)-protein interactions using the rate dialysis method suggest that there are two high affinity metal binding sites on annexin V, to which Tb(3+) binds with an average dissociation constant, Kd, of about 2.11 x 10(-7) M. The Ln(3+) seemed to assist the anticoagulant action of annexin V because it binds more strongly to phospholipid than Ca(2+) does. Annexin V had the same ability to bind phospholipids in 10 mu M Ln(3+) as it did in 1 InM Ca(2+), showing that it binds to anionic phospholipids with Ln(3+) more strongly than it does with Ca(2+).

Annexin A5↗

PubMed1995

Effects of chelating agents on testicular toxicity in mice caused by acute exposure to nickel.

N-Benzyl-D-glucaminedithiocarbamate (BGD), diethyldithiocarbamate (DDTC), dihydroxyethyldithiocarbamate (DHED), trans-1,2-cyclohexanediamine N,N,N',N'-tetraacetic acid (CDTA), and meso-2,3-dimercaptosuccinic acid (DMSA) were studied for their protective effects against the testicular toxicity in mice induced by acute exposure to nickel (Ni). Mice were injected intraperitoneally with NiCl2 (5 mgNi/kg) and 30 min or 24 h later, they were injected intraperitoneally with chelating agents (400 mumol/kg). Ni injection increased lipid peroxidation and concentrations of Ca and Fe in the testes, liver, and kidney, and decreased the testicular weight and the fertility rate. At 30 min after Ni treatment, the chelating agents other than CDTA effectively depressed Ni concentration in the testes. At 24 h after Ni treatment, DMSA, BGD, and DDTC were effective in mobilizing Ni from the testes. DMSA, BGD, and CDTA significantly prevented the increase in the lipid peroxidation, the increase in the concentrations of Ca and Fe in the testes, liver, and kidney, and the decrease in the fertility rate caused by Ni injection. Treatment with DMSA or BGD was more effective than that with the others in decreasing the testicular Ni concentration, resulting in effective protection against Ni-induced testicular damage.

Animals↗

PubMed1995

[Effect of the GH-PRL superfamily on circulating plasma insulin-like growth factor-1].

To elucidate the effects of growth hormone (GH), prolactin (PRL), and human placental lactogen (hPL) on the regulation of insulin-like growth factor (IGF-1), we compared plasma IGF-1 levels, the pattern of circulating IGF-1-IGF-binding protein complexes (IGF-1 complexes), and unsaturated binding protein (USBP) levels among 1) naturally growing Wistar rats at several developmental stages, 2) rats subcutaneously administered GH, and 3) hypophysectomized rats treated with each of the three hormones. We further evaluated the in vitro secretion of IGF-1 by primary cultured rat hepatocytes, following exposure to the hormones singly or in combination. Plasma IGF-1 and USBP levels were determined by radioimmunoassay and competitive radioassay, respectively. IGF-1 complexes were separated from plasma and culture medium by Sephadex G150 and HPLC gel-chromatography, respectively. The results were as follows. 1) In naturally growing rats, plasma IGF levels were low during fetal life and after birth until 28 days of age, and thereafter increased rapidly to reach an adult level by 35 days. At 35 days, the molecular distribution of IGF-1 switched from an infantile pattern (only 40Kd IGF-1 complex) to an adult form (IGF-1 complexes with both 40Kd and 150Kd proteins). In addition, 150Kd USBP became detectable after 28 days. 2) Administration of GH for 3 days to 13-day-old rats induced 150Kd USBP 9 days earlier than in controls, while plasma IGF-1 levels remained comparable throughout the period examined. 3) In the hypophysectomized rats, plasma IGF-1 levels decreased to approximately one fifth of those in untreated rats, accompanied by the disappearance of 150Kd USBP and 150Kd IGF-1 complex. However, when GH (but not PRL or hPL) was continuously administered for 72 hrs, plasma IGF-1 levels and the circulating profile of IGF-1 complexes were nearly restored to those in control rats. 4) Addition of GH (but not PRL) to the culture medium caused hepatocytes to secrete IGF-1, consisting of only the 40Kd IGF-1 complex. This effect was blocked by the simultaneous addition of hPL with GH. These findings indicate that, of the hormones analyzed, GH is the most important regulator of the plasma IGF-1 concentration and circulating complex forms during the developmental periods in rats, as is also thought to be the case in humans.

Animals↗

PubMed1995

The utility of chelating agents as antidotes for nephrotoxicity of gold sodium thiomalate in adjuvant-arthritic rats.

The effects of 2,3-dimercaptopropane sulphonate (DMPS) and N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine) against the renal damage induced by gold sodium thiomalate (AuTM) in adjuvant-arthritic rats were studied. Arthritic rats induced by adjuvant using Mycobacterium butyricum were injected intraperitoneally with a chelating agent (0.6 mmol/kg) immediately after intramuscular injection of AuTM (0.066 mmol/kg) every other day for 21 days. Treatment with DMPS and bucillamine prevented increases in the urinary excretion of protein, aspartate aminotransferase, and glucose and blood urea nitrogen level after AuTM injection. AuTM prevented the increase in both adjuvant-injected and uninjected hind-feet volumes. The prevention of these inflamed lesions by AuTM was not affected by DMPS and bucillamine. These chelating agents decreased the gold concentration in the kidney and liver after AuTM administration, but did not affect the hepatic and renal concentrations of copper, zinc, iron, and calcium except the renal copper level after AuTM. These findings suggest that DMPS and bucillamine are very useful antidotes for gold toxicity.

Animals↗

PubMed1995

Impaired cholinergic peripheral vasodilation and its relationship to hyperemic calf blood flow response and exercise intolerance in patients with chronic heart failure.

This study examined the peripheral endothelium-dependent vasodilatory response to acetylcholine and the endothelium-independent vasodilatory response to nitroprusside in 19 patients with chronic heart failure and eight controls. These peripheral blood flow responses were compared with hyperemic calf blood flow changes after maximum leg exercise and 5-min femoral occlusion. The peripheral blood flow response to forearm intra-arterial infusion of acetylcholine and sodium nitroprusside, and reactive hyperemic calf blood flow changes were measured by plethysmography. All peripheral blood flow responses were significantly reduced in patients with chronic heart failure (P < 0.05). Reduction of acetylcholine-mediated changes in peripheral blood flow was correlated with exercise-induced calf blood flow response (r = 0.51, P < 0.05), but not with occlusion-induced calf blood flow response (r = 0.02, NS). Sodium nitroprusside-mediated changes were not correlated with any reactive hyperemic blood flow responses (exercise: r = 0.27, NS; occlusion: r = 0.11, NS). When the patients were divided into two subgroups based on the median exercise-induced calf blood flow change, the subgroup with the lower calf blood flow response showed a reduction in exercise capacity (anaerobic threshold: 11.8 +/- 0.6 vs. 14.6 +/- 1.0 ml/kg/min; P < 0.05). These findings suggest that endothelial dysfunction is related to a decrease in exercise-induced skeletal muscle blood flow and exercise capacity in patients with chronic heart failure.

Acetylcholine↗

PubMed1995

Effects of dithiocarbamates and cadmium on the enzymatic activities in liver, kidney and blood of mice.

The effects of N-benzyl-D-glucamine dithiocarbamate (BGD), diethyldithiocarbamate (DDTC), and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) on the enzymatic activities in mice were studied. The mice were given i.v. injections of these chelating agents (1 mmol/kg) and 3 h later the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GTP), alkaline phosphatase (ALP), leucine aminopeptidase (LAP), and cholinesterase (ChE) in the liver, kidney, and blood were determined. These enzymatic activities were little changed by treatment with these chelating agents. Cadmium (Cd) administration markedly decreased the activities of AST and ALT in the liver and kidney and greatly increased these enzymatic activities in blood. The changes in the enzymatic activities by treatment with Cd were prevented by injection of BGD (1 mmol/kg). These results indicate that BGD, DDTC, and HBGD were not toxic to the liver or kidney of mice and that BGD treatment protected against the acute hepatic and renal toxicity induced by Cd.

Alanine Transaminase↗

PubMed1995

Tubulin dynamics in neuronal axons of living zebrafish embryos.

The mechanism of cytoskeletal protein transport, especially the question of what kind of form the cytoskeletal proteins assume during transport in neurons in situ, has been an important, as yet unsettled issue. To clear up this matter, we adopted the embryonic zebrafish as a living animal model and applied the fluorescence recovery after photobleaching (FRAP) method. The zebrafish embryo is appropriate for this kind of study because of its transparency during the early developmental stage, allowing the observation of neurons that incorporate the microinjected fluorescent tubulin directly under fluorescence microscopy. FRAP revealed no movement of the bleached zone proximodistally, where fluorescence recovered gradually (recovery half-time, 44.2 +/- 11.2 min; n = 36), suggesting that the polymers are stationary but dynamic and that the true moving form could be small oligomers or heterodimers.

Animals↗

PubMed1995

Ruptured dissecting aneurysm of the peripheral anterior cerebral artery--case report.

A 27-year-old male presented with intracranial hemorrhage due to rupture of an idiopathic dissecting aneurysm in the A4 segment of the left anterior cerebral artery (ACA). This is a very rare location. He was successfully treated by resection of the aneurysm without neurological deficits. Surgical intervention is recommended for patients with intracranial hemorrhage due to ruptured dissecting aneurysm of the ACA to prevent rebleeding.

Adult↗

PubMed1995

Protective effect of N-benzyl-D-glucamine dithiocarbamate against renal toxicity in rats during repeated cis-diamminedichloroplatinum administrations.

The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) against the renal toxicity caused by repeated injections of cis-diamminedichloroplatinum (DDP) were studied in rats. The rats were injected i.p. with BGD (2.0 mmol/kg) immediately after i.v. injection of DDP (20 mumol/kg), and after 10 and 20 days they received repeated treatments with the same doses of DDP and BGD. Treatment with BGD prevented nephrotoxicity after repeated DDP administrations. Repeated DDP injections increased lipid peroxidation in the kidney and decreased GSH concentration in the kidney at 5 days after the third injection of DDP. BGD treatment prevented the increase in lipid peroxidation and the decrease in the GSH concentration caused by repeated administration of DDP. The determination of activities of antioxidant enzymes in the kidney showed that catalase activity decreased after repeated DDP administrations and that superoxide dismutase activity tended to decrease. Changes in activities of these enzymes were prevented by BGD treatment. The platinum concentrations in kidney and liver were decreased by BGD treatment. These results indicate that BGD treatment prevents the accumulation of platinum in the kidney after repeated administrations of DDP, resulting in protection against the DDP-induced renal toxicity.

Animals↗

PubMed1994

Effect of angiotensin-converting enzyme inhibitors on endothelium-dependent peripheral vasodilation in patients with chronic heart failure.

OBJECTIVES: This study was performed to determine whether acute inhibition of angiotensin-converting enzyme restores impaired endothelium-dependent vasorelaxation in patients with chronic heart failure. BACKGROUND: Recent reports have demonstrated that endothelium-dependent vasodilation induced by cholinergic stimuli is attenuated in the peripheral vascular bed of patients with chronic heart failure. METHODS: We examined the effects of local intraarterial infusion of enalaprilat (0.6 micrograms/min per 100 ml tissue volume) on responses initiated by acetylcholine or sodium nitroprusside in the forearm vascular bed in 8 normal subjects, 12 patients with mild heart failure (New York Heart Association functional classes I and II) and 10 patients with more advanced heart failure (functional classes III and IV). Forearm blood flow was measured by means of venous occlusion plethysmography. RESULTS: Although enalaprilat alone did not affect basal forearm blood flow, it significantly augmented the increase in forearm blood flow induced by acetylcholine in normal subjects (p < 0.01) and in those with mild heart failure (p < 0.05). However, the effect was not found in patients with more advanced heart failure. Coinfusion of enalaprilat did not enhance sodium nitroprusside-induced vasodilation in any of the groups. To explore the mechanism of the inhibitor's effect, an additional 20 patients with mild heart failure (functional class II) were pretreated with a cyclooxygenase inhibitor, acetylsalicylic acid (n = 10) or an inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (n = 10), followed by administration of acetylcholine with or without enalaprilat. Acetylsalicylic acid reduced the converting enzyme inhibitor's effect, whereas NG-monomethyl-L-arginine failed to block the augmentation of blood flow. CONCLUSIONS: These results suggest that inhibition of angiotensin-converting enzyme potentiates endothelium-dependent vasodilation induced by cholinergic stimuli, presumably through modulation of prostaglandin metabolism, in the peripheral vasculature of patients with mild chronic heart failure.

Acetylcholine↗

PubMed1994

Comparative effects of chelating agents on distribution, excretion, and renal toxicity of gold sodium thiomalate in rats.

The effects of various chelating agents, such as (2S)-1-(3-mercaptopropionyl)-L-proline (captopril), N-(2-mercaptopropionyl)-glycine (tiopronin), L-cysteine (L-Cys), D-cysteine (D-Cys), N-acetyl-L-cysteine (L-NAC), N-benzyl-D-glucamine dithiocarbamate (BGD), and ethylenediaminetetraacetate (EDTA), on the distribution, excretion, and renal toxicity of gold sodium thiomalate (AuTM) in rats were investigated. Rats were intraperitoneally injected with the chelating agents (1.2 mmol/kg each) immediately after intravenous injection of AuTM (0.026 mmol/kg). Treatment with captopril or tiopronin significantly prevented increases in the urinary excretion of protein, aspartate aminotransferase (AST), and glucose and the blood urea nitrogen (BUN) level after AuTM injection. L-NAC and D-Cys significantly prevented increases in the urinary excretion of protein, AST, and glucose after AuTM injection, but did not reduce to control levels. Treatment with BGD, EDTA, or L-Cys did not prevent AuTM-induced increases in the urinary excretion of protein, AST, and glucose and BUN level. Tiopronin significantly increased the urinary excretion of gold. Captopril slightly promoted both the urinary and fecal excretion of gold, resulting in the significant increase in the total excretion of the metal. Tiopronin and captopril significantly decreased the gold concentration in the kidney and liver. L-Cys, D-Cys, L-NAC, BGD, and EDTA had no significant effect on the excretion or distribution of gold at 7 days after AuTM injection. These results indicate that tiopronin and captopril can ameliorate the renal toxicity induced by AuTM. In addition, the comparative effects of 2,3-dimercaptopropane sulfonate (DMPS), N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine), captopril, and tiopronin at various dose levels (1.2, 0.4 or 0.2 mmol/kg) on the distribution and renal toxicity of gold were studied. DMPS was effective in removing gold from the kidney and in protecting against the renal toxicity after AuTM injection at the even lower dose level (0.2 mmol/kg). Bucillamine and tiopronin protected against the renal toxicity of gold at dose levels of 0.4 and 1.2 mmol/kg and captopril ameliorated the gold toxicity only at higher dose level (1.2 mmol/kg).

Animals↗

PubMed1994

Mechanism of mobilization of renal and hepatic cadmium by dithiocarbamates in mice.

To clarify the mechanism of mobilization of renal and hepatic cadmium (Cd) by N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) in mice exposed to Cd, the effects of pretreatment with probenecid, an organic anion transport inhibitor, or with acivicin, a gamma-glutamyltranspeptidase (gamma-GTP) inhibitor and ureter-ligation were investigated on the excretion and distribution of chelating agents and Cd. The renal contents of BGD and HBGD were increased by ureter-ligation and decreased by acivicin pretreatment. The mobilizing effect of BGD on the renal Cd was inhibited by probenecid pretreatment. The action of HBGD in removing Cd from the kidney was inhibited by both probenecid pretreatment and ureter-ligation. These results suggest that BGD and HBGD are mainly taken up into the renal tubular cells through the basolateral membrane which is dependent on the action of gamma-GTP; that the Cd-BGD complex formed in the tubular cells is secreted by a probenecid-sensitive organic anion transport system through the basolateral membrane; and that the Cd-HBGD complex formed in the tubular cells is secreted to the tubular lumen by an organic anion transport system through the brush border membrane. Probenecid pretreatment increased the hepatic contents of BGD and HBGD and also promoted the effects of these chelating agents in removing Cd from the liver, indicating an inhibitory effect of probenecid on the glucuronidation of BGD and the secretion of HBGD from the kidney. These results suggest that BGD and HBGD are taken up into the liver and secreted from the organ to the bile by a transport system other than a probenecid-sensitive transport mechanism.

Animals↗

PubMed1994

Attenuated endothelium-dependent peripheral vasodilation and clinical characteristics in patients with chronic heart failure.

Impairment of endothelium-dependent vasodilation has recently been reported in the peripheral vascular bed in patients with chronic heart failure. However, the clinical implications of this type of vascular dysfunction have yet to be elucidated. We have determined the degree of impairment of endothelium-dependent vasodilation as evaluated by acetylcholine-induced changes in forearm blood flow and compared this to various clinical parameters in 23 patients with chronic heart failure. Cumulative changes in forearm blood flow induced by acetylcholine (3.0 and 4.5 micrograms/min/dl tissue volume) were significantly lower in patients with chronic heart failure than in normal controls (10.1 +/- 8.0 ml/min/100 ml vs 20.4 +/- 11.7 ml/min/100 ml tissue volume; p < 0.01). In patients with heart failure, no significant relation was found between acetylcholine-induced changes in forearm blood flow and age, sex, duration of symptoms, duration of hospital stay, or resting hemodynamic parameters, although a significant positive correlation was observed with peak oxygen uptake (r = 0.53, p < 0.05) and ventilatory threshold (r = 0.42, p < 0.05). These observations suggest that the impairment of endothelium-dependent peripheral vasodilation may be one of the factors contributing to exercise intolerance in patients with chronic heart failure, probably resulting from its limiting effect on nutritive skeletal muscle blood flow during exercise.

Acetylcholine↗

PubMed1994

Differential dynamics of neurofilament-H protein and neurofilament-L protein in neurons.

Neurofilaments (NFs) are composed of triplet proteins, NF-H, NF-M, and NF-L. To understand the dynamics of NFs in vivo, we studied the dynamics of NF-H and compared them to those of NF-L, using the combination of microinjection technique and fluorescence recovery after photobleaching. In the case of NF-L protein, the bleached zone gradually restored its fluorescence intensity with a recovery half time of approximately 35 min. On the other hand, recovery of the bleached zone of NF-H was considerably faster, taking place in approximately 19 min. However, in both cases the bleached zone was stationary. Thus, it was suggested that NF-H is the dynamic component of the NF array and is interchangeable, but that it assembles with the other neurofilament triplet proteins in a more exchangeable way, implying that the location of NF-H is in the periphery of the core NF array mainly composed of NF-L subunits. Immunoelectron microscopy investigations of the incorporation sites of NF-H labeled with biotin compounds also revealed the lateral insertion of NF-H subunits into the preexisting NF array, taking after the pattern seen in the case of NF-L. In summary, our results demonstrate that the dynamics of the L and H subunit proteins in situ are quite different from each other, suggesting different and separated mechanisms or structural specialization underlying the behavior of the two proteins.

Animals↗

PubMed1994

Symptomatic middle cerebral artery stenosis and occlusion: comparison of three-dimensional time-of-flight magnetic resonance angiography with conventional angiography.

The usefulness of magnetic resonance (MR) angiography using the three-dimensional time-of-flight method for the characterization of symptomatic middle cerebral artery (MCA) occlusive lesions was evaluated in 10 patients with MCA occlusion and 10 with MCA stenosis. All lesions were symptomatic and documented by conventional angiography. There was no false-negative MR angiogram that failed to demonstrate the MCA occlusive lesion. MR angiography correctly evaluated the location of lesions and the difference between stenosis and occlusion. Stenosis appeared as a focal signal loss (< 1.0 cm) of the MCA at the site of stenosis, and occlusion as a complete signal loss of the MCA distal to the site of occlusion. However, MR angiography could not distinguish diffuse stenosis and one point stenosis demonstrated by conventional angiography. MR angiography is a useful noninvasive diagnostic method for evaluating occlusive lesions of the MCA in symptomatic patients.

Adult↗

PubMed1994

Protective effects of dithiocarbamates against renal toxicity of cis-diamminedichloroplatinum in rats.

Sodium diethyldithiocarbamate (DDTC), sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), and sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD) were evaluated for efficacy as inhibitors of cis-diamminedichloroplatinum (DDP)-induced nephrotoxicity in a rat model. Treatments with 2.0 mmol/kg of BGD, HBGD, and CBGD immediately after DDP (20 mumol/kg) injection effectively prevented the nephrotoxic effects of DDP, but administration of DDTC immediately after DDP injection afforded a small protection. Concurrent treatment with 0.5 or 1.0 mmol/kg of HBGD, or 1.0 mmol/kg of CBGD could prevent DDP-induced renal damage. A significant decrease in weight loss was also observed in these dithiocarbamate-rescued rats. The platinum concentrations in liver and kidney were significantly decreased by BGD, HBGD, and CBGD treatments, respectively. The antitumor efficacy of DDP in the Walker 256 carcinoma-bearing rats was not affected by administration of HBGD (1.0 mmol/kg) or CBGD (1.0 mmol/kg). The results of this study indicated that the injection of HBGD or CBGD to rats treated with DDP can protect against DDP-induced nephrotoxicity more effectively than DDTC or BGD.

Animals↗

PubMed1994

Effects of chelating agents on tissue distribution and excretion of nickel in mice.

N-Benzyl-D-glucaminedithiocarbamate (BGD), diethyldithiocarbamate (DDTC), di-hydroxyethyldithiocarbamate (DHED), trans-1,2-cyclohexanediamine N,N,N',N'-tetra-acetic acid (CDTA), and 2,3-dimercaptosuccinic acid (DMSA) were studied for their relative efficacies in the distribution and excretion of nickel in mice exposed to nickel. Mice were injected intraperitoneally with NiCl2 (5mgNi/kg) and 30 min or 24 hr later, they were injected intraperitoneally with chelating agents (400 mumol/kg). At 30 min after treatment with nickel, these chelating agents all significantly enhanced the fecal excretion of nickel, and DMSA significantly increased the urinary excretion of the metal. At 24 hr after nickel treatment, BGD, DDTC, and DHED significantly increased the fecal excretion of nickel and BGD was the most effective on the fecal excretion of nickel. CDTA and DMSA significantly enhanced the urinary excretion of the metal. At 30 min after nickel treatment, chelating agents other than CDTA effectively depressed nickel concentration in the kidney, lung, and testes. BGD, CDTA, and DMSA significantly reduced the nickel concentration in the liver. However, DDTC and DHED caused the redistribution of nickel to the brain. At 24 hr after nickel treatment, these chelating agents were effective in mobilizing nickel from the kidney, and chelating agents other than DHED were effective in mobilizing nickel from the liver, lung, and testes. These results indicate that the injection of BGD or DMSA at both 30 min and 24 hr after treatment with nickel can remove nickel from the body without redistribution of nickel to other tissues, such as brain, more effectively than DDTC, DHED, and CDTA. Furthermore, the pattern of excretion of nickel after treatment with the chelating agents was related to the partition coefficients of the nickel-chelating agent complexes.

Animals↗