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Biomedical subjects

T Fujitani

Publications and source records attributed to T Fujitani.

At least 37 records · Page 2Linked to original sources
PubMed1994

Lidocaine protects hippocampal neurons against ischemic damage by preventing increase of extracellular excitatory amino acids: a microdialysis study in Mongolian gerbils.

Extracellular levels of amino acids in the hippocampal CA1 region of the gerbil were analyzed by a microdialysis-HPLC procedure. Transient forebrain ischemia produced significant increase in aspartate, glutamate, glycine and taurine (760%, 1070%, 190% and 1210%, respectively), and neuronal blockade by perfusion with a lidocaine (4 mM)-containing medium resulted in 67%, 79%, 58% and 59% reduction in the peak values of each amino acid, respectively. On the other hand, an intracerebroventricular administration of lidocaine, 0.8 mumol or more, produced a protective effect against delayed damage of hippocampal CA1 pyramidal cells, which was caused by bilateral carotid artery occlusion for 4 min. The results suggest that lidocaine may protect neurons against ischemic damage, by preventing the ischemia-induced rise of extracellular concentration of excitatory amino acid.

Animals↗
PubMed1994

Chronic toxicity studies of piperonyl butoxide in F344 rats: induction of hepatocellular carcinoma.

Male and female F344 rats (30-33 rats/group) were administered piperonyl butoxide (alpha-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propylto luene) in the diet at levels of 0 (control), 0.6, 1.2, and 2.4% for nearly 2 years. Beginning at about 40 weeks, 10 rats in the 1.2% treated male group died due to cecal hemorrhages. Piperonyl butoxide induced hepatocellular carcinoma in both sexes in a dose-dependent manner. Hepatocellular carcinoma was found even in the 1.2% treated male group (incidence, 26.7%), and incidences in the 2.4% groups of males and females were 80.0 and 57.7% respectively of all those surviving. Piperonyl butoxide also caused essential thrombocythemia with a dose-response relationship. Hemorrhages in stomach and cecum, anemia, degenerative lesions of alveoli, and nephrotoxicity were also observed related to exposure. These results indicate that piperonyl butoxide is a hepatocarcinogen to the rat.

Animals↗
PubMed1994

Piperonyl butoxide induces hepatocellular carcinoma in male CD-1 mice.

Male CD-1 mice in groups of 52, 53 or 100 were administered piperonyl butoxide (alpha-[2-(2-butoxyethoxy)ethoxy-4,5-methylenedioxy-2-propyltol uene) in the diet at levels of 0 (control), 0.6 and 1.2% for 12 months. Hepatocellular carcinoma was induced in treated groups in a dose-dependent manner but not in the control group. The incidences of hepatocellular carcinoma were 11.3 and 52.0% in mice given 0.6 and 1.2% piperonyl butoxide, indicating that piperonyl butoxide can cause hepatocellular carcinoma in mice as it is known to do in rats.

Animals↗
PubMed1994

Developmental toxicity evaluation of piperonyl butoxide in CD-1 mice.

Piperonyl butoxide was administered to pregnant mice by gavage at a level of 0 (control), 1065, 1385 and 1800 mg/kg body weight only on day 9 of gestation. The animals were sacrificed on day 18 of gestation. Early and late foetal deaths were significantly increased in the higher dose groups and those effects were significantly dose-related. The average body weights of male and female foetuses were significantly reduced in a dose-related fashion. The external malformation of oligodactyly in forelimbs was significantly increased in higher treatment groups in a dose-related manner. The dose levels of piperonyl butoxide in the present study produced adverse effects on developmental parameters.

Abnormalities, Drug-Induced↗
PubMed1993

Hepatotoxicity of piperonyl butoxide in male F344 rats.

Male F344 rats were given 0, 0.6, 1.2 or 2.4% of piperonyl butoxide in the diet. At 1, 2, 4 or 12 weeks after the beginning of the experiment, liver and kidney weight and serum clinical parameters were determined and livers and kidneys were examined with light microscopy. From 1 or 2-12 weeks, distinct increase of liver weight, changes in serum clinical parameters for liver damage, oval cell proliferation, bile duct hyperplasia, single cell necrosis, enlarged and vacuolated hepatocytes, enlarged nuclei and anisonucleosis were seen in treated rats. From 4-12 weeks, cell infiltration, focal necrosis, multinucleated hepatocytes and prominent nucleoli of hepatocytes were seen in treated rats. At 12 weeks microgranulomas were seen in treated rats. Especially in rats of the 2.4% group at 12 weeks, severe enlargement of hepatocytes, severe enlargement of nuclei and multinucleated hepatocyte were seen, suggesting preneoplastic alteration. Relative kidney weights and serum urea nitrogen levels were increased in treated rats from 1 or 2-12 weeks and at 12 weeks, atrophy of proximal tubules, dilation of tubules, cell infiltration, fibrosis and accumulation of yellow-brown pigment in the proximal tubular cells were seen.

Administration, Oral↗
PubMed1993

Subacute toxicity of piperonyl butoxide in ICR mice.

Piperonyl butoxide, alpha-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propyltol uene, is a pesticide synergist. ICR mice of both sexes were maintained on diet containing 0, 0.1, 0.3 or 0.9% of piperonyl butoxide for 20 days. At the end of the experimental period, they were necropsied. Selected organs were weighed and serum chemistries were analyzed. In male and female mice of the 0.9% group, body weight, kidney and spleen weight were depressed in comparison to those of control group. Liver weight of the 0.3 and 0.9% group of both sexes were significantly higher than those of control group. Mice of the 0.9% group of both sexes had increased serum levels of cholesterol, total protein, gamma-glutamyl transpeptidase. Histological examination of livers from mice of the 0.9% group by light microscopy showed enlarged hepatocytes, anisonucleosis and single cell necrosis. The results indicated that subacute toxicity of piperonyl butoxide in ICR mice was directed primarily at liver.

Animals↗
PubMed1993

Short-term effect of sodium benzoate in F344 rats and B6C3F1 mice.

F344 rats and B6C3F1 mice of each sex were administered 0, 1.81, 2.09 or 2.40% (for rats) and 0, 2.08, 2.50 or 3.00% (for mice) of sodium benzoate in the diet for 10 days. In male rats of the 2.4% group, relative liver and kidney weight, serum levels of albumin, total protein and gamma-glutamyl transpeptidase were significantly increased and enlarged hepatocytes with glassy cytoplasm were seen using light microscopy. In male mice of the 3.0% group, absolute liver weights and serum cholesterol and phospholipid levels were significantly increased, and enlargement, vacuolation and necrosis of hepatocytes were evident.

Animals↗
PubMed1992

Acute renal toxicity of thiabendazole (TBZ) in ICR mice.

The acute toxic effects of thiabendazole [2-(4'-thiazolyl)benzimidazole; TBZ] on the kidneys of ICR mice were investigated. The mice were given 0, 250, 500 or 1000 mg TBZ/kg body weight by gavage (using olive oil as a vehicle), and the kidneys were subjected to pathological examination at 1, 3, 5 or 24 hr after dosing. Gross findings were slight enlargement and the presence of whitish areas (white maculae) in kidneys of treated mice at 3, 5 or 24 hr after dosing. Histological findings were desquamation of degenerated cells in proximal tubules of treated mice at 1 hr. Dilation of proximal, distal and collecting tubules was apparent in treated mice at 3, 5 and 24 hr. TBZ-induced renal injury was reduced by pretreatment with inducers of the microsomal monooxygenase system (sodium phenobarbital, beta-naphthoflavone and 3-methylcholanthrene) and were enhanced by pretreatment with inhibitors of that system (2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride and piperonyl butoxide). The concentration of TBZ in blood at 1 or 5 hr after dosing was lower in mice pretreated with microsomal monooxygenase system inducers and was higher in those pretreated with the inhibitors, than in those given TBZ alone. These results suggest that TBZ-induced renal injury may be attributable to the parent compound rather than its metabolites. Measurement of organic ion uptake into renal slices revealed significant depression of [1-14C]tetraethylammonium bromide (TEA) uptake in treated mice at 1 or 5 hr, whereas uptake of p-[glycyl-2-3H]aminohippurate (PAH) was not depressed at 1 or 5 hr after dosing. The reduction in uptake of TEA is interpreted as the result of competitive suppression of the tubular transport of TEA by TBZ. TBZ-induced renal injury was reduced by organic cation transport inhibitors [N'-methylnicotinamide (NMN) or thiamine] but not by organic anion transport inhibitor [p-(dipropylsulphamyl)benzoic acid probenecid], suggesting that the reduction of TBZ-induced renal injury is the result of competitive suppression of the tubular transport of TBZ by NMN or thiamine.

Administration, Oral↗
PubMed1992

Sub-acute toxicity of piperonyl butoxide in F344 rats.

Piperonyl butoxide, alpha-[2-(2-Butoxyethoxy)ethoxy]-4,5-methylenedioxy- 2-propyltoluene, is a pesticide synergist. F344 rats of both sex were maintained on diets containing 0, 0.6, 1.2 or 2.4% of piperonyl butoxide for 13 weeks. At the end of experimental period, they were necropsied. Selected organs were weighted and serum was analyzed by clinical chemistry. In male and female rats of the 2.4%-group, body weight gains were depressed, macroscopically, hepatomegaly was marked and liver weights were significantly higher than those of the control group. In male and female rats of all treated groups, relative kidney weights were significantly increased in a dose-dependent manner. Rats of the 2.4%-group had increased levels of albumin, cholesterol, urea nitrogen and gamma-glutamyl transpeptidase. Examination of livers of the male 2.4%-group by light microscopy showed enlarged hepatocytes with glassy cytoplasm and fatty deposition. On occasion, there was coagulative necrosis of a few hepatocytes in the periportal area and oval cell proliferation. The kidney of treated rats showed atrophy of epithelium in the proximal convoluted tubules. These results indicated that toxicity of piperonyl butoxide in rats was directed primarily to the liver and kidney.

Animals↗
PubMed1991

New metabolites of thiabendazole and the metabolism of thiabendazole by mouse embryo in vivo and in vitro.

Thiabendazole [2-(4'-thiazolyl)benzimidazole; TBZ], a teratogen in ICR mice, is known to be mainly metabolized to 5-hydroxy-TBZ (5-OH-TBZ) and its conjugates in domestic and laboratory animals. Besides the known metabolites of TBZ, 4-hydroxy-TBZ and 2-acetylbenzimidazole (ABI) were identified as new metabolites of TBZ in the urine of F344 rats and ICR mice. 5-OH-TBZ and ABI, as well as TBZ, were found in the embryos of ICR mice given TBZ orally on day 10 of gestation. In the whole-embryo culture system, 5-OH-TBZ and ABI in the medium, and TBZ, 5-OH-TBZ and ABI in the embryo were detected after 24 hr of culture in 25 or 50 micrograms TBZ ml. However, the amount of metabolites in the embryo in vitro was very small compared with that detected in vivo, whereas the amount of TBZ was comparable. Furthermore, the mouse embryo homogenate, at organogenesis, metabolized TBZ to 5-OH-TBZ or ABI. The specific activity required by this homogenate to form 5-OH-TBZ or ABI was less than 1/1000 of that of the liver microsomal fraction. The results suggested that mouse embryos at organogenesis could metabolize TBZ, although most of the metabolites in the embryo in vivo came from the dam.

Animals↗
PubMed1991

A multi-arterial clamping method with arterial hypotension does not bring about complete brain ischemia in dogs.

The completeness of brain ischemia with a multi-arterial clamping method in dogs was examined using EEG, evoked potentials (EPs) and vessel staining with Evans blue. EEG was monitored by bipolar parietal lead. EPs stimulating electrodes were inserted into the first thoracic (T1) epidural space and recording electrodes into the C2 epidural space, brain stem and cerebral cortex. EPs were measured at 30 s intervals with 50 measurements each time using 3.0 mA current of 100 microseconds duration. In dogs in which brain ischemia was brought about by ventricular fibrillation (VF group, n = 5) EEG disappeared within 40 s in all dogs and the amplitudes of EPs at the C2 spinal cord, brain stem and cerebral cortex after 10 min ischemia were 57%, 0% and 0%, respectively. In the dogs in which a multi-arterial clamping method (clamping internal thoracic arteries, brachiocephalic trunk and left subclavian artery while lowering systolic arterial pressure (AP) below 50 Torr) was used (AC group, n = 5) EEG was still recognizable at 5 min in 2 dogs and the amplitudes of EPs at the C2, brain stem and cerebral cortex at 10 min ischemia were 103%, 53% and 0%, respectively. Stainings with Evans blue were observed in all soft tissue at and below thoracic level, entire intervertebral venous plexus, venous sinuses of cranial dura mater and spinal cord below the lower part of cervical region. Bright red fluorescence by Evans blue was observed microscopically in the vessels of the spinal cord, brain stem and cerebrum (1 dog only). In conclusion a multi-arterial clamping method with arterial hypotension brings about only incomplete brain ischemia.

Animals↗
PubMed1989

Isolation of a new human fetal liver cytochrome P450 cDNA clone: evidence for expression of a limited number of forms of cytochrome P450 in human fetal livers.

From a human fetal liver cDNA library, a new cDNA clone (lambda HFL10) was isolated using an antiserum to P450 HFLa, which has been isolated from livers of human fetuses. Cytochrome P450 cDNAs, namely lambda hPA6, lamda hP2-1, and lambda hPD4 which were highly homologous to cDNA clones, pHY13, Hp1-1, and phP450j, respectively, were also isolated from the cDNA library of human adult livers. Using these cDNA clones as probes together with Lambda HFL10, Northern blot analysis was conducted to determine whether all of these cytochromes were expressed in human fetal livers. The results clearly showed that only P450 HFL10 mRNA was detected in human fetal livers. This result supports the allegation that there is a much more limited number of forms of cytochrome P450 in human fetal livers than in adult livers.

Amino Acid Sequence↗
PubMed1989

Glutathione and cysteine enhance and diethylmaleate reduces thiabendazole teratogenicity in mice.

The effects of cysteine (CYS), glutathione (GSH) and diethylmaleate (DM) on the teratogenicity of thiabendazole (TBZ) were investigated. On day 9 of gestation mice were given ip a dose of 0, 50 or 100 mg CYS/kg body weight, or 0, 400 or 800 mg GSH/kg, or 0, 0.05, 0.10, 0.15 or 0.60 DM/kg. One hr later they were dosed orally with 0, 250, 500 or 1000 mg TBZ/kg. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. The number of malformed foetuses was increased in mice pretreated with CYS or GSH and was decreased in those pretreated with DM, in comparison with numbers in the corresponding group treated with TBZ alone GSH pretreatment enlarged the area under the curve (AUC) of TBZ and 5-hydroxyTBZ, a representative metabolite, in foetal tissue. DM pretreatment reduced the AUC of TBZ and 5-hydroxyTBZ.

Abnormalities, Drug-Induced↗
PubMed1989

Effects of thiabendazole on the kidneys of ICR mice.

The effects of thiabendazole (TBZ) on the kidneys of male and female Crj:CD-1 (ICR) mice were investigated. The mice were given 0, 250 or 500 mg TBZ/kg body weight/day by gavage (using olive oil as a vehicle) for 1, 3, 5 or 7 days. The 24-hr urine volumes of treated mice were increased, significantly so in male mice given the high dose of TBZ. Protein was present in the urine of both control and treated mice throughout the experiment but electrophoresis of the protein showed the presence of a relatively high-molecular-weight protein in the urine of the treated mice. Levels of serum urea nitrogen were decreased in treated mice, but serum creatinine levels did not differ from those of controls. Relative kidney weights tended to be dose-dependently increased in comparison with the controls. Pathological examination showed that after one dose (at either level) the kidneys of males and females were swollen and white maculae were present. Microscopic examination revealed dilation of the proximal, distal and collecting tubules with flattening and degeneration of the tubular epithelium. Tubular dilation was severe in high-dose male mice. These histological changes paralleled the alterations in the 24-hr urine volume. These data suggested that the increased urine volume may be caused primarily by the prevention of reabsorption of water in the distal and collecting tubules. Electron microscopy revealed the flattening of foot processes of podocytes and oedematous changes in the mesangium of glomeruli in TBZ-treated mice. We conclude that TBZ given by gavage in olive oil affects the kidneys of ICR mice.

Animals↗
PubMed1989

Cloning of human cytochrome P-450 cDNA and its expression in Saccharomyces cerevisiae.

A human cytochrome P-450 cDNA clone, lambda hPA6, was isolated from a human adult liver cDNA library. The expression plasmid pHM3 delta 2 was constructed by insertion of lambda hPA6 and a synthetic DNA into the yeast mRNA and reduced carbon monoxide-difference spectra of the yeast microsomes revealed that only the yeast transformed by the expression plasmid pHM3 delta 2 produced foreign cytochrome P-450. In addition, the expressed protein reacted with antiserum to P-450-HM2, a form probably identical with P-450MP, and showed a detectable level of mephenytoin 4-hydroxylase activity.

Amino Acid Sequence↗