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Biomedical subjects

A Yoshitake

Publications and source records attributed to A Yoshitake.

81 records · Page 5Linked to original sources
PubMedDate not supplied

Effects of pyrethroid insecticides on gap junctional intercellular communications in Balb/c3T3 cells by dye-transfer assay.

The effects of fenvalerate, esfenvalerate, permethrin, cypermethrin, deltamethrin, p-chlorophenylisovaleric acid (CPIA, major metabolite of fenvalerate) and DDT, a liver tumor promoter, on gap junctional intercellular communication (GJIC) were examined in Balb/c3T3 cells by dye-transfer assay. Separate groups of Balb/c3T3 cells were exposed to the chemicals for 1 day. On the following day, GJIC was measured by counting the number of dye-transferring cells per injection of Lucifer Yellow under a fluorescent microscope. Fenvalerate, esfenvalerate, permethrin, cypermethrin, deltamethrin and DDT inhibited GJIC at noncytotoxic concentrations, while CPIA did not inhibit GJIC even at a cytotoxic concentration. It is concluded that the examined pyrethyroid insecticides, but not a metabolite, have inhibitory effects on GJIC in Balb/c3T3 cells.

3T3 Cells↗
PubMedDate not supplied

Effects of fenvalerate and esfenvalerate on hepatic gap junctional intercellular communication in rats.

Effects of in vivo exposure with fenvalerate, esfenvalerate and DDT on hepatic gap junctional intercellular communication (GJIC) in Sprague-Dawley (SD) rats were examined by in vivo/in vitro dye-transfer assay and by immunohistochemical staining of connexin 32 (Cx32, major liver gap junction protein). Fenvalerate (75 mg/kg/day), esfenvalerate (25 mg/kg/day), DDT (50 mg/kg/day) and corn oil (vehicle control, 5 ml/kg/day) were administered orally once a day. Animals were killed at weeks 1, 2, 4 and 6 after starting the experiment. In the fenvalerate- and esfenvalerate-groups, no compound-related changes in GJIC and Cx32 expression were observed. On the contrary, in the DDT-group, average sizes of the dye spread after injection of Lucifer Yellow decreased at weeks 1, 2 and 4, and the area per GJ spot shown by Cx32-immunohistochemical staining decreased at weeks 4 and 6. It is concluded that neither fenvalerate nor esfenvalerate inhibits hepatic GJIC with in vivo exposure.

Animals↗
PubMedDate not supplied

Immunohistochemical demonstration of the gap junctional protein connexin 32 and proliferating cell nuclear antigen in glutathione S-transferase placental form-negative lesions of rat liver induced by diethylnitrosamine and clofibrate.

The distributions of a gap junctional protein, connexin 32 (cx 32), and proliferating cell nuclear antigen (PCNA) were examined immunohistochemically in glutathione S-transferase placental form (GST-P)-negative foci, induced in rat liver by initiation with diethylnitrosamine (DEN, 200 mg/kg) followed by promotion with clofibrate (1% in diet) in an in vivo medium-term assay system for hepatocarcinogenesis. The results were compared to those in GST-P-positive foci induced by DEN alone. The treatment with clofibrate caused the appearance of GST-P-negative foci, increased in size as compared to GST-P-positive foci in the same liver or induced by the DEN alone. The proportion of PCNA-positive hepatocytes in GST-P-negative foci was significantly higher than in the surrounding parenchyma, indicating increased cell proliferation. The numbers of cx 32-positive spots per hepatocyte in GST-P-negative foci were clearly decreased, reaching 65.4% at week 20 and 51.8% at week 30 of values for surrounding normal hepatocytes. In GST-P-positive foci induced by DEN, only a slight decrease (80%) was observed at week 8. These findings show that a positive association between the sustained inhibition of gap junctional intercellular communication and increased cell proliferation of GST-P-negative foci in Fischer-344 male rats induced with DEN and promoted with clofibrate.

Animals↗
PubMedDate not supplied

Effect of phenobarbital on hepatic gap junctional intercellular communication in rats.

The effects of in vivo exposure to phenobarbital (PB) on hepatic gap junctional intercellular communication (GJIC) and connexin protein expression in Sprague-Dawley rats were examined by in vivolin vitro dye-transfer assay, immunohistochemical staining, and by Western blot analysis. PB (50 mg/kg) was administered orally once a day for up to 6 wk. The average size of the dye spread after injection of Lucifer Yellow decreased at week 1 and remained at the same level until week 6. The area and number of connexin 32 (Cx32) spots per hepatocyte in the central zone of liver lobules decreased from week 1 to week 6, but no change of Cx32 spots in the peripheral zone was observed. The average area and number of connexin 26 (Cx26) spots per hepatocytes showed no clear change through the experimental periods. The decreased level of Cx32 protein in plasma membranes was observed in the PB group. These results suggest that PB, a liver tumor-promoting agent, inhibits hepatic GJIC in vivo in rats and that aberrant Cx32 protein expression and/or localization may be responsible for this effect.

Animals↗
PubMedDate not supplied

Pharmacokinetics of SM-10888 and its metabolites depending on their physicochemical properties.

To investigate how the physicochemical properties and pharmacokinetics of SM-10888 are altered by metabolic reactions, physicochemical and pharmacokinetic parameters of its phase I and phase II metabolites were determined. The metabolic pathways of SM-10888 in rats include oxidation at the C1 position (via the hydroxylated metabolite M3 to the cyclic ketone M4) and glucuronidation of both SM-10888 and M3 (SMG and M3G). Partition coefficients between n-octanol/pH 7.4 buffer (logP*) were determined to be 2.23 for SM-10888, 1.59 for M3, 2.66 for M4, -1.37 for SMG, and -1.72 for M3G. The phase I metabolite M3 showed lower lipophilicity and serum protein binding at pH 7.4, and larger renal clearance (CLr) than SM-10888. In contrast, the further oxidized metabolite M4 demonstrated higher lipophilicity and protein binding and lower CLr than SM-10888 and M3. Among these nonconjugated forms, only the pKa value of M4 was found to be below 7.4 (6.2 for M4, 8.5 for SM-10888, and 8.0 for M3), indicating that M4 exists in a more lipophilic nonionized form at the physiological pH, whereas SM-10888 and M3 are present as ionized forms. The significant shift in pKa of M4 could be the result of a cooperative effect of the electron withdrawing carbonyl group and resonating structure allowing hydrogen bond formation between CO and NH2 group, and might explain its high lipophilicity and low CLr. Glucuronidation significantly increased hydrophilicity with CLr's in excess of the glomerular filtration rate, suggesting involvement of active transport.

Aminacrine↗