The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 18 , Issue 1
Showing 1-6 articles out of 6 articles from the selected issue
  • Kang CHIN, Chung Jae LEE, Kong Ook SEO, Kwang Ho KO, Yukio KUROIWA
    1993 Volume 18 Issue 1 Pages 11-19
    Published: February 25, 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Selectivity of lead effect to phenylethanolamine N-methyltransferase (PNMT) activity in regions of brain from rats postnatally exposed to lead was tested. Three groups of animals were prepared; (1) Rats exposed to lead at a low dose (0.05% PbAcetate: PbAc); (2) Rats exposed to lead at a high dose (0.2% PbAc); (3) Age-matched normal control rats. At 2, 4, 6 and 8 weeks of age weight of whole brain and body in each group were measured. At the same age activities of PNMT and Na+/K+-ATPase were examined on 4 brain regions of each animal. Exposure of rats to lead generally decreased activity of Na+/K+-ATPase and showed alternative change of those of PNMT. Brain regions where changes of PNMT activity were detected without concomitant changes of Na+/K+-ATPase activity, were telencephalon and pons/medulla at 2 weeks of age and telencephalon at 4 weeks of age in rats exposed to lead at a low dose, and those in rats exposed to lead at a high dose were pons/medulla at 8 weeks of age. These data imply that adrenergic nervous system in the brain regions described above could selectively be affected by lead.
    Download PDF (958K)
  • Kang CHIN, Sun Kwon SONG, Jae Hoon CHEONG, Kwang Ho KO, Yukio KUROIWA
    1993 Volume 18 Issue 1 Pages 21-29
    Published: February 25, 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Selectivity of lead effect on dopamine β-hydroxylase activity in regions of brain from rats postnatally exposed to lead was tested. Three groups of animals were prepared; (1) Rats exposed to lead at a low dose (0.05% PbAcetate: PbAc); (2) Rats exposed to lead at a high dose (0.2% PbAc); (3) Age-matched normal control rats. At 2, 4, 6 and 8 weeks of age weight of whole brain and body in each group were measured. At the same ages activities of dopamine β-hydoroxylase and Na+/K+-ATPase were measured in 5 brain regions of each animal. Exposure of rats to lead generally decreased Na+/K+-ATPase activity and showed alternative changes of dopamine β-hydroxylase activity were detected without concomitant changes of Na+/K+-ATPase activity were telencephalon and pons/medulla at 2 weeks of age and telencephalon, diencephalon and pons/medulla at 4 weeks of age and midbrain and pons/medulla at 6 weeks of age and cerebellum at 8 weeks of age in rats exposed to lead at a low dose, and those in rats exposed to lead at a high dose were midbrain at 6 weeks of age and cerebellum at 8 weeks of age. These data imply that noradrenergic nervous system in the brain regions described above could selectively be affected by lead.
    Download PDF (966K)
  • Yasuteru SHIROSHITA, Masaru MINAMI, Toru ENDO, Yoshio MONMA, Masahiro ...
    1993 Volume 18 Issue 1 Pages 31-41
    Published: February 25, 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    The protective effect of 4-hydroxy-2-methyl-N-[2-(tetrazol-5-yl)-phenyl]-2H-1, 2-benzothiazine-3-carboxamide-1, 1-dioxide monosodium salt (HX-1920) on the nephrotoxicity of cisplatin was studied in rats. Effects of HX-1920 on antitumor activity and emesis induced by cisplatin were also examined using mice and ferrets, respectively. All 10 rats injected with both HX-1920 and LD&lt50&gt of cisplatin survived for 14 days. After 24 hr, co-administration of HX-1920 significantly increased the urinary excretion of cisplatin in rats. HX-1920 also significantly inhibited the cisplatin-induced elevation of urinary N-acetyl-β-D-glucosaminidase, blood urea nitrogen and plasma creatinine concentrations in rats. HX-1920 had no effect on the number of white blood cell. HX-1920 tended to reduce the emesis induced by cisplatin in ferrets. Furthermore, there was no difference in the survival curve between the cisplatin group and the HX-1920 plus cisplatin group in mice inoculated with P 388 1eukemia cells. Thus, HX-1920 did not modify the antitumor activity of cisplatin. These results suggest that HX-1920 has a protective effect on the nephrotoxicity of cisplatin without inhibiting its antitumor activity.
    Download PDF (1028K)
  • Tetsuo MISAWA, Sadayoshi SHIGETA
    1993 Volume 18 Issue 1 Pages 43-48
    Published: February 25, 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Developmental and behavioral effects of aluminum administration were studied in THA rats. To three groups of pregnant rats were administered single dose of 0, 900 or 1, 800 mg/kg of aluminum chloride on the day 15 of gestation by gavage. Significant differences were observed between the aluminum treated offspring and controls in terms of body weight, timing of pinna detachment and eye opening, and appearances of auditory startle. Slower learning acquisition was observed in treated groups. The longer latency and more rearings in the open field test were observed in 1, 800 mg/kg treated females. These results suggest that single dose of aluminum chloride during prenatal period affects the development and behavior in rats.
    Download PDF (723K)
  • Atsuya TAKAGI, Nana KAWASAKI, Junko MOMMA, Yoshitaka AIDA, Yasuo OHNO, ...
    1993 Volume 18 Issue 1 Pages 49-55
    Published: February 25, 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Effects of 2, 2'-methylenebis (4-ethyl-6-tert-butylphenol) (MBEBP) on hepatic mitochondrial oxidative phosphorylation in vitro, and on hepatic peroxisomal enzymes activities and microsomal mixed-function oxidase activities were studied. 1. A low concentration of MBEBP, less than 50μM, increased state 4 respiration and decreased state 3 respiration. However, a higher concentration of MBEBP, greater than 100μM, acted as a respiratory inhibitor. Therefore, MBEBP was found to act as an uncoupler of oxidative phosphorylation in rat liver mitochondria. 2. MBEBP significantly decreased peroxisomal enzymes, cyanide-insensitive palmitoyl-CoA oxidizing activity and catalase activity in the livers of rats fed 0.2, 1.0 or 5.0% MBEBP for 4 weeks. 3. In microsomal enzyme assay, NADPH cytochrome c reductase activity was significantly increased, however, cytochrome P-450, cytochrome b5 levels, aminopyrine N-demethylase and benzo [a] pyrene hydroxylase activities were not significantly increased in the livers of rats fed 1.0 or 5.0% MBEBP for 4 weeks. The weight loss and the decrease of serum triglyceride level observed in the MBEBP-treated rats seemed to be caused by its uncoupling effects, which might also be the cause of the testicular damage induced by MBEBP.
    Download PDF (809K)
  • Shunji HOSOKAWA, Jun NAKAMURA, Seiichi ITO, Masakazu MURAKAMI, Mariko ...
    1993 Volume 18 Issue 1 Pages 57-67
    Published: February 25, 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    To assess the toxicological significance of thyroidal tumor observed slightly in a long-term rat study with diniconazole, (E)-1-(2, 4-dichlorophenyl)-4, 4-dimethyl-2-(1, 2, 4-triazol-1-yl)-1-penten-3-ol, a 3-month subacute feeding study was conducted in male Crj: CD (SD) rats by administering diniconazole in diet at concentrations of 0, 100, 1, 000, or 2, 000 ppm. Examinations mainly for thyroid functions were performed at Weeks 2, 4 and 13. Measurement of serum hormone levels revealed continuous decreases in serum thyroxine (T4) and free T4 levels at and above 1, 00 ppm and increase in serum thyroid stimulating hormone (TSH) level at 2, 000 ppm concurrently with liver weight and hepatic UDP-glucuronyltransferase (UDP-GT) increases at and above 1, 000 ppm. No changes were observed in serum triiodothyronine (T3) and free T3 levels. Increase in thyroid uptake of &lt125&gtI and organification of &lt125&gtI in the thyroid at 2, 000 ppm and thyroid follicular cell hyperplasia at and above 1, 000 ppm were also observed. However, no compound-related changes were observed in autopsy and organ weight in the thyroid. Based on the above results, diniconazole induces increases in the hepatic UDP-GT activity and the thyroid hormone excretion from the liver. The increased excretion of thyroid hormones causes decrease in serum T4 and free T4 levels, triggering the feedback mechanism of the pituitary gland, promotion of TSH release from the pituitary gland and increase in serum TSH level. The increased serum TSH level probably leads to increased &lt125&gtI uptake of thyroid and thyroid follicular cell hyperplasia. Thus, the thyroid tumorigenesis in rats treated with diniconazole is due to the secondary overstimulant effect on the thyroid by increased serum TSH level. The toxicological significance in humans is extremely low and it is unlikely that diniconazole would increase thyroid tumor in humans even if diniconazole were to alter normal thyroid hormone level in humans.
    Download PDF (1420K)
feedback
Top