The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
Volume 24 , Issue 5
Showing 1-10 articles out of 10 articles from the selected issue
  • Shinro SADANOBU, Masaki WATANABE, Chika NAKAMURA, Masakatsu TEZUKA
    1999 Volume 24 Issue 5 Pages 375-381
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Some in vitro tests were performed using 1, 3-dithia-2-thioxo-cyclopent-4-ene (DT827A) to evaluate its mode of action on hepatoprotection. Experiments with leucine, uridine and thymidine uptakes using L-132 cells showed no increase in leucine uptake, but did show a tendency toward increases in both uridine and thymidine uptakes, which suggested a stimulating effect on RNA and DNA synthesis in vitro. DT827A did not influence GSH levels in the HepG2 cultured cell system, and did not show inhibition of cytochrome P450 2E1 in microsomes obtained from mouse liver. There may be no possibility for DT827A to protect a liver injury through its influence on liver GSH levels and inhibiting metabolic activation of CCl4 in this in vitro system. However, the inhibitory effect of DT827A on lipid peroxidation was observed in vitro, the same as the observation in vivo. Furthermore, when DT827A was incubated with Alamar Blue in the presence of a mixture of mouse liver S9 and mitochondrial fractions for 20 hr, DT827A showed more reducibility than it did in a case of non-incubation, and it was suggested that DT827A would be metabolized in the S9-mitochondrial fraction in vitro to show an increase of Alamar Blue reducibility. The protective effect of DT827A on a liver injury is due neither to its influence on liver GSH levels nor inhibition of the metabolic activation of CCl4, but a possible mechanism of action for the DT827 series of compounds to indicate an antioxidative effect would be brought about by the role of the compounds as a radical scavenger as well as its reductive effect.
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  • Nobuyuki FUKUISHI, Nobuaki MATSUI, Reiko KANOH, Masaaki AKAGI
    1999 Volume 24 Issue 5 Pages 383-391
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Quinolones have a broad antibacterial spectrum against Gram-negative and Gram-positive bacteria. The compounds, however, have a few adverse effects, such as convulsion and toxicity to articular cartilage. We observed that some quinolones such as Naldixic acid, Ofloxacin, and Norfloxacin have osteoclast-inducing effects. All quinolones we tested produced tumor necrosis factor-alpha and prostaglandin E2, and have potency as osteoclast inducers to cultured cells. These results suggest that some quinolones affect osteoclast induction or activation, and this may be related to the production of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2).
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  • Alok CHATTOPADHYAY, Mahitosh SARKAR, Ronojoy SENGUPTA, Gargi ROYCHOWDH ...
    1999 Volume 24 Issue 5 Pages 393-397
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Copper chloride treatment adversely affects testicular activity in albino rats. To investigate its antitesticular effects mature (120 days) Wistar strain albino rats were treated intraperitoneally (i.p.) with copper chloride at doses of 1000, 2000 and 3000 μg/kg body weight/day for 26 days. Significant reduction of testicular and accessory sex organs (seminal vesicle, ventral prostate) weight, along with inhibition of testicular Δ5-3β-hydroxysteroid dehydrogenase (Δ5-3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity and reduction in plasma testosterone level, were observed at the doses of 2000 and 3000 μg/kg body weight/day. The degree of inhibition in all the parameters were increased with the increase of dosage. But no significant change was observed in the above parameters when the animals were treated with 1000 μg/kg body weight/day dose. This suggests that copper produces a suppressive influence on male reproductive activity, mainly on testicular weight and steroidogenesis and accessory sex organ weight in a dose-dependent manner.
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  • Kazue SAKEMI, Makoto USAMI, Katsuyoshi MITSUNAGA, Yasuo OHNO, Mitsuhir ...
    1999 Volume 24 Issue 5 Pages 399-405
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Toxicokinetics of 2-mercaptobenzimidazole (MBI) and 2-mercaptomethylbenzimidazole (MMBI), rubber antioxidants with thioureylene structure, were compared after single oral administration in rats. Male Wistar rats received single oral administration of 2, 10, 50 and 250 mg/kg of MBI or MMBI. The serum and urine concentrations of MBI and MMBI were determined by HPLC. MBI and MMBI showed similar Cmax values, but the former disappeared slower in the serum than the latter and resulted in its larger AUC values. Analyses of MBI, MMBI and their desulfurated metabolites in urine suggested that these differences were due to their metabolic elimination rates. On the other hand, MBI and MMBI caused similar acute toxicities, such as loss of locomotive activity, ataxic gait, adoption of prone or side position and coma, being severer with higher serum concentrations at the moment. Similar acute toxicities between MBI and MMBI were explained by similar Cmax values at the same dose. It was suggested from these results that the slower disappearance and larger AUC values of MBI in the serum compared to MMBI might explain the strong thyroid toxicity which has been observed by repeated administration of MBI, but very weak thyroid toxicity by MMBI.
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  • Yoshiki BAN, Urumi ASANABE, Satoru INAGAKI, Minoru SASAKI, Toshio NAKA ...
    1999 Volume 24 Issue 5 Pages 407-413
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    α-chlorohydrin (ACH) is a known male reproductive toxicant and produces antifertility in rats. The present experiments were performed to determine the relationship between sperm motions and reproductive function, and to further examine the possible mechanism for antifertility. ACH was administered to male rats for 9 days at 1, 3 and 10 mg/kg/day. The males were mated with untreated females and their reproductive status was determined. All mated males failed to impregnate females at 10 mg/kg/day. Low pregnancy rate associated with a decreased implant number was seen at 3 mg/kg/day. When sperm motions were analyzed using the CellSoftTM computer-assisted sperm analyzer, percentage of motile sperm, curvilinear velocity (VCL) and amplitude of lateral head displacement (ALH) were reduced at 10 mg/kg/day. At 3 mg/kg/day, VCL and ALH were reduced but the percentage of motile sperm was comparable to that of controls. In order to examine a possible mechanism for the effect of ACH on fertility, the number of sperm reaching the oviducts of mated females and the number of fertilized eggs was evaluated. Half of the females mated with ACH-treated males at 3 mg/kg/day had very low sperm numbers in the oviducts. At 10 mg/kg/day, all the mated females had a very low sperm number. The percent of fertilized eggs in the oviducts of mated females was decreased in a dose-dependent manner. These findings suggest that the effect of ACH on fertility was directly related to decreased VCL and ALH as well as percentage of motile sperm, and by the mechanism in which the sperm number reaching the oviducts after mating was reduced, so the reduction resulted in only a rare chance to fertilize.
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  • Masanori MURAKOSHI, Rie IKADA, Masashi TAGAWA
    1999 Volume 24 Issue 5 Pages 415-420
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    In order to confirm the relationship between sex hormone administration and glutathione-peroxidase (GSH-PO) in the rat ventral prostate, the levels of GSH-PO mRNA, GSH-PO activity, and lipid peroxide (TBA) value in the ventral prostate were investigated. Male Crj:CD(SD)IGS rats were divided into six experimental groups. Group 1 consisted of intact controls. In group 2, rats were sacrificed two days after castration. In groups 3 and 4, rats were subcutaneously administered 1 mg/animal of testosterone daily for three or seven days after two days of castration, respectively. In groups 5 and 6, rats were subcutaneously administered 1 mg/animal of testosterone plus 0.01 mg/animal of 17β-estradiol (E2) daily for three or seven days after two days of castration, respectively. GSH-PO activity of the ventral prostate homogenate for testosterone or testosterone plus E2 administration to the castrated rat was increased and the TBA value was remarkably decreased. The prostatic GSH-PO mRNA level was diminished in the castrated rat ventral prostate, but was increased by testosterone or testosterone plus E2 administration. In particular, the GSH-PO mRNA level of testosterone plus E2-treated animals was higher than that of testosterone-treated animals. These findings strongly suggest that expression of GSH-PO in the rat ventral prostate is considered to be testosterone- or E2-dependent. Furthermore, it is suggested that the transcription of prostatic GSH-PO mRNA was regulated by testosterone or E2 and de novo synthesis of GSH-PO would thus be regulated at transcription level by testosterone or E2.
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  • Seigo YAMAMOTO, Tomoshi NISHIZAWA, Kasuke NAGANO, Shigetoshi AISO, Tat ...
    1999 Volume 24 Issue 5 Pages 421-424
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    To investigate the development of resistance to chloroform toxicity, a 4-week inhalation study was conducted in which BDF1 male mice were exposed to a low level of chloroform for an initial two-week period, and thereafter the exposure concentration was increased for a second two-week period. The animals were exposed to inhalation of chloroform vapor 6 hr per day, 5 days per week, with clinical observation and measurement of body weight conducted. These results demonstrate that pre-exposure to chloroform at a low dose level induced resistance to a higher dose of chloroform in male mice. This resistance was dependent on the pre-exposure concentration.
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  • Sandip CHATTOPADHYAY, Sampa GHOSH(PAL), Sankar CHAKI, Jogen DEBNATH, D ...
    1999 Volume 24 Issue 5 Pages 425-431
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Effect of arsenic on ovarian steroidogenesis at the dose available in drinking water at wide areas of West Bengal is reported here. Weights of ovary, uterus and vagina along with biochemical activities of ovarian Δ5-3β-hydroxysteroid dehydrogenase (Δ5-3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD) and plasma levels of LH, FSH and estrogen were measured in mature rats of the Wistar strain at diestrous phase following subchronic treatment with sodium arsenite at a dose of 0.4 ppm/rat/day for 16 days (4 estrous cycles) and 28 days (7 estrous cycles). A significant reduction in plasma levels of LH, FSH and estrogen along with significant diminution in the activities of ovarian Δ5-3β-HSD and 17β-HSD were observed following sodium arsenite treatment for 28 days. This duration of treatment also resulted in a marked degree in diminution in the weights of ovary, uterus and vagina, but 16 days of treatment did not exhibit any significant effect on these above parameters. Arsenic-treated rats exhibited a prolonged diestrous phase in the estrous cycle in contrast to control rats having 4 days of a regular estrous cycle. Deposition of arsenic in ovary, uterus, vagina and plasma was also monitored in arsenic-treated rats. The results of our experiment suggest that duration of arsenic treatment is the critical factor for its adverse effect on ovarian activities at the dose within the range noted in drinking water at several areas of West Bengal in India.
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  • Masahito SHIMIZU, Naoki YOSHIMI, Yasuhiro YAMADA, Kengo MATSUNAGA, Kun ...
    1999 Volume 24 Issue 5 Pages 433-439
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    The modifying effects of chlorogenic acid (CA) on N-methyl-N-nitrosourea (MNU)-induced glandular stomach carcinogenesis were investigated in five groups of male F344 rats. Rats in Groups 1 through 3 were given MNU in drinking water at a concentration of 400 ppm for 12 weeks. Animals of Group 1 were then kept on the basal diet alone, and those of Group 2 or 3 were fed a diet containing 500 or 250 ppm CA for a subsequent 22 weeks. Group 4 was exposed to CA alone through the experimental period (36 weeks), and Group 5 was given the basal diet continuously and treated as a control. At the end of the experiment, the incidence of glandular stomach carcinoma of Group 3 was significantly smaller than that of Group 1 (p<0.03). The incidence of adenomatous hyperplasia of Group 2 was also significantly lower than that of Group 1 (p<0.02). In addition, the proliferating cell nuclear antigen (PCNA) labeling index of the epithelial cells from the non-neoplastic mucosa in rats of Group 2 or 3 was significantly smaller than that of Group 1 (p<0.0001). These results suggest that CA has a chemopreventive effect on MNU-induced rat glandular stomach carcinogenesis by exposure during the post-initiation phase, and CA may be a promising agent for prevention of human stomach cancer.
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  • [in Japanese], [in Japanese]
    1999 Volume 24 Issue 5 Pages App147-App158
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
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