著者

Yin Jinzhu Zhang Qinli Yang Jin Kang Pan Huang Jianjun Niu Qiao

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.40, no.3, pp.365-373, 2015-06-01 (Released:2015-05-09)

参考文献数

46

被引用文献数

15

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Toxic and harmful factors co-exist in the environment; these factors often interact to induce combined toxicity, which is the main focus of toxicological research. Furthermore, a large number of studies have shown that aluminum (Al) and benzo[a]pyrene (BaP) are neurotoxic and target the central nervous system to cause neuronal apoptosis. Because we are exposed to both Al and BaP in the air, water, food, and even medicine, the combined effects of these agents in humans must be examined. The present study examines the ability of Al and BaP co-exposure to intensify neuronal apoptosis. The primary neurons of newborn rats were cultured for 5 days, and cells from the same batch that were growing well were selected and assigned to the blank control group, the solvent control group (DMSO+S9+maltol), BaP groups (10, 40 μmol/L), Al (mal)3 groups (50, 100, 400 μmol/L) and co-exposure groups with different combinations of BaP and Al (mal)3. The cell viabilities indicated that 10 μM BaP or 50 μM Al (mal)3 was mildly toxic, and we selected 10 μM BaP+50 μM Al (mal)3 for subsequent co-exposure experiments. The morphological characteristics of cell apoptosis were much more obvious in the co-exposure group than in the Al-exposed cells or the BaP-exposed cells, as observed with a transmission electron microscope and a fluorescence inverted microscope. The apoptotic rates and caspase-3 activity quantitatively significantly differed between the co-exposure and Al-exposure groups, while the BaP-exposure group did not significantly differ from the control group. These results indicate that Al and BaP co-exposure exert synergistic effects on neuronal cell apoptosis.

著者

Tomoka Hisaki Maki Aiba née Kaneko Masahiko Yamaguchi Hitoshi Sasa Hirokazu Kouzuki

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.40, no.2, pp.163-180, 2015-04-01 (Released:2015-03-14)

参考文献数

19

被引用文献数

26

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Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum “no observed effect level” (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

著者

Ryo Kamata Fujio Shiraishi Shinji Takahashi Akira Shimizu Daisuke Nakajima Shiho Kageyama Takushi Sasaki Kyosuke Temma

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.38, no.6, pp.903-912, 2013-12-01 (Released:2013-11-09)

参考文献数

27

被引用文献数

7

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In the 1950s to 1970s developed countries reported declines in populations of raptorial and fish-eating birds and dichlorodiphenyltrichloroethane (DDT) and its metabolites were considered causative substances because they accumulated significantly in the tissues of wild birds and animals. However, except for the estrogenic effects of o,p’-DDT, a minor component of commercial DDT, there has been no compelling evidence that DDT directly affects avian reproductive systems. To assess the possible impact of DDT on development and reproduction of birds, exposure experiments to the major component of commercial DDT, p,p’-DDT, and its persistent metabolite, p,p’-dichlorodiphenyldichloroethylene (DDE), were performed using Japanese quail (Coturnix japonica) eggs; the test substances (3 to 100 μg/g) were injected into the yolk prior to incubation, and hatched chicks were raised to adulthood. p,p’-DDT had no significant effects on the morphology and function of the reproductive systems, although the hatchability of treated eggs was reduced at the highest dose (100 μg/g). High doses of p,p’-DDE slightly enhanced the eggshell forming ability of female quails; eggshell mass and thickness were increased at 30 μg/g or more although no morphological changes were observed in the oviduct. Transcriptions of the CYP11A1 gene in the ovaries, and of AHR and ARNT in the livers, of adult females were significantly increased at 3 μg/g or more of p,p’-DDT. Except for low hatchability, transovarian exposure to p,p’-DDT or p,p’-DDE did not markedly impair the avian reproductive systems, but the hormonal actions of these compounds are likely to change reproductive and hepatic functions even after maturation.

著者

長谷川 雅哉 鍋島 俊隆

出版者

日本毒性学会

雑誌

Journal of toxicological sciences (ISSN:03881350)

巻号頁・発行日

vol.27, pp.11-16, 2002-12-25

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ダイエット商品には根強い需要がある。中国の健康茶をイメージさせるダイエット食品に対して,日本の消費者は無防備である。個人輸入やインターネット販売によって,法の網をかいくぐり,危険な健康食品ややせ薬が,消費者の手元に簡単に届くことが,大きな社会問題となっている。中国製ダイエット食品による健康被害が報告された。これらのダイエット食品に含まれており,問題となっているのが食欲抑制剤「フェンフルラミン」である。これは,食欲抑制効果を期待して人為的に添加されたものと推察されている。フェンフルラミンは,中枢性セロトニン(5-HT)作動性食欲抑制薬であり,肥満症の治療に使用される。フェンフルラミンの5-HT神経系を介した精神神経学的副作用について,数多くの報告があり,不安を惹起し,認知機能,睡眠,人格などに影響を与えるのではないかと考えられている。フェンフルラミンの投与により,持続的な脳内5-HTレベルの低下を伴う,うつ状態が誘導される。原因として5-HT神経繊維の脱落および5-HT再取り込み部位の減少が報告されている。フェンフルラミンの濫用はまれであるが,薬物濫用歴のある者がフェンフルラミンを濫用したケースがあり,多幸症,知覚変化,非現実感のような症状が発現している。動物実験では依存性獲得は認められていない。フェンフルラミンの過量投与により,精神障害,振せん(震え),眠気,錯乱,紅潮,発熱,発汗,腹痛,過呼吸,散瞳,廻旋眼振,反射亢進・抑制,頻拍,痙攣,昏睡,心室性期外収縮,心室細動,心停止が起こる可能性が有る。米国では,フェンフルラミンを含む食欲抑制剤によって,心臓弁への副作用が発見され,1997年に販売を禁止,回収を指示している。

著者

Nagaraja Haleagrahara Cheng Jun Siew Kumar Ponnusamy

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.38, no.1, pp.25-33, 2013-02-01 (Released:2013-01-29)

参考文献数

25

被引用文献数

21 72 3

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The catecholaminergic neurotoxin 6-hydroxydopamine is used to lesion dopaminergic pathways in the experimental animal models of Parkinson’s disease. The present study was aimed to evaluate the combined treatment with bioflavonoid quercetin (QN) and desferrioxamine (DFO) on 6-hydroxydopamine (6-OHDA) – induced neurotoxicity in the striatum of rats. Adult, male Sprague - Dawley rats were divided into control, sham lesion, 6-OHDA treated (300 µg, intracisternal), 6-OHDA with QN (50 mg/kg) treated, 6-OHDA with DFO (50 mg/kg) treated and 6-OHDA with QN and DFO treated groups. Striatal dopamine, protein carbonyl content (PCC), glutathione (GSH) and superoxide dismutase (SOD) were estimated. There was a significant increase (p < 0.05) in PCC and decrease in dopamine, GSH and SOD level and striatal neuronal number with 6-OHDA treatment. QN and DFO treatment significantly (p < 0.05) reduced these changes showing a significant neuronal protection. Combined treatment has a more significant effect (p < 0.05) in protecting the neurons and increasing the antioxidant enzymes in the striatum. In conclusion, an antioxidant with iron chelator treatment showed a significant neuroprotective effect against 6-hydroxydopamine (6-OHDA) by preventing dopaminergic neuronal loss and maintaining the striatal dopamine level.

著者

菊森 幹人 西田 伊久男 西村 孝義 安平 公夫 中井 伸子 西口 保幸 岩倉 啓子 長沢 久充 鷲見 信好

出版者

日本毒性学会

雑誌

Journal of toxicological sciences (ISSN:03881350)

巻号頁・発行日

vol.20, pp.153-163, 1995-12-25

参考文献数

12

被引用文献数

9

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Montirelinをマウス, ラットでは静脈内および筋肉内投与, イヌでは静脈内投与した後, 14日間の観察を行い, 単回投与毒性を検討した。1. LD_<50>値は, マウス静脈内投与で雌雄とも500mg/kg以上, ラット静脈内投与で雌雄とも200 mg/kg以上, マウス, ラットの筋肉内投与で雌雄とも20 mg/kg以上と推定された。また, イヌ静脈内投与で最小致死量は雌雄とも200 mg/kg以上であると推定された。2. 一般症状として, マウス静脈内投与では投与中〜投与後30分に振戦, 自発運動の減少が125 mg/kg以上の投与群で認められ, マウス筋肉内投与では投与後5分〜投与後2時間に振戦が5 mg/kg以上の投与群で認められた。ラット静脈内投与では投与中〜投与直後に振戦が50 mg/kg以上の投与群で,自発運動の減少, 失調性歩行が200 mg/kg投与群で認められ, ラット筋肉内投与では投与後5分〜投与後30分に振戦が5 mg/kg以上の投与群で, 流涎が20 mg/kg投与群で認められた。また, イヌ静脈内投与では投与中〜投与後6時間に興奮, かみつき, 発声, 散瞳, 流涎, 排尿, 排便, 舌なめずり, 嘔吐, 心拍数増加, パンティング, 体温上昇, 振戦および結膜充血が12.5mg/kg以上の投与群で認められた。3. 体重, 摂餌・摂水量の推移および病理学的検査では, 被験物質投与に起因したと思われる変化は認められなかった。(試験期間 : マウスi.v. ; 1985年9月17日〜1985年12月10日, マウスi.m. ; 1987年3月2日〜1987年8月31日, ラットi.v. ; 1985年9月17日〜1985年11月30日, ラットi.m. ; 1987年3月2日〜1987年8月31日, イヌi.v. ; 1985年12月10日〜1986年4月30日)

著者

Keisuke Nakayama Masaaki Nakayama Hiroyuki Terawaki Yaeko Murata Toshinobu Sato Masahiro Kohno Sadayoshi Ito

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.34, no.6, pp.699-702, 2009-12-01 (Released:2009-12-01)

参考文献数

13

被引用文献数

5 9

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Carbonated soft drinks reportedly contain methylglyoxal (MG), which is strongly associated with human carbonyl stress. We sought to evaluate the effects of carbonated drink intake on human carbonyl stress. We measured MG levels in 4 commercial beverage brands, and evaluated the changes in plasma MG in healthy subjects following the intake of carbonated drinks. By 30 min after intake of samples containing high glucose and high MG, the levels of plasma MG, glucose, insulin and uric acid had increased significantly, and then returned to basal levels by 120 min. After intake of the low-calorie carbonated samples containing little MG, there were no increases in plasma MG. Our results suggest that glucose-containing carbonated soft drinks are associated with increases in not only glucose but also carbonyl burden.

著者

Fan Wang Chonglei Li Wei Liu Yihe Jin

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.37, no.4, pp.739-748, 2012-08-01 (Released:2012-08-01)

参考文献数

46

被引用文献数

16 52

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Volatile organic compounds (VOCs) are the main substances causing multiple chemical sensitivity reactions in human. The effects of single VOCs exposure on airway inflammatory responses in mice lung have been reported. Previous studies have demonstrated the role of reactive oxygen species (ROS) in lung inflammation induced by single VOCs inhalation. However, effects of VOCs exposure on NO signaling and neurological signaling pathways in airway remain less clear. We exposed male Kunming mice to filtered air (0) and four types of VOCs mixture (formaldehyde, benzene, toluene, and xylene) treated air. Group 1 is 1.0, 1.1, 2.0 and 2.0 mg/m3, group 2 is 3.0, 3.3, 6.0 and 6.0 mg/m3, group 3 is 5.0, 5.5, 10.0 and 10.0 mg/m3, group 4 is 10.0, 11.0, 20.0 and 20.0 mg/m3, which respectively corresponded to 10, 30, 50 and 100 times of indoor air quality standard in China 2 hr per day, 5 days per week, for 2 weeks in the whole body exposure chamber. One day following VOCs exposure, we collected lung, bronchoalveolar lavage fluid (BALF) from each mouse and examined oxidative stress markers, cellular infiltration and production of cytokines, neurotrophin and substance P. We found that VOCs exposure influenced significantly NOS activity, GSH, or IL-6 concentration. The number of total cells, macrophages and eosinophils increased significantly in group 4. In addition, the production of interferon-gamma (IFN-γ) and substance P were significantly decreased. In contrast, neurotrophin-3 production in BALF was significantly increased in group 3 and 4. Our findings suggest that NO signaling pathways may induce airway inflammatory in short term VOCs exposure mice and the airway inflammatory response may be modulated by neurological signaling.

著者

Kiyonori Kai Takashi Yamaguchi Yu Yoshimatsu Junzo Kinoshita Munehiro Teranishi Wataru Takasaki

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.38, no.2, pp.269-277, 2013-04-01 (Released:2013-03-28)

参考文献数

21

被引用文献数

20 41

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A sensitive urinary biomarker for acute kidney injury (AKI) was investigated in beagle dogs with nephrotoxicity induced by gentamicin. Gentamicin sulphate at 25 or 50 mg/kg was injected (s.c.) for 9 days, and conventional urinalysis, ELISA assay of neutrophil gelatinase-associated lipocal (NGAL) in urine, blood chemistry, and pathological examinations were performed. The dog given gentamicin at 25 mg/kg only showed slight deposition of lysosomal granules in the proximal tubular epithelium of the kidneys without any other significant changes even though urinary NGAL was elevated on Day 10 (day of necropsy). In the dog receiving gentamicin at 50 mg/kg, increases in urinary NGAL were observed on Days 3 and 5, and absence of urination, marked increases in serum urea nitrogen and creatinine, enlargement and discoloration of the kidneys with marked necrosis, and swelling of proximal epithelium were observed. In conclusion, urinary NGAL is considered to be a candidate as a sensitive predictable biomarker of AKI in the gentamicin-induced nephrotoxicity model in dogs.

著者

浜田 知久馬

出版者

日本毒性学会

雑誌

Journal of toxicological sciences (ISSN:03881350)

巻号頁・発行日

vol.23, no.5, pp.App.185-App.189, 1998-12

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統計パッケージの普及に伴い, 毒性試験で用いられる統計手法も高度化しているが, わが国では, 生物統計学の専門家が不足しているため, 毒性試験の現場では統計学の利用について混乱が起きている。本稿では, 毒性試験において統計学を誤用しないために注意すべき点, 特によく用いられる検定と多重比較の意義, 統計パッケージと決定樹の利用の際の問題点, 論文における統計手法と結果の記載の注意点を総論的に述べる。

著者

浜田 知久馬

出版者

日本毒性学会

雑誌

Journal of toxicological sciences (ISSN:03881350)

巻号頁・発行日

vol.23, no.5, pp.185-189, 1998-12-17

参考文献数

5

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統計パッケージの普及に伴い, 毒性試験で用いられる統計手法も高度化しているが, わが国では, 生物統計学の専門家が不足しているため, 毒性試験の現場では統計学の利用について混乱が起きている。本稿では, 毒性試験において統計学を誤用しないために注意すべき点, 特によく用いられる検定と多重比較の意義, 統計パッケージと決定樹の利用の際の問題点, 論文における統計手法と結果の記載の注意点を総論的に述べる。

著者

寺澤 桂太郎 渡部 和義 寺林 幹夫 蔵元 茂 横本 泰樹 大谷 京子 島村 和位 山下 和正

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.17, pp.1-15, 1992-12-26

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FUT-187の急性毒性をマウス, ラットでは経口, 皮下および静脈内投与により, イヌでは経口投与により検討し以下の成績を得た。1 LD_<50>値は, マウスでは経口投与で雄; 4,395mg/kg, 雌; 3,626mg/kg, 皮下投与群で雄; 6,284mg/kg, 雌; 5,492mg/kg, 静脈内投与で雄; 39.4mg/kg, 雌; 41.4mg/kgであった。ラットでは経口投与で雄; 4,653mg/kg, 雌; 3,761mg/kg,皮下投与で雄; 6,799mg/kg, 雌; 3,343mg/kg, 静脈内投与で雄; 21.8mg/kg, 雌で15.8mg/kgであった。イヌでは3,000mg/kg付近と推定された。2 一般状態観察においては, マウスおよびラットの各投与経路にほぼ共通して投与後に腹這い姿勢, 痙攣, 吃逆, チアノーゼ, 自発運動の減少, 立毛および流涎等がみられた。イヌでは嘔吐および自発運動の減少, 腹臥, 横臥, 蹲り姿勢, 歩行失調および流涎等が観察された。3 剖検では, マウスおよびラットの経口投与で, 胃の膨満, 胃と肝の癒着, 消化管における硬化, 斑状出血または糜欄等がみられた。皮下投与では投与部位に被験物質の貯留および壊死等が観察された。イヌでは死亡例に消化管粘膜の赤色化あるいは粗造化が見られ病理組織学的に消化管粘膜の剥離, 変性, うっ血ないし出血が, 生存例では雌の高用量群で小腸の絨毛の萎縮がみられた。

著者

Yoshifumi Takahashi Shozo Tsuruta Akiko Honda Yasuyuki Fujiwara Masahiko Satoh Akira Yasutake

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.37, no.3, pp.663-666, 2012-06-01 (Released:2012-06-01)

参考文献数

8

被引用文献数

5

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Dental amalgam is a source of exposure to elemental mercury vapor in the general population. The aim of this study was to elucidate the effect of elemental mercury vapor exposure from dental amalgam restorations on gene expression profiles. Out of 26,962 rat genes, mercury vapor was found to increase the expression of 1 gene (Atp1b3) and decrease the expression of 1 gene (Tap1) in the cerebrum, increase the expression of 1 gene (Dnaja2) in the cerebellum, increase the expression of 2 genes (Actb and Timm23) and decrease the expression of 1 gene (Spink3) in the liver, increase the expression of 2 genes (RT1-Bb and Mgat5) and decrease the expression of 6 genes (Tnfaip8, Rara, Slc2a4, Wdr12, Pias4 and Timm13) in the kidney.

著者

山本 郁男

出版者

日本毒性学会

雑誌

Journal of toxicological sciences (ISSN:03881350)

巻号頁・発行日

vol.20, no.5, pp.App.119-App.124, 1995-11-25

著者

Sato Jun Yamamoto Yasuhito Nakamura Tsuneaki ISHIDA Shigeru TAKAGI Yutaka

出版者

日本毒性学会

雑誌

Journal of toxicological sciences (ISSN:03881350)

巻号頁・発行日

vol.30, no.4, pp.339-347, 2005-12-21

被引用文献数

2 3

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We evaluated the toxicity of tetradecanoic acid methyl ester sodium salt (C14-MES), a major component of fabric detergents, following the test guidelines of the Organization for Economic Cooperation and Development. The rat acute oral LD_<50> was 1,000 mg/kg in males and 500 mg/kg in females. Applying the combined repeated dose and reproductive/developmental toxicity screening test (ReproTox), we exposed groups of Crj:CD (SD) IGS rats to C14-MES in the diet at concentrations of 0, 0.3, 0.6, or 1.2%. We observed decreases in fibrinogen levels and longer prothrombin time at the 1.2% treated level in females and decreases in serum triglyceride levels in both sexes at the 0.6% and 1.2% treatment levels, but the effects were not clinically significant. The no-observed-effect-level (NOEL) for repeated dose toxicity was 0.3% (175 mg/kg body weight/day for males, 249 for females). The NOEL for reproduction/developmental toxicity was 1.2% (740 mg/kg for males, 1039 for females). C14-MES was negative in the reverse gene mutation assay and the chromosomal aberration test and did not induce skin sensitization in the guinea pig maximization test. These data confirm that C14-MES is of low hazard potential.

著者

岡崎 修三 山崎 英一 田村 一利 星谷 達 穴吹 一広 田中 英嗣 田中 剛太郎

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.17, pp.91-122, 1992-11-30

被引用文献数

1 1

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合成糖質コルチコイド製剤, PNFゲルの0.125, 0.5および2.0mg/kg/dayをCrj: CD(SD)系雌雄ラットに52週間経皮投与し, 反復投与毒性を検討するとともに, 8週間休薬による回復性について検討した。1. PNFゲル2.0mg/kg投与群では, 投与部皮膚の非薄化, 体重増加抑制傾向, 白血球数の減少, GOTおよびGPT活性の上昇, 遊離脂肪酸の増加, α_1-グロブリン分画比率の低下, 胸腺, 脾臓および副腎重量の減少と肉眼的な投与部皮膚の非薄化がみられた。病理組織学的には, 胸腺の萎縮, 副腎束状帯の萎縮, 投与部での皮膚付属器の萎縮を伴う皮膚の非薄化と肝臓小葉周辺帯で核肥大を伴う肝細胞の肥大がみられた。2. PNFゲル0.5mg/kg投与群では, 投与部皮膚の非薄化と, α_1-グロブリン分画比率の低下がみられた。また, 組織学的には投与部位で皮膚付属器の萎縮を伴う皮膚の非薄化がみられた。3. PNFゲルの0.125mg/kg投与群では被験物質投与に起因する変化はみられなかった。4. 8週間の休薬により, 投与部皮膚における変化が2.0mg/kg投与群にみられたが, 投与終了時と比較して軽減化を示し, その他の変化は消失しておたことからいずれも可逆性の変化と判断された。 5. 以上の結果から, 本試験におけるPNFゲルの確実中毒量は0.5mg/kg/dayであり, 無影響量は0.125mg/kg/dayと判断された。

著者

關橋 薫 齋藤 宏美 佐々木 有

出版者

日本毒性学会

雑誌

Journal of toxicological sciences (ISSN:03881350)

巻号頁・発行日

vol.27, pp.1-8, 2002-12-25

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甘味料ステビア抽出物の安全性試験の一環として,ステビア抽出物およびその代謝物であるステビオールの遺伝毒性をコメットアッセイで評価した。ステビオールはin vitroとin vivoの両方で,ステビア抽出物はin vivoで検討した。in vitroコメットアッセイではヒトリンパ芽球細胞株TK6およびWTK-1を用いた。ステビオールの1000μg/mlでは著しい細胞生存率の低下がみられたことから,生細胞数が70%を下回らない濃度としてラット肝由来の代謝活性化系の有無に関わらず500μg/ml以下で評価した。代謝活性化系の有無に関わらず500μg/ml以下で統計学的に有意なDNA損傷の増加はみられなかった。以上の結果から,本試験条件下において,ステビオールには代謝活性化系の有無に関わらずin vitroでDNA損傷誘発性はないと考えられた。ステビア抽出物およびステビオールの致死用量は2000mg/kg以上であることから,最高用量を2000mg/kgとしてマウスに単回強制経口投与し,3および24時間後に肝,腎,胃,結腸,精巣でDNA損傷性を検討した(ステビア抽出物では肝,胃,結腸のみ)。ステビア抽出物およびステビオール投与群では,いずれの臓器においても統計学的に有意なDNA損傷の増加はみられなかった。以上の結果から,本試験条件下において,ステビア抽出物およびステビオールには評価対象としたマウスのいずれの臓器に対してもDNA損傷誘発性はないと考えられた。

著者

Kazuhiko Imaizumi Shogo Sato Mari Kumazawa Natsuko Arai Shoko Aritoshi Shunta Akimoto Yuko Sakakibara Yu Kawashima Kaoru Tachiyashiki

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.36, no.1, pp.109-116, 2011-02-01 (Released:2011-02-01)

参考文献数

23

被引用文献数

13 16

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Red peppers are used as a spice for enhancing the palatability of foods. Two major capsaicinoids, dihydrocapsaicin (DHC) and capsaicin (CAP) are responsible for up to 90% of the total pungency of pepper fruits. These capsaicinoids are known to enhance energy metabolism and thermogenesis. However, there is a little information on the effects of capsaicinoids on the lipolysis and carbohydrate metabolism. We studied the effects of DHC and CAP on plasma glucose, free fatty acid (FFA) and glycerol concentrations in rats. Male six-week-old Sprague Dawley rats were divided into the DHC, CAP and control groups. Each capsaicinoid (dose = 3 mg/kg BW/day) was subcutaneously administered to rats for 10 days. DHC increased markedly plasma glucose, FFA and glycerol concentrations on day 1-10 by 14-35%, 61-103% and 108-174%, respectively, as compared with those of the control group. CAP increased relatively plasma glucose concentrations on day 1-3 by 15-17%, as compared with the control group. However, there were no significant differences in plasma glucose concentrations on day 7-10 among three groups. On the contrary, CAP did not change plasma FFA and glycerol concentrations on day 1-3. However, CAP increased markedly plasma FFA and glycerol concentrations on day 7-10 by 54-89% and 92-98%, respectively, as compared with the control group. DHC and CAP did not change the weights of white (perirenal and periepididymal) and brown (interscapular) adipose tissues. In conclusion, the effects of capsaicinoids on plasma glucose, FFA and glycerol concentrations were relatively higher in the DHC than in the CAP, and capsaicinoids did not change the weight of white and brown adipose tissues.

著者

OHNO Yasuo

出版者

日本毒性学会

雑誌

Journal of toxicological sciences (ISSN:03881350)

巻号頁・発行日

vol.22, no.4, 1997-10-15

著者

Bao-qiu Li Xin Dong Shi-hong Fang Gui-qin Yang Ji-you Gao Jian-xin Zhang Fang-min Gu Hua Zhao

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.35, no.3, pp.279-286, 2010-06-01 (Released:2010-06-01)

参考文献数

23

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Aim: Non-cell corynebacterium parvum product (NCPP) is a new preparation of corynebacterium parvum (CP), an immunomodulator that displays anticancer activities. It is prepared by nanotechnology and is intended to minimize the side effects of CP. The aim of the present study was to evaluate the immunogenicity and systemic toxicity of NCPP compared with CP in animals. Methods: 30 monkeys were randomly divided into 5 groups and given CP (3 mg/monkey), three doses of NCPP (9, 3, 1 mg/monkey) and 0.9% normal saline (NS, 4 ml/monkey) individually by intramuscular injection twice a week for 13 weeks. The immunogenicity and systemic toxicity of NCPP and CP were compared. Results: NCCP and CP caused histopathological changes in the liver, spleen and kidney, but pathologic changes in NCCP-treated groups were slighter than that in the CP group. Only 9 mg/monkey of NCPP caused the similar damage as the CP in intensity. Deposition of immune complexes in the glomerular basement membrane was observed only in the CP group. ELISA detection showed that the anti-CP antibody was at a high level, while the anti-NCPP antibody was at low level and disappeared during the recovery period. Conclusion: Our study has led to the view that NCPP is safer than CP.