著者

竹本 稔 松尾 弘也 小黒 元春 河内 泰英

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.19, no.SupplementII, pp.249-262, 1994-10-15 (Released:2008-02-21)

参考文献数

10

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The antigenicity tests of Tazobactam/piperacillin (TAZ/PIPC), tazobactam (TAZ: β-lactamase inhibitor) and piperacillin (PIPC: penicillin antibiotic) were performed in mice and guinea pigs. The following results were obtained. 1. TAZ/PIPC, TAZ or PIPC had no immunogenicity and allergenicity in either passive cutaneous anaphylaxis (PCA) test using BALB/c and C3H/He mice or in PCA test using guinea pigs. 2. Guinea pigs sensitized with TAZ/PIPC, TAZ or PIPC showed no anaphylactic symptons in active systemic anaphylaxis (ASA) test. 3. Guinea pig PCA tests using protein conjugates as sensitizing and challenging antigens showed positive reactions. Immunological cross-reactivity tests were performed by using these conjugates in guinea pig PCA reaction. Results showed that TAZ/PIPC and PIPC cross-reacted with penicillin G (PCG) and ampicillin (ABPC), but not with cephalothin (CET) and cephmetazol (CMZ). TAZ did not cross-react with PCG, ABPC, CET or CMZ. 4. From the results of the passive hemagglutination (PHA) test, no antibody against TAZ/PIPC, TAZ or PIPC was detected. 5. In direct Coombs' test using human blood, TAZ/PIPC, TAZ, PCG and CET showed positive reactions at 20∼80, 5∼20, 80 and 10∼20 mg/ml, respectively. 6. The results of a test on in vitro covalent binding activity with human serum albumin indicated that the order of binding potency was CET>CMZ>ABPC>PCG=PIPC>TAZ under the physiological condition (pH 7.2∼7.4), and was CMZ>CET>ABPC>PIPC>TAZ>PCG under the alkaline condition (pH 10.0∼10.5), respectively.

著者

大内田 昭信 谷口 明美 河内 泰英 前田 泰宏 樫原 昭裕 大前 重男

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.19, no.SupplementII, pp.263-280, 1994-10-15 (Released:2008-02-21)

参考文献数

17

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TAZ/PIPCの安全性試験の一環として, tazobactam(TAZ), piperacillin(PIPC)およびそれらの配合剤(TAZ/PIPC)について変異原性の有無を検討するために, 細菌を用いた復帰突然変異試験, 培養細胞を用いた染色体異常試験およびICR雄マウスを用いた小核試験を実施した。1. TAZ, PIPCおよびTAZ/PIPCの復帰突然変異試験ではS. typhimurium TA100, TA98, TA1535, TA1537, およびE. coli WP2uvrAを用いて, 抗菌作用が認められる用量を最高に以下公比2~2.5で減じた7段階の用量で実施した。TAZ, PIPCおよびTAZ/PIPCは代謝活性化の有無にかかわらず, いずれの菌株も溶媒対照群と比較して復帰変異コロニー数の用量に依存した明らかな増加は認められなかった。2. TAZ, PIPCおよびTAZ/PIPCの染色体異常試験では培養細胞CHLを用い, 直接法および代謝活性化法の両法において10mMを最高に以下公比2で減じた3~4用量の処理群について染色体標本を観察した。TAZ, PIPCおよびTAZ/PIPCは直接法および代謝活性化法のいずれにおいても染色体の構造異常あるいは数的異常の出現頻度は0~3.0%で, 溶媒対照群と差がなかった。3. TAZおよびTAZ/PIPCの小核試験では625, 1250, 2500, 5000 mg/kgの投与用量で, PIPCでは625, 1250, 2500 mg/kgの投与用量で実施した。TAZ, PIPCおよびTAZ/PIPCにおけるMNPCEの出現率はそれぞれ0.02~0.17%, 0.02~0.1%および0.03~0.07%であり, 用量依存性はみられなかった。また, 背景データを用いた判定法でも陰性であった。4. 上記の結果より, TAZ, PIPCおよびTAZ/PIPCには変異原性は認められなかった。

著者

林 泰司 矢田 英昭 穴井 真紀子 馬野 高昭 河津 孝二 穴井 俊二 梶原 利彦 山崎 寛治

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.19, no.SupplementII, pp.145-153, 1994-10-15 (Released:2008-02-21)

参考文献数

7

被引用文献数

1

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TAZ/PIPCおよびTAZのマウス, ラットおよびイヌにおける単回投与毒性を検討し, 以下の結果を得た。1. マウスおよびラッ卜ではTAZ/PIPC, TAZともすべての投与経路において軟便がみられ, 皮下, 腹腔内および静脈内投与では自発運動の低下あるいは呼吸数の減少などもみられた。TAZ/PIPCの静脈内投与の死亡例では, マウスで振戦, ラットで間代性痙攣を呈し死亡し, 剖検では肺の充血, 出血または水腫, 消化管の出血などがみられた。また, TAZ/PIPCを投与した生存例の一部に脾の腫大がみられた。2. イヌではTAZ/PIPC投与により嘔吐がみられ, TAZ投与により嘔叶, 呼吸異常, 軟梗あるいは下痢便などがみられた。3. マウスおよびラットでは, 本剤の刺激性による投与部位の脱毛(皮下投与), 尾部の壊死(静脈内投与), イヌでは投与前肢の跛行がみられ, 剖検では壊死, 出血, 腹膜炎(腹腔内投与)などがみられた。4. TAZ/PIPCでは, マウスおよびラットの経口, 皮下および腹腔内投与でのLD50値は, 5,000mg/kg 以上(雌雄)であった。静脈内投与ではマウスが5,000mg/kg以上(雄), 4,565mg/kg(雌), ラットが3,157mg/kg(雄), 3,992mg/kg(雌), イヌが5,000 mg/kg以上であった。TAZでは, マウスおよびラット(雌雄)の経口, 皮下, 腹腔内, 静脈内投与およびイヌの静脈内投与ではLD50値は5,000 mg/kg以上であった。

著者

Xiaoting Jin Bin Xue Qunfang Zhou Ruijun Su Zhuoyu Li

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.43, no.2, pp.101-111, 2018 (Released:2018-02-26)

参考文献数

36

被引用文献数

70

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Mitochondria can be used as important biomarkers of pollutants on human health, and fine particulate matter (PM2.5) has been documented to cause respiratory damage. However, current studies about the relationship between PM2.5 and mitochondria in respiratory tract are limited and warrant further detailed investigations. Hence, the study was aimed to evaluate effects of PM2.5 on mitochondrial structure, investigate the link between PM2.5-induced mitochondrial disorder and respiratory damage, and delineate the possible mechanisms using both in vitro and in vivo models. PM2.5 exposure resulted in damage of mitochondrial structure, including mitochondrial dynamic, DNA biogenesis and morphological alteration 16HBE cells. Furthermore, PM2.5 elevated ROS formation. However, DPI and NAC (inhibitor of ROS) in supplement restored PM2.5-induced mitochondrial disorder. PM2.5 also contributed to the 16HBE cells apoptosis via mitochondrial pathway. Additionally, the results coincided with the in vivo data which were obtained from bronchial tissues of SD rats exposed to PM2.5 for 30 days. Collectively, this study uncovers that PM2.5 leads to the disorder of mitochondrial structure via ROS generation, and then results in respiratory damage. It provides further understanding about the detrimental effect of PM2.5 on respiratory damage, and reveals a mechanistic basis for preventing outcomes in polluted environments.

著者

Kanako Noritake Toshihiko Aki Moe Kimura Takeshi Funakoshi Kana Unuma Koichi Uemura

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.42, no.5, pp.545-551, 2017-10-01 (Released:2017-09-13)

参考文献数

31

被引用文献数

2

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We reported previously that when mouse atrium-derived HL-1 cardiomyocytes undergo apoptosis upon exposure to 2% ethanol, the cellular cytoskeleton is severely disrupted and the anti-apoptotic transcriptional co-activator Yes-associated protein (YAP) is inactivated. Consistent with our previous observations, the expression of connective tissue growth factor (CTGF), an anti-apoptotic growth factor and a target of YAP, decreases in a time-dependent manner during exposure to 2% ethanol. The restoration of YAP activation rescues the cells from apoptosis: both the retrovirus-mediated expression of constitutively active YAP and the stabilization of the actomyosin cytoskeleton by jasplakinolide prevent cell death. In contrast, YAP inhibitors have no effect on cell death, confirming the inactivation of YAP in ethanol-exposed cells. Thus, a decrease in actin tension and YAP inactivation should be crucially involved in the cytotoxicity of ethanol on HL-1 cardiomyocytes.

著者

Hongquan Zhu

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.42, no.2, pp.233-240, 2017-04-01 (Released:2017-03-17)

参考文献数

23

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この論文は撤回されました。

著者

Shuji Tsuda

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.41, no.Special, pp.SP27-SP36, 2016-12-20 (Released:2016-12-20)

参考文献数

57

被引用文献数

66

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Perfluoroalkyl substances (PFASs) are persistent environmental contaminants. Perfluorooctane sulfonate (PFOS) and Perfluorooctanoic acid (PFOA) are representatives of PFASs. Recently, the U.S. Environmental Protection Agency (US EPA) set the health advisory level as 70 parts per trillion for lifetime exposure to PFOS and PFOA from drinking water, based on the EPA’s 2016 Health Effects Support Documents. Then, a monograph on PFOA was made available online by the International Agency for Research on Cancer, where the agency classified PFOA as “possibly carcinogenic to humans” (Group 2B). The distinction between PFOS and PFOA, however, may not be easily understood from the above documents. This paper discussed differential toxicity between PFOS and PFOA focusing on neurotoxicity, developmental toxicity and carcinogenicity, mainly based on these documents. The conclusions are as follows: Further mechanistic studies may be necessary for ultrasonic-induced PFOS-specific neurotoxicity. To support the hypothesis for PFOS-specific neonatal death that PFOS interacts directly with components of natural lung surfactant, in vivo studies to relate the physicochemical effects to lung collapse may be required. PFOA-induced DNA damage secondary to oxidative stress may develop to mutagenicity under the condition where PFOA-induced apoptosis is not sufficient to remove the damaged cells. A study to find whether PFOA induces apoptosis in normal human cells may contribute to assessment of human carcinogenicity. Studies for new targets such as hepatocyte nuclear factor 4α (HNF4α) may help clarify the underlying mechanism for PFOA-induced carcinogenicity.

著者

Ikuo Horii

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.41, no.Special, pp.SP49-SP67, 2016-12-31 (Released:2017-03-01)

参考文献数

65

被引用文献数

7

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Pharmaceutical (drug) safety assessment covers a diverse science-field in the drug discovery and development including the post-approval and post-marketing phases in order to evaluate safety and risk management. The principle in toxicological science is to be placed on both of pure and applied sciences that are derived from past/present scientific knowledge and coming new science and technology. In general, adverse drug reactions are presented as “biological responses to foreign substances.” This is the basic concept of thinking about the manifestation of adverse drug reactions. Whether or not toxic expressions are extensions of the pharmacological effect, adverse drug reactions as seen from molecular targets are captured in the category of “on-target” or “off-target”, and are normally expressed as a biological defense reaction. Accordingly, reactions induced by pharmaceuticals can be broadly said to be defensive reactions. Recent molecular biological conception is in line with the new, remarkable scientific and technological developments in the medical and pharmaceutical areas, and the viewpoints in the field of toxicology have shown that they are approaching toward the same direction as well. This paper refers to the basic concept of pharmaceutical toxicology, the differences for safety assessment in each stage of drug discovery and development, regulatory submission, and the concept of scientific considerations for risk assessment and management from the viewpoint of “how can multidisciplinary toxicology contribute to innovative drug discovery and development?” And also realistic translational research from preclinical to clinical application is required to have a significant risk management in post market by utilizing whole scientific data derived from basic and applied scientific research works. In addition, the significance for employing the systems toxicology based on AOP (Adverse Outcome Pathway) analysis is introduced, and coming challenges on precision medicine are to be addressed for the new aspect of efficacy and safety evaluation.

著者

Xin Cao Yuji Nakamura Takeshi Wada Hiroko Izumi-Nakaseko Kentaro Ando Atsushi Sugiyama

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.41, no.3, pp.439-447, 2016-06-01 (Released:2016-05-17)

参考文献数

21

被引用文献数

14

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Since amantadine-induced long QT syndrome has been clinically reported, we investigated its electropharmacological effects to estimate the extent of proarrhythmic risk by using the halothane-anesthetized beagle dogs (n = 4). Amantadine in doses of 0.1, 1 and 10 mg/kg was infused over 10 min with a pause of 20 min under the monitoring of multiple cardiovascular variables. J-Tpeak and Tpeak-Tend were separately measured on the lead II electrocardiogram to precisely analyze the net balance between inward and outward current modifications by amantadine. The low dose increased the ventricular contractile force, but suppressed the intraventricular conduction. The middle dose prolonged the QT interval besides enhancing the changes induced by the low dose. The high dose increased the mean blood pressure, left ventricular end-diastolic pressure and total peripheral resistance, and accelerated the atrioventricular nodal conduction, but decreased the cardiac output besides enhancing the changes induced by the middle dose. A reverse use-dependence was confirmed in the repolarization delay. Amantadine hardly affected the J-Tpeak, but prolonged the Tpeak-Tend. Amantadine can be considered to stimulate Ca2+ channel but inhibit Na+ and K+ channels in the in situ heart. J-Tpeak and Tpeak-Tend analysis suggests that amantadine may possess modest risk for arrhythmia.

著者

Biswadev BISHAYI Subhashree ROYCHOWDHURY Soumya GHOSH Mahuya SENGUPTA

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.27, no.3, pp.139-146, 2002 (Released:2003-01-31)

参考文献数

25

被引用文献数

30 89

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Effect of Tinospora cordifolia extract on modulation of hepatoprotective and immunostimulatory functions in carbon tetrachloride (CCl4) intoxicated mature rats is reported here. Administration of CCl4 (0.7 ml/kg body weight for 7 days) produces damage in the liver as evident by estimation of enzymes such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transminase (SGPT) and alkaline phosphatase (ALP) as well as serum bilirubin level. CCl4 administration also causes immunosuppressive effects as indicated by phagocytic capacity, chemotactic migration and cell adhesiveness of rat peritoneal macrophages. However, treatment with T. cordifolia extract (100 mg/kg body weight for 15 days) in CCl4 intoxicated rats was found to protect the liver, as indicated by enzyme level in serum. A significant reduction in serum levels of SGOT, SGPT, ALP, bilirubin were observed following T. cordifolia treatment during CCl4 intoxication. Treatment with T. cordifolia extract also deleted the immunosuppressive effect of CCl4, since a significant increment in the functional capacities of rat peritoneal macrophages (PMφ) was observed following T. cordifolia treatment. The results of our experiment suggest that treatment by T. cordifolia extract may be the critical remedy for the adverse effect of CCl4 in liver function as well as immune functions.

著者

Kanae Umeda Yaichiro Kotake Masatsugu Miyara Keishi Ishida Seigo Sanoh Shigeru Ohta

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.41, no.2, pp.255-264, 2016-04-01 (Released:2016-03-10)

参考文献数

46

被引用文献数

12 18

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GluR2, an α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit, plays important roles in neuronal survival. We previously showed that exposure of cultured rat cortical neurons to several chemicals decreases GluR2 protein expression, leading to neuronal toxicity. Methoxychlor, the bis-p-methoxy derivative of dichlorodiphenyltrichloroethane, and fenvalerate, a synthetic pyrethroid chemical, have been used commercially as agricultural pesticides in several countries. In this study, we investigated the effects of long-term methoxychlor and fenvalerate exposure on neuronal glutamate receptors. Treatment of cultured rat cortical neurons with 1 or 10 µM methoxychlor and fenvalerate for 9 days selectively decreased GluR2 protein expression; the expression of other AMPA receptor subunits GluR1, GluR3, and GluR4 did not change under the same conditions. Importantly, the decreases in GluR2 protein expression were also observed on the cell surface membrane where AMPA receptors typically function. In addition, both chemicals decreased neuronal viability, which was blocked by pretreatment with 1-naphtylacetylspermine, an antagonist of GluR2-lacking AMPA receptors, and MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. These results suggest that long-term exposure to methoxychlor and fenvalerate decreases GluR2 protein expression, leading to neuronal death via overactivation of GluR2-lacking AMPA and NMDA receptors.

著者

Kyoichi ASANO Masaya YAMANO Kiyoshi HARUYAMA Etuo IKAWA Kazumasa NAKANO Masayasu KURONO Osamu WADA

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.19, no.SupplementII, pp.131-143, 1994-10-15 (Released:2008-02-21)

参考文献数

15

被引用文献数

3 4 6

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A histopathological study was performed to examine the influence of propagermanium and germanium dioxide (GeO2) on chemically induced renal lesions in rats. Animals were treated with adriamycin or mercuric chloride to induce glomerular or proximal tubular damage, and then given drinking water containing propagermanium (480 or 2, 400 ppm solution) or GeO2 (300 or 1, 500 ppm solution: equivalent to propagermanium in terms of germanium contents). The distal tubular epithelium after 8 weeks dosage with the 1, 500 ppm solution of GeO2 was characterized by vacuolization and deposits of PAS-positive material not only in adriamycin-treated rats, but also in normal rats. In contrast, propagermanium administration was not associated with any alteration in the changes induced by adriamycin or mercuric chloride. We previously clarified that propagermanium had no biochemical influence on the renal function of these renal injured rats. The histological demonstration that this compound does not exert renal toxicity, even when given at a high dosage to renal injured rats, further indicates that it would not exacerbate renal dysfunction already present. This confirms that propagermanium may be a safe compound for use in individuals with compromised kidneys.

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

24

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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

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 66 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

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

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。