Toxicity and recovery in the pregnant mouse after gestational exposure to the cyanobacterial toxin, cylindrospermopsin.

Toxicity and recovery in the pregnant mouse after gestational exposure to the cyanobacterial toxin, cylindrospermopsin.
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DOI:
10.1002/jat.1586
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发表时间:
2011-04
影响因子:
3.3
通讯作者:
Rosen, M. B.
Rosen, M. B.
中科院分区:
医学4区
文献类型:
--
作者:
Chernoff, N.;Rogers, E. H.;Zehr, R. D.;Gage, M. I.;Malarkey, D. E.;Bradfield, C. A.;Liu, Y.;Schmid, J. E.;Jaskot, R. H.;Richards, J. H.;Wood, C. R.;Rosen, M. B.

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草珊瑚素(CYN)是一种由世界范围内的淡水蓝藻产生的三环生物碱毒素。CYN是牲畜和人类在口服接触CYN后中毒的原因。本研究探讨了CYN在妊娠不同阶段对妊娠小鼠的毒性作用。评价了恢复过程和个体对毒素的反应。通过临床检查、组织病理学、生物化学和基因表达监测CYN的不良反应,直至给药后4周。妊娠期(GD)8-12天的暴露诱导的致死率显著高于GD 13 -17天的暴露。在两组中均观察到眶周、胃肠道和尾远端肿胀。两组中指示肝损伤的血清标志物(丙氨酸氨基转移酶、天冬氨酸氨基转移酶和山梨醇脱氢酶)均升高; GD 8 -12动物中肾功能不全标志物(血尿素氮和肌酐)升高。在血清标志物异常组的肝脏(小叶中心坏死)和肾脏(间质性炎症)中观察到组织学。在最终剂量后24小时,参与核糖体生物发生、异生物质和脂质代谢、炎症反应和氧化应激的基因的表达谱发生改变。给药后1周,大体、组织学和血清参数恢复正常,但在GD 13 -17组中发现肝脏/体重比增加和1例胃肠道出血。基因表达变化持续至给药后两周,并在四周后恢复正常。个体动物对CYN暴露的反应表明,给药组内动物间存在高度显著的变异性。
Cylindrospermopsin (CYN) is a tricyclic alkaloid toxin produced by fresh water cyanobacterial species worldwide. CYN has been responsible for both livestock and human poisoning after oral exposure to CYN. This study investigated the toxicity of CYN to pregnant mice exposed during different segments of gestation. The course of recovery and individual responses to the toxin were evaluated. Adverse effects of CYN were monitored up to four weeks post dosing by clinical examination, histopathology, biochemistry, and gene expression. Exposure on gestational days (GD) 8–12 induced significantly more lethality than GD13–17 exposure. Periorbital, gastrointestinal and distal tail hemorrhages were seen in both groups. Serum markers indicative of hepatic injury (alanine amino transferase, aspartate amino transferase and sorbitol dehydrogenase) were increased in both groups; markers of renal dysfunction (blood urea nitrogen and creatinine) were elevated in the GD8–12 animals. Histopathology was observed in the liver (centrilobular necrosis) and kidney (interstitial inflammation) in groups exhibiting abnormal serum markers. The expression profiles of genes involved in ribosomal biogenesis, xenobiotic and lipid metabolism, inflammatory response and oxidative stress were altered 24 hours after the final dose. One week after dosing, gross, histological and serum parameters had returned to normal although increased liver/body weight ratio and one instance of gastrointestinal bleeding was found in the GD13–17 group. Gene expression changes persisted up to two weeks post dosing and returned to normal by four weeks. Responses of individual animals to CYN exposure indicated highly significant inter-animal variability within the treated groups.
DOI: 10.3390/ijms9112146
发表时间: 2008-11
影响因子: 5.6
作者:
Doi K;Ishigami N;Sehata S
通讯作者: Sehata S
DOI: 10.1080/15287390701434877
发表时间: 2007-01-01
影响因子: 2.6
作者:
Bain, Peter;Shaw, Glen;Patel, Bharat
通讯作者: Patel, Bharat
DOI: 10.1002/tox.10108
发表时间: 2003-04-01
影响因子: 4.5
作者:
Fergusson, KM;Saint, CP
通讯作者: Saint, CP
DOI: 10.1080/07438140309353943
发表时间: 2003-12-01
影响因子: 1.5
作者:
Dobberfuhl, DR
通讯作者: Dobberfuhl, DR
DOI: 10.1111/j.1529-8817.2004.03118.x
发表时间: 2004-04-01
影响因子: 2.9
作者:
Briand, JF;Leboulanger, C;Dufour, P
通讯作者: Dufour, P