Comparison of murine anorectic responses to the 8-ketotrichothecenes 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, fusarenon X and nivalenol.
Comparison of murine anorectic responses to the 8-ketotrichothecenes 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, fusarenon X and nivalenol.
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DOI：
10.1016/j.fct.2012.03.055
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发表时间：
2012-06
期刊：
影响因子：
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通讯作者：
Wenda Wu;B. Flannery;Y. Sugita‐Konishi;M. Watanabe;Haibin Zhang;J. Pestka
中科院分区：
文献类型：
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作者：
Wenda Wu;B. Flannery;Y. Sugita‐Konishi;M. Watanabe;Haibin Zhang;J. Pestka
虽然已经在几种动物模型中描述了由白腐霉烯真菌毒素脱氧雪腐镰刀菌烯醇（DON）诱导的食物拒绝，但对结构相关的8-酮白腐霉烯、3-乙酰脱氧雪腐镰刀菌烯醇（3-ADON）、15-乙酰脱氧雪腐镰刀菌烯醇（15-ADON）、镰孢菌酮X（FX）和雪腐镰刀菌烯醇（NIV）的厌食作用知之甚少。在这里，我们比较了这些同系物诱导小鼠厌食症的能力。正如先前观察到的DON，B6 C3 F1雌性小鼠在腹膜内（IP）和口服暴露后对3-ADON和15-ADON的厌食反应是短暂的，仅持续几个小时，摄食量在16小时内恢复到对照水平。对于两种ADON，IP暴露后的无可见不良作用水平（NOAEL）和最低可见不良作用水平（LOAEL）分别为0.5和1 mg/kg bw，经口暴露后分别为1和2.5 mg/kg bw。相比之下，IP和口服FX和NIV后48 - 96小时持续拒食。对于IP和口服FX暴露，NOAEL为0.025 mg/kg bw，LOAEL为0.25 mg/kg bw，而IP暴露后NIV的NOAEL和LOAEL分别为0.01和0.1 mg/kg bw，口服暴露后分别为0.1和1 mg/kg bw。这些数据和先前的DON研究都表明，与口服暴露相比，IP给药时对8-酮基二氢噻吩的厌食反应总是更大，并且对于IP暴露遵循NIV>FX>DON 13-ADON 15-ADON的近似等级顺序，对于口服暴露遵循FX>NIV>DON 13-ADON 15-ADON的近似等级顺序。毒性效力数据，如这里所描述的将适用于未来的比较风险评估，这一重要的群体的马鞭草烯真菌毒素。
While induction of food refusal by the trichothecene mycotoxin deoxynivalenol (DON) has been described in several animal models, much less is known about the anorectic effects of structurally related 8-ketotrichothecenes, 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX) and nivalenol (NIV). Here, we compared the capacities of these congeners to induce anorexia in the mouse. As previously observed for DON, anorectic responses to 3-ADONand 15-ADON in the B6C3F1 female mouse following both intraperitoneal (IP) and oral exposure were transient, lasting only a few hours, with food intake recovering to control levels within 16h. For both ADONs, the no observed adverse effect levels (NOAEL) and lowest observed adverse effect levels (LOAEL) were 0.5 and 1mg/kg bw following IP exposure, respectively, and 1 and 2.5mg/kg bw after oral exposure, respectively. In contrast, food refusal persisted from 48 to 96h following IP and oral exposure to FX and NIV. For both IP and oral FX exposure, the NOAEL was 0.025mg/kg bw and LOAEL was 0.25mg/kg bw, whereas the NOAELs and LOAELs for NIV were 0.01 and 0.1mg/kg bw, respectively, after IP exposure and 0.1 and 1mg/kg bw, respectively, following oral exposure. Both these data and a prior DON study suggest that anorectic responses to 8-ketotrichothecenes were always greater when administered IP as compared to oral exposure and follow an approximate rank order of NIV>FX>DON≈3-ADON≈15-ADON for IP exposure and FX>NIV>DON≈3-ADON≈15-ADON for oral exposure. Toxic potency data such as is described here will be applicable to future comparative risk assessments for this important group of trichothecene mycotoxins.