三唑醇杀菌剂在雄性丽斑麻蜥体内的对映选择性降解、蓄积和肝毒性研究

三唑醇(triadimenol, TN)是一种广泛使用的手性三唑类杀菌剂,它含有2个手性中心,4个手性对映体,包括对映体A(A1(R,S)和A2(S,R))以及对映体B(B1(R,R)和B2(S,S))。为了研究三唑醇在爬行动物体内的对映选择性行为和潜在的肝毒性,将雄性丽斑麻蜥分别一次经口暴露和28 d长期暴露于三唑醇(100 mg·kg~(-1) body weight),一次经口暴露结果显示,三唑醇进入大脑和肾中的浓度低于肝、性腺、皮肤和尾,B2(S,S)和B1(R,R)对映体具有相似的代谢速率。代谢过程中A1(R,S)的浓度明显高于A2(S,R),并且在暴露后12 h出现二次上升,这可能是A2(S,R)在体内手性转换为A1(R,S)导致。丽斑麻蜥长期(28 d)暴露于三唑醇后,性腺和肾中无明显蓄积现象,皮和尾中浓度显著高于其他组织,各个组织中三唑醇趋向于保持外消旋状态。三唑醇暴露后肝中主要的代谢基因cyp1a1c、yp3a4c、yp2b1和cyp2d3的表达量都出现明显上升,组织病理学分析进一步显示,三唑醇暴露后的肝组织出现组织空泡、血窦阻塞的症状,说明三唑醇对肝组织具有一定的毒性作用。上述结果为手性农药对爬行动物的生态毒理学评价提供了重要依据。

The Enantioselective Metabolism, Bioaccumulation and Hepatic Toxicity of Triadimenol in Male Eremias argus

Triadimenol (TN) is a widely used triazole fungicide with two chiral centers and 2 pairs of diastereoisomers, TN-A (A1(R,S) and A2(S,R)) and TN-B (B1(R,R) and B2(S,S)). To investigate the enantioselective behaviors and potential hepatic toxicity of triadimenol toward reptiles, in the present study, male Eremias argus was orally exposed to racemic triadimenol (100 mg kg^-1 body weight) for one time and for 28 d respectively. After one-time exposure, the results showed that the concentrations of triadimenol in brain and kidney were significantly lower than those in other tissues. The B1(R,R) and B2(S,S) enantiomers possessed similar degradation process in all tissues. However, the concentrations of A1(R,S) were much higher than that of A2(S,R) at the first 24 h. Notably, the levels of A1(R,S) in liver, kidney, skin and tails increased again at 12 h post-dose. This phenomenon implicates that A2(S,R) may transform to A1(R,S), leading to a higher level of A1(R,S) in vivo and during the enterohepatic circulation, only A1(R,S) was obviously absorbed again. After exposure to triadimenol for 28 d, no obvious residues were observed in gonads. Skin and tails were the main bioaccumulation tissues. The concentrations of each pair of diastereoisomers were almost equal in all tissues, suggesting that the racemate was the most stable status in vivo. The metabolic genes including cyp1a1, cyp3a4, cyp2b1, cyp2d3 in liver were significantly up-regulated after exposure to triadimenol for 28 d, implicating its potential disruption toward hepatic function. The histopathological analysis further revealed the liver tissue injury including vacuolation of cytoplasm and sinusoid inflammation. These results revealed the enantioselective behaviors and hepatic toxicity of triadimenol in male Eremias argus and provided important data for the ecotoxicological assessment of chiral triazole fungicides.