Carboxylesterase-dependent cytotoxicity of dibasic esters (DBE) in rat nasal explants.
Carboxylesterase-dependent cytotoxicity of dibasic esters (DBE) in rat nasal explants.
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大鼠鼻外植体中二元酯（DBE）的羧酸酯酶依赖性细胞毒性。
DOI：
10.1016/0041-008x(91)90209-w
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发表时间：
1991
影响因子：
3.8
通讯作者：
M. Bogdanffy
中科院分区：
文献类型：
--
作者：
Bruce A. Trela;M. Bogdanffy
二酸酯（DBE）是己二酸二甲酯（DMA）、戊二酸二甲酯（DMG）和琥珀酸二甲酯（DMS）的溶剂混合物，用于油漆和涂料工业。亚慢性吸入毒性研究表明，DBE诱导大鼠鼻腔的嗅觉上皮轻度变性，而不是呼吸上皮。羧酸酯酶介导的单个二酸酯的水解在嗅觉中比在呼吸粘膜匀浆中更有效。在本研究中，利用体外培养的大鼠鼻腔外植体系统来确定DBE毒性是否依赖于非特异性羧酸酯酶的代谢激活。将雌性大鼠鼻腔嗅觉区和呼吸区的外植体在含有10-100 mm DMA、DMG或DMS的Williams培养基E中孵育2小时。DBE引起鼻外植体酸性磷酸酶释放量的剂量相关增加，这是细胞毒性的生化指标。高效液相色谱分析显示羧酸酯酶介导的单甲基酯代谢产物的形成平行增加。鼻外植体系统中二酸代谢物的产生并不完全依赖于浓度。嗅觉组织的代谢物浓度和酸性磷酸酶释放通常大于呼吸组织。dbe诱导的细胞毒性和酸性代谢物的产生在大鼠切除的鼻组织中被预处理为双（对硝基苯）磷酸，一种羧酸酯酶抑制剂。本研究提出了一种可行的体外评估有机酯对大鼠鼻腔细胞毒性的方法。结果表明，在该系统条件下，DBE为弱鼻毒性物质。进一步证明DBE毒性依赖于羧酸酯酶介导的激活。其他有机酯在吸入后引起的鼻毒性也有类似的机制。
Dibasic esters (DBE) are a solvent mixture of dimethyl adipate (DMA), dimethyl glutarate (DMG), and dimethyl succinate (DMS) used in the paint and coating industry. Subchronic inhalation toxicity studies have demonstrated that DBE induce a mild degeneration of the olfactory, but not the respiratory, epithelium of the rat nasal cavity. Carboxylesterase-mediated hydrolysis of the individual dibasic esters is more efficient in olfactory than in respiratory mucosal homogenates. In the present study, an in vitro system of cultured rat nasal explants was utilized to determine if DBE toxicity is dependent on a metabolic activation by nonspecific carboxylesterase. Explants from both the olfactory and the respiratory regions of the female rat nasal cavity were incubated for 2 hr in Williams' medium E containing 10–100 mm DMA, DMG, or DMS. DBE caused a dose-related increase in nasal explant acid phosphatase release, a biochemical index of cytotoxicity. HPLC analysis demonstrated parallel increases in the carboxylesterase-mediated formation of monomethyl ester metabolites. Diacid metabolite production in the nasal explant system was not entirely concentration-dependent. Metabolite concentrations and acid phosphatase release were generally greater in olfactory than respiratory tissues. DBE-induced cytotoxicity and acid metabolite production were markedly attenuated in nasal tissue excised from rats which were pretreated with bis (p-nitrophenyl)phosphate, a carboxylesterase inhibitor. This study presents a viable in vitro method for assessing organic ester cytotoxicity in the rat nasal cavity. It was shown that DBE are weak nasal toxicants under the conditions of this system. It was further demonstrated that DBE toxicity is dependent on a carboxylesterase-mediated activation. A similar mechanism was proposed for the nasal toxicity induced by other organic esters following inhalation exposure.
大鼠肝细胞中琥珀酸单甲酯和其他酯的糖异生。
影响因子：
3.9
作者：
Rognstad,R
通讯作者：
Rognstad,R
影响因子：
3.8
作者：
NEWTON, JF;KUO, CH;HOOK, JB
通讯作者：
HOOK, JB
F344 大鼠和叙利亚仓鼠上呼吸道中吸入的乙酸乙酯的首过代谢。
影响因子：
3.8
作者：
Morris,JB
通讯作者：
Morris,JB