Lake B G, Rijcken W R, Gray T J, Foster J R, Gangolli S D
Acta Pharmacol Toxicol (Copenh). 1984 Mar;54(3):167-76. doi: 10.1111/j.1600-0773.1984.tb01913.x.
The oral administration of di-n-octyl phthalate (DNOP), mono-n-octyl phthalate (MNOP), di-(2-ethylhexyl) phthalate (DEHP) and clofibrate to young male Sprague-Dawley rats for 14 days resulted in liver enlargement. Morphological examination of liver sections from DEHP and clofibrate treated rats, but not from either DNOP or MNOP treated animals, revealed increased numbers of peroxisomes (microbodies). Both DEHP and clofibrate treatment markedly stimulated the activities of certain peroxisomal marker enzymes whereas DNOP and MNOP produced only marginal effects. Similarly both DEHP and clofibrate, but not DNOP or MNOP, increased microsomal cytochrome P-450 content and markedly stimulated microsomal lauric acid hydroxylation activity. The results thus demonstrate that whilst the branched chain phthalate ester DEHP induced peroxisomal proliferation, the straight chain analogue DNOP and its metabolite MNOP were essentially inactive. In addition, DEHP treatment appeared to induce similar form(s) of cytochrome P-450 in rat liver to those previously described after clofibrate administration.
对幼年雄性斯普拉格 - 道利大鼠口服邻苯二甲酸二正辛酯（DNOP）、邻苯二甲酸单正辛酯（MNOP）、邻苯二甲酸二（2 - 乙基己基）酯（DEHP）和氯贝丁酯14天会导致肝脏肿大。对DEHP和氯贝丁酯处理的大鼠肝脏切片进行形态学检查，而非DNOP或MNOP处理的动物，发现过氧化物酶体（微体）数量增加。DEHP和氯贝丁酯处理均显著刺激了某些过氧化物酶体标记酶的活性，而DNOP和MNOP仅产生轻微影响。同样，DEHP和氯贝丁酯均增加了微粒体细胞色素P - 450含量，并显著刺激了微粒体月桂酸羟化活性，而DNOP和MNOP则无此作用。结果表明，支链邻苯二甲酸酯DEHP可诱导过氧化物酶体增殖，而直链类似物DNOP及其代谢物MNOP基本无活性。此外，DEHP处理似乎在大鼠肝脏中诱导出与氯贝丁酯给药后先前描述的相似形式的细胞色素P - 450。
