Effects of miglyol 812 on rats after 4 weeks of gavage as compared with methylcellulose/tween 80
Effects of miglyol 812 on rats after 4 weeks of gavage as compared with methylcellulose/tween 80
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DOI：
10.1080/01480540500262839
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发表时间：
2005-01-01
影响因子：
2.6
通讯作者：
Furst, SM
中科院分区：
文献类型：
--
作者：
Sellers, RS;Antman, M;Furst, SM
Miglyol 812是一种中链甘油三酯，在毒理学研究中用作辅料，以改善供试化合物的溶解度/吸收。作为一项大型毒理学研究的一部分，15只Wistar Han IGS大鼠/性别/组经口灌胃给予10 mL/kg/天100% Miglyol 812或0.5%甲基纤维素/0.1%吐温80水溶液（MC-T），持续4周，随后4周不给药，以评价该辅料在长期给药中的潜在作用。相对于传统赋形剂如MC-T的长期毒理学研究。给药期间明显的临床体征包括接受Miglyol 812处理的12/15只雄性和11/15只雌性出现软便和/或粘液便，但接受MC-T处理的动物中没有出现软便和/或粘液便。与MC-T给药动物相比，Miglyol 812给药动物的体重增加减少6-7%，具有统计学显著性。与MC-T相比，临床生化参数的统计学显著性变化包括血尿素氮降低（雄性和雌性分别为50%和29%）、胆固醇升高（雄性和雌性分别为1.6倍和1.5倍）、降低。总蛋白（雄性和雌性分别为6%和8%）、球蛋白降低（雄性和雌性分别为15%和11%）和甘油三酯升高（雄性和雌性分别为2.8倍和1.7倍）。雄性动物的绝对和相对胸腺重量分别降低28%和24%，雌性动物的绝对和相对胸腺重量分别降低18%和17%，而无组织学变化。组织学检查显示，Miglyol 812给药组5/10只雄性和7/10只雌性动物的肺泡组织细胞增多伴肺局灶性间质炎症，而MC-T给药组仅1/10只雄性和1/10只雌性动物出现肺泡组织细胞增多伴肺局灶性间质炎症。在恢复期内，所有效应均可逆。本研究的结果表明，100% miglyol 812产生可逆的胃肠道效应，体重增加沿着减少，同时伴有几个血清化学参数的变化。因此，在长期啮齿动物毒理学研究中，经口灌胃给药时，不应认为其无毒。
Miglyol 812 is a medium-chain triglyceride used in toxicology studies as an excipient to improve test compound solubility/absorption. As part of a larger toxicology study, 15 Wistar Han IGS rats/sex/group were dosed by oral gavage for 4 weeks with 10 mL kg(-1) day(-1) of 100% Miglyol 812 or 0.5% methyleellulose/0.1% Tween 80 in water (MC-T) followed by 4 weeks without treatment to evaluate the potential effects of this excipient in long-term toxicology studies relative to a traditional excipient such as MC-T. Clinical signs evident during the dosing phase included soft and/or mucoid stool in 12/15 males and 11/15 females treated with Miglyol 812 but in no animals treated with MC-T. Animals treated with Miglyol 812 had a 6-7% statistically significant reduction in body weight gain as compared to MC-T-treated animals. Statistically significant changes in clinical chemistry parameters as compared to MC-T included decreased blood urea nitrogen (50% and 29% in males and females, respectively), increased cholesterol (1.6-fold and 1.5-fold in males and females, respectively), decreased. total protein (6% and 8% in males and females, respectively), decreased globulins (15% and 11% in males and females, respectively), and increased triglycerides (2.8-fold and 1.7-fold in males and females, respectively). Absolute and relative thymic weights decreased 28% and 24%, respectively, in males, and 18% and 17%, respectively, in females without histological alterations. Histopathology revealed increased alveolar histiocytosis with focal interstitial inflammation in lungs in 5/10 males and 7/10 females treated with Miglyol 812 compared to only 1/10 males and 1/10 females treated with MC-T. All effects were reversible during the recovery period. Results of this study indicate that 100% miglyol 812 produces reversible gastrointestinal effects and decreases in body weight gains along with changes in several serum chemistry parameters. Therefore, it should not be considered innocuous when delivered by oral gavage in long-term rodent toxicology studies.