Wiesenfeld Paddy L, Garthoff Larry H, Sobotka Thomas J, Suagee Jessica K, Barton Curtis N
U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Applied Research and Safety Assessment, Division of Toxicology, Neurotoxicity and In Vitro Toxicology Branch, Laurel, MD, USA.
J Appl Toxicol. 2007 Sep-Oct;27(5):421-33. doi: 10.1002/jat.1198.
The oral toxicity of a single administration by gavage (10, 20 or 30 mg kg(-1) body weight) of colchicine (COL) was determined in young, mature male and female Sprague-Dawley rats. The effect of COL was evaluated in the presence or absence of additional treatment variables that included vehicle and lipopolysaccharide (LPS) pre-exposure. The vehicle for COL was either Half and Half cream (H & H) or saline, and each group included pretreatment with either saline or a low, minimally toxic dose (83 microg kg(-1) body weight) of LPS. Colchicine toxicity in both male and female age-matched rats was characterized by progressively more severe dose-related clinical signs of toxicity. These included mortality, decreased body weight and feed intake during the first several days after dosing, with recovery thereafter in surviving animals. There were differences in the severity of the toxic response to COL between male and female rats. The most notable sex-related difference was in COL lethality. Female rats were two times more susceptible to the lethal effects of COL than male rats. Saline or H & H delivery vehicles did not result in any apparent qualitative or quantitative differences in COL toxicity. LPS pretreatment significantly potentiated COL lethality in both males and females, although the potentiation in males was greater than in females. LPS pretreatment modestly increased the COL induced anorexic effect in surviving males, but not in surviving female animals. LPS did not appear to modulate either the body weights or clinical signs of COL induced toxicity in surviving males or females.
通过灌胃法单次给予秋水仙碱（COL，剂量为10、20或30 mg kg⁻¹体重），测定其对年轻、成年雄性和雌性Sprague-Dawley大鼠的口服毒性。在存在或不存在其他治疗变量（包括赋形剂和脂多糖（LPS）预暴露）的情况下评估COL的作用。COL的赋形剂为半对半乳膏（H & H）或生理盐水，每组包括用生理盐水或低剂量、最低毒性剂量（83 μg kg⁻¹体重）的LPS进行预处理。年龄匹配的雄性和雌性大鼠的秋水仙碱毒性均表现为与剂量相关的毒性临床症状逐渐加重。这些症状包括死亡率、给药后头几天体重下降和采食量减少，随后存活动物恢复。雄性和雌性大鼠对COL的毒性反应严重程度存在差异。最显著的性别相关差异在于COL的致死率。雌性大鼠对COL致死作用的易感性是雄性大鼠的两倍。生理盐水或H & H给药载体在COL毒性方面未导致任何明显的定性或定量差异。LPS预处理显著增强了雄性和雌性大鼠的COL致死率，尽管雄性大鼠的增强作用大于雌性大鼠。LPS预处理适度增加了COL对存活雄性大鼠的厌食作用，但对存活雌性动物没有影响。LPS似乎并未调节存活雄性或雌性大鼠中COL诱导的毒性的体重或临床症状。
