US Army Medical Research Institute of Chemical Defense, Analytical Toxicology Division, Neurobehavioral Toxicology Branch, Aberdeen Proving Ground, MD 21010-5400, United States.
Neurotoxicology. 2011 Jun;32(3):342-9. doi: 10.1016/j.neuro.2011.03.001. Epub 2011 Mar 17.
To evaluate the role of diet composition on nerve agent toxicity, rats were fed four distinct diets ad libitum for 28 d prior to challenge with 110 μg/kg (1.0 LD(50), sc) soman. The four diets used were a standard rodent diet, a choline-enriched diet, a glucose-enriched diet, and a ketogenic diet. Body weight was recorded throughout the study. Toxic signs and survival were evaluated at key times for up to 72 h following soman exposure. Additionally, acquisition of discriminated shuttlebox avoidance performance was characterized beginning 24h after soman challenge and across the next 8 d (six behavioral sessions). Prior to exposure, body weight was highest in the standard diet group and lowest in the ketogenic diet group. Upon exposure, differences in soman toxicity as a function of diet became apparent within the first hour, with mortality in the glucose-enriched diet group reaching 80% and exceeding all other groups (in which mortality ranged from 0 to 6%). At 72 h after exposure, mortality was 100% in the glucose-enriched diet group, and survival approximated 50% in the standard and choline-enriched diet groups, but equaled 87% in the ketogenic diet group. Body weight loss was significantly reduced in the ketogenic and choline-enriched diet groups, relative to the standard diet group. At 1 and 4h after exposure, rats in the ketogenic diet group had significantly lower toxic sign scores than all other groups. The ketogenic diet group performed significantly better than the standard diet group on two measures of active avoidance performance. The exacerbated soman toxicity observed in the glucose-enriched diet group coupled with the attenuated soman toxicity observed in the ketogenic diet group implicates glucose availability in the toxic effects of soman. This increased glucose availability may enhance acetylcholine synthesis and/or utilization, thereby exacerbating peripheral and central soman toxicity.
为了评估饮食成分对神经毒剂毒性的作用，将大鼠自由摄取四种不同的饮食 28 天，然后用 110μg/kg（1.0LD50，sc）梭曼进行挑战。使用的四种饮食分别为标准啮齿动物饮食、胆碱富集饮食、葡萄糖富集饮食和生酮饮食。在整个研究过程中记录体重。在暴露于梭曼后关键时间点评估毒性症状和存活情况，最长可达 72 小时。此外，在梭曼暴露后 24 小时开始并在接下来的 8 天（6 个行为会话）内评估获得的辨别穿梭回避表现。暴露前，标准饮食组的体重最高，生酮饮食组的体重最低。暴露后，饮食对梭曼毒性的影响差异在第一个小时内变得明显，葡萄糖富集饮食组的死亡率达到 80%，超过所有其他组（死亡率范围为 0 至 6%）。暴露后 72 小时，葡萄糖富集饮食组的死亡率为 100%，标准和胆碱富集饮食组的存活率接近 50%，但生酮饮食组的存活率为 87%。与标准饮食组相比，生酮饮食组和胆碱富集饮食组的体重减轻明显减少。暴露后 1 小时和 4 小时，生酮饮食组的毒性症状评分明显低于所有其他组。生酮饮食组在两项主动回避表现测量上的表现明显优于标准饮食组。葡萄糖富集饮食组观察到的梭曼毒性加剧，以及生酮饮食组观察到的梭曼毒性减弱，表明葡萄糖的可用性对梭曼的毒性作用有影响。这种增加的葡萄糖可用性可能增强乙酰胆碱的合成和/或利用，从而加剧外周和中枢梭曼毒性。
