State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, China.
PLoS One. 2013;8(2):e56877. doi: 10.1371/journal.pone.0056877. Epub 2013 Feb 25.
Caenorhbditis elegans has being vigorously used as a model organism in many research fields and often accompanied by administrating with various drugs. The methods of delivering drugs to worms are varied from one study to another, which make difficult in comparing results between studies.
METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the drug absorption efficiency in C. elegans using five frequently used methods with resveratrol with low aqueous solubility and water-soluble 5-Fluoro-2'-deoxyuridine (FUDR) as positive compounds. The drugs were either applied to the LB medium with bacteria OP50, before spreading onto Nematode Growth Medium (NGM) plates (LB medium method), or to the NGM with live (NGM live method) or dead bacteria (NGM dead method), or spotting the drug solution to the surface of plates directly (spot dead method), or growing the worms in liquid medium (liquid growing method). The concentration of resveratrol and FUDR increased gradually within C. elegans and reached the highest during 12 hours to one day and then decreased slowly. At the same time point, the higher the drug concentration, the higher the metabolism rate. The drug concentrations in worms fed with dead bacteria were higher than with live bacteria at the same time point. Consistently, the drug concentration in medium with live bacteria decreased much faster than in medium with dead bacteria, reach to about half of the original concentration within 12 hours.
Resveratrol with low aqueous solubility and water-soluble FUDR have the same absorption and metabolism pattern. The drug metabolism rate in worms was both dosage and time dependent. NGM dead method and liquid growing method achieved the best absorption efficiency in worms. The drug concentration within worms was comparable with that in mice, providing a bridge for dose translation from worms to mammals.
秀丽隐杆线虫作为一种模式生物,被广泛应用于许多研究领域,并且经常与各种药物联合使用。不同研究中给药方式差异较大,导致难以对研究结果进行比较。
方法/主要发现:我们使用 5 种常用方法,以低水溶性的白藜芦醇和水溶性 5-氟-2'-脱氧尿苷(FUDR)作为阳性化合物,评估了药物在秀丽隐杆线虫中的吸收效率。将药物要么施加在含有 OP50 细菌的 LB 培养基中,然后铺在 NGM 平板上(LB 培养基法),要么施加在含有活(NGM 活法)或死(NGM 死法)细菌的 NGM 中,要么直接将药物溶液点到平板表面(点死法),或者让线虫在液体培养基中生长(液体生长法)。白藜芦醇和 FUDR 在秀丽隐杆线虫内的浓度逐渐增加,在 12 小时至一天内达到最高值,然后缓慢下降。与此同时,药物浓度越高,代谢速率越高。在相同时间点,用死菌喂养的线虫中的药物浓度高于用活菌喂养的线虫。同样,活细菌培养基中的药物浓度比死细菌培养基中的药物浓度下降得更快,在 12 小时内降至原始浓度的约一半。
低水溶性的白藜芦醇和水溶性的 FUDR 具有相同的吸收和代谢模式。线虫中的药物代谢率与剂量和时间有关。NGM 死法和液体生长法在对线虫的吸收效率最高。线虫内的药物浓度与小鼠相当,为从线虫到哺乳动物的剂量转换提供了桥梁。