van den Boogert J, van Hillegersberg R, de Rooij F W, de Bruin R W, Edixhoven-Bosdijk A, Houtsmuller A B, Siersema P D, Wilson J H, Tilanus H W
Laboratory for Experimental Surgery, Erasmus University, Medical Faculty, Rotterdam, Netherlands.
J Photochem Photobiol B. 1998 Jun 15;44(1):29-38. doi: 10.1016/s1011-1344(98)00102-x.
In this study, the biodistribution of 5-aminolaevulinic acid (ALA) and accumulation of protoporphyrin IX (PpIX) in rats have been examined. Two groups of 21 WAG/Rij rats are given 200 mg/kg ALA orally or intravenously. Six rats serve as controls. At 1, 2, 3, 4, 6, 12 and 24 h after ALA administration, ALA and porphyrin concentrations are measured in 18 tissues and fluids. Liver enzymes and renal-function tests are measured to determine ALA toxicity. In both groups ALA concentration is highest in kidney, bladder and urine. After oral administration, high concentrations are also found in duodenal aspirate and jejunum. Mild, short-lasting elevation of creatinine is seen in both treatment groups. Porphyrins, especially PpIX, accumulate mainly in duodenal aspirate, jejunum, liver and kidney (> 10 nmol/g tissue), less in oesophagus, stomach, colon, spleen, bladder, heart, lung and nerve (2-10 nmol/g tissue), and only slightly in plasma, muscle, fat, skin and brain (< 2 nmol/g tissue). In situ synthesis of porphyrins rather than enterohepatic circulation contributes to the PpIX accumulation. Confocal laser scanning microscopy shows selective porphyrin fluorescence in epithelial layers. Peak levels and total production of porphyrins are equal after oral and intravenous ALA administration.
administration of 200 mg/kg ALA results in accumulation of photosensitive concentrations of PpIX, 1 to 6 h after ALA administration, in all tissues except muscle, fat, skin and brain. Knowledge of the time-concentration relationship should be helpful in selecting dosages, routes of administration and timing of ALA photodynamic therapy.
在本研究中，已检测了5-氨基乙酰丙酸（ALA）在大鼠体内的生物分布以及原卟啉IX（PpIX）的蓄积情况。将两组各21只WAG/Rij大鼠分别经口或静脉给予200mg/kg的ALA。6只大鼠作为对照。在给予ALA后的1、2、3、4、6、12和24小时，测定18种组织和体液中的ALA和卟啉浓度。检测肝酶和肾功能试验以确定ALA的毒性。在两组中，ALA浓度在肾脏、膀胱和尿液中最高。经口给药后，十二指肠抽吸物和空肠中也发现高浓度。两个治疗组均可见肌酐轻度、短暂升高。卟啉，尤其是PpIX，主要蓄积于十二指肠抽吸物、空肠、肝脏和肾脏（>10nmol/g组织），在食管、胃、结肠、脾脏、膀胱、心脏、肺和神经中较少（2 - 10nmol/g组织），而在血浆、肌肉、脂肪、皮肤和大脑中仅有少量蓄积（<2nmol/g组织）。卟啉的原位合成而非肠肝循环导致了PpIX的蓄积。共聚焦激光扫描显微镜显示上皮层有选择性的卟啉荧光。经口和静脉给予ALA后，卟啉的峰值水平和总产量相等。
给予200mg/kg的ALA会导致在给予ALA后1至6小时，除肌肉、脂肪、皮肤和大脑外的所有组织中蓄积光敏浓度的PpIX。了解时间 - 浓度关系应有助于选择ALA光动力疗法的剂量、给药途径和时机。
