Tan W C, Krasner N, O'Toole P, Lombard M
Department of Gastroenterology, Fazakerley Hospital, Liverpool.
Gut. 1997 Jul;41(1):14-8. doi: 10.1136/gut.41.1.14.
Aminolaevulinic acid (ALA) is an endogenous substrate in the haem biosynthetic pathway. Protoporphyrin IX (PPIX), the immediate haem precursor in the pathway, has photoexcitable properties. Exogenous ALA has been used previously as a precursor agent in photodynamic therapy (PDT). Its main advantage is a short half-life and hence reduced incidence of skin photosensitivity. ALA can be toxic, however, causing, for example, transient increases in liver enzyme concentrations when given systemically and this may be dose related.
To assess whether accumulation of PPLX and ultimately the efficacy of PDT could be improved by modulating both ends of the haem biosynthetic pathway.
Gastric cancer cells (MKN 28) were incubated with ALA (0-1000 mumolar) and desferrioxamine (0-800 mumolar) for 24 hours before exposure to argon-pumped dye laser (630 nm) at different energy levels (0-40 J/cm2). Cell viability was assessed by use of the methyl-tetrazolium (MTT) assay four hours after exposure to light.
Total PPIX accumulation increased linearly with increasing extracellular concentrations of ALA up to 1 mmolar (r = 0.973, p < 0.005). Adding 200 molar of desferrioxamine trebled PPIX accumulation over the same period of incubation. Cell viability after exposure to light decreased with low doses (0-30 mumolar) of desferrioxamine (r = 0.976, p = 0.024). However, higher doses of desferrioxamine (more than 40 molar) seemed to confer a protective effect against PDT.
PDT using ALA can be improved by removal of available iron with desferrioxamine. The reason for the protective effect of desferrioxamine seen at higher doses is not clear.
氨基乙酰丙酸（ALA）是血红素生物合成途径中的内源性底物。该途径中血红素的直接前体原卟啉IX（PPIX）具有光激发特性。外源性ALA此前已被用作光动力疗法（PDT）的前体药物。其主要优点是半衰期短，因此皮肤光敏性发生率降低。然而，ALA可能有毒，例如全身给药时会导致肝酶浓度短暂升高，这可能与剂量有关。
评估通过调节血红素生物合成途径的两端，是否可以提高PPIX的积累以及最终提高PDT的疗效。
胃癌细胞（MKN 28）在暴露于不同能量水平（0 - 40 J/cm²）的氩泵染料激光（630 nm）之前，先用ALA（0 - 1000微摩尔）和去铁胺（0 - 800微摩尔）孵育24小时。光照4小时后，使用甲基四氮唑（MTT）法评估细胞活力。
直至1毫摩尔，总PPIX积累随细胞外ALA浓度升高呈线性增加（r = 0.973，p < 0.005）。在相同孵育期内，添加200微摩尔去铁胺使PPIX积累增加两倍。低剂量（0 - 30微摩尔）去铁胺处理后，光照后细胞活力下降（r = 0.976，p = 0.024）。然而，更高剂量的去铁胺（超过40微摩尔）似乎对PDT具有保护作用。
使用去铁胺去除可用铁可改善ALA介导的PDT。高剂量去铁胺出现保护作用的原因尚不清楚。
