Muhvich K H, Anderson L H, Criswell D W, Mehm W J
Division of Altitude and Hyperbaric Physiology, Armed Forces Institute of Pathology, Washington, DC 20306-6000.
Undersea Hyperb Med. 1993 Dec;20(4):321-8.
Leishmania braziliensis panamensis promastigotes were exposed in vitro to amphotericin B (AmB), menadione, or phenazine methosulfate under normoxic conditions. Promastigotes were also exposed to hyperoxia alone (100% O2 at total pressures of 101.3 or 253.3 kPa), or combined with drugs. After incubation for 24 h at 27 degrees C, viable promastigotes were stained with fluorescein diacetate and counted using epifluorescence microscopy. Hyperbaric hyperoxia alone (PO2 = 229.3 kPa) was as effective as AmB alone (0.2 microM); both reduced the number of viable promastigotes to approximately 13% of the original inoculum. In addition, AmB in a hyperbaric hyperoxic environment killed more promastigotes (97% of the original inoculum) than AmB in normoxic (PO2 = 21.1 kPa) or hyperoxic conditions (PO2 = 91.7 kPa). Finally, AmB in hyperbaric hyperoxia killed significantly more (75%) promastigotes than hyperbaric hyperoxia alone. High oxygen tensions did not significantly alter the lethal effects of either menadione or phenazine methosulfate. In conclusion, the lethal effects of low dose AmB in Leishmania promastigotes were augmented by hyperbaric hyperoxia in vitro, but only at oxygen doses too high to be tolerated by human patients.
在常氧条件下，将巴拿马利什曼原虫前鞭毛体体外暴露于两性霉素B（AmB）、甲萘醌或硫酸吩嗪。前鞭毛体还单独暴露于高氧环境（在总压力为101.3或253.3 kPa下的100%氧气），或与药物联合暴露。在27℃孵育24小时后，用荧光素二乙酸酯对存活的前鞭毛体进行染色，并使用落射荧光显微镜进行计数。单独的高压高氧（PO2 = 229.3 kPa）与单独使用AmB（0.2 microM）的效果相同；两者均将存活的前鞭毛体数量减少至原始接种量的约13%。此外，在高压高氧环境中的AmB比在常氧（PO2 = 21.1 kPa）或高氧条件（PO2 = 91.7 kPa）下的AmB杀死更多的前鞭毛体（原始接种量的97%）。最后，高压高氧环境中的AmB比单独的高压高氧杀死的前鞭毛体显著更多（75%）。高氧张力并未显著改变甲萘醌或硫酸吩嗪的致死作用。总之，体外高压高氧增强了低剂量AmB对利什曼原虫前鞭毛体的致死作用，但仅在人类患者无法耐受的高氧剂量下。
