Blair S L, Rose D M, Sachar S, Burt M E
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
J Surg Res. 1996 Oct;65(2):165-8. doi: 10.1006/jsre.1996.0360.
Glutathione (GSH) is important in protecting rapidly dividing intestinal cells against free radicals generated following radiation. L-2-Oxo-thiazolidine (OTZ) promotes GSH synthesis through increased cysteine delivery. We hypothesize that oral supplementation with OTZ will augment GSH levels and decrease the incidence of bacterial translocation after abdominal radiation, and these effects will be abrogated by treating with a blocker of GSH synthesis, buthionine sulfoximine (BSO). Fischer rats received by oral gavage either OTZ (OTZ/rad), OTZ plus BSO (OTZ/BSO/rad), or saline (sal/rad) 4 hr prior to and 18 hr after radiation. One group underwent saline gavage and no radiation (ctl/sal). On Day 4, animals were sacrificed and mesenteric lymph nodes (MLN) were cultured. Liver and jejunum were removed for GSH analysis by HPLC. Nonradiated, ctl/sal had higher levels of hepatic and jejunal GSH than ctl/rad (13.0 +/- 1.2 vs 9.7 +/- 1.5, 11.2 +/- 1.0 vs 7.8 +/- 2.5 micromol/g dry wt, P < 0.05). Supplementation with OTZ (OTZ/rad) increased hepatic and jejunal GSH levels but treatment with OTZ and BSO (OTZ/BSO/rad) eliminated this benefit (12.0 + 2.6 vs 9.5 + 1.7, 10.1 + 2.4 vs 5.9 + 1.3 micromol/g dry wt, P < 0.05). Ctl/rad had a high rate of positive MLN cultures (80%) compared to ctl/sal and OTZ/rad (10 and 30%, P < 0.05). Treatment with OTZ and BSO (OTZ/BSO/rad vs OTZ/rad, 70 and 30%, P < 0.05) reversed the benefit of OTZ supplementation. This study demonstrated whole abdominal radiation depleted both hepatic and jejunal levels of GSH. Uniquely, OTZ supplementation restored hepatic and jejunal levels of GSH and decreased rate of bacterial translocation.
谷胱甘肽（GSH）对于保护快速分裂的肠道细胞免受辐射后产生的自由基的伤害至关重要。L-2-氧代噻唑烷（OTZ）通过增加半胱氨酸的输送来促进GSH的合成。我们推测，口服补充OTZ将提高GSH水平，并降低腹部辐射后细菌移位的发生率，而用GSH合成阻滞剂丁硫氨酸亚砜胺（BSO）进行治疗将消除这些作用。在辐射前4小时和辐射后18小时，通过口服灌胃给予Fischer大鼠OTZ（OTZ/rad）、OTZ加BSO（OTZ/BSO/rad）或生理盐水（sal/rad）。一组接受生理盐水灌胃且未接受辐射（ctl/sal）。在第4天，处死动物并培养肠系膜淋巴结（MLN）。取出肝脏和空肠，通过高效液相色谱法进行GSH分析。未接受辐射的ctl/sal组肝脏和空肠中的GSH水平高于ctl/rad组（分别为13.0±1.2对9.7±1.5、11.2±1.0对7.8±2.5微摩尔/克干重，P<0.05）。补充OTZ（OTZ/rad）可提高肝脏和空肠中的GSH水平，但用OTZ和BSO治疗（OTZ/BSO/rad）消除了这种益处（分别为12.0+2.6对9.5+1.7、10.1+2.4对5.9+1.3微摩尔/克干重，P<0.05）。与ctl/sal和OTZ/rad组相比，ctl/rad组MLN培养阳性率很高（80%）（分别为10%和30%，P<0.05）。用OTZ和BSO治疗（OTZ/BSO/rad组与OTZ/rad组相比，分别为70%和30%，P<0.05）逆转了补充OTZ的益处。这项研究表明，全腹辐射会降低肝脏和空肠中的GSH水平。独特的是，补充OTZ可恢复肝脏和空肠中的GSH水平，并降低细菌移位率。
