Aw T Y, Williams M W, Gray L
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130.
Am J Physiol. 1992 Jan;262(1 Pt 1):G99-106. doi: 10.1152/ajpgi.1992.262.1.G99.
The absorption and lymphatic transport of peroxidized MaxEPA fish oil was studied using the lymph fistula rat to determine the role of mucosal glutathione (GSH) in intestinal metabolism of luminal lipid hydroperoxides. Decreasing intestinal GSH concentrations with buthionine sulfoximine (BSO, 1.15 +/- 0.20 nmol/g), diethyl maleate (DEM, 0.93 +/- 0.26 nmol/g), phorone (1.46 +/- 0.14 nmol/g), or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, 1.54 +/- 0.18 nmol/g) compared with control (2.60 +/- 0.38 nmol/g) resulted in higher luminal recovery of the infused lipid hydroperoxide (% of infused dose): BSO (87.8 +/- 4.8%), DEM (86.1 +/- 1.3%), phorone (78.1 +/- 2.1%), and BCNU (71.7 +/- 4.8%) compared with control (52.8 +/- 4.3%). These results suggest that decreased elimination of luminal peroxidized lipids is associated with decreased tissue GSH. Treatment of rats with BSO, DEM, phorone, or BCNU resulted in dramatic increases in appearance of peroxidized lipids in lymph over 6-h lipid infusion (54.7 +/- 3.7, 57.7 +/- 4.6, 46.4 +/- 2.7, and 42.1 +/- 3.9 nmol, respectively) compared with control (20.5 +/- 3.4 nmol). The results are consistent with decreased intracellular metabolism of absorbed hydroperoxides and enhanced transport into lymph under GSH-deficient conditions. The current findings suggest that the function of the mucosal GSH peroxidase/oxidized glutathione (GSSG) reductase system may play an important role in intestinal handling of luminal lipid hydroperoxides. A compromised function of this detoxication mechanism in GSH-deficient states can significantly alter the metabolic fate of dietary peroxidized lipids.
使用淋巴瘘大鼠研究了过氧化的MaxEPA鱼油的吸收和淋巴转运，以确定黏膜谷胱甘肽（GSH）在肠腔内脂质氢过氧化物代谢中的作用。用丁硫氨酸亚砜胺（BSO，1.15±0.20 nmol/g）、马来酸二乙酯（DEM，0.93±0.26 nmol/g）、佛尔酮（1.46±0.14 nmol/g）或1,3-双（2-氯乙基）-1-亚硝基脲（BCNU，1.54±0.18 nmol/g）降低肠内GSH浓度，与对照组（2.60±0.38 nmol/g）相比，导致注入的脂质氢过氧化物在肠腔内的回收率更高（注入剂量的百分比）：BSO（87.8±4.8%）、DEM（86.1±1.3%）、佛尔酮（78.1±2.1%）和BCNU（71.7±4.8%），而对照组为（52.8±4.3%）。这些结果表明，肠腔内过氧化脂质消除减少与组织GSH降低有关。用BSO、DEM、佛尔酮或BCNU处理大鼠，在6小时脂质输注期间，淋巴中过氧化脂质的出现显著增加（分别为54.7±3.7、57.7±4.6、46.4±2.7和42.1±3.9 nmol），而对照组为（20.5±3.4 nmol）。结果与吸收的氢过氧化物细胞内代谢减少以及在GSH缺乏条件下向淋巴转运增强一致。目前的研究结果表明，黏膜GSH过氧化物酶/氧化型谷胱甘肽（GSSG）还原酶系统的功能可能在肠腔内脂质氢过氧化物的处理中起重要作用。在GSH缺乏状态下，这种解毒机制功能受损会显著改变膳食过氧化脂质的代谢命运。
