Orall-2-Oxo-4-thiazolidine Reduces Bacterial Translocation after Radiation in the Fischer Rat

Abstract

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 μmol/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 μmol/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.