ORAL L-2-OXO-4-THIAZOLIDINE REDUCES BACTERIAL TRANSLOCATION AFTER RADIATION IN THE FISCHER RAT

Glutathione (GSH) is important in protecting rapidly dividing intestin al cells against free radicals generated following radiation, L-2-Oxo- thiazolidine (OTZ) promotes GSH synthesis through increased cysteine d elivery. We hypothesize that oral supplementation with OTZ will augmen t GSH levels and decrease the incidence of bacterial translocation aft er abdominal radiation, and these effects will be abrogated by treatin g with a blocker of GSH synthesis, buthionine sulfoximine (BSO). Fisch er rats received by oral gavage either OTZ (OTZ/rad), OTZ plus BSO (OT Z/BSO/rad), or saline (sal/rad) 4 hr prior to and 18 hr after radiatio n. One group underwent saline gavage and no radiation (ctl/sal). On Da y 4, animals were sacrificed and mesenteric lymph nodes (MLN) were cul tured. Liver and jejunum were removed for GSH analysis by HPLC. Nonrad iated, ctl/sal had higher levels of hepatic and jejunal GSH than ctl/r ad (13.0 +/- 1.2 vs 9.7 +/- 1.5, 11.2 +/- 1.0 vs 7.8 +/- 2.5 mu mol/g dry wt, P < 0.05). Supplementation with OTZ (OTZ/rad) increased hepati c 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 mu mol/g dry wt, P < 0.05). Ctl/rad had a high rate of positive ML N 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 demonst rated whole abdominal radiation depleted both hepatic and jejunal leve ls of GSH. Uniquely, OTZ supplementation restored hepatic and jejunal levels of GSH and decreased rate of bacterial translocation. (C) 1996 Academic Press, Inc.