Fig. 4.

The animal experiments shown in the figure were reviewed and approved by the IACUC of the University of Tennessee Health Science Center and the University of Tokushima, Japan. A: OTP prevents infection-induced weight loss. C57BL/6 mice were infected on day 0 with C. rodentium orally. Mice received placebo or OTP (0.1 or 1 mg/kg sc) on days 1–14 (#P < 0.05; *P < 0.01). OTP significantly reduced weight loss in animals infected with C. rodentium compared with infected animals not receiving OTP. Error bars represent SEM; control groups n = 4, other groups n = 5–6. B: Effect of delayed administration of OTP on the fluid accumulation ratio in the open loop cholera toxin (CTX) model. CTX was administered at 0 h and OTP (1 mg/kg po) was administered with delays between 0 and 3 h after CTX administration. Samples were collected 6 h after CTX administration. CTX significantly increases fluid accumulation compared with vehicle (**P < 0.005). Delaying administration by up to 2 h after CTX administration results in significantly reduced fluid accumulation than that in animals receiving CTX and vehicle (*P < 0.001). Error bars represent SEM; n = 6 per group. C: LPA₂-specific agonists, RP-2 and DBIBB, reduce aspirin-induced stomach erosions in BALB/C mice (n = 5 per group). Aspirin (300 mg/kg body weight) was made up in 3% w/v carboxymethyl cellulose, and 200 μl of this suspension was delivered into the stomach via oral gavage. For details of the model see (56). The drugs (1 mM stock) were made up in PBS containing 0.1% mouse serum albumin in 3% carboxymethyl cellulose, and 200 μl was administered 15 min after the aspirin suspension via oral gavage. Mice were euthanized 2.5 h after the first treatment and stomachs were dissected and photographed. The length of erosions was measured using the ImageJ program (The National Institutes of Health, Bethesda, MD) and compared with the vehicle group using Student’s t-test. Note that RP-2 and DBIBB significantly reduced the total length of stomach erosions. D: Representative images of stomachs from mice that were treated with aspirin, LPA (1 mM), and OTP (1 mM). Note that the bloody erosions are almost completely absent in the OTP-treated stomach. Panels A and B are taken with permission and edits from Thompson et al. (54).