Fig. 4: Treatment with inhibitor 3 demonstrates inhibition of GUS and protection against diarrhea caused by CPT-11 damage in mice. | Communications Biology

Fig. 4: Treatment with inhibitor 3 demonstrates inhibition of GUS and protection against diarrhea caused by CPT-11 damage in mice.

From: Entropy-driven binding of gut bacterial β-glucuronidase inhibitors ameliorates irinotecan-induced toxicity

Fig. 4

a Inhibition of GUS in vivo. Mice were given 3 via oral gavage. After 1 h, fluorescein-di-β-d-glucuronide (FDGiCu; 500 µg in 100 µL) was injected intravenously. The hydrolysis product (fluorescein) generated in the gut was quantified over a 2 h period by in vivo imaging (excitation 465 nm, emission 520 nm). The maximum fluorescein fluorescence was observed 60 min after injection of vehicle control. At 2 h post injection, most of the FDGiCu has been excreted and thus fluorescence is reduced. The region of interest (ROI) was analyzed with Living Image Software. b Effect of inhibitor 3 to protect against diarrhea caused by CPT-11. Diarrhea severity was scored as described in methods. Mice receiving CPT-11 (blue squares) experienced severe diarrhea from days 7–11, whereas mice receiving inhibitor 3 with CPT-11 (red triangles) displayed significantly reduced diarrhea (Welch’s unpaired t-test, day 9, p = 0.3632; day 10, *p = 0.0284; day 11, ***p = 0.0005; day 12, **p = 0.0057).

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