Fig. 6.

Waixenicin A inhibits intestinal Mg²⁺ absorption and causes hypomagnesemia without affecting aberrant cyst formation in AOM-treated mice. a-d Mice fed with the control diet were intraperitoneally (i.p.) injected with vehicle (n = 4), vehicle and waixenicin A (waixA; 8 mg/kg; n = 6), AOM (10 mg/kg; n = 12), or AOM and waixA (n = 6) once a week for 3 weeks and sacrificed 2 weeks after the last injection. For waixA and its vehicle control, mice were given the i.p. injection 1 day before each AOM administration. Serum, urinary, fecal, and bone samples were collected for Mg²⁺ analysis (*p < 0.05 vs. vehicle). e Normalized average current development of human TRPM7 (hTRPM7) overexpressed in HEK293-TREx induced with tetracycline for 18–24 h [13] and assessed at +80 mV. Cells were either pre-incubated for 30 min. with 1 μM AOM and continued presence of AOM in the bath during the experiment (n = 6), or not (control; n = 4), or 1 μM AOM was acutely applied in standard external bath solution as indicated by the black bar (n = 3). f Average ACF-formation (filled circles) and colon length (filled triangles) in mice treated with vehicle, waixenicin A (8 mg/kg), or in combination with AOM (10 mg/kg; n = 4–6). Measurements are from mice in (a-d). Error bars indicate S.E.M. Open circles represent data points from individual animals. g Mg²⁺ concentrations in serum from control (n = 4) and AOM-treated (10 mg/kg; n = 10) mice fed with the control (0.05% Mg²⁺) or the Mg²⁺-deficient (0.003% Mg²⁺) diet sacrificed 2 weeks after the last of three AOM injections. Mice were kept on the control or Mg²⁺-deficient diet for 2 week before AOM injections. h Average ACF-formation (filled circles) and colon length (filled triangles) in mice from panel f (*p < 0.05 vs. AOM; n = 3–9). Open circles represent data points from individual animals