Fig 4. Effect of UDCA bile acid supplementation.
(A) and (B) effects of UDCA bile acid supplementation on the activity of CYP450 catalysed reactions in the Npc1 mouse model of plus or minus 0.5% ursodeoxycholic acid (UDCA, w/w) measured at (A) 6 weeks and (B) 9 weeks of age, shown as a function of percent of age-matched control littermates. Methoxyresorufin-O-dealkylation (MROD); ethoxyresorufin-O-dealkylation (EROD); pentoxyresorufin-O-dealkylation (PROD); benzoxyresorufin-O-dealkylation (BROD). Data are presented as mean ± SEM, n = 6 (3 males and 3 females), * p—value < 0.05, ** p—value < 0.01, *** p—value < 0.001, **** p—value < 0.0001 calculated using an unpaired nonparametric test Mann-Whitney test. (C) Relative protein quantitation of Cyp3a isolated from liver of 6-week old male mice found a significant decrease in Npc1+/- and Npc1-/- untreated mice compared Npc1+/+ untreated mice. UDCA treatment restored Npc1-/- Cyp3a levels to that of Npc1+/+ mice while have no effect on the Npc1+/- or Npc1+/+ Cyp3a values. (D) Relative protein quantitation of Cyp1a2 isolated from liver of 6-week old male mice found a significant decrease in Npc1+/- and Npc1-/- untreated mice compared Npc1+/+ untreated mice. UDCA treatment restored Npc1-/- Cyp1a2 levels to that of Npc1+/+ mice while decreasing the levels for Npc1+/- and Npc1+/+ Cyp1a2 values. Data are presented as mean ± SD, n = 3. * p—value < 0.05, ** p—value < 0.01, *** p—value < 0.001 calculated using two-tailed, unpaired t test. (F) Representative western blot analysis of Cyp3a and Cyp1a2 in the mouse model of Npc1 plus or minus UDCA treatment.