Vitamin D3 Is Transformed into 1,25(OH)2D3 by Triggering CYP3A11(CYP3A4) Activity and Hydrolyzing Midazolam

Abstract

BackgroundVitamin D3 (VD3) is a commonly used supplement in clinical practice. Cytochrome P450 3A11 (CYP3A11) is the most important monomeric enzyme involved in metabolism of drugs. This study aimed to investigate effects of vitamin D3 (VD3) on CYP3A11 activity.Material/MethodsForty male Sprague-Dawley (SD) rats were randomly divided a Control group (peanut oil 0.1 ml/kg/d), a Low-VD3 group (100 IU/kg/d), a Medium-VD3 group (400 IU/kg/d), and a High-VD3 (1600 IU/kg/d) group. Blood samples were collected from the jugular vein after midazolam (MDZ) administration. CYP3A11 expressions in liver and colon were detected by Western blotting and immunohistochemistry (IHC) assay. The concentration of serum 25(OH)D3 and serum 1,25(OH)2D3 were evaluated using ELISA. Effects of different dosages of vitamin D3 on metabolism of MDZ were evaluated using high-performance liquid chromatography (HPLC).ResultsVitamin D3 significantly enhanced serum 25(OH)D3 and 1,25(OH)2D3 levels in rats compared to Control rats (p<0.05). Expressions of hepatic CYP3A11 were more than 10-fold higher in rats treated with vitamin D3 compared to Control rats (p<0.05). Expressions of colon CYP3A11 were 5-fold higher than in Control rats (p<0.05). CYP3A11 expressions in vitamin D3-treated groups were significantly higher compared to the Control group (p<0.05). MDZ levels were significantly higher in vitamin D3-treated rats compared to that in Control rats (p<0.05). Concentrations of serum MDZ at every sampling point were remarkably lower in the vitamin D3-treated rats than in Control rats (p<0.05).ConclusionsVitamin D3 was transformed into 1,25(OH)2D3 by triggering CYP3A11 and CYP3A11 activity and by hydrolyzing MDZ.

Streptozotocin-induced Diabetes Represses Hepatic CYP2R1 Expression but Induces Vitamin D 25-Hydroxylation in Male Mice

“…However, it is not known if CYP3A11 has any vitamin D 25-hydroxylase activity. Recently, Zhu et al demonstrated that vitamin D3 treatment increases the levels of hepatic Cyp3a11 , and it was accompanied by high circulating plasma 25-OH-D and 1α,25(OH) 2 D levels ( 26 ). However, they did not measure the hepatic Cyp2r1 expression level ( 26 ), and the contribution of CYP3A11 to the increased 25-OH-D is unclear.…”

“…Recently, Zhu et al demonstrated that vitamin D3 treatment increases the levels of hepatic Cyp3a11 , and it was accompanied by high circulating plasma 25-OH-D and 1α,25(OH) 2 D levels ( 26 ). However, they did not measure the hepatic Cyp2r1 expression level ( 26 ), and the contribution of CYP3A11 to the increased 25-OH-D is unclear. Interestingly, in our study, the hepatic Cyp3a11 level was positively and significantly correlated with the plasma 25-OH-D level.…”

Effects of Vitamin D3 on Intestinal Flora in a Mouse Model of Inflammatory Bowel Disease Treated with Rifaximin

“…It has also been confirmed in our previous research that by activating CYP3A4 activity and hydrolyzing midazolam, VD3 can ultimately be transformed into 1,25(OH)2D3 [ 16 ]. In vitro studies showed that rifaximin can induce cytopigment P450 3A4 isoenzyme, but clinical studies have indicated that rifaximin has no obvious effect on drug metabolism [ 17 , 18 ].…”