Simulated Microgravity Altered the Metabolism of Loureirin B and the Expression of Major Cytochrome P450 in Liver of Rats

Abstract

Loureirin B (LB) is the marker compound of dragon blood (DB), which exhibits great potentials in protecting astronauts’ health against radiation and simulated microgravity (SM). Pharmacokinetics of LB is reported to be significantly altered by SM. Here, we investigated key metabolic features of LB in rat liver microsome (RLM) and the effects of SM on LB metabolism as well as on expression of major hepatic cytochrome P450 (CYP450) isoforms. Ten metabolites were tentatively identified based on fragmentation pathways using LC-MS/MS method and elimination kinetics of LB followed a typical Michaelis–Menten equation (Vmax was 1.32 μg/min/mg and Km was 13.33 μg/mL). CYP1A2, CYP2C11, CYP2D1, and CYP3A2 were involved in the metabolism of LB and the relative strength was: CYP3A2 > CYP2C11 > CYP2D1 > CYP1A2. Comparative studies suggested that elimination of LB in RLM was remarkably increased by 3-day and 14-day SM, and the generation of identified metabolites was affected as well. Additionally, 3-day and 14-day SM showed obvious regulatory effects on the expression of major CYP450 isoforms, which might contribute to the increased elimination of LB. The data provided supports for the application of DB as a protective agent and the reasonable use of current medications metabolized by hepatic CYP450 in space missions.

Simulated Microgravity Inhibits the Proliferation of Chang Liver Cells by Attenuation of the Major Cell Cycle Regulators and Cytoskeletal Proteins

“…A recent study showed that microgravity induced lipid dysregulation in the mouse liver [ 20 ], and SMG similarly affected rat liver function by altering the metabolism of loureirin B and the expression of major cytochrome P450 [ 21 ]. The liver is one of the largest organs in the human body and plays an important role in the metabolism of carbohydrates, proteins, and lipids [ 22 ].…”

Dragon’s Blood Regulates Rac1-WAVE2-Arp2/3 Signaling Pathway to Protect Rat Intestinal Epithelial Barrier Dysfunction Induced by Simulated Microgravity

“…These compounds showed decreased absorption, slower elimination, and double peaks in concentration–time curves in SMG rats. Metabolism of LB in the SMG rat liver microsome; LA, LC, DHF in the human liver microsome, and altered expression of drug-metabolizing enzymes in liver and intestine of SMG rats have been reported in our previous studies [ 58 , 59 , 60 ]. Altered drug-metabolizing enzymes and PK behaviors of DB compounds may be related to the therapeutic effects of DB in SMG rats.…”

Temporal effects of three-dimensional clinostat treatment on bone and serum metabolome in C57BL/J mice: a new method of simulating microgravity effect

“…Studies have shown [42][43][44] that microgravity changes metabolites in the body, and therefore we examined the metabolomics of the SB and MC groups. Serum specimens were subjected to untargeted metabolomics analysis to identify the hematic metabolic pro les among the two groups tested (Fig.…”