RNA Adduction Resulting from the Metabolic Activation of Myristicin by P450 Enzymes and Sulfotransferases.

Autor:	He Y; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China., Cheng Z; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China., Zhang J; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China., Chen Y; Department of Pain, Affiliated Hospital of, Guizhou Medical University, Guiyang, Guizhou 550004, China.; School of Anesthesiology, Guizhou Medical University, Guiyang, Guizhou 550004, China.; School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, China., Zhao G; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Tang H; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.; School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, China., Liao Y; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China., Ye T; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China., Peng Y; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Li W; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China., Zheng J; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China.
Jazyk:	angličtina
Zdroj:	Journal of agricultural and food chemistry [J Agric Food Chem] 2024 Jul 17; Vol. 72 (28), pp. 15971-15984. Date of Electronic Publication: 2024 Jul 03.
DOI:	10.1021/acs.jafc.4c01676
Abstrakt:	Myristicin (MYR) mainly occurs in nutmeg and belongs to alkoxy-substituted allylbenzenes, a class of potentially toxic natural chemicals. RNA interaction with MYR metabolites in vitro and in vivo has been investigated in order to gain a better understanding of MYR toxicities. We detected two guanosine adducts (GA1 and GA2), two adenosine adducts (AA1 and AA2), and two cytosine adducts (CA1 and CA2) by LC-MS/MS analysis of total RNA extracts from cultured primary mouse hepatocytes and liver tissues of mice after exposure to MYR. An order of nucleoside adductions was found to be GAs > AAs > CAs, and the result of density functional theory calculations was in agreement with that detected by the LC-MS/MS-based approach. In vitro and in vivo studies have shown that MYR was oxidized by cytochrome P450 enzymes to 1'-hydroxyl and 3'-hydroxyl metabolites, which were then sulfated by sulfotransferases (SULTs) to form sulfate esters. The resulting sulfates would react with the nucleosides by S N 1 and/or S N 2 reactions, resulting in RNA adduction. The modification may alter the biochemical properties of RNA and disrupt RNA functions, perhaps partially contributing to the toxicities of MYR.
Databáze:	MEDLINE
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