Effects of 1α,25-dihydroxyvitamin D3 on the pharmacokinetics and biodistribution of ergothioneine, an endogenous organic cation/carnitine transporter 1 substrate, in rats

Abstract

Purpose This study aimed to investigate the effects of 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) on the expression levels of organic cation/carnitine transporter 1 (OCTN1) as well as the pharmacokinetics and biodistribution of ergothioneine, an OCTN1 substrate, in rats. Methods Rats pretreated with 1,25(OH) 2 D 3 (2.56 nmol/kg/day) for four days were administered ergothioneine (2 mg/kg) intravenously. The expression levels of rat OCTN1 (rOCTN1) in organs were determined using real-time quantitative polymerase chain reaction. Ergothioneine levels in plasma, urine, and organs (with and without intravenous injection of exogenous ergothioneine) were determined using liquid chromatography-tandem mass spectrometry. Results 1,25(OH) 2 D 3 pretreatment resulted in a significant decrease in rOCTN1 mRNA expression levels in the kidney and brain, a significant increase in basal plasma levels of ergothioneine (from 48 h), and a significant decrease in the tissueplasma partition coefficient (K p ) in all tissues (except the heart and lungs) and the basal urine levels of ergothioneine. After intravenous administration, the pharmacokinetic profiles of ergothioneine were consistent with the basal levels of endogenous ergothioneine, with an increase in AUC ∞ by 85%, a significant decrease in total clearance by 49%, and a decrease in V ss by 32% in 1,25(OH) 2 D 3 -treated rats. The K p value and urinary recovery of ergothioneine also decreased in the 1,25(OH) 2 D 3treated group. Conclusion This study showed the effects of 1,25(OH) 2 D 3 on the expression and function of rOCTN1 by investigating the interaction between 1,25(OH) 2 D 3 and ergothioneine. Dose adjustment and possible changes in bioavailability should be considered before the co-administration of vitamin D or its active forms and OCTN1 substrates.

Development and validation of an LC–MS/MS method for the determination of BLU-945, a fourth-generation EGFR tyrosine kinase inhibitor, in rat and mouse plasma: application to a pharmacokinetic study in rats

“…The animals were provided ad libitum access to both food and water in plastic cages under the specific conditions: a 12/12 h light/dark cycle, room temperature maintained at 20-25 °C, and relative humidity set at 40-60%. Before oral administration, the rats were fasted for 14 h. Pharmacokinetic studies were performed as reported previously (Yoon et al 2020;Vo et al 2022;Le et al 2023). Anesthesia was performed via intraperitoneal injection with Rompun ® (Bayer AG, Leverkusen, Germany) and Zoletil ® (Vibrac, Westlake, TX, USA).…”

Does Lactobacillus reuteri influence ergothioneine levels in the human body?

“…However, animals and humans are not known to synthesise ET, but instead accumulate it from dietary sources [21], especially mushrooms [22,23], via the action of a specific transporter, the organic cation transporter-novel, type 1 (OCTN1) [24], which after validation of its specificity is now widely named as the ET transporter (ETT) [25][26][27]. Studies in humans and other animals have shown that ET is avidly taken up and retained by the body [21,[27][28][29][30], which in addition to the existence of a selective transporter suggests that this compound may play important physiological roles.…”