Effect of X‐ray irradiation on pharmacokinetics of irinotecan hydrochloride and expression of <scp>CES</scp>1 and <scp>CYP</scp>3A1 in rats

Qiao, Yan; Wang, Xuejun; Xin, Yuanyao; Nian, Yongqiong; Yang, Jing; Duan, Yabin; Li, Xiangyang

doi:10.1111/fcp.12456

Cited by 4 publications

(4 citation statements)

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“…The irradiation period was set to 20 s and 100 s for the 1 Gy and 5 Gy doses, respectively. We applied 1 and 5 Gy to the rats to simulate the relevant dosage range for the daily treatment of a human torso and in the interest of safety and workability, as described in our previous report (Duan et al, 2015;Li et al, 2019;Qiao et al, 2019).…”

Section: Chemicals Reference Standards and Solventsmentioning

confidence: 99%

“…Liver tissues were collected and immediately frozen in liquid nitrogen. Liver microsomes were prepared via differential centrifugation according to our previous reports (Li et al, 2014a;Li et al, 2014b;Qiao et al, 2019). Briefly, after the liver samples were thawed and weighed, two volumes of ice-cold Tris-HCl buffer at pH 7.4 containing 0.25 M sucrose (50 mmol/L) were added.…”

Section: Preparation Of Hepatic Microsomesmentioning

confidence: 99%

“…Investigations into preventing and treating irradiation damage, drug efficacy, and mitigating the effects of irradiation on the pharmacokinetics of drugs, such as 5-fluorouracil, cisplatin, and irinotecan hydrochloride, have been conducted for years (Hsieh et al, 2011;Duan et al, 2015;Tsai et al, 2015;Spetz et al, 2018;Qiao et al, 2019). These studies have observed significant differences in the characteristics of drugs in experimental rats after irradiation exposure.…”

Section: Introductionmentioning

confidence: 99%

“…Investigations into changes in the activity and expression of cytochrome P450 due to X-ray irradiation are scarce. The effects of X-ray irradiation exposure on CYP3A1 and carboxylesterase (CES) expression in rats have recently been investigated by our team (Marchenko et al, 2010;Qiao et al, 2019). However, no reports on changes in CYP1A2 and CYP2E1 expression levels and activity due to X-ray irradiation have been published to date.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of X-Ray Irradiation on the Activity and Expression Levels of CYP1A2 and CYP2E1 in Rats

Wang

et al. 2020

Front. Pharmacol.

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The objective of this study was to investigate the regulation of X-ray irradiation and its effect on the activity and protein and mRNA expression levels of CYP1A2 and CYP2E1 in rats. Rats were randomly divided into 0 Gy (control), 1 Gy (low-dose irradiation), and 5 Gy (high-dose irradiation) groups. CYP1A2 and CYP2E1 activity was evaluated from changes in pharmacokinetic parameters of caffeine and chlorzoxazone, respectively. The plasma concentrations of the probe drugs were determined by high-performance liquid chromatography (HPLC). Enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) tests were used to analyze the protein and mRNA expression levels of CYP1A2 and CYP2E1, respectively. The AUC 0-12 of caffeine was decreased by 1.7-and 2.5-fold, and the CL was increased by 1.8-and 2.6-fold in the 1 Gy and 5 Gy groups, respectively, compared to the 0 Gy group. The AUC 0-10 of chlorzoxazone was 1.4-and 1.8-fold lower, and the CL was 1.4-and 1.9-fold higher in the 1 Gy and 5 Gy groups, respectively, compared to the 0 Gy group. The metabolism of caffeine and chlorzoxazone increased under X-ray irradiation as CL levels increased and AUC levels decreased, suggesting that CYP1A2 and CYP2E1 activity is enhanced in rats after X-ray irradiation. Compared to that of the 0 Gy group, the protein expression level of CYP1A2 was measured as 28.3% and 38.9% higher in the 1 Gy and 5 Gy groups, respectively. The protein expression level of CYP2E1 was 48.4% higher in the 5 Gy group compared to the 0 Gy group, and there was no statistically significant difference between 0 Gy and 1 Gy. Compared to the 0 Gy group, the mRNA expression level of CYP1A2 was 200% and 856.3% higher in the 1 Gy and 5 Gy group, respectively, whereas the mRNA expression level of CYP2E1 was 89.0% and 192.3% higher in the 1 Gy and 5 Gy groups, respectively. This study reveals significant changes in the activity and protein and mRNA expression levels of CYP1A2 and CYP2E1 in rats after exposure to X-ray irradiation. AnimalsSprague Dawley SPF rats (200 ± 20 g, certificate No. 2007-001) of both sexes were provided by the laboratory animal center at Xi'an Jiaotong University Medical College, China. They were adapted for a week at 23 ± 2°C with a constant humidity level of 55% ± 5% under a cycle of 12 h of dark conditions and given ad libitum Li et al. X-Ray Irradiation and CYP1A2 and CYP2E1 Frontiers in Pharmacology | www.frontiersin.org January 2020 | Volume 10 | Article 1575 2

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Section: Chemicals Reference Standards and Solventsmentioning

confidence: 99%

Section: Preparation Of Hepatic Microsomesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of X-Ray Irradiation on the Activity and Expression Levels of CYP1A2 and CYP2E1 in Rats

Wang

et al. 2020

Front. Pharmacol.

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Exposure to High-Altitude Environment Is Associated with Drug Transporters Change: microRNA-873-5p-Mediated Alteration of Function and Expression Levels of Drug Transporters under Hypoxia

et al. 2021

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Hypoxia is the main characteristic of a high-altitude environment, affecting drug metabolism. However, so far, the mechanism of miRNA involved in the regulation of drug metabolism and transporters under high-altitude hypoxia is still unclear. This study aims to investigate the functions and expression levels of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 2 (MRP2), breast cancer resistance protein (BCRP), peptide transport 1 (PEPT1), and organic anion-transporting polypeptides 2B1 (OATP2B1) in rats and Caco-2 cells after exposure to high-altitude hypoxia. The protein and mRNA expression of MDR1, MRP2, BCRP, PEPT1, and OATP2B1 were determined by Western blot and qPCR. The functions of MDR1, MRP2, BCRP, PEPT1, and OATP2B1 were evaluated by determining the effective intestinal permeability and absorption rate constants of their specific substrates in rats under high-altitude hypoxia, and uptake and transport studies were performed on Caco-2 cells. To screen the miRNA associated with hypoxia, Caco-2 cells were examined by high throughput sequencing. We observed that the miR-873-5p was significantly decreased under hypoxia and might target MDR1 and pregnane X receptor (PXR). To clarify whether miR-873-5p regulates MDR1 and pregnane X receptor (PXR) under hypoxia, Caco-2 cells were transfected with mimics or inhibitors of miR-873-5p and negative control (NC). The function and expression of drug transporters were found to be significantly increased in rats and Caco-2 cells under hypoxia. We found that miR-873-5p regulated MDR1 and PXR expression. Herein, it is shown that miRNA may affect

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Exposure to High Altitude Environment Is Associated With Drug Metabolism Change: miRNA-873-5p-Mediated Alteration of Function and Expression Levels of Drug Transporters Under Hypoxia

et al. 2021

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Effect of X‐ray irradiation on pharmacokinetics of irinotecan hydrochloride and expression of CES1 and CYP3A1 in rats

Cited by 4 publications

References 27 publications

Regulation of X-Ray Irradiation on the Activity and Expression Levels of CYP1A2 and CYP2E1 in Rats

Regulation of X-Ray Irradiation on the Activity and Expression Levels of CYP1A2 and CYP2E1 in Rats

Exposure to High-Altitude Environment Is Associated with Drug Transporters Change: microRNA-873-5p-Mediated Alteration of Function and Expression Levels of Drug Transporters under Hypoxia

Exposure to High Altitude Environment Is Associated With Drug Metabolism Change: miRNA-873-5p-Mediated Alteration of Function and Expression Levels of Drug Transporters Under Hypoxia

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