The Activity, Protein, and mRNA Expression of CYP2E1 and CYP3A1 in Rats after Exposure to Acute and Chronic High Altitude Hypoxia

Li, Xiangyang; Wang, Xuejun; Li, Yongping; Zhu, Junbo; Su, Xiaodong; Yao, Xingchen; Fan, Xueru; Duan, Yabin

doi:10.1089/ham.2014.1026

Cited by 13 publications

(10 citation statements)

References 30 publications

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“…The liver tissues were immediately frozen in liquid nitrogen. The liver microsomes were prepared using differential centrifugation according to our previous reports . Briefly, liver samples were thawed and weighed, and two volumes of ice‐cold homogenization medium (50 mmol/L Tris‐HCl buffer at pH 7.4 containing 0.25 m sucrose) were then added.…”

Section: Methodsmentioning

confidence: 99%

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

Qiao

Wang

Xin

et al. 2019

Fundamemntal Clinical Pharma

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Concurrent chemoradiation with irinotecan hydrochloride (CPT‐11) is accepted for cancer treatment. However, the effects of X‐ray irradiation on chemotherapeutics in the plasma remain unclear. We evaluated the pharmacokinetics of CPT‐11 in rats after exposure to X‐ray irradiation and examined the changes of protein and mRNA expression of CES1 and CYP3A1. The X‐ray irradiation with 1 Gy and 5 Gy was delivered to the whole body of rats. CPT‐11 at 30 and 60 mg/kg, respectively, was intravenously infused 24 h after irradiation. CPT‐11 was determined by RP‐HPLC in plasma. ELISA and PCR were used to analyze the protein and mRNA expression of CES1 and CYP3A1, respectively. Compared with control rats, the X‐ray irradiation decreased the AUC of CPT‐11 (30 mg/kg) by 15.6% at 1 Gy and 39.0% at 5 Gy and increased the CL by 60.0% at 5 Gy. The X‐ray irradiation could also decrease the AUC of CPT‐11 (60 mg/kg) and increase the CL. In addition, the protein and mRNA expression of CES1 and CYP3A1 were increased significantly in rats after irradiation. This study found significant changes in the pharmacokinetics of CPT‐11 in rats after exposure to X‐ray irradiation, and they might be due to significant increases in the expressions of CYP3A1 and CES1. The pharmacokinetics of CPT‐11 should be rechecked, and the optimal CPT‐11 dose should be reevaluated during concurrent chemoradiation therapy.

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Section: Methodsmentioning

confidence: 99%

“…The expression of CES1 and CYP3A1 was determined by ELISA according to our previous reports . Briefly, to establish a bland well without any solution, 50 μL of standard and 40 μL of sample diluted solution were added to standard and sample wells with a biotin‐conjugated antibody specific to CES1 and CYP3A1, respectively.…”

Section: Methodsmentioning

confidence: 99%

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

Qiao

Wang

Xin

et al. 2019

Fundamemntal Clinical Pharma

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“…CYP1A2 and CYP2E1 activities in rats were identified using the previously reported "cocktail" method (Li et al, 2014a;Li et al, 2014b). Caffeine and chlorzoxazone served as probe substrates of CYP1A2 and CYP2E1, respectively.…”

Section: Measurement Of Rat Cyp1a2 and Cyp2e1 Activitymentioning

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%

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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“…The measurement of CYP2E1 mRNA expression Quantitative real-time reverse transcription polymerase chain reaction (QT-PCR) was used to measure the levels of CYP2E1 mRNA in the liver [16] . The total RNA was extracted from the frozen livers using the TRIzol reagent (Invitrogen Co, Carlsbad, CA, USA) according to the manufacturer's instructions.…”

Section: Animalsmentioning

confidence: 99%

Chronic administration of caderofloxacin, a new fluoroquinolone, increases hepatic CYP2E1 expression and activity in rats

et al. 2016

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Aim: Caderofloxacin is a new fluoroquinolone that is under phase III clinical trials in China. Here we examined the effects of caderofloxacin on rat hepatic cytochrome P450 (CYP450) isoforms as well as the potential of caderofloxacin interacting with co-administered drugs. Methods: Male rats were treated with caderofloxacin (9 mg/kg, ig) once or twice daily for 14 consecutive days. The effects of caderofloxacin on CYP3A, 2D6, 2C19, 1A2, 2E1 and 2C9 were evaluated using a "cocktail" of 6 probes (midazolam, dextromethorphan, omeprazole, theophylline, chlorzoxazone and diclofenac) injected on d 0 (prior to caderofloxacin exposure) and d 15 (after caderofloxacin exposure). Hepatic microsomes from the caderofloxacin-treated rats were used to assess CYP2E1 activity and chlorzoxazone metabolism. The expression of CYP2E1 mRNA and protein in hepatic microsomes was analyzed with RT-PCR and Western blotting, respectively. Results: Fourteen-day administration of caderofloxacin significantly increased the activity of hepatic CYP2E1, leading to enhanced metabolism of chlorzoxazone. In vitro microsomal study confirmed that CYP2E1 was a major metabolic enzyme involved in chlorzoxazone metabolism, and the 14-d administration of caderofloxacin significantly increased the activity of CYP2E1 in hepatic microsomes, resulting in increased formation of 6-hydroxychlorzoxazone. Furthermore, the 14-d administration of caderofloxacin significantly increased the expression of CYP2E1 mRNA and protein in liver microsomes, which was consistent with the pharmacokinetic results. Conclusion: Fourteen-day administration of caderofloxacin can induce the expression and activity of hepatic CYP2E1 in rats. When caderofloxacin is administered, a potential drug-drug interaction mediated by CYP2E1 induction should be considered.

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The Activity, Protein, and mRNA Expression of CYP2E1 and CYP3A1 in Rats after Exposure to Acute and Chronic High Altitude Hypoxia

Cited by 13 publications

References 30 publications

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

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

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

Chronic administration of caderofloxacin, a new fluoroquinolone, increases hepatic CYP2E1 expression and activity in rats

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