Effects of Radiation on Drug Metabolism: A Review

Li, Xiangyang; Yang, Jing; Qiao, Yan; Duan, Yabin; Xin, Yuanyao; Nian, Yongqiong; Zhu, Lin; Liu, Guiqin

doi:10.2174/1389200220666190405171303

Cited by 11 publications

(6 citation statements)

References 56 publications

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“…During simultaneous chemotherapy and radiotherapy, the metabolism and clearance of certain drugs increase, while the half-life, average residence time, and area under the curve decrease. The expression changes of cytochrome P450 and drug transporter are consistent with the pharmacokinetic changes of certain drugs under radiation [31]. The contents of CYP2C29, CYP2E1, and CYP1A2 in the liver of mice exposed to space flight and microgravity for 30 days were significantly changed compared with the ground control group.…”

Section: Discussionsupporting

confidence: 58%

Potential of Dragon’s Blood as a Space Radiation Protectant Especially on Brain-Liver Bystander Effect

Han

et al. 2022

Space Sci Technol

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During space manned missions, radiation is a serious health risk. Radiation can not only directly cause damage to target organs but also trigger side effects to affect nontarget organs. Dragon’s Blood (DB) is a traditional Chinese Dai medicine that has been proven to exhibit radioprotective effects in our lab previously. It can alleviate brain damage, hematopoietic dysfunction, and gastrointestinal damage caused by radiation in rats, but its mechanism of action is not clear yet. In order to study the effect of brain irradiation on the damage to the liver and the protective effects of Dragon’s Blood, herein, liquid chromatography coupled with a mass spectrometer was used to analyze the total differential protein expression in the rat liver after 30 Gy Co60γ-ray whole-brain irradiation with/without administration of Dragon’s Blood for 10 days before irradiation. A total of 4557 proteins were identified in the rat liver. A total of 299 coexpressed differential proteins were screened in the RAD/CON group indicating that brain radiation significantly affected the liver’s metabolic system (such as drug and arachidonic acid metabolism), chemical carcinogenesis, and peroxisome process. A total of 85 differential proteins were screened in the DB/RAD group. Results indicated that Dragon’s Blood significantly regulated the expression of 26 proteins to normal levels (Msrb2, Txnrd2, Samm50, Pir, Pex11a, etc.) mainly through regulating the metabolism and redox homeostasis process. The results of molecular docking and network pharmacology found that the main effective radiation protection components in Dragon’s Blood are natural chalcones, flavan, and phenolic derivatives.

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Section: Discussionsupporting

confidence: 58%

Potential of Dragon’s Blood as a Space Radiation Protectant Especially on Brain-Liver Bystander Effect

Han

et al. 2022

Space Sci Technol

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“…Radiation therapy affects the pharmacokinetics of the anti-neoplastic drugs, as it alters the protein and mRNA expressions of drug-metabolizing enzymes and has an indispensable effect on the circulation of the blood and lymphatic system as well as in the hepatobiliary excretion (Chen, et al 2017;Li et al, 2019). Ionizing radiation induced acute or chronic metabolic oxidative stress generates reactive oxygen and nitrogen species ROS/NOS and contribute to RT-induced cell senescence; as it intervenes with cellular proteins, DNA and phospholipids membrane (Gupta et al, 2020).…”

Section: Metabolomics and Radiotherapymentioning

confidence: 99%

Metabolomics in Radiotherapy: Current Paradigms and Future Perspectives

Shreya¹,

Kumar²,

Singh³

et al. 2022

IJZI

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Over the last 100 years, much advancement has been made towards understanding the hallmarks of cancer and finding an amicable solution for the treatment of cancer. Still, understanding the clinical management of cancer with its increasing incidence in the 21st century poses great challenge. Radiation therapy is one of the significant modalities which remain an important component as far as cancer treatment is concerned. The main goal of the treatment is to prevent the multiplication of cancer cells and further metastasis. Human exposure to ionizing radiation (IR) has a great impact on the metabolic processes in the normal cells and tissues apart from tumor cells. Therefore, analysis of the metabolites in the stress–responsive pathways and generating a multi-metabolite profiles of the personnel having a great potential in the identification of robust biomarkers that help in predicting the radiation toxicology. This facilitates studying in–depth, the molecular response of cells in response to radiotherapy. In this review, we have focused on the active role of metabolomics in studying the post-radiotherapy changes in the patients and the identification of unique pathways that can be targeted to alleviate the harmful effects of radiation exposure.

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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%

“…To date, our understanding of the role of nonchemical factors, including biophysical influences, disorders, pathological states, and various constitutional properties of interindividual variations in hepatic drug metabolism, remains limited (Jones et al, 1989;Vesell, 1997). Irradiation is considered to be one of the oldest and most common pathogenic factors (Li et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Irradiation pertains to the process of distributing energy into space or matter using waves and particles (Repacholi, 2017;Li et al, 2019). Ionizing and non-ionizing irradiation have been extensively utilized in medicine, agriculture, food processing, national defense, and daily activities, and they have also negatively influenced human health (Sato and Zouain, 2012;Sutlief, 2015;Andrianov et al, 2015;von Neubeck et al, 2015).…”

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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Effects of Radiation on Drug Metabolism: A Review

Cited by 11 publications

References 56 publications

Potential of Dragon’s Blood as a Space Radiation Protectant Especially on Brain-Liver Bystander Effect

Potential of Dragon’s Blood as a Space Radiation Protectant Especially on Brain-Liver Bystander Effect

Metabolomics in Radiotherapy: Current Paradigms and Future Perspectives

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

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