Exploring cytochrome P450 under hypoxia: potential pharmacological significance in drug metabolism and protection against high-altitude diseases.

High-altitude hypoxia affects the human respiratory, central nervous, cardiovascular, and endocrine systems. These outcomes affect the expression of cytochrome P450 (CYP), the most important family of metabolic enzymes in the body that is involved in the metabolism of both exogenous and endogenous substances (such as arachidonic acid, vitamins, and steroids). Hypoxia influences CYP expression and activity, mediating changes in drug and endogenous substance metabolism, with endogenous metabolites playing a significant role in controlling high-altitude diseases.

Pharmacokinetics of Midazolam in Plasma and Brain Tissue of Rats after Exposure to Acute and Chronic High Altitude Hypoxia.

Tian, Lu, Guiqin Liu, Qin Zhao, Junjun Han, Yue Lin, Wang, Jia, Delong Duo, Duan Yabin, Zhu Junbo, and Li Xiangyang. Pharmacokinetics of midazolam in plasma and brain tissue of rats after exposure to acute and chronic high altitude hypoxia. 00:00-00, 2025.

Blood-Brain Barrier Permeability is Affected by Changes in Tight Junction Protein Expression at High-Altitude Hypoxic Conditions-this may have Implications for Brain Drug Transport.

Changes to blood-brain barrier structure and function may affect the delivery of drugs into the brain. It is worthwhile to exploring more study on how the blood-brain barrier changes in structure and function and how that affects drug transport in high-altitude hypoxic environment. The DIA high-throughput sequencing technique indicate that the rats blood-brain barrier has been identified to have 7252 proteins overall and 8 tight junction proteins, among which Claudin-7 was a plateau-specific tight junction protein under high-altitude hypoxia, and based on the interaction network study, 2421 proteins are found to interact with one another, with ZO-1 being the primary target.

Biological and molecular characterization of pydiflumetofen and phenamacril dual-resistant Fusarium graminearum strains.

Background: Fusarium head blight (FHB) caused by Fusarium graminearum species complex (FGSG) remains a major challenge to cereal crops and resistance to key fungicides by the pathogen threatens control efficacy. Pydiflumetofen, a succinate dehydrogenase inhibitor, and phenamacril, a cyanoacrylate fungicide targeting myosin I, have been applied to combat this disease. Nonetheless, emergence of pydiflumetofen resistance in a subset of field isolates alongside laboratory-induced facile generation of phenamacril-resistant isolates signals a critical danger of resistance proliferation.

New strategy for rational use of antihypertensive drugs in clinical practice in high-altitude hypoxic environments.

High-altitude hypoxic environments have critical implications on cardiovascular system function as well as blood pressure regulation. Such environments place patients with hypertension at risk by activating the sympathetic nervous system, which leads to an increase in blood pressure. In addition, the high-altitude hypoxic environment alters the metabolism and antihypertensive effects of antihypertensive drugs, which changes the activity and expression of drug-metabolizing enzymes and drug transporters.

Relationship between blood-brain barrier changes and drug metabolism under high-altitude hypoxia: obstacle or opportunity for drug transport?

The blood-brain barrier is essential for maintaining the stability of the central nervous system and is also crucial for regulating drug metabolism, changes of blood-brain barrier's structure and function can influence how drugs are delivered to the brain. In high-altitude hypoxia, the central nervous system's function is drastically altered, which can cause disease and modify the metabolism of drugs . Changes in the structure and function of the blood-brain barrier and the transport of the drug across the blood-brain barrier under high-altitude hypoxia, are regulated by changes in brain microvascular endothelial cells, astrocytes, and pericytes, either regulated by drug metabolism factors such as drug transporters and drug-metabolizing enzymes.

High-altitude Hypoxia Influences the Activities of the Drug-Metabolizing Enzyme CYP3A1 and the Pharmacokinetics of Four Cardiovascular System Drugs.

(1) Background: High-altitude hypoxia has been shown to affect the pharmacokinetic properties of drugs. Although there is a high incidence of cardiovascular disease among individuals living in high-altitude areas, studies on the effect of high-altitude hypoxia on the pharmacokinetic properties of cardiovascular drugs are limited. (2) Methods: The aim of this study was to evaluate the pharmacokinetics of nifedipine, bosentan, simvastatin, sildenafil, and their respective main metabolites, dehydronifedipine, hydroxybosentan, simvastatin hydroxy acid, and N-desmethyl sildenafil, in rats exposed to high-altitude hypoxia.

Bacterial Communities in the Endophyte and Rhizosphere of White Radish () in Different Compartments and Growth Conditions.

Endophyte resources have important research value in multiresistance breeding, ecological protection, germicide development, and other fields. In this study, high-throughput sequencing (Illumina-MiSeq) technology was employed to analyse the diversity and community composition of white radish () endophytes and rhizosphere bacteria in different compartments and cultivation conditions, including greenhouse and open field cultivation, at both the phylum and genus levels. Alpha diversity index analysis showed that the bacterial richness and diversity values of rhizosphere bacteria were higher than those of endophytes in different compartments.

Colonization and Interaction of Bacteria Associated With Chinese Chives Affected by Ecological Compartments and Growth Conditions.

Chinese chive has a long history of planting in China. At present, there are many studies on endophytic bacteria and rhizosphere microorganisms of Chinese chive, but the effects of ecological compartment and growth conditions on bacterial communities in Chinese chives are unclear. Here, we aimed to elucidate the differences in bacterial a-diversity, β-diversity, community structure, core species differences, interaction networks and predicted metabolic functions among bacterial communities in different ecological compartments (the phylloplane, leaf endosphere, stem endosphere, root endosphere, and rhizosphere) in Chinese chives in an open field, a solar greenhouse, an arched shed, and a hydroponic system.

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.

Hypoxia is the main characteristic of a high-altitude environment, affecting drug metabolism. However, so far, the mechanism of microRNA (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 colon cancer (Caco-2) cells after exposure to high-altitude hypoxia.

Pharmacokinetics of Acetaminophen and Metformin Hydrochloride in Rats After Exposure to Simulated High Altitude Hypoxia.

The pharmacokinetic characteristics of drugs were altered under high altitude hypoxia, thereby affecting the absorption, distribution, metabolism, and excretion of drug. However, there are few literatures on the pharmacokinetic changes of antipyretic and pain-relieving drugs and cardiovascular system drugs at high altitude. This study aimed to evaluate the pharmacokinetics of acetaminophen and metformin hydrochloride in rats under simulated high altitude hypoxia condition.

A Decade's Review of miRNA: A Center of Transcriptional Regulation of Drugmetabolizing Enzymes and Transporters under Hypoxia.

Background: Hypoxia has a negative effect on the cardiovascular system, nervous system, and metabolism, which contributes to potential changes in drug absorption, distribution, metabolism, and excretion (ADME). However, hypoxia can also alter the expression of microRNA (miRNA), thereby regulating drug-metabolizing enzymes, transporters, and ADME genes, such as hypoxia-inducible factor, inflammatory cytokine, nuclear receptor, etc. Therefore, it is crucial to study the role of miRNA in the regulation of drug-metabolizing enzymes and transporters under hypoxia.

Protection against X-Ray Irradiation Injury by Chinese Caterpillar Medicinal Mushroom Ophiocordyceps sinensis (Ascomycetes) Polysaccharides in Mice.

Polysaccharides are one of the main active ingredients of Ophiocordyceps sinensis, a traditional Chinese medicinal mushroom. In this study, we investigated the protective effect of O. sinensis polysaccharides (CSPs) against X-ray irradiation in mice.

Regulation of High-Altitude Hypoxia on the Transcription of CYP450 and UGT1A1 Mediated by PXR and CAR.

Little is known about what roles the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) play in drug metabolism in high-altitude hypoxia. Likewise, the potential interaction of nuclear receptors and drug metabolism enzymes during drug metabolism of high-altitude hypoxia is not fully understood. In this work, we investigated the effects of high-altitude hypoxia on transcriptional regulation of cytochrome P450 (CYP450) and UDP-glucuronosyltransferase 1A1 (UGT1A1) genes mediated by PXR and CAR proteins.

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

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.

Effects of Radiation on Drug Metabolism: A Review.

Background: Radiation is the fourth most prevalent type of pollution following the water, air and noise pollution. It can adversely affect normal bodily functions. Radiation alters the protein and mRNA expression of drugmetabolizing enzymes and drug transporters and the pharmacokinetic characteristics of drugs, thereby affecting drug absorption, distribution, metabolism, and excretion.

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

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.

Effects of yak-activated protein on hematopoiesis and related cytokines in radiation-induced injury in mice.

The aim of the present study was to investigate the protective effects of yak-activated protein on hematopoiesis and cytokine function in radiation-induced injury in mice. A total of 180 Kunming mice were randomly divided into three groups (A, B and C). Of these, 60 were randomly divided into a normal control group, a radiation model group, a positive control group and 3 yak-activated protein groups (high, medium and low dose groups; 10, 5 and 2.

[Protective Effect of Lycium ruthenicum on Peripheral Blood System Against Radiation Injury in Mice].

Objective: To study the protective effect of Lycium ruthenicum on peripheral blood system against radiation injury in mice.

Methods: Kunming mice were randomly divided into control group, model group, positive group and Lycium ruthenicum high dose (8 g/kg), middle dose (4 g/kg) and low dose (2 g/kg)treatment groups that experimented three days after irradiation. In the same way, groups were set at 7 days and 14 days after irradiation respectively.

Pharmacokinetics of Lidocaine Hydrochloride Metabolized by CYP3A4 in Chinese Han Volunteers Living at Low Altitude and in Native Han and Tibetan Chinese Volunteers Living at High Altitude.

To investigate the pharmacokinetics of lidocaine hydrochloride metabolized by cytochrome P450 3A4 (CYP3A4) in Chinese Han volunteers living at low altitude (LA) and in native Han and Tibetan Chinese volunteers living at high altitude, lidocaine hydrochloride 10 mg was given by intramuscular injection to 3 groups: Han volunteers living at LA, and native Han and Tibetan volunteers living at a high altitude. Blood samples were collected before the (baseline) study drug was given and at 0.25, 0.

Protective Effect of Lycium ruthenicum Murr. Against Radiation Injury in Mice.

The protective effect of Lycium ruthenicum Murr. against radiation injury was examined in mice. Kunming mice were randomly divided into a control group, model group, positive drug group and L.

The activity, protein, and mRNA expression of CYP2E1 and CYP3A1 in rats after exposure to acute and chronic high altitude hypoxia.

The effects of exposure to acute and chronic high altitude hypoxia on the activity and expression of CYP2E1 and CYP3A1 were examined in rats. Rats were divided into low altitude (LA, 400 m), acute moderate altitude hypoxia (AMH, 2800 m), chronic moderate altitude hypoxia (CMH, 2800 m), acute high altitude hypoxia (AHH, 4300 m), and chronic high altitude hypoxia groups (CHH, 4300 m). Probe drugs were administrated orally to all five groups.

Effect of exposure to acute and chronic high-altitude hypoxia on the activity and expression of CYP1A2, CYP2D6, CYP2C9, CYP2C19 and NAT2 in rats.

We investigated the effect of exposure to acute and chronic high-altitude hypoxia (AHH and CHH) on the activity and expression of CYP1A2, CYP2D6, CYP2C9, CYP2C19 and NAT2 in rats. The rats were divided into plain (400 m), acute middle-altitude hypoxia (2,800 m), chronic middle-altitude hypoxia (2,800 m), AHH (4,300 m) and CHH (4,300 m). After probe drugs had been orally administered to the rats of the 5 groups, the serum or urine concentration of the probe drug and its metabolite was determined by reversed-phase HPLC.