The effects of metronidazole on Cytochrome P450 Activity and Expression in rats after acute exposure to high altitude of 4300 m

Wang, Rong; Sun, Yuhuan; Yin, Qiang; Xie, Hua; Li, Wenbin; Wang, Chang; Guo, Jin; Hao, Ying; Tao, Rui; Jia, Zhengping

doi:10.1016/j.biopha.2016.11.024

Cited by 15 publications

(8 citation statements)

References 36 publications

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“…In this study, the incidence of AR and CR was 56.78% and 55.08%, which was higher than that of other plain areas in China, with the same time, detection method, and judgment standard, such as Shanghai [ 20 ] (AR16.49% and CR3.43%), Guangdong [ 21 ] (AR13.00% and CR10.00%), and Beijing (AR14.92% and CR5.66), with a statistically significant difference ( P < 0.05) [ 22 ]. Moreover, research has shown that [ 23 ] hypoxia at high altitude has a remarkable impact on the activities and behaviors of organisms, which may change the expression and activity of drug metabolism enzymes. In aspirin and clopidogrel treatment of antiplatelet reaction, high incidence of AR and CR in the high-altitude area may be relevant to the genetic background of the population.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Reactivity of Aspirin and Clopidogrel and Its Influencing Factors in Patients with Coronary Heart Disease at High Altitude

Chang

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Objective. To evaluate the efficacy of dual-antiplatelet treatment (DAPT) in patients with coronary heart disease (CHD) at high altitude by using thrombelastogram (TEG) and to analyze the related biochemical factors affecting drug reactivity. Methods. Totally 118 CHD patients who admitted to the Qinghai People’s Hospital from September 2019 to September 2020 were enrolled in the group. Those people have lived in Qinghai for a long time. Seven days after DAPT, venous blood was collected on an empty stomach in the early morning of the next day; blood routine, coagulation function, and biochemical items were tested. Thrombelastogram (TEG) was used to draw curves to calculate platelet, coagulation and fibrinolysis functions, and drug inhibition rate. Patients were divided into the aspirin resistance (AR) group, clopidogrel resistance (CR) group, dual-antiplatelet drug resistance (DAR) group, and drug-sensitive group according to different inhibition rates. The drug efficacy was analyzed, and the clinical data, biochemical indexes, and TEG parameters of each group were compared to identify the risk factors of drug resistance. Results. Those 118 CHD patients at high altitude were incorporated into the study, ranging from 38 to 84 years of age, including 81 males (68.64%) and 37 females (31.36%). The platelet function and coagulation-fibrinolysis function were detected by TEG, and MATHROMBI, MAADP, and MAAA were higher than the reference range. There were 82 cases (69.49%) of drug resistance, 36 cases (32.53%) of drug sensitivity, 17 cases (14.41%) of AR alone, and 16 cases (12.71%) of CR alone. There was no significant difference in age, gender, BMI, oxygen saturation, TG, GFR, and history of diabetes and hypertension between ACS and CCS groups ( P > 0.05 ). PLT and FIB in the ACS group were higher than those in the CCS group, and the difference was statistically significant ( P < 0.05 ). In addition, MATHROMBIN, MAFIBRIN, E, A, A30, and coagulation composite index were also higher than those in the CCS group, with a statistically significant difference ( P < 0.05 ). Univariate analysis and logistic regression analysis suggested that age, HbA1c, FBG, and diabetes were the main factors of drug resistance. Conclusion. Antiplatelet drugs aspirin and clopidogrel resistance are associated with increased age, elevated HbA1c and FBG, and diabetes. Therefore, it is necessary to take reasonable treatment measures based on the actual situation of patients.

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Section: Discussionmentioning

confidence: 99%

Analysis of the Reactivity of Aspirin and Clopidogrel and Its Influencing Factors in Patients with Coronary Heart Disease at High Altitude

Chang

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…What's more, high-altitude alone is a critical factor leading to liver and renal injury as well. On the one hand, staying at plateau areas caused liver dysfunction through endoplasmic reticulum stress and subsequent apoptosis, decreased expression content of hepatic microsomal enzyme, and might also be related to the enzyme's activity changes ( 22 , 23 ). On the other hand, exposure to high-altitude exerted significant effects on kidney injury by the alteration of cilia length and function which was resulted from the renal hypoperfusion caused by the chronic hypobaric hypoxic environment ( 24 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

The Clinical Differences of Patients With Traumatic Brain Injury in Plateau and Plain Areas

Yang¹,

Peng

He³

et al. 2022

Front. Neurol.

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ObjectiveTraumatic brain injury (TBI) is a leading cause of death and disability, which tends to have a worse clinical recovery if it occurs in plateau areas than in plain areas. To explore the underlying cause of this outcome preliminarily, this retrospective study was conducted to compare the clinical differences of patients with TBI in plateau and plain areas.MethodsIn this study, 32 patients with TBI in plateau areas (altitude ≥ 4,000 m) and 32 in plain areas (altitude ≤ 1,000 m) were recruited according to the inclusion and exclusion criteria from June 2020 to December 2021. The collected data and compared parameters include clinical features, head CT presentations and Marshall classifications, hematology profile, lipid profile, coagulation profile, and multiorgan (cardiac, liver, renal) function within 24 h of hospital admission, as well as the treatment method and final outcome.ResultsThere were no obvious differences in demographic characteristics, including gender, age, height, and weight, between patients with TBI in plateau and plain areas (all P > 0.05). Compared to patients with TBI in plain areas, the time before hospital admission was longer, heartbeat was slower, systolic blood pressure (SBP) was lower, and hospital stays were longer in patients with TBI in plateau areas (all P < 0.05). More importantly, elevated red blood cells (RBCs) count and hemoglobin (HGB) level, enhanced coagulation function, and higher rates of multiorgan (cardiac, liver, and renal) injury were found in patients with TBI in plateau areas (all P < 0.05).ConclusionPatients with TBI in plateau areas presented with altered clinical characteristics, enhanced coagulation function, and aggravated predisposition toward multiorgan (cardiac, liver, and renal) injury, compared to patients with TBI in plain areas. Future prospective studies are needed to further elucidate the influences of high altitude on the disease course of TBI.

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“…Finally, this study analyzed the pathological changes of rat liver tissue and the expression of CYP3A4. After acute hypoxia, rat liver tissue has many inflammatory cell infiltration and edema, which may affect the metabolism of the drug ( Wang et al, 2017 ). The analysis of CYP3A4 protein expression further indicated that acute hypoxia significantly down-regulated the protein expression of CYP3A4.…”

Section: Discussionmentioning

confidence: 99%

“…Previous work showed that the expression and activity of the metabolic enzyme CYP2C9 under acute hypoxia were not affected, and the expression of CYP3A4 may be altered ( Wang et al, 2017 ). As part of our continued exploration of high altitude hypoxia-mediated drug metabolism ( Zhang et al, 2018 , 2019 , 2020 ), the change of CYP3A4 with increasing altitude and the effect of this alteration on the pharmacokinetics of its substrate sildenafil are issues of our concern.…”

Section: Introductionmentioning

confidence: 99%

Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil

Zhang

Wang

2022

Front. Physiol.

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The effects of metronidazole on Cytochrome P450 Activity and Expression in rats after acute exposure to high altitude of 4300 m

Cited by 15 publications

References 36 publications

Analysis of the Reactivity of Aspirin and Clopidogrel and Its Influencing Factors in Patients with Coronary Heart Disease at High Altitude

Analysis of the Reactivity of Aspirin and Clopidogrel and Its Influencing Factors in Patients with Coronary Heart Disease at High Altitude

The Clinical Differences of Patients With Traumatic Brain Injury in Plateau and Plain Areas

Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil

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