Evidence map›Paper›PMID 39522097›Full record

ArticleEuropean journal of drug metabolism and pharmacokinetics2025

Hypertensive Nephropathy Changes the Expression of Drug-Metabolizing Enzymes and Transporters in Spontaneously Hypertensive Rat Liver and Kidney.

Yueqing Pan, Zhuan Yang, Minlong Wei, Yulin Gan, Menghua Liu, Wei Zou

Abstract read
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In one paragraph

Article in European journal of drug metabolism and pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Mechanisms and Therapeutic Advances of PXR in Metabolic Diseases and Cancer.International journal of molecular sciences · 2025
    Review
  3. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Yueqing PanGuangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, 1023 Shatai South Road, Baiyun District, Guangzhou, 510515, Guangdong, China.
Zhuan YangGuangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, 1023 Shatai South Road, Baiyun District, Guangzhou, 510515, Guangdong, China.
Minlong WeiGuangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, 1023 Shatai South Road, Baiyun District, Guangzhou, 510515, Guangdong, China.
Yulin GanGuangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, 1023 Shatai South Road, Baiyun District, Guangzhou, 510515, Guangdong, China.
Menghua LiuGuangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, 1023 Shatai South Road, Baiyun District, Guangzhou, 510515, Guangdong, China. liumenghua@smu.edu.cn.
Wei ZouChangsha Research and Development Center on Obstetric and Gynecologic Traditional Chinese Medicine Preparation, NHC Key Laboratory of Birth Defects Research, Prevention and Treatment, Hunan Provincial Maternal and Child Health Care Hospital, No. 53 Xiangchun Road, Kaifu District, Changsha, 410008, Hunan, China. zouwei3@foxmail.com.

Funding

National Natural Science Foundation of China 82374138
6 · The paper itself

Abstract

BACKGROUND AND

objectivesHypertensive nephropathy (HN) has become one of the main causes of end-stage renal disease. Drug combination therapy is a common clinical treatment for HN. However, the impact of HN on drug-metabolizing enzymes and transporters, which may lead to drug-drug interactions (DDIs) and even trigger toxic side effects, remains unclear. The aim of this study was to investigate changes in major drug-metabolizing enzymes and transporters in the liver and kidney of HN rats to improve the scientific foundations for the clinical treatment of HN.

methodsSpontaneously hypertensive rats (SHRs) were used as an animal HN model because their hypertension is similar to that of humans. Wistar-Kyoto rats (WKYs) were used as the control group. Body weight, blood pressure, hematoxylin-eosin (HE) staining and biochemical analysis were performed to evaluate whether the HN model was successfully constructed. Quantitative real-time polymerase chain reaction (PCR) and western blotting were used to evaluate the mRNA and protein expression of drug-metabolizing enzymes, transporters and related nuclear transcription factors.

resultsIn HN rats, the mRNA expression of the drug-metabolizing enzymes cytochrome P450 (Cyp) 2b1, Cyp2c11, Cyp3a1 and Cyp7a1 was significantly upregulated. The protein level of CYP3A1 was consistent with its mRNA expression. Interestingly, the mRNA expression of the hepatic transporters organic cation transporter (Oct) 1, Oct2, organic anion transporter (Oat) 1, Oat2, multidrug resistant protein (Mrp) 2, multidrug resistance (Mdr) 1, organic anion transporting polypeptide (Oatp) 1b2 and na+/taurocholate cotransporting polypeptide (Ntcp) was also markedly upregulated. This may be directly influenced by the upregulation of the expression of the nuclear receptors farnesoid X receptor (Fxr), pregnane X receptor (Pxr), liver X-activated receptor (Lxr) and constitutive androstane receptor (Car). In the kidney of HN rats, the mRNA level of the drug-metabolizing enzyme Cyp2b1 significantly increased, while levels of Cyp1a1, Cyp2c11, Cyp3a1 and Cyp3a2 did not significantly change. The mRNA expression of the transporters multidrug and toxin extrusion (Mate) 1 and Mrp2 was obviously increased but was markedly depressed for peptide transporters (Pept) 1 and Pept2. These changes may be related to the cross effects of Pxr, Fxr and Car in kidney.

conclusionHN pathological status can alter the expression of drug-metabolizing enzymes and transporters in the liver and kidney to varying degrees, thus affecting the disposition of substrate drugs in vivo. This suggests that to avoid potential risks, caution should be exercised when administering combination therapy for HN treatment.

Indexed as

Hypertension, RenalKidneyLiverMembrane Transport ProteinsAnimalsCytochrome P-450 Enzyme SystemDisease Models, AnimalMaleNephritisRatsRats, Inbred SHRRats, Inbred WKYCytochrome P-450 Enzyme SystemMembrane Transport Proteins

Identifiers

PMID39522097

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