Dysregulation of Mucosal Membrane Transporters and Drug-Metabolizing Enzymes in Ulcerative Colitis

Erdmann, Pascal; Bruckmueller, Henrike; Martín, Paul; Busch, Diana; Haenisch, Sierk; Müller, Janett; Wiechowska–Kozłowska, Anna; Partecke, Lars Ivo; Heidecke, Claus–Dieter; Cascorbi, Ingolf; Droździk, Marek; Oswald, Stefan

doi:10.1016/j.xphs.2018.09.024

Cited by 48 publications

(57 citation statements)

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“…It has been found that SNP of miRNA-146 rs2910164, but not miR-196 rs11614913, was associated with lowered risk of UC in the Asian population, but not Caucasian population18 . On the contrary, in the Caucasian population, both miRNA-196 rs11614913 and miRNA-146a rs2910164 polymorphisms were found to be predictors of lowered risk of UC19 . Moreover, miRNA-196a2 rs11614913 was associated with a lowered risk of colorectal cancer in UC patients, whereas miRNA-146a rs2910164 did not have a similar relation28 .…”

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confidence: 75%

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Diagnostic and therapeutic value of micro-RNAs in inflammatory bowel disease

Berezin

Poplyonkin

2020

Biomed. Res. Ther.

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Inflammatory bowel disease (IBD) is a heterogeneous chronic idiopathic inflammatory disease that includes ulcerative colitis (UC) and Crohn's disease with uncertain etiology and pathogenesis. The prevalence of IBD has steadily increased worldwide, affecting numerous groups of people in both developed and developing countries. Current guidelines are being re-defined with the aim for patients with established IBD to achieve mucosal healing and complete morphological figures with minimal drug toxicity, to diminish the likelihood of extra-intestinal manifestations and dysplasia/ colorectal cancer, and to prevent the need for surgery. Many patients with established IBD may require conventional treatment, as well as alternative treatment, due to non-response, loss of response, or intolerance to treatment regimen. In this context, stratification of risk and management of IBD could be based on personified strategy predominantly allocated to core components of pathogenesis of the disease. MicroRNAs (miRNAs) are defined as non-coding short RNAs which are involved in various stages of the natural evolution of IBD. Recent animal and clinical studies have shown the role of single nucleotide polymorphisms (SNPs) and signature of miRNAs in susceptibility to IBD, risk of clinical and histological exacerbation, and remission. The aim of the review is to summarize the knowledge regarding use of miRNAs as biomarkers and molecular targets in IBD.

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confidence: 75%

“…nuclear factor-κB, Stat1/ Stat3, etc. ), and worsening of post-transcriptional regulation of IL-10 release [17][18][19] . All these processes are crucial for IBD initiation and development.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and therapeutic value of micro-RNAs in inflammatory bowel disease

Berezin

Poplyonkin

2020

Biomed. Res. Ther.

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“…This phenomenon might be caused by the corresponding pathologic change of colitis, and the changes will alter the disposition of drugs in the body. On one hand, the decreased activities of phase I and II metabolizing enzymes were observed in IBD patients, [22] including CYP450 enzymes, [23,24] transporters (P-glycoprotein) [25] and conjugative enzymes (UDP-glucuronosyltransferases) [26] both in liver and intestines. [27] The impairment of drug-metabolizing enzymes or drug transporters can influence the fate of drugs in vivo, [28] which might be one of the main reasons for the reduction of Table 1 The linear equation, correlation coefficients (R 2 ), linear ranges and lower limit of quantification (LLOQ) of 5-hydroxy-4-methoxycanthin-6-one (PQ-A) and 1-methoxicabony-b-carboline (PQ-B) in rat biological samples elimination rate of PQ-A in colitis.…”

Section: Discussionmentioning

confidence: 99%

A comparative study on pharmacokinetics and tissue distribution of 5-hydroxy-4-methoxycanthin-6-one and its metabolite in normal and dextran sodium sulfate-induced colitis rats by HPLC-MS/MS

Liu

Zhang

Chen

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives This study aimed to investigate the existing form of 5-hydroxy-4methoxycanthin-6-one (PQ-A) in vivo after oral administration and the effects on its pharmacokinetics and tissue distribution by colitis. Methods A rapid HPLC-MS/MS method was established to simultaneously determine PQ-A and its main metabolite, 1-methoxicabony-b-carboline (PQ-B), in biological samples acquired from normal and dextran sodium sulfate (DSS)induced colitic rats administered orally with PQ-A. Then, the pharmacokinetics of both PQ-A and PQ-B, and tissue distribution of PQ-A in the above two states were analysed. Key findings The pharmacokinetic results showed that the prototype of PQ-A was the main existing form in both physiological and pathological conditions. And significant difference between the above two status in pharmacokinetics of PQ-A was observed, such as higher exposure and longer elimination in colitis than that in normal rats. It suggested that the pharmacokinetics of medications for colitis was affected by enteritis. The tissue distribution studies displayed that PQ-A mainly accumulated in intestinal tract. Especially, the distribution of PQ-A in intestinal tract was increased obviously in colitic rats. Conclusions These results contributed to further illuminate the ADME process of PQ-A in different status and were prospected to be the reference to the clinical application of similar medicines in pathological states. Consequently, the pathological changes in enteritis may be associated with changes in all phases of pharmacokinetic processes, including absorption, distribution, metabolism and excretion (ADME). Accessing to the previous research, other similar studies have adequately demonstrated the differences in pharmacokinetics under physiological and pathological conditions. Research shows that diabetes, liver injury, inflammation, cerebral ischaemia and other diseases could alter the drug's metabolism. [5] For example, it is reported that the pharmacokinetic characteristics of phlorizin were significantly changed in type 2 diabetes colitic rats, especially the bioavailability was significantly higher than that in normal rats. [6] It suggested that the pharmacokinetics of drugs is influenced by the internal environment when organisms are

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“…Notably, UGT1A9 , UGT1A1 , and UGT1A6 are expressed in the liver and kidney cortex and basally expressed in the colon, while UGT1A10 and UGT1A1 are highly and specifically expressed in the transverse colon and the terminal ileum of the small intestine, indicating that these two proteins may indeed be core drivers of IBD-specific GRNs [ 20 ]. Multiple sources have associated genetic variants of UGT1A genes with ulcerative colitis and IBD in humans [ 21 , 22 , 23 , 24 ], functionally implicating decreased expression of these proteins during inflammatory states in disease. Erdmann and colleagues suggest inflammatory processes occurring during IBD may alter the expression of UGT proteins, as their expression is negatively correlated with several inflammatory cytokines [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Multiple sources have associated genetic variants of UGT1A genes with ulcerative colitis and IBD in humans [ 21 , 22 , 23 , 24 ], functionally implicating decreased expression of these proteins during inflammatory states in disease. Erdmann and colleagues suggest inflammatory processes occurring during IBD may alter the expression of UGT proteins, as their expression is negatively correlated with several inflammatory cytokines [ 22 ]. The Reactome functional network, generated from the IBD dataset proteins ( Figure 11 ), suggests that the UGT proteins hypothetically interact as a distinct group, however this is driven only by the homology between the proteins.…”

Section: Discussionmentioning

confidence: 99%

Biomarker Prioritisation and Power Estimation Using Ensemble Gene Regulatory Network Inference

Aziz

Acharjee

Williams

et al. 2020

IJMS

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Inferring the topology of a gene regulatory network (GRN) from gene expression data is a challenging but important undertaking for gaining a better understanding of gene regulation. Key challenges include working with noisy data and dealing with a higher number of genes than samples. Although a number of different methods have been proposed to infer the structure of a GRN, there are large discrepancies among the different inference algorithms they adopt, rendering their meaningful comparison challenging. In this study, we used two methods, namely the MIDER (Mutual Information Distance and Entropy Reduction) and the PLSNET (Partial least square based feature selection) methods, to infer the structure of a GRN directly from data and computationally validated our results. Both methods were applied to different gene expression datasets resulting from inflammatory bowel disease (IBD), pancreatic ductal adenocarcinoma (PDAC), and acute myeloid leukaemia (AML) studies. For each case, gene regulators were successfully identified. For example, for the case of the IBD dataset, the UGT1A family genes were identified as key regulators while upon analysing the PDAC dataset, the SULF1 and THBS2 genes were depicted. We further demonstrate that an ensemble-based approach, that combines the output of the MIDER and PLSNET algorithms, can infer the structure of a GRN from data with higher accuracy. We have also estimated the number of the samples required for potential future validation studies. Here, we presented our proposed analysis framework that caters not only to candidate regulator genes prediction for potential validation experiments but also an estimation of the number of samples required for these experiments.

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Dysregulation of Mucosal Membrane Transporters and Drug-Metabolizing Enzymes in Ulcerative Colitis

Cited by 48 publications

References 89 publications

Diagnostic and therapeutic value of micro-RNAs in inflammatory bowel disease

Diagnostic and therapeutic value of micro-RNAs in inflammatory bowel disease

A comparative study on pharmacokinetics and tissue distribution of 5-hydroxy-4-methoxycanthin-6-one and its metabolite in normal and dextran sodium sulfate-induced colitis rats by HPLC-MS/MS

Biomarker Prioritisation and Power Estimation Using Ensemble Gene Regulatory Network Inference

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