FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4285992874> ?p ?o ?g. }

• W4285992874 endingPage "1150" @default.
• W4285992874 startingPage "1142" @default.
• W4285992874 abstract "Gut microbiota play an important role in the pathophysiology of type 2 diabetic mellitus (T2DM) and biodisposition of drugs. Our previous study demonstrated that T2DM rats had the decreased plasma exposure of clopidogrel active metabolite (Clop-AM) due to upregulation of P-glycoprotein (P-gp). However, whether the change to clopidogrel (Clop) disposition under T2DM condition is associated with gut microbiota needs to be elucidated. In the study, we used an antibiotic cocktail consisting of ampicillin, vancomycin, metronidazole, and neomycin to disrupt gut microbiota and observed their influence on pharmacokinetic profiles of Clop-AM. Antibiotic administration markedly alleviated T2DM rats' phenotype including hyperglycemia, insulin resistance, oxidative stress, inflammation, hyperlipidemia, and liver dysfunction. Meanwhile, treatment with antibiotics significantly reversed the reduced systemic exposure of Clop-AM in T2DM rats relative to control rats, which was associated with the decreased intestinal P-gp level that might promote Clop absorption, resulting in more Clop transformation to Clop-AM. Fecal microbiome analysis exhibited a serious disruption of gut microbiota after antibiotic treatment with the sharply reduced microbial load and the altered microbial composition. Interestingly, an in vitro study showed that antibiotics had no influence on P-gp mRNA leve in SW480 cells, suggesting the microbiome disruption, not the direct role of antibiotics on P-gp expression, contributes to the altered P-gp level and Clop disposition in T2DM rats. The findings add new insights into the potential impact of gut microbiota on Clop biodisposition. Significance Statement 1.Antibiotics increase systemic exposure of Clop-AM in T2DM rats, which is associated with the downregulation of P-gp level.2.Antibiotics-induced disruption of gut microbiota, not direct effect of antibiotics on P-gp and CYPs expression, contributes to the altered Clop disposition.3.Antibiotics also alleviate T2DM phenotype including hyperglycemia, hyperlipidemia, insulin resistance, liver dysfunction and inflammation." @default.
• W4285992874 created "2022-07-21" @default.
• W4285992874 creator A5001077129 @default.
• W4285992874 creator A5011997460 @default.
• W4285992874 creator A5012286710 @default.
• W4285992874 creator A5019539636 @default.
• W4285992874 creator A5038556283 @default.
• W4285992874 creator A5041695604 @default.
• W4285992874 creator A5068230674 @default.
• W4285992874 date "2022-07-20" @default.
• W4285992874 modified "2023-10-16" @default.
• W4285992874 title "Antibiotics-Induced Disruption of Gut Microbiota Increases Systemic Exposure of Clopidogrel Active Metabolite in Type 2 Diabetic Rats" @default.
• W4285992874 cites W1528948449 @default.
• W4285992874 cites W1952796400 @default.
• W4285992874 cites W1964067479 @default.
• W4285992874 cites W1982371325 @default.
• W4285992874 cites W1991372259 @default.
• W4285992874 cites W2011132772 @default.
• W4285992874 cites W2042317328 @default.
• W4285992874 cites W2071841602 @default.
• W4285992874 cites W2083089709 @default.
• W4285992874 cites W2088107344 @default.
• W4285992874 cites W2095000788 @default.
• W4285992874 cites W2097746233 @default.
• W4285992874 cites W2104969665 @default.
• W4285992874 cites W2112931540 @default.
• W4285992874 cites W2113787373 @default.
• W4285992874 cites W2123460944 @default.
• W4285992874 cites W2135989088 @default.
• W4285992874 cites W2145425156 @default.
• W4285992874 cites W2154940301 @default.
• W4285992874 cites W2163878401 @default.
• W4285992874 cites W2170902262 @default.
• W4285992874 cites W2178586952 @default.
• W4285992874 cites W2283545615 @default.
• W4285992874 cites W2284126852 @default.
• W4285992874 cites W2389836803 @default.
• W4285992874 cites W2399094506 @default.
• W4285992874 cites W2468194934 @default.
• W4285992874 cites W2558041282 @default.
• W4285992874 cites W2767257558 @default.
• W4285992874 cites W2772771534 @default.
• W4285992874 cites W2810492961 @default.
• W4285992874 cites W2884737885 @default.
• W4285992874 cites W2892246459 @default.
• W4285992874 cites W2898348856 @default.
• W4285992874 cites W2945336651 @default.
• W4285992874 cites W2989442801 @default.
• W4285992874 cites W2996234046 @default.
• W4285992874 cites W2999497945 @default.
• W4285992874 cites W3041953640 @default.
• W4285992874 cites W3197603787 @default.
• W4285992874 doi "https://doi.org/10.1124/dmd.122.000906" @default.
• W4285992874 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35858690" @default.
• W4285992874 hasPublicationYear "2022" @default.
• W4285992874 type Work @default.
• W4285992874 citedByCount "0" @default.
• W4285992874 crossrefType "journal-article" @default.
• W4285992874 hasAuthorship W4285992874A5001077129 @default.
• W4285992874 hasAuthorship W4285992874A5011997460 @default.
• W4285992874 hasAuthorship W4285992874A5012286710 @default.
• W4285992874 hasAuthorship W4285992874A5019539636 @default.
• W4285992874 hasAuthorship W4285992874A5038556283 @default.
• W4285992874 hasAuthorship W4285992874A5041695604 @default.
• W4285992874 hasAuthorship W4285992874A5068230674 @default.
• W4285992874 hasBestOaLocation W42859928741 @default.
• W4285992874 hasConcept C134018914 @default.
• W4285992874 hasConcept C203014093 @default.
• W4285992874 hasConcept C2777391703 @default.
• W4285992874 hasConcept C2777477808 @default.
• W4285992874 hasConcept C2779306644 @default.
• W4285992874 hasConcept C2779841869 @default.
• W4285992874 hasConcept C501593827 @default.
• W4285992874 hasConcept C539455810 @default.
• W4285992874 hasConcept C86803240 @default.
• W4285992874 hasConcept C89423630 @default.
• W4285992874 hasConcept C98274493 @default.
• W4285992874 hasConceptScore W4285992874C134018914 @default.
• W4285992874 hasConceptScore W4285992874C203014093 @default.
• W4285992874 hasConceptScore W4285992874C2777391703 @default.
• W4285992874 hasConceptScore W4285992874C2777477808 @default.
• W4285992874 hasConceptScore W4285992874C2779306644 @default.
• W4285992874 hasConceptScore W4285992874C2779841869 @default.
• W4285992874 hasConceptScore W4285992874C501593827 @default.
• W4285992874 hasConceptScore W4285992874C539455810 @default.
• W4285992874 hasConceptScore W4285992874C86803240 @default.
• W4285992874 hasConceptScore W4285992874C89423630 @default.
• W4285992874 hasConceptScore W4285992874C98274493 @default.
• W4285992874 hasIssue "9" @default.
• W4285992874 hasLocation W42859928741 @default.
• W4285992874 hasLocation W42859928742 @default.
• W4285992874 hasOpenAccess W4285992874 @default.
• W4285992874 hasPrimaryLocation W42859928741 @default.
• W4285992874 hasRelatedWork W1006218191 @default.
• W4285992874 hasRelatedWork W2431019625 @default.
• W4285992874 hasRelatedWork W2886914658 @default.
• W4285992874 hasRelatedWork W2902527856 @default.
• W4285992874 hasRelatedWork W3104326469 @default.

• next