Regulation profile of phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs) components towards UDP-glucuronosyltransferases (UGTs) isoforms

Gao, Xin; Qu, Hengyan; Ai, Chun-Zhi; Cao, Yun‐Feng; Huang, Ting; Chen, Jianxing; Zeng, Jia; Sun, Xiaoyu; Hong, Mo; Gonzalez, Frank J.; Liu, Ze Yuan; Fang, Zhong‐Ze

doi:10.3109/00498254.2014.966174

Cited by 12 publications

(17 citation statements)

References 19 publications

(22 reference statements)

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“…The majority of LPCs are derived from PCs, and are formed through different mechanisms (24). A number of them are catalyzed by the glycoprotein lecithin cholesterol acyltransferase (25), whereas others are synthesized from PC hydrolysis via the secretory phospholipase A2 family (26).…”

Section: Trend ------------------------------------------------------mentioning

confidence: 99%

Probiotic pre-administration reduces mortality in a mouse model of cecal ligation and puncture-induced sepsis

Chen

Gui

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. A number of clinical trials have demonstrated that the use of probiotics has the potential to prevent nosocomial infections. However, the mechanism underlying probiotic-induced anti-infection and sepsis remains to be investigated. In the present study, 200 µl/day of Lactobacillus rhamnosus GG (LGG) or normal saline (control) was orally administrated to 4-week-old C57BL6 mice 4 weeks prior to cecal ligation and puncture (CLP). A number of mice were sacrificed 24 h after CLP, and the remaining mice were used for survival studies. Ileum tissues were collected to evaluate the injury on the intestine. Blood samples were also obtained to investigate the changed metabolic pattern in mice that underwent different treatments using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). In the survival studies, the mortality of CLP-induced septic mice pretreated with LGG was significantly lower compared with untreated mice (P= 0.029). Ileum mucosal damage was evident in the control septic mice. Based on the data of UPLC-QTOF-MS, phosphatidylcholines were increased and lysophosphatidylcholines (LPCs) that contained polyunsaturated fatty acids were decreased in septic mice, whereas saturated fatty acid LPCs reveal no significant difference between septic and sham mice. In addition, the metabolic profile in the septic mice pretreated with LGG was much closer to that of sham mice compared with control septic mice. The results of the present study suggest that probiotic pre-administration reduces the mortality in septic mice by decreasing ileum mucosal damage, increasing the gut barrier integrity and altering global serum metabolic profiles.

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Section: Trend ------------------------------------------------------mentioning

confidence: 99%

Probiotic pre-administration reduces mortality in a mouse model of cecal ligation and puncture-induced sepsis

Chen

Gui

et al. 2016

Experimental and Therapeutic Medicine

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“…Among them, taurolithocholic acid (TLCA) exhibited the strongest inhibition towards UGT isoforms . The lipid components phosphatidylcholine (PC) and lysophosphatidylcholines (LPC) showed strong inhibition towards UGT isoforms . Some drugs also exhibited inhibitory behavior on the activity of UGT isoforms.…”

Section: Discussionmentioning

confidence: 99%

Chiral Inhibition of Rivaroxaban Derivatives Towards UDP‐Glucuronosyltransferase (UGT) Isoforms

Yao¹,

Liu

et al. 2015

Chirality

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Rivaroxaban is an oral direct factor Xa (FXa) inhibitor clinically used to prevent and treat thromboembolic disorders. Drug-drug interaction (DDI) exist for rivaroxaban and the inhibitors of CYP3A4/5. This study aims to investigate the inhibition of rivaroxaban and its derivatives with a chiral center towards UDP-glucuronosyltransferases (UGTs). Chemical synthesis was performed to obtain rivaroxaban derivatives with different chiral centers. UGTs supersomes-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was employed to evaluate the inhibition potential towards various UGT isoforms. A significant influence of rivaroxaban derivatives towards UGT1A3 was observed. Chiral centers produce different effects towards the effect of four pairs of rivaroxaban derivatives towards UGT1A3 activity, with stronger inhibition potential of S1 than R1, but stronger inhibition capability of R2, R3, R4 than S2, S3, and S4. Competitive inhibition of R3 and R4 towards UGT1A3 was demonstrated by Dixon and Lineweaver-Burk plots. In conclusion, the significant influence of rivaroxaban derivatives towards UGT1A3's activity was demonstrated in the present study. The chirality centers highly affected the inhibition behavior of rivaroxaban derivatives towards UGT1A3.

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“…4‐MU, a nonspecific probe substrate for all the UGT isoforms, was employed to investigate the inhibition of zaltoprofen enantiomers towards the activity of UGT isoforms. The incubation and analytical methods have been previously described . In brief, the typical incubation system (total volume = 200 μL) contained recombinant UGTs, 5 mM UDPGA, 5 mM MgCl 2 , 50 mM Tris–HCl (pH = 7.4), and 4‐MU in the absence or presence of different concentrations of (R)‐zaltoprofen or (S)‐zaltoprofen.…”

Section: Methodsmentioning

confidence: 99%

“…The incubation time and protein concentration have been demonstrated to ensure the linear glucuronidation reaction. The concentration of 4‐MU used was equal to known K m or S 50 values reported in the previous literatures . After a 5‐min preincubation, UDPGA was added to initiate the glucuronidation reaction, and after the incubation the reaction was terminated with 100 μL acetonitrile with 7‐hydroxycoumarin (100 μM) as internal standard.…”

Section: Methodsmentioning

confidence: 99%

“…The inhibitory capability of various xenobiotics and endogenous substances towards the activity of UGT isoforms has been reported. For example, lipid components showed strong inhibition towards UGT isoforms, including UGT1A4, 1A6, 1A8, 1A9, and 2B7 . Indinavir inhibited UGT1A1‐catalyzed glucuronidation of bilirubin, and resulted in the elevation of unconjugated bilirubin in serum …”

Section: Introductionmentioning

confidence: 99%

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Chirality Influence of Zaltoprofen Towards UDP‐Glucuronosyltransferases (UGTs) Inhibition Potential

Jia

Wang

et al. 2015

Chirality

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Zaltoprofen (ZLT) is a nonsteroidal antiinflammation drug, and has been clinically employed to treat rheumatoid arthritis, osteoarthritis, and other chronic inflammatory pain conditions. The present study aims to investigate the chirality influence of zaltoprofen towards the inhibition potential towards UDP-glucuronosyltransferases (UGTs) isoforms. In vitro a recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation incubation system was employed to investigate the inhibition of (R)-zaltoprofen and (S)-zaltoprofen towards UGT isoforms. The inhibition difference capability was observed for the inhibition of (R)-zaltoprofen and (S)-zaltoprofen towards UGT1A8 and UGT2B7, but not for other tested UGT isoforms. (R)-zaltoprofen exhibited noncompetitive inhibition towards UGT1A8 and competitive inhibition towards UGT2B7. The inhibition kinetic parameters were calculated to be 35.3 μM and 19.2 μM for UGT1A8 and UGT2B7. (R)-zaltoprofen and (S)-zaltoprofen exhibited a different inhibition type towards UGT1A7. Based on the reported maximum plasma concentration of (R)-zaltoprofen in vivo, a high drug-drug interaction between (R)-zaltoprofen and the drugs mainly undergoing UGT1A7, UGT1A8, and UGT2B7-catalyzed glucuronidation was indicated.

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Regulation profile of phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs) components towards UDP-glucuronosyltransferases (UGTs) isoforms

Cited by 12 publications

References 19 publications

Probiotic pre-administration reduces mortality in a mouse model of cecal ligation and puncture-induced sepsis

Probiotic pre-administration reduces mortality in a mouse model of cecal ligation and puncture-induced sepsis

Chiral Inhibition of Rivaroxaban Derivatives Towards UDP‐Glucuronosyltransferase (UGT) Isoforms

Chirality Influence of Zaltoprofen Towards UDP‐Glucuronosyltransferases (UGTs) Inhibition Potential

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