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Albumin-bound kynurenic acid is an appropriate endogenous biomarker for assessment of the renal tubular OATs-MRP4 channel

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Journal of Pharmaceutical Analysis 2023年第10期13卷 1205-1220页

作者： Yanrong Ma Fenglin Ran Mingyan Xin Xueyan Gou Xinyi Wang Xinan Wu The First School of Clinical Medicine Lanzhou UniversityLanzhou730000China School of Pharmacy Lanzhou UniversityLanzhou730000China

Renal tubular secretion mediated by organic anion transporters(OATs)and the multidrug resistanceassociated protein 4(MRP4)is an important means of drug and toxin ***,there are no biomarkers to evaluate their *** aim of this study was to identify and characterize an endogenous biomarker of the renal tubular OATs-MRP4 ***-six uremic toxins were selected as candidate compounds,of which kynurenic acid was identified as a potential biomarker by assessing the protein-binding ratio and the uptake in OAT1-,OAT3-,and MRP4-overexpressing cell ***1/3 and MRP4 mediated the transcellular vectorial transport of kynurenic acid in *** kynurenic acid concentration was dramatically increased in rats treated with a rat OAT1/3(rOAT1/3)inhibitor and in rOAT1/3 double knockout(rOAT1/3^(-/-))rats,and the renal concentrations were markedly elevated by the rat MRP4(rMRP4)*** acid was not filtered at the glomerulus(99%of albumin binding),and was specifically secreted in renal tubules through the OAT1/3-MRP4 channel with an appropriate affinity(Km)(496.7 mM and 382.2 mM for OAT1 and OAT3,respectively)and renal clearance half-life(t1/2)in vivo(3.7±0.7 h).There is a strong correlation in area under the plasma drug concentration-time curve(AUC0et)between cefmetazole and kynurenic acid,but not with creatinine,after inhibition of *** addition,the phase of increased kynurenic acid level is earlier than that of creatinine in acute kidney injury *** results suggest that albumin-bound kynurenic acid is an appropriate endogenous biomarker for adjusting the dosage of drugs secreted by this channel or predicting kidney injury.

关键词： Transporter Biomarker kynurenic acid Renal tubular excretion

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Stability of serum kynurenine and kynurenic acid under different sttorage conditions

Stability of serum kynurenine and kynurenic acid under diffe...

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中华医学会第八次全国检验医学学术会议暨中华医学会检验分会成立30周年庆典大会

作者：唐爱国肖乐东罗昔波中南大学湘雅二医院检验科湖南省邵阳市第一人民医院检验科

Objective Kynurenine(KYN) and kynurenic acid(KYNA)are crucially involved in the pathogenesis of several neurologic disorders. This study investigates effects of the storage conditions on the stability of serum KYN and... 详细信息

关键词： HPLC Kynurenine kynurenic acid Serum Stability Tryptophan

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G protein-coupled receptor 35 attenuates nonalcoholic steatohepatitis by reprogramming cholesterol homeostasis in hepatocytes

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1128-1144页

作者： Xiaoli Wei Fan Yin Miaomiao Wu Qianqian Xie Xueqin Zhao Cheng Zhu Ruiqian Xie Chongqing Chen Menghua Liu Xueying Wang Ruixue Ren Guijie Kang Chenwen Zhu Jingjing Cong Hua Wang Xuefu Wang Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityHefei 230036China Department of Pharmacy Huainan First People's Hospitalthe First Affiliated Hospital of Anhui University of Science and TechnologyHuainan 232001China School of Pharmacy Anhui Medical UniversityHefei 230032China Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Medical UniversityHefei 230032China

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease *** accumulation“sensitizes”the liver to insult and leads to nonalcoholic steatohepatitis(NASH).G protein-coupled receptor 35(GPR35)is involved in metabolic stresses,but its role in NAFLD is *** report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol ***,we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose(HFCF)diet-induced steatohepatitis,whereas loss of GPR35 had the opposite *** of the GPR35 agonist kynurenic acid(Kyna)suppressed HFCF diet-induced steatohepatitis in ***/GPR35 induced expression of StAR-related lipid transfer protein 4(STARD4)through the ERK1/2 signaling pathway,ultimately resulting in hepatic cholesterol esterification and bile acid synthesis(BAS).The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1(CYP7A1)and CYP8B1,promoting the conversion of cholesterol to bile *** protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown ***4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in *** findings indicate that the GPR35–STARD4 axis is a promising therapeutic target for NAFLD.

关键词： G protein-coupled receptor 35 kynurenic acid Steatohepatitis Cholesterol Bile acid STARD4 ACAT2 CYP7A1

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Differences of Plasma Levels of Tryptophan, Serotonin, 5-Hydroxyindole Acetic acid, and Kynurenine between Healthy People and Patients of Major Monopolar Depression at Various Age and Gender

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Food and Nutrition Sciences 2020年第6期11卷 431-441页

作者： Hiroi Tomioka Junichi Masuda Akikazu Takada Akira Iwanami Department of Psychiatry School of Medicine Showa University Tokyo Japan Department of Psychiatry Showa University Northern Yokohama Hospital Yokohama Japan Global Application Development Center Shimadzu Corporation Tokyo Japan International Projects on Food and Health (NPO) Tokyo Japan

Background: It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of major monopolar depression (MMD). Methods: Ultra high-speed liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive patients. Results: There are no significant differences between plasma levels of TRP between HC and MMD. Plasma levels of TRP of HC are higher in young men, young women, old men, and old women in this order. Serotonin (5-HT) levels are higher in MMD than HC. Plasma levels of 5-HIAA of HC are also higher than those of patients of MMD. Plasma levels of kynurenine (KYN) of healthy old men and old women are higher than those of young men and old women. Plasma levels of KYN are higher in old women and young men of MMD than those of HC. Conclusion: Plasma levels of 5-HT are higher in patients of MMD than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation may increase plasma levels of 5-HT in MMD.

关键词： Depression Monopolar Depression Bipolar Depression Tryptophan Serotonin 5-Hydroxyindole Acetic acid Kynurenine 3-Hydroxykynurenine kynurenic acid Anthranilic acid Xanthurenic acid Indole-3-Acetic acid SSRI (Selective Serotonin Reuptake Inhibitor) SNRI (Serotonin Norepinephrine Reuptake Inhibitor)

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