PMID- 31745068
OWN - NLM
STAT- MEDLINE
DCOM- 20200420
LR  - 20211204
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 25
DP  - 2019 Nov 20
TI  - Zafirlukast, a Cysteinyl Leukotriene Receptor 1 Antagonist, Reduces the Effect of 
      Advanced Glycation End-Products in Rat Renal Mesangial Cells In Vitro.
PG  - 8753-8763
LID - 10.12659/MSM.918187 [doi]
AB  - BACKGROUND Zafirlukast is an antagonist of cysteinyl leukotriene receptor 1 
      (CysLTR1). Advanced glycation end-products (AGEs) are formed by the glycation of 
      lipids and proteins in hyperglycemia, including diabetes mellitus. Zafirlukast 
      has not previously been studied in diabetic nephropathy. This study aimed to 
      investigate the effects of zafirlukast on rat renal mesangial cells cultured with 
      AGEs in vitro. MATERIAL AND METHODS Mesangial cells were cultured in AGEs (0, 20, 
      50, 100 mug/ml), and with AGEs (100 mug/ml) and zafirlukast (2.5 mum, 5 mum, and 100 
      mum). An enzyme-linked immunoassay (ELISA) was used to measure the levels of tumor 
      necrosis factor-alpha (TNF-alpha), interleukin-1ss (IL-1ss), IL-6, and monocyte 
      chemoattractant protein-1 (MCP-1). Reactive oxygen species (ROS) were assessed by 
      intracellular fluorescence measurement of 2'-7'-dichlorodihydrofluorescein 
      diacetate (DCFH-DA), and detection kits were used to measure malondialdehyde 
      (MDA), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), and 
      superoxide dismutase (SOD). Cell apoptosis was assessed by flow cytometry, and 
      Western blot was used to measure protein levels. RESULTS In mesangial cells 
      cultured with AGEs, markers of inflammation, oxidative stress, and apoptosis and 
      levels of CysLTR1 increased, and these effects were reduced by zafirlukast in a 
      dose-dependent manner. The effects of zafirlukast as a CysLTR1 antagonist 
      protected mesangial cells from the effects of AGE in vitro. CONCLUSIONS 
      Zafirlukast, a CysLTR1 antagonist, reduced the levels of inflammatory cytokines, 
      markers of oxidative stress, and cell apoptosis induced by AGE in mesangial cells 
      in a dose-dependent way. Future in vivo studies are needed to investigate the 
      potential role for zafirlukast in models of diabetic nephropathy.
FAU - Yan, Liping
AU  - Yan L
AD  - Administration Division, Weifang People's Hospital, Weifang, Shandong, China 
      (mainland).
FAU - Sun, Ani
AU  - Sun A
AD  - Infection Control Office, Weifang People's Hospital, Weifang, Shandong, China 
      (mainland).
FAU - Xu, Xinwei
AU  - Xu X
AD  - Nephrology Department, Weifang People's Hospital, Weifang, Shandong, China 
      (mainland).
LA  - eng
PT  - Journal Article
DEP - 20191120
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Indoles)
RN  - 0 (Phenylcarbamates)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Leukotriene)
RN  - 0 (Sulfonamides)
RN  - 0 (Tosyl Compounds)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - LRF7RW46ID (leukotriene D4 receptor)
RN  - XZ629S5L50 (zafirlukast)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Experimental/metabolism
MH  - Diabetic Nephropathies/metabolism
MH  - Glutathione Peroxidase/metabolism
MH  - Glycation End Products, Advanced/*drug effects/metabolism
MH  - Indoles
MH  - Inflammation/pathology
MH  - Malondialdehyde/metabolism
MH  - Mesangial Cells/drug effects
MH  - Oxidative Stress/*drug effects
MH  - Phenylcarbamates
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Leukotriene/metabolism
MH  - Sulfonamides
MH  - Superoxide Dismutase/metabolism
MH  - Tosyl Compounds/metabolism/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC6880630
COIS- Conflict of interest None.
EDAT- 2019/11/21 06:00
MHDA- 2020/04/21 06:00
PMCR- 2019/11/20
CRDT- 2019/11/21 06:00
PHST- 2019/11/21 06:00 [entrez]
PHST- 2019/11/21 06:00 [pubmed]
PHST- 2020/04/21 06:00 [medline]
PHST- 2019/11/20 00:00 [pmc-release]
AID - 918187 [pii]
AID - 10.12659/MSM.918187 [doi]
PST - epublish
SO  - Med Sci Monit. 2019 Nov 20;25:8753-8763. doi: 10.12659/MSM.918187.