Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration

Autor: Agnieszka Gęgotek, Marek Toczek, Katarzyna Bielawska, Elżbieta Skrzydlewska, Ewa Ambrożewicz, Michał Biernacki
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
CB2
cannabinoid receptor type 2
Cannabinoid receptor
Hypertension
Renal
GSH
reduced glutathione
Clinical Biochemistry
DHA
docosahexaenoic acid
Blood Pressure
AA
arachidonic acid
8-OHdG
8-hydroxy-2’-deoxyguanosine
HO-1
heme oxygenase 1
Pharmacology
Kidney
Biochemistry
Receptor
Cannabinoid
CB2
COX1
cyclooxygenase 1
NADA
N-arachidonoyl dopamine
chemistry.chemical_compound
p-cJun
phosphorylated Jun proto-oncogene
URB597
[3-(3-carbamoylphenyl)phenyl] N-cyclohexylcarbamate
Redox balance
Receptor
Cannabinoid
CB1
Fatty acid amide hydrolase
MAGL
monoacylglycerol lipase
Rats
Inbred SHR
CB1
cannabinoid receptor type 1
CO
carbonyl groups
TNF-α
tumor necrosis factor alpha
FAAH
fatty acid amide hydrolase
lcsh:QH301-705.5
Phospholipids
LOX
lipoxygenase
TRPV1
vanilloid receptor 1
lcsh:R5-920
Anandamide
Bach1
basic leucine zipper transcription factor 1
Endocannabinoid system
NOX
NADPH oxidase
Keap1
Kelch-like ECH-associated protein 1
medicine.anatomical_structure
AM3506
5-(4-hydroxyphenyl) pentanesulfonyl fluoride
Benzamides
AEA
N-arachidonoylethanolamine
anandamide
Hypertension
Nrf2
nuclear factor erythroid 2
lipids (amino acids
peptides
and proteins)
lcsh:Medicine (General)
Oxidation-Reduction
DOCA
deoxycorticosterone acetate
Research Paper
COX-2
cyclooxygenase 2
8-isoPGF2α
F2 -isoprostanes
GSH-Px
glutathione peroxidase
SHR
spontaneously hypertensive rats
p21
cyclin-dependent kinase inhibitor 1
Amidohydrolases
03 medical and health sciences
ROS
reactive oxygen species
2-AG
2-arachidonoylglycerol
4-HNE
4-hydroxynonenal
medicine
Animals
Humans
cPLA2
cytosolic phospholipase A2
MDA
malondialdehyde
XO
xanthine oxidase
KAP1
KRAB-associated protein-1
NPs-A4/J4
A4/J4-neuroprostanes
SBP
systolic blood pressure
Organic Chemistry
Kidney metabolism
URB597
p62
nucleoporin p62
Cu/Zn–SOD
superoxide dismutase
Rats
030104 developmental biology
chemistry
lcsh:Biology (General)
WKY
Wistar Kyoto rats
GSSG-R
glutathione reductase
Kidney disorder
Carbamates
CAT
catalase
Reactive Oxygen Species
MAPK
mitogen-activated protein kinase
Zdroj: Redox Biology, Vol 15, Iss C, Pp 41-50 (2018)
Redox Biology
ISSN: 2213-2317
Popis: Primary and secondary hypertension is associated with kidney redox imbalance resulting in enhanced reactive oxygen species (ROS) and enzymes dependent phospholipid metabolism. The fatty acid amide hydrolase inhibitor, URB597, modulates the levels of endocannabinoids, particularly of anandamide, which is responsible for controlling blood pressure and regulating redox balance. Therefore, this study aimed to compare the effects of chronic URB597 administration to spontaneously hypertensive rats (SHR) and rats with secondary hypertension (DOCA-salt rats) on the kidney metabolism associated with the redox and endocannabinoid systems. It was shown fatty acid amide hydrolase (FAAH) inhibitor decreased the activity of ROS-generated enzymes what resulted in a reduction of ROS level. Moreover varied changes in antioxidant parameters were observed with tendency to improve antioxidant defense in SHR kidney. Moreover, URB597 administration to hypertensive rats decreased pro-inflammatory response, particularly in the kidneys of DOCA-salt hypertensive rats. URB597 had tendency to enhance ROS-dependent phospholipid oxidation, estimated by changes in neuroprostanes in the kidney of SHR and reactive aldehydes (4-hydroxynonenal and malondialdehyde) in DOCA-salt rats, in particular. The administration of FAAH inhibitor resulted in increased level of endocannabinoids in kidney of both groups of hypertensive rats led to enhanced expression of the cannabinoid receptors type 1 and 2 in SHR as well as vanilloid receptor 1 receptors in DOCA-salt rats. URB597 given to normotensive rats also affected kidney oxidative metabolism, resulting in enhanced level of neuroprostanes in Wistar Kyoto rats and reactive aldehydes in Wistar rats. Moreover, the level of endocannabinoids and cannabinoid receptors were significantly higher in both control groups of rats after URB597 administration. In conclusion, because URB597 disturbed the kidney redox system and phospholipid ROS-dependent and enzymatic-dependent metabolism, the administration of this inhibitor may enhance kidney disorders depending on model of hypertension, but may also cause kidney disturbances in control rats. Therefore, further studies are warranted.
Graphical abstract fx1
Highlights • URB597 has tendency to decrease kidney oxidative conditions. • URB597 differentiates Nrf2 pathway response in kidney of SHR and DOCA-salt rats. • URB597 enhances level of phospholipid peroxidation products and endocannabinoids. • URB597 reduces pro-inflammatory response particularly in kidney of DOCA-salt rats.
Databáze: OpenAIRE
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