Suramin enhances the urinary excretion of VEGF-A in normoglycemic and streptozotocin-induced diabetic rats.
Animals
Blood Glucose
/ drug effects
Diabetes Mellitus, Experimental
/ chemically induced
Diabetic Nephropathies
/ metabolism
Kidney
/ drug effects
Male
Matrix Metalloproteinase 9
/ metabolism
Rats
Rats, Wistar
Streptozocin
/ pharmacology
Suramin
/ pharmacology
Vascular Endothelial Growth Factor A
/ urine
Diabetes
Glomerulus
Kidney
P2-receptors
Streptozotocin
Vascular endothelial growth factor A
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
21
12
2020
accepted:
13
02
2021
revised:
11
02
2021
pubmed:
27
2
2021
medline:
15
12
2021
entrez:
26
2
2021
Statut:
ppublish
Résumé
Vascular endothelial growth factor A (VEGF-A) and P2-receptors (P2Rs) are involved in the pathogenesis of diabetic nephropathy. The processing of VEGF-A by matrix metalloproteinases (MMP) regulates its bioavailability. Since the ATP-induced release of MMP-9 is mediated by P2Rs, we investigated the effect of suramin on VEGF-A excretion in urine and the urinary activity of total MMP and MMP-9. The effect of suramin (10 mg/kg, ip) on VEGF-A concentration in serum and its excretion in urine was investigated in streptozotocin (STZ)-induced diabetic rats over a 21-day period. The rats received suramin 7 and 14 days after a single STZ injection (65 mg/kg, ip). A 24-h collection of urine was performed on the day preceding the administration of STZ and the first administration of suramin and on the day before the end of the experiment. The VEGF-A in serum and urine, albumin in urine, and total activity of MMP and MMP-9 in urine were measured using immunoassays. Diabetic rats are characterized by a sixfold higher urinary excretion of VEGF-A. Suramin potentiates VEGF-A urinary excretion by 36% (p = 0.046) in non-diabetic and by 75% (p = 0.0322) in diabetic rats but it did not affect VEGF-A concentration in the serum of non-diabetic and diabetic rats. Urinary albumin excretion as well as total MMP and MMP-9 activity was increased in diabetic rats, but these parameters were not affected by suramin. Suramin increases the urinary excretion of VEGF-A in normoglycemia and hyperglycaemia, possibly without the involvement of MMP-9. Suramin may be used as a pharmacological tool enhancing VEGF-A urinary secretion.
Sections du résumé
BACKGROUND
BACKGROUND
Vascular endothelial growth factor A (VEGF-A) and P2-receptors (P2Rs) are involved in the pathogenesis of diabetic nephropathy. The processing of VEGF-A by matrix metalloproteinases (MMP) regulates its bioavailability. Since the ATP-induced release of MMP-9 is mediated by P2Rs, we investigated the effect of suramin on VEGF-A excretion in urine and the urinary activity of total MMP and MMP-9.
METHODS
METHODS
The effect of suramin (10 mg/kg, ip) on VEGF-A concentration in serum and its excretion in urine was investigated in streptozotocin (STZ)-induced diabetic rats over a 21-day period. The rats received suramin 7 and 14 days after a single STZ injection (65 mg/kg, ip). A 24-h collection of urine was performed on the day preceding the administration of STZ and the first administration of suramin and on the day before the end of the experiment. The VEGF-A in serum and urine, albumin in urine, and total activity of MMP and MMP-9 in urine were measured using immunoassays.
RESULTS
RESULTS
Diabetic rats are characterized by a sixfold higher urinary excretion of VEGF-A. Suramin potentiates VEGF-A urinary excretion by 36% (p = 0.046) in non-diabetic and by 75% (p = 0.0322) in diabetic rats but it did not affect VEGF-A concentration in the serum of non-diabetic and diabetic rats. Urinary albumin excretion as well as total MMP and MMP-9 activity was increased in diabetic rats, but these parameters were not affected by suramin.
CONCLUSION
CONCLUSIONS
Suramin increases the urinary excretion of VEGF-A in normoglycemia and hyperglycaemia, possibly without the involvement of MMP-9. Suramin may be used as a pharmacological tool enhancing VEGF-A urinary secretion.
Identifiants
pubmed: 33635529
doi: 10.1007/s43440-021-00236-0
pii: 10.1007/s43440-021-00236-0
pmc: PMC8180480
doi:
Substances chimiques
Blood Glucose
0
Vascular Endothelial Growth Factor A
0
vascular endothelial growth factor A, rat
0
Streptozocin
5W494URQ81
Suramin
6032D45BEM
Matrix Metalloproteinase 9
EC 3.4.24.35
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
841-846Subventions
Organisme : Narodowym Centrum Nauki
ID : 2016/23/B/NZ5/02632
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