Limits...
The effects of A2B receptor modulators on vascular endothelial growth factor and nitric oxide axis in chronic cyclosporine nephropathy.

Patel L, Thaker A - J Pharmacol Pharmacother (2015 Jul-Sep)

Bottom Line: The analysis of mRNA expression of A2B receptor and VEGF was performed.The effects of A2B AR modulators were prominent in CsA-treated animals compared with control animals suggesting CsA treatment may upregulate A2B ARs.The mRNA expression of A2B AR was increased after 5 weeks of CsA.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Anand, Gujarat, India.

ABSTRACT

Introduction: To investigate the actions of adenosine A2B receptor modulators on VEGF and NO levels in CsA nephropathy.

Materials and methods: Nephropathy was induced by administrating 25 mg/kg (s.c) of CsA for 5 weeks. The VEGF and NO levels were measured in kidney tissue. Serum creatinine, creatinine clearance, urinary albumin excretion, blood urea nitrogen, kidney pathology score were measured to assess renal function. The analysis of mRNA expression of A2B receptor and VEGF was performed.

Results: Administration of CsA for 5 weeks induced adverse renal function. The mRNA expression of VEGF was reduced in renal tissue after 5 weeks of CsA treatment. The renal VEGF and NO levels were also reduced in these animals. In vivo administration of A2B adenosine receptor agonist increased renal VEGF which was inhibited by a selective A2B AR antagonist (MRS1754) in CsA-treated animals. The increase in VEGF was associated with reversal of adverse renal functions. The effects of A2B AR modulators were prominent in CsA-treated animals compared with control animals suggesting CsA treatment may upregulate A2B ARs. The mRNA expression of A2B AR was increased after 5 weeks of CsA.

Conclusions: A2B AR modulators may provide new therapeutic options to retard CsA nephropathy by mediating renal VEGF and NO.

No MeSH data available.


Related in: MedlinePlus

Effect of adenosine receptor modulators on (a) serum creatinine, (b) creatinine clearance, (c) BUN and (d) UAE in control and CsA-treated animals. Data are means (±sem) *P < 0.05 vs. control group, #P < 0.05 vs. CsA group, **P < 0.05 vs. CsA + NECA group, n = 6
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4544136&req=5

Figure 1: Effect of adenosine receptor modulators on (a) serum creatinine, (b) creatinine clearance, (c) BUN and (d) UAE in control and CsA-treated animals. Data are means (±sem) *P < 0.05 vs. control group, #P < 0.05 vs. CsA group, **P < 0.05 vs. CsA + NECA group, n = 6

Mentions: The administration of CsA for 5 weeks adversely affected renal function parameters. Serum creatinine [Figure 1a] was increased and creatinine clearance [Figure 1b] was reduced after 5 weeks of CsA treatment. Similarly, BUN [Figure 1c] and UAE [Figure 1d] were increased in CsA-treated animals compared with control animals. Urine albumin levels in control animals were below the detection limit of the method employed for analysis. The treatment with NECA recovered BUN, serum creatinine, creatinine clearance and UAE in CsA-treated mice. MRS1754 inhibited the effects of NECA on renal function parameters, but interestingly it did not completely inhibit the action of NECA on serum creatinine clearance. Moreover, no change in renal functions was found in control animals after 2 weeks of treatment with A2B receptor modulators, NECA and MRS1754.


The effects of A2B receptor modulators on vascular endothelial growth factor and nitric oxide axis in chronic cyclosporine nephropathy.

Patel L, Thaker A - J Pharmacol Pharmacother (2015 Jul-Sep)

Effect of adenosine receptor modulators on (a) serum creatinine, (b) creatinine clearance, (c) BUN and (d) UAE in control and CsA-treated animals. Data are means (±sem) *P < 0.05 vs. control group, #P < 0.05 vs. CsA group, **P < 0.05 vs. CsA + NECA group, n = 6
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4544136&req=5

Figure 1: Effect of adenosine receptor modulators on (a) serum creatinine, (b) creatinine clearance, (c) BUN and (d) UAE in control and CsA-treated animals. Data are means (±sem) *P < 0.05 vs. control group, #P < 0.05 vs. CsA group, **P < 0.05 vs. CsA + NECA group, n = 6
Mentions: The administration of CsA for 5 weeks adversely affected renal function parameters. Serum creatinine [Figure 1a] was increased and creatinine clearance [Figure 1b] was reduced after 5 weeks of CsA treatment. Similarly, BUN [Figure 1c] and UAE [Figure 1d] were increased in CsA-treated animals compared with control animals. Urine albumin levels in control animals were below the detection limit of the method employed for analysis. The treatment with NECA recovered BUN, serum creatinine, creatinine clearance and UAE in CsA-treated mice. MRS1754 inhibited the effects of NECA on renal function parameters, but interestingly it did not completely inhibit the action of NECA on serum creatinine clearance. Moreover, no change in renal functions was found in control animals after 2 weeks of treatment with A2B receptor modulators, NECA and MRS1754.

Bottom Line: The analysis of mRNA expression of A2B receptor and VEGF was performed.The effects of A2B AR modulators were prominent in CsA-treated animals compared with control animals suggesting CsA treatment may upregulate A2B ARs.The mRNA expression of A2B AR was increased after 5 weeks of CsA.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Anand, Gujarat, India.

ABSTRACT

Introduction: To investigate the actions of adenosine A2B receptor modulators on VEGF and NO levels in CsA nephropathy.

Materials and methods: Nephropathy was induced by administrating 25 mg/kg (s.c) of CsA for 5 weeks. The VEGF and NO levels were measured in kidney tissue. Serum creatinine, creatinine clearance, urinary albumin excretion, blood urea nitrogen, kidney pathology score were measured to assess renal function. The analysis of mRNA expression of A2B receptor and VEGF was performed.

Results: Administration of CsA for 5 weeks induced adverse renal function. The mRNA expression of VEGF was reduced in renal tissue after 5 weeks of CsA treatment. The renal VEGF and NO levels were also reduced in these animals. In vivo administration of A2B adenosine receptor agonist increased renal VEGF which was inhibited by a selective A2B AR antagonist (MRS1754) in CsA-treated animals. The increase in VEGF was associated with reversal of adverse renal functions. The effects of A2B AR modulators were prominent in CsA-treated animals compared with control animals suggesting CsA treatment may upregulate A2B ARs. The mRNA expression of A2B AR was increased after 5 weeks of CsA.

Conclusions: A2B AR modulators may provide new therapeutic options to retard CsA nephropathy by mediating renal VEGF and NO.

No MeSH data available.


Related in: MedlinePlus