P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected]

PLoS One. 2014 Jun 18;9(6):e97452. doi: 10.1371/journal.pone.0097452. eCollection 2014.

Abstract

Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v.) and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L). By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3')-O-(4-benzoylbenzoyl) adenosine5'-triphosphate (specific agonist) and adenosine triphosphate (nonspecific agonist) (all p<0.05). All these alterations were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy) in DM groups. Lipoperoxidation was strongly correlated with P2X(7) receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7) receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Administration, Oral
  • Albuminuria / metabolism
  • Albuminuria / physiopathology
  • Albuminuria / prevention & control*
  • Animals
  • Antioxidants / pharmacology*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / prevention & control*
  • Exercise Therapy
  • Gene Expression
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / physiopathology
  • Lipid Peroxidation / drug effects
  • Male
  • Oxidative Stress
  • Physical Conditioning, Animal
  • Purinergic P2X Receptor Agonists / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Purinergic P2X7 / genetics*
  • Receptors, Purinergic P2X7 / metabolism
  • Streptozocin

Substances

  • Antioxidants
  • Purinergic P2X Receptor Agonists
  • Receptors, Purinergic P2X7
  • 3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
  • Streptozocin
  • Adenosine Triphosphate
  • Acetylcysteine

Grants and funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Apoio a Universidade Federal de São Paulo (FAP).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.