title: P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].
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.
authors.affiliation: Department of Medicine, Nephrology Division, UNIFESP, Sao Paulo, Brazil.
authors.forename: Adelson M
authors.initials: AM
authors.lastname: Rodrigues
authors.affiliation: Department of Physiology, Cardiovascular Division, UNIFESP, Sao Paulo, Brazil.
authors.forename: Cassia T
authors.initials: CT
authors.lastname: Bergamaschi
authors.affiliation: Department of Neurology/Neurosurgery, UNIFESP, Sao Paulo, Brazil.
authors.forename: Maria Jose S
authors.initials: MJ
authors.lastname: Fernandes
authors.affiliation: Department of Biochemistry, UNIFESP, Sao Paulo, Brazil.
authors.forename: Edgar J
authors.initials: EJ
authors.lastname: Paredes-Gamero
authors.affiliation: Department of Biochemistry, UNIFESP, Sao Paulo, Brazil.
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Buri
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Curi
authors.affiliation: Department of Biophysics, Molecular Biology Division, UNIFESP, Sao Paulo, Brazil.
authors.forename: Alice T
authors.initials: AT
authors.lastname: Ferreira
authors.affiliation: Department of Pathology, Investigative Pathology Division, UNIFESP, Sao Paulo, Brazil.
authors.forename: Sergio R R
authors.initials: SR
authors.lastname: Araujo
authors.affiliation: Department of Medicine, Nephrology Division, UNIFESP, Sao Paulo, Brazil.
authors.forename: Giovana R
authors.initials: GR
authors.lastname: Punaro
authors.affiliation: Department of Medicine, Nephrology Division, UNIFESP, Sao Paulo, Brazil.
authors.forename: Fabiane R
authors.initials: FR
authors.lastname: Maciel
authors.affiliation: Department of Medicine, Nephrology Division, UNIFESP, Sao Paulo, Brazil.
authors.forename: Guilherme B
authors.initials: GB
authors.lastname: Nogueira
authors.affiliation: Department of Medicine, Nephrology Division, UNIFESP, Sao Paulo, Brazil; Department of Medicine, Emergency Division, UNIFESP, Sao Paulo, Brazil.
authors.forename: Elisa M S
authors.initials: EM
authors.lastname: Higa
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000284:Administration, Oral; D000419:Albuminuria / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D005081:Exercise Therapy; D015870:Gene Expression; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058486:Receptors, Purinergic P2X7 / Q000235:genetics* / Q000378:metabolism; D013311:Streptozocin
chemical_list: D000975:Antioxidants; D058911:Purinergic P2X Receptor Agonists; D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D013311:Streptozocin; D000255:Adenosine Triphosphate; D000111:Acetylcysteine