Inhibition of the P2X7 receptor improves renal function via renin-angiotensin system and nitric oxide on diabetic nephropathy in rats
| Autor: | Robson Serralha, Lilian Caroline Gonçalves de Oliveira, Moises Nascimento, António Moitinho Rodrigues, Margaret Gori Mouro, Deyse Lima, Dulce Elena Casarini, Giovana R. Punaro, E.M.S. Higa |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Diabetic nephropathy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Diabetes mellitus Renin–angiotensin system TBARS Medicine General Pharmacology Toxicology and Pharmaceutics Creatinine Kidney business.industry General Medicine Streptozotocin medicine.disease Drug vehicle 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry business medicine.drug |
| Zdroj: | Life Sciences. 251:117640 |
| ISSN: | 0024-3205 |
| Popis: | Aim To evaluate the effects of P2X7 receptor blockade on renin-angiotensin system (RAS) in rats with diabetic nephropathy (DN). Main methods Wistar rats were unilaterally nephrectomized and received streptozotocin for diabetes mellitus (DM) induction; control animals (CTL) received the drug vehicle. The animals were submitted to P2X7 receptor silencing, forming the group (DM + siRNA). The animals were placed in metabolic cages for data collection and evaluation of renal function; at the end of the protocol, the kidney was removed for analysis of P2X7, renin, angiotensin-converting enzyme (ACE), ACE2, angiotensin, thiobarbituric acid reactive substance levels (TBARS), nitric oxide (NO) and qualitative histological. Key findings The metabolic profile was attenuated in DM + siRNA vs. DM and there was a significant improvement in creatinine, urea and proteinuria levels in the same group. Renin expression was significantly decreased in DM + siRNA vs. DM. ACE and ACE2 were significantly reduced in DM + siRNA vs. DM. TBARS levels were decreased and NO showed an increase in DM + siRNA vs. DM, both significant. All histological alterations were improved in DM + siRNA vs. DM. Significance Data have shown that although silencing of the P2X7 receptor did not decrease fasting glucose, it promoted an improvement in the metabolic profile and a significant recovery of renal function, revealing a protective action by the inhibition of this receptor. This effect must have occurred due to the inhibition of RAS and the increase of NO, suggesting that the use of P2X7 receptors inhibitors could be used as adjuvant therapy against DN progression. |
| Databáze: | OpenAIRE |
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