Inhibition of the P2X7 receptor improves renal function via renin-angiotensin system and nitric oxide on diabetic nephropathy in rats
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Aim To evaluate the effects of P2X 7 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 P2X 7 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 P2X 7, 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 P2X 7 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 P2X 7 receptors inhibitors could be used as adjuvant therapy against DN progression.
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In rats with diabetic nephropathy, P2X7 receptor expression decreased ACE activity and Ang II levels, which might increase ACE2 expression and counteract SARS-CoV-2-induced inflammatory exacerbation.
“Furthermore, in rats with diabetic nephropathy, P2X7 receptor expression decreased ACE activity and Ang II levels [120], which might increase ACE2 expression [43] and counteract SARS-CoV-2-induced inflammatory exacerbation.”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [120]
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- Authors
- Nascimento, M., Punaro, G. R., Serralha, R. S., Lima, D. Y., Mouro, M. G., Oliveira, L. C. G., Casarini, D. E., Rodrigues, A. M., & Higa, E. M. S.
- Affiliations
- Universidade Federal de São Paulo (BR)
- Corresponding author
- Punaro, G.R.
- ORCID
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 251
- Pages
- 117640
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W3014156744
- Cited by
- 12
- References
- 53
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 314 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Keywords
- P2X7 receptor, diabetic nephropathy, renin-angiotensin system, nitric oxide, siRNA knockdown, angiotensin-converting enzyme, ACE2, oxidative stress, proteinuria, renal function, streptozotocin-induced diabetes, adjuvant therapy
- MeSH terms
- Animals, Diabetes Mellitus, Experimental, Diabetic Nephropathies, Male, Nitric Oxide, Renin-Angiotensin System, Streptozocin, Rats, Wistar, Gene Silencing, RNA, Small Interfering, Rats, Receptors, Purinergic P2X7
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