Evidence map›Paper›PMID 40810171›Full record

ArticleACS pharmacology & translational science2025

Targeting α‑Klotho Protein by Agmatine and Pioglitazone Is a New Avenue against Diabetic Nephropathy.

Yasmena O Azar, Sherehan M Ibrahim, Hala F Zaki, Shimaa M Elshazly, Ghada A Badawi

Abstract read
In one paragraph

Article in ACS pharmacology & translational science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Current Controversies on Adequate Circulating Vitamin D Levels in CKD.International journal of molecular sciences · 2025
    Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Yasmena O AzarDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University, El-Arish 45511, Egypt.ORCID https://orcid.org/0000-0002-0591-1124
Sherehan M IbrahimDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.ORCID https://orcid.org/0000-0003-3495-3451
Hala F ZakiDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Shimaa M ElshazlyDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44549, Egypt.
Ghada A BadawiDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University, El-Arish 45511, Egypt.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM). Several mechanisms have been proposed for DN pathogenesis; however, it remains a progressive risk for DM patients. For the first time, the current study aimed to investigate the nephroprotective effects of agmatine and pioglitazone through modulating α-klotho, anti-ERS, anti-inflammatory, and antipyroptotic properties in ameliorating DN. A single intraperitoneal injection of streptozotocin (STZ) (52.5 mg/kg), preceded by nicotinamide (NA) (50 mg/kg, i.p.), induced DN. NA provided partial protection to insulin-secreting β-cells against the severe damage caused by STZ. Agmatine (100 mg/kg, i.p.) was injected daily for 6 weeks after modeling DN, either alone or in combination with pioglitazone (5 mg/kg, p.o.). DN rats showed a marked decrease in blood glucose (BG) levels, body weight, serum urea levels, serum creatinine (Cr) levels, and histopathological alterations, besides reducing renal α-klotho content associated with upregulating ATF4/IRE1α/NLRP3 renal content along with increasing HMGB1/NF-κB protein expression. On the contrary, agmatine and pioglitazone improved animals' body weights, BG, serum urea, and Cr levels. Moreover, agmatine and pioglitazone inhibited renal NLRP3 content, reducing oxidative stress and inflammatory cascades. They also upregulated renoprotective α-klotho and decreased renal ATF4/IRE1α/TXNIP/NLRP3 content associated with a decrease in renal HMGB1/NF-κB protein expression. Briefly, besides its antidiabetic effect, agmatine, along with pioglitazone, shows promise as a treatment for DM and DN via mediating α-klotho/ERS/HMGB1/NF-κB/NLRP3 inflammasome signaling pathways.

Indexed as

AgmatineDNERSNLRP3α-klotho

Identifiers

PMID40810171
PMCPMC12340625

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.