Evidence mapPaperPMID 37235213Full record

ArticleToxics2023

Platelet Rich Plasma and Adipose-Derived Mesenchymal Stem Cells Mitigate Methotrexate-Induced Nephrotoxicity in Rat via Nrf2/Pparγ/HO-1 and NF-Κb/Keap1/Caspase-3 Signaling Pathways: Oxidative Stress and Apoptosis Interplay.

Farooq A Wani, Mahrous A Ibrahim, Shimaa H Ameen, Amira E Farage, Zinab Abd-Elhady Ali, Khaldoon Saleh, Medhat M Farag, Mohammed U Sayeed, Muhannad A Y Alruwaili, Abdulsalam H F Alruwaili and 2 more

Open access · goldAbstract read
In one paragraph

Article in Toxics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
5.8field-weighted citation impact, top 4% of its field
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

14 citing papers in PubMed, 20 citations in OpenAlex.

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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

12 authors at 6 institutions in 2 countries.

Farooq A WaniPathology Department, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia.ORCID 0000-0002-8614-3293
Mahrous A IbrahimForensic Medicine and Clinical Toxicology, College of Medicine, Jouf University, Sakaka 41412, Saudi Arabia.
Shimaa H AmeenForensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Zagazig University, Alsharqia 44519, Egypt.
Amira E FarageDepartment of Anatomy, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
Zinab Abd-Elhady AliVice Deanship for Academic Affairs, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
Khaldoon SalehVice Deanship for Academic Affairs, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.ORCID 0000-0002-6736-6379
Medhat M FaragMedical Biochemistry Department, College of Medicine, Shaqra University, Shaqra 11961, Saudi Arabia.
Mohammed U SayeedPathology Department, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia.
Muhannad A Y AlruwailiCollege of Medicine, Jouf University, Sakaka 72388, Saudi Arabia.
Abdulsalam H F AlruwailiCollege of Medicine, Jouf University, Sakaka 72388, Saudi Arabia.
Ahmad Z A AljaredCollege of Medicine, Jouf University, Sakaka 72388, Saudi Arabia.
Rania A GalhomHuman Anatomy and Embryology Department, Faculty of Medicine, Suez Canal University (SCU), Ismailia 41522, Egypt.
Jouf University · SAImam Abdulrahman Bin Faisal University · SASuez Canal University · EGKafrelsheikh University · EGShaqra University · SAZagazig University · EG

Funding

Al Jouf University DSR-2021-01-03138
6 · The paper itself

Abstract

backgroundthe nephrotoxicity of methotrexate (MTX) is observed in high-dose therapy. Moreover, low-dose MTX therapy for rheumatic diseases is debatable and claimed to cause renal impairment. This study aimed at studying the effect of methotrexate in repeated low doses on rat kidneys and assessing the efficacy of adipose-derived mesenchymal stem cells (AD-MSCs) and platelet rich plasma (PRP) for attenuating this effect.

methodsForty-two male Wistar rats were used, 10 rats were donors of AD-MSCs and PRP, 8 rats served as control, and the remaining rats were subjected to induction of nephrotoxicity by MTX intraperitoneal injection once weekly for successive 8 weeks and then assigned into 3 groups of 8 animals each: Group II: received MTX only. Group III: received MTX + PRP. Group IV: received MTX + AD-MSCs. After one month, rats were anaesthetized, serum-sampled, and renal tissue removed for biochemical, histological, and ultrastructural evaluation.

resultsthere was significant tubular degeneration, glomerulosclerosis, fibrosis, decreased renal index, along with increased levels of urea and creatinine in the MTX group compared to the control group. Immunohistochemical expression of caspase-3 and iNOS in the renal tissue was significantly increased in group II compared to groups III and IV. Biochemical results revealed higher tissue malondialdehyde (MDA) concentration in the MTX-injected group which decreased significantly in co-treatment with either AD-MSC or PRP + MTX. MSC promoted the activation of the Nrf2/PPARγ/HO-1 and NF-κB/Keap1/caspase-3 pathways, increased antioxidant enzyme activities, reduced lipid peroxidation levels, and alleviated oxidative damage and apoptosis. PRP showed therapeutic effects and molecular mechanisms similar to MSC. Furthermore, MSC and PRP treatment significantly reduced MTX-induced upregulation of the pro-inflammatory (NF-κB, interleukin-1ß, and TNF-α), oxidative stress (Nrf-2, hemoxygenase-1, glutathione, and malondialdehyde), and nitrosative stress (iNOS) markers in the kidney.

conclusionrepeated administration of low-dose MTX resulted in massive renal tissue toxicity and deterioration of renal function in rats which proved to be attenuated by PRP and AD-MSCs through their anti-inflammatory, anti-apoptotic and anti-fibrotic properties.

Indexed as

apoptosiscaspase-3methotrexateMSCsnephrotoxicityoxidative stressPCR

Identifiers

PMID37235213
PMCPMC10223329
OpenAlexW4366827021

What Socratic holds

Textmetadata
LicenceCC BY
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.