Evidence map›Paper›PMID 26894882›Full record

ArticleKidney & blood pressure research2016

Protective Effect of Tempol on Acute Kidney Injury Through PI3K/Akt/Nrf2 Signaling Pathway.

Gensheng Zhang, Qiaoling Wang, Qin Zhou, Renjun Wang, Minze Xu, Huiping Wang, Lei Wang, Christopher S Wilcox, Ruisheng Liu, En Yin Lai

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Kidney & blood pressure research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.

  1. Pooled it
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  16. All-Oncology letters · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 3 countries.

Gensheng ZhangDepartment of Physiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Qiaoling Wang
Qin Zhou
Renjun Wang
Minze Xu
Huiping Wang
Lei Wang
Christopher S Wilcox
Ruisheng Liu
En Yin Lai
Czech Academy of Sciences, Institute of Physiology · CZFirst Affiliated Hospital Zhejiang University · CNFlorida College · USGeorgetown University · USJilin Normal University · CNUniversity of South Florida · US

Funding

Renal Vascular Oxidative Stress in HypertensionP01HL068686 · NHLBI · GEORGETOWN UNIVERSITY · PI JOSE, PEDRO A., SANDBERG, KATHRYN L · 2001 to 2017
$28.8M
REGULATION OF RENAL FUNCTION AND BP BY THROMBOXANER37DK036079 · NIDDK · GEORGETOWN UNIVERSITY · PI WILCOX, CHRISTOPHER S · 2003 to 2012
$5.2M
NITRIC OXIDE SYNTHASE IN THE JUXTAGLOMERULAR APPARATUSR01DK049870 · NIDDK · GEORGETOWN UNIVERSITY · PI WILCOX, CHRISTOPHER S · 1994 to 2014
$4.6M
Regulation of Renal Function and BP by ThromboxaneR01DK109272 · NIDDK · GEORGETOWN UNIVERSITY · PI WELCH, WILLIAM J, WILCOX, CHRISTOPHER S · 2016 to 2019
$1.4M
Tubuloglomerular feedback and salt-sensitive hypertensionR01DK098582 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI LIU, RUISHENG · 2013 to 2016
$1.3M
Primary cilia and modulation of the renal microcirculationR01DK099276 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI LIU, RUISHENG · 2014 to 2017
$980k
REGULATION OF RENAL FUNCTION AND BP BY THROMBOXANER01DK036079 · NIDDK · UNIVERSITY OF FLORIDA · PI WILCOX, CHRISTOPHER S · 1986 to 2002
$830k
NHLBI NIH HHS HL-68686NHLBI NIH HHS P01 HL068686NIDDK NIH HHS DK098582NIDDK NIH HHS DK099276NIDDK NIH HHS R01 DK036079NIDDK NIH HHS R01 DK049870NIDDK NIH HHS R01 DK098582NIDDK NIH HHS R01 DK099276NIDDK NIH HHS R01 DK109272NIDDK NIH HHS R37 DK036079
6 · The paper itself

Abstract

BACKGROUND/

aimsTempol is a protective antioxidant against ischemic injury in many animal models. The molecular mechanisms are not well understood. Nuclear factor erythroid 2-related factor (Nrf2) is a master transcription factor during oxidative stress, which is enhanced by activation of protein kinase C (PKC) pathway. Another factor, tubular epithelial apoptosis, is mediated by activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, Akt) signaling pathway during renal ischemic injury. We tested the hypothesis that tempol activates PKC or PI3K/Akt/Nrf2 pathways to transcribe many genes that coordinate endogenous antioxidant defense.

methodsThe right renal pedicle was clamped for 45 minutes and the left kidney was removed to study renal ischemia/reperfusion (I/R) injury in C57BL/6 mice. The response was assessed from serum parameters, renal morphology and renal expression of PKC, phosphorylated-PKC (p-PKC), Nrf2, heme oxygenase-1 (HO-1), Akt, phosphorylated-Akt (p-Akt), pro-caspase-3 and cleaved caspase-3 in groups of sham and I/R mice given vehicle, or tempol (50 or 100 mg/kg, intraperitoneal injection).

resultsThe serum malondialdehyde (MDA, marker of reactive oxygen species) doubled and the BUN and creatinine increased 5- to 10-fold after I/R injury. Tempol (50 or 100 mg/kg) prevented the increases in MDA but only tempol (50 mg/kg) lessened the increases in BUN and creatinine and moderated the acute tubular necrosis. I/R did not change expression of PKC or p-PKC but reduced renal expression of Nrf2, p-Akt, HO-1 and pro-caspase-3 and increased cleaved caspase-3. Tempol (50 mg/kg) prevented these changes produced by I/R whereas tempol (100 mg/kg) had lesser or inconsistent effects.

conclusionTempol (50 mg/kg) prevents lipid peroxidation and attenuates renal damage after I/R injury. The beneficial pathway apparently is not dependent on upregulation or phosphorylation of PKC, at lower tempol doses, does implicate upregulation of Akt with expression of Nrf2 that could account for the increase in the antioxidant gene HO-1 and a reduction in the cleavage of the cellular damage marker pro-caspase-3.

Indexed as

Acute Kidney InjuryAnimalsAntioxidantsCyclic N-OxidesDose-Response Relationship, DrugLipid PeroxidationMaleMiceMice, Inbred C57BLNF-E2-Related Factor 2Oxidative StressPhosphatidylinositol 3-KinaseProto-Oncogene Proteins c-aktSignal TransductionSpin LabelsTreatment OutcomeAntioxidantsCyclic N-OxidesNfe2l2 protein, mouseNF-E2-Related Factor 2Phosphatidylinositol 3-KinaseProto-Oncogene Proteins c-aktSpin Labelstempol

Identifiers

PMID26894882
PMCPMC4841277
OpenAlexW2278487979

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.