Evidence map›Paper›PMID 24400007›Full record

ArticleFrontiers in immunology2013

l-Citrulline Protects from Kidney Damage in Type 1 Diabetic Mice.

Maritza J Romero, Lin Yao, Supriya Sridhar, Anil Bhatta, Huijuan Dou, Ganesan Ramesh, Michael W Brands, David M Pollock, Ruth B Caldwell, Stephen D Cederbaum and 4 more

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

Article in Frontiers in immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

28 citing papers in PubMed, 48 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Review
  5. Diabetic nephropathy: Role of nitric oxide.Nitric oxide : biology and chemistry · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. The intervention effect ofFrontiers in pharmacology · 2022
    Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
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

14 authors at 2 institutions in 1 country.

Maritza J RomeroDepartment of Pharmacology and Toxicology, Georgia Regents University , Augusta, GA , USA ; Department of Anesthesiology and Perioperative Medicine, Georgia Regents University , Augusta, GA , USA ; Vascular Biology Center, Georgia Regents University , Augusta, GA , USA.
Lin YaoDepartment of Pharmacology and Toxicology, Georgia Regents University , Augusta, GA , USA.
Supriya SridharVascular Biology Center, Georgia Regents University , Augusta, GA , USA.
Anil BhattaDepartment of Pharmacology and Toxicology, Georgia Regents University , Augusta, GA , USA.
Huijuan DouVascular Biology Center, Georgia Regents University , Augusta, GA , USA.
Ganesan RameshVascular Biology Center, Georgia Regents University , Augusta, GA , USA ; Department of Medicine, Georgia Regents University , Augusta, GA , USA.
Michael W BrandsDepartment of Physiology, Georgia Regents University , Augusta, GA , USA.
David M PollockDepartment of Pharmacology and Toxicology, Georgia Regents University , Augusta, GA , USA ; Department of Medicine, Georgia Regents University , Augusta, GA , USA.
Ruth B CaldwellVascular Biology Center, Georgia Regents University , Augusta, GA , USA ; Department of Cell Biology and Anatomy, Georgia Regents University , Augusta, GA , USA ; Department of Ophthalmology, Georgia Regents University , Augusta, GA , USA ; VA Medical Center, Georgia Regents University , Augusta, GA , USA.
Stephen D CederbaumIntellectual and Developmental Disabilities Research Center/Neuropsychiatric Institute (IDDRC/NPI), University of California Los Angeles School of Medicine , Los Angeles, CA , USA.
C Alvin HeadDepartment of Anesthesiology and Perioperative Medicine, Georgia Regents University , Augusta, GA , USA.
Zsolt BagiVascular Biology Center, Georgia Regents University , Augusta, GA , USA.
Rudolf LucasDepartment of Pharmacology and Toxicology, Georgia Regents University , Augusta, GA , USA ; Vascular Biology Center, Georgia Regents University , Augusta, GA , USA ; Division of Pulmonary Medicine, Georgia Regents University , Augusta, GA , USA.
Robert W CaldwellDepartment of Pharmacology and Toxicology, Georgia Regents University , Augusta, GA , USA ; Department of Physiology, Georgia Regents University , Augusta, GA , USA.
Georgia Regents Medical Center · USUniversity of California, Los Angeles · US

Funding

Cellular Mechanisms of Retinopathy: Role of ArginaseR01EY011766 · NEI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI CALDWELL, ROBERT WILLIAM, CALDWELL, RUTH B · 1998 to 2021
$6.7M
L-arginine metabolism in diabetes-induced coronary dysfunctionR01HL070215 · NHLBI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI CALDWELL, ROBERT WILLIAM · 2002 to 2011
$2.3M
Flow-induced coronary vasospasm in diabetic patientsR01HL104126 · NHLBI · NEW YORK MEDICAL COLLEGE · PI BAGI, ZSOLT · 2010 to 2014
$1.9M
Netrin-1 Signaling in Ischemia Reperfusion Injury of the KidneyR01DK083379 · NIDDK · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI RAMESH, GANESAN · 2010 to 2014
$1.4M
Novel Strategies for prevention of diabetic vascular dysfunction.R24DK094765 · NIDDK · AUGUSTA UNIVERSITY · PI CALDWELL, ROBERT WILLIAM, CALDWELL, RUTH B · 2012 to 2012
$444k
NEI NIH HHS R01 EY011766NHLBI NIH HHS R01 HL070215NHLBI NIH HHS R01 HL104126NIDDK NIH HHS R01 DK083379NIDDK NIH HHS R24 DK094765
6 · The paper itself

Abstract

rationaleDiabetic nephropathy (DN) is a major cause of end-stage renal disease, associated with endothelial dysfunction. Chronic supplementation of l-arginine (l-arg), the substrate for endothelial nitric oxide synthase (eNOS), failed to improve vascular function. l-Citrulline (l-cit) supplementation not only increases l-arg synthesis, but also inhibits cytosolic arginase I, a competitor of eNOS for the use of l-arg, in the vasculature.

aimsTo investigate whether l-cit treatment reduces DN in streptozotocin (STZ)-induced type 1 diabetes (T1D) in mice and rats and to study its effects on arginase II (ArgII) function, the main renal isoform.

methodsSTZ-C57BL6 mice received l-cit or vehicle supplemented in the drinking water. For comparative analysis, diabetic ArgII knock out mice and l-cit-treated STZ-rats were evaluated.

resultsl-Citrulline exerted protective effects in kidneys of STZ-rats, and markedly reduced urinary albumin excretion, tubulo-interstitial fibrosis, and kidney hypertrophy, observed in untreated diabetic mice. Intriguingly, l-cit treatment was accompanied by a sustained elevation of tubular ArgII at 16 weeks and significantly enhanced plasma levels of the anti-inflammatory cytokine IL-10. Diabetic ArgII knock out mice showed greater blood urea nitrogen levels, hypertrophy, and dilated tubules than diabetic wild type (WT) mice. Despite a marked reduction in collagen deposition in ArgII knock out mice, their albuminuria was not significantly different from diabetic WT animals. l-Cit also restored nitric oxide/reactive oxygen species balance and barrier function in high glucose-treated monolayers of human glomerular endothelial cells. Moreover, l-cit also has the ability to establish an anti-inflammatory profile, characterized by increased IL-10 and reduced IL-1β and IL-12(p70) generation in the human proximal tubular cells.

conclusionl-Citrulline supplementation established an anti-inflammatory profile and significantly preserved the nephron function during T1D.

Indexed as

arginasediabetic nephropathyglomerulosclerosisIL-10l-citrulline

Identifiers

PMID24400007
PMCPMC3871963
OpenAlexW1975698396

What OpenQuestion 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 OpenQuestion graph.