L-Citrulline: A Non-Essential Amino Acid with Important Roles in Human Health

Aguayo, Encarna; Martínez-Sánchez, Ascensión; Fernández-Lobato, B; Alacid, Fernando

doi:10.3390/app11073293

Cited by 52 publications

(38 citation statements)

References 143 publications

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“…The role of citrulline in the regulation of immune function is increasingly being recognized. Citrulline is a nutritionally non-essential amino acid which plays an important role in arginine biosynthesis, the nitric oxide cycle, and the urea cycle ( 32 ). The metabolism of citrulline is unique in that it is not used by the intestine or taken up by the liver and, thus, bypasses splanchnic extraction ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Association of citrulline concentration at birth with lower respiratory tract infection in infancy: Findings from a multi-site birth cohort study

Snyder

Gebretsadik²,

Turi³

et al. 2022

Front. Pediatr.

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Assessing the association of the newborn metabolic state with severity of subsequent respiratory tract infection may provide important insights on infection pathogenesis. In this multi-site birth cohort study, we identified newborn metabolites associated with lower respiratory tract infection (LRTI) in the first year of life in a discovery cohort and assessed for replication in two independent cohorts. Increased citrulline concentration was associated with decreased odds of LRTI (discovery cohort: aOR 0.83 [95% CI 0.70–0.99], p = 0.04; replication cohorts: aOR 0.58 [95% CI 0.28–1.22], p = 0.15). While our findings require further replication and investigation of mechanisms of action, they identify a novel target for LRTI prevention and treatment.

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Section: Discussionmentioning

confidence: 99%

Association of citrulline concentration at birth with lower respiratory tract infection in infancy: Findings from a multi-site birth cohort study

Snyder

Gebretsadik²,

Turi³

et al. 2022

Front. Pediatr.

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“…Magnusson M. et al reported that higher levels of L-citrulline in subjects with no CVD at baseline were associated with cardiovascular risk during 12 years of follow-up; L-citrulline was also cross-sectionally related to CAS [ 63 ]. It was shown that the disturbances of the L-arginine-NO-L-citrulline pathway in diabetes and metabolic syndrome are closely related to inflammation and oxidative stress [ 64 ]—the hallmarks of diabetic vascular complications [ 36 ]. At the same time, it was demonstrated that L-citrulline supplementation increases NO levels [ 65 ], improves insulin resistance, and decreases HbA1c and concentrations of inflammatory markers in patients with T2D [ 66 , 67 ].…”

Section: Discussionmentioning

confidence: 99%

Carotid Artery Disease in Subjects with Type 2 Diabetes: Risk Factors and Biomarkers

Климонтов

Koroleva

Khapaev

et al. 2021

JCM

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Carotid atherosclerosis (CA) and, especially, carotid artery stenosis (CAS), are associated with a high risk of cardiovascular events in subjects with type 2 diabetes (T2D). In this study, we aimed to identify risk factors and biomarkers of subclinical CA and CAS in T2D individuals. High-resolution ultrasonography of carotid arteries was performed in 389 patients. Ninety-five clinical parameters were evaluated, including diabetic complications and comorbidities; antihyperglycemic, hypolipidemic, and antihypertensive therapy; indices of glycemic control and glucose variability (GV); lipid panels; estimated glomerular filtration rate (eGFR); albuminuria; blood cell count; and coagulation. Additionally, serum levels of calponin-1, relaxin, L-citrulline, and matrix metalloproteinase-2 and -3 (MMP-2, -3) were measured by ELISA. In univariate analysis, older age, male sex, diabetes duration, GV, diabetic retinopathy, chronic kidney disease, coronary artery disease, peripheral artery disease, and MMP-3 were associated with subclinical CA. In addition to these factors, long-term arterial hypertension, high daily insulin doses, eGFR, and L-citrulline were associated with CAS. In multivariate logistic regression, age, male sex, BMI, GV, and eGFR predicted CA independently; male sex, BMI, diabetes duration, eGFR, and L-citrulline were predictors of CAS. These results can be used to develop screening and prevention programs for CA and CAS in T2D subjects.

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“…L-citrulline is used to prevent endothelial dysfunction in cardiovascular diseases and diabetes, and treat erectile dysfunction. In addition, due to its role in arginine metabolism, L-citrulline is a potential agent for treating cancer [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Antitumor Effects of L-citrulline on Hela Cervical Cancer Cell Lines

Eren

Gurer

Gursoy

et al. 2022

ACAMC

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Introduction: Cervical cancer is the deadliest gynecological malignancy. This study aims to examine the anticancer effects of L-citrulline on HeLa cell culture. Materials-Methods: HeLa cells were cultured in complete Eagle's minimum essential medium. HeLa cells were seeded in 96-well plates and incubated with L-citrulline. After incubation, MTT dye was added and incubated. Annexin- V technique was used to test the apoptosis. The activated caspases of HeLa cells by L-citrulline exposure were measured with the Caspase 3/7 technique. One-way variance analysis was conducted for statistical analysis by using GraphPad Prism 6.0 for Windows. Results: L-citrulline showed its toxicity on HeLa cells in a dose-dependent manner in application times of 24 and 48 hours. The IC50 dose of L-citrulline was 0.19 and 0.16 mg/mL at 24 and 48 hours, respectively. When HeLa cells were exposed to an IC50 dose of L-citrulline for 24 hours, the percentages of the dead, early apoptotic, and late apoptotic cells were detected to be 0.75%, 23.05%, and 12.75%, respectively. The differences in the wideness of the scratch area were observed at the initial stage and after 24 hours of applying L-citrulline. Conclusion: L-citrulline showed its toxicity on HeLa cells in a dose-dependent manner. Based on Annexin and Caspase findings, it can be concluded that L-citrulline exerted a pro-apoptotic effect on HeLa cells in only a short exposure time. L-citrulline also showed a migration inhibitory effect. The findings of this study indicate L-citrulline to be worthy of investigation for its anticancer activities in vitro and in vivo, and as a candidate for cancer therapy.

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L-Citrulline: A Non-Essential Amino Acid with Important Roles in Human Health

Cited by 52 publications

References 143 publications

Association of citrulline concentration at birth with lower respiratory tract infection in infancy: Findings from a multi-site birth cohort study

Association of citrulline concentration at birth with lower respiratory tract infection in infancy: Findings from a multi-site birth cohort study

Carotid Artery Disease in Subjects with Type 2 Diabetes: Risk Factors and Biomarkers

Antitumor Effects of L-citrulline on Hela Cervical Cancer Cell Lines

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