Arginine or citrulline associated with a statin stimulates nitric oxide production in bovine aortic endothelial cells

Berthe, Marie-Clotilde; Bernard, Mélisande; Rasmusen, Carole; Darquy, Sylviane; Cynober, Luc; Couderc, Rémy

doi:10.1016/j.ejphar.2011.08.018

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…However, the combination of citrulline and atorvastatin appears necessary to attain a significant reduction in fat mass accretion under DIO conditions. We hypothesized that the synergistic effects of the combination involved an improved production of NO by eNOS as described by Berthe et al (2011) in endothelial cells. In the present study, the metabolic adaptations induced in vivo by the combination of citrulline and atorvastatin were consistent with those observed on glucose homeostasis, visceral obesity and liver steatosis, when NO production was enhanced (Duplain et al, 2001;Cook et al, 2004;Schild et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…In humans, one 7-day-long study showed no effect of citrulline supplementation on fasting insulin in healthy adults (Thibault et al, 2011). Interestingly, combining citrulline with atorvastatin was recently shown to potentiate NO production in endothelial cells (Berthe et al, 2011). This was mediated through an increased bioavailability of arginine, due to citrulline, and to an enhanced activity of the NO-generating enzyme eNOS because the statins, apart from their ability to decrease cholesterol synthesis, also increase eNOS expression and activity (Berthe et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Combining citrulline with atorvastatin preserves glucose homeostasis in a murine model of diet‐induced obesity

Capel

Chabrier

Pitois

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSENO is a crucial regulator of energy and lipid metabolism, whose homeostasis is compromised during obesity. Combination of citrulline and atorvastatin potentiated NO production in vitro. Here we have assessed the effects of this combination in mice with diet-induced obesity (DIO). EXPERIMENTAL APPROACHC57BL/6J male mice were given a standard diet (control) or a high fat-high sucrose diet (DIO) for 8 weeks. DIO mice were then treated with DIO alone, DIO with citrulline, DIO with atorvastatin or DIO with citrulline and atorvastatin (DIOcit-stat) for 3 weeks. Thereafter, body composition, glucose tolerance, insulin sensitivity and liver fat metabolism were measured. KEY RESULTSDIOcit-stat mice showed lower body weight, fat mass and epididymal fat depots compared with other DIO groups. Unlike other DIO groups, glucose tolerance and insulin sensitivity of DIOcit-stat, along with blood glucose and insulin concentrations in response to feeding, were restored to control values. Refeeding-induced changes in liver lipogenic activity were also reduced in DIOcit-stat mice compared with those of DIO animals. This was associated with decreased gene expression of the transcription factor SREBP-1, liver X receptor α, ChREBP and of target lipogenic enzymes in the liver of DIOcit-stat mice compared with those of other DIO groups. CONCLUSIONS AND IMPLICATIONSThe citrulline-atorvastatin combination prevented fat mass accumulation and maintained glucose homeostasis in DIO mice. Furthermore, it potentiated inhibition of hepatic de novo lipogenesis activity. This combination has potential for preservation of glucose homeostasis in patients receiving statin therapy. AbbreviationsACC1 and Acc1, acetyl-CoA carboxylase 1; AMPKα, AMP-activated protein kinase α; ChREBP and Chrebp, carbohydrate-responsive element-binding protein; FAS and Fasn, fatty acid synthase; GPAM and Gpam, glycerol-3-phosphate acyltransferase; LXRα and Lxrα, liver X receptor α; RQ, respiratory quotient; SCD1 and Scd1, stearoyl-Coenzyme A desaturase 1; SREBP-1 and Srebf1, sterol regulatory element-binding transcription factor 1; VCO 2 , carbon dioxide production; VO 2 , oxygen consumption BJP British Journal of Pharmacology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combining citrulline with atorvastatin preserves glucose homeostasis in a murine model of diet‐induced obesity

Capel

Chabrier

Pitois

et al. 2015

British J Pharmacology

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“…Several studies in porcine and human models have reported L-Cit as a potent precursor for NO synthesis (70,35,71,72), however, this is yet to be ascertained in poultry. Our study hypothesized that L-Cit, as an endogenous precursor of arginine, would modulate NO synthesis when supplemented in diets.…”

Section: Plasma Metabolites and Circulating No Levelsmentioning

confidence: 99%

Dietary L-Citrulline supplementation modulates nitric oxide synthesis and anti-oxidant status of laying hens during summer season

Uyanga

Jiao

Zhao

et al. 2020

Preprint

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Background L-Citrulline (L-Cit), a non-protein amino acid, has been implicated in several physiological functions including anti-inflammatory, anti-oxidative, and hypothermic roles, however, there is paucity of information with regards to its potential in poultry production. This study was designed to investigate the effects of dietary L-Cit supplementation on the production performance, nitric oxide production and anti-oxidant status of laying hens during summer periods. Hy-line laying hens (n = 288, 34 weeks old) were allotted to four treatment with 6 replicates of 12 chickens each. Dietary treatments of control (basal diets), 0.25%, 0.50% and 1.00% L-Cit supplementation were fed to chickens for eight (8) weeks. Production performance, egg quality characteristics, nitric oxide production and antioxidant properties were measured. Blood samples were collected at 4th and 8th weeks of experiment. ResultsAir temperature monitoring indicated average minimum and maximum recordings of 25.02 0 C and 31.01 0 C respectively. Dietary supplementation with L-Cit did not significantly (P > 0.05) influence the production performance, plasma biochemistry and rectal temperatures of laying hens. Egg shape index was increased with L-Cit diet, similarly, albumen heights and Haugh units also tended (P < 0.10) to improve with higher L-Cit supplementation. Plasma nitric oxide (NO x ) concentration was observed to increase with highest contents at 1% L-Cit supplementation. Likewise, nitric oxide synthase (NOS) enzyme activity for both total NOS (tNOS) and inducible NOS (iNOS) were upregulated with increasing L-Cit levels, although, tNOS was not affected at week 4. Anti-oxidant enzymes including catalase and superoxide dismutase (SOD) were increased with L-Cit supplementation, however, SOD activity was unchanged at week 4. Total anti-oxidant capacity increased with L-Cit groups at week 8. L-Cit supplementation attenuated the extent of lipid peroxidation measured by malondialdehyde levels, and also inhibited glutathione peroxidase activity. ConclusionDietary L-Cit supplementation enhanced nitric oxide synthesis, promoted antioxidant defense systems, and tended to improve internal egg quality traits of laying hens during summer season. 1% Production performanceEgg production and egg weights were recorded daily from different replicates, while body weights and feed intake were recorded on a weekly basis throughout the experimental period. Data computed were feed conversion ratio, laying rate, and egg mass based on the data recorded.Air and rectal temperature monitoring

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“…eNOS is expressed primarily in vascular endothelial cells and regulates the function of blood vessels by influencing vascular tone, permeability, and proliferation and by inhibiting platelet aggregation (Vallence and Chan, ). Therefore, a decrease in eNOS activity leads to endothelial dysfunction, and the maintenance of NO production represents a therapeutic target to slow the progression of cardiovascular diseases (Berthe et al, ). NO is involved in S ‐nitrosylation of proteins, which is a principal protein post‐translational modification and plays a role in cell signaling events (Hess and Stamler, ).…”

Section: Introductionmentioning

confidence: 99%

Erythrocyte nitric oxide synthase as a surrogate marker for mercury-induced vascular damage: The modulatory effects of naringin

et al. 2013

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In this study, endothelial nitric oxide synthase activity and nitric oxide (NO) production by human erythrocytes in the presence and absence of mercuric chloride (HgCl2 ), L-arginine (L-ARG), N ω- nitro-L-arginine methyl ester (L-NAME), and naringin (NAR) were investigated. In addition, the levels of reduced glutathione (GSH) and related enzymes were estimated in erythrocytes hemolysate. The protein carbonyl content (PCC) and thiobarbituric acid-reactive substances (TBARS) levels were also determined. The results of this study revealed that the treatment of erythrocytes with either HgCl2 or L-NAME induced a significant decrease in NOS activity and nitrite levels compared with control cells. Furthermore, mercury exposure significantly increased the levels of PCC and TBARS but reduced the GSH level. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase (GST) were inhibited. The exposure of erythrocytes to HgCl2 in combination with L-ARG, NAR, or both ameliorated the investigated parameters compared with erythrocytes incubated with HgCl2 alone. These results indicate that mercury exposure decreased both erythrocyte NOS activity and nitrite production, and that these parameters might be indicative of mercury exposure. The data also suggest that concomitant treatment with NAR can restore NO bioavailability through either its metal-chelating properties or its antioxidant activity.

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Arginine or citrulline associated with a statin stimulates nitric oxide production in bovine aortic endothelial cells

Cited by 9 publications

References 33 publications

Combining citrulline with atorvastatin preserves glucose homeostasis in a murine model of diet‐induced obesity

Combining citrulline with atorvastatin preserves glucose homeostasis in a murine model of diet‐induced obesity

Dietary L-Citrulline supplementation modulates nitric oxide synthesis and anti-oxidant status of laying hens during summer season

Erythrocyte nitric oxide synthase as a surrogate marker for mercury-induced vascular damage: The modulatory effects of naringin

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