Vol 5, No 2 (2018) > Mini Review Article >

L-citrulline as Alternative Pharmacological Substance in Protecting Against Cardiovascular Disease

Andrea Laurentius , Gregorius Bhaskara Wikanendra , Tzeto Han Cong , Wawaimuli Arozal

 

Abstract:

Cardiovascular disease (CVD) has contributed average 30% of global death diagnoses. Attempts of physicians to transiently relieve CVD came down to using focally targeted drugs. Struggle to find other treatment strategies is done to discover alternatives that serve to not only cure, but also prevent CVDs, or that do not require such a precise administration in order to minimize side-effects. This review would offer using L-citrulline as potential therapeutics in treating and preventing CVDs. This compound, found mostly in Citrus sp., contains chemical trait that could affect other bodily physiology, especially boosting nitric oxide (NO) production. Enhancing NO bioavailability suppresses the risk of myocardial oxidative stress due to ischemia and cardiac pressure-overload, as well as pulmonary hypertension. So, understanding of L-citrulline effects on endothelial nitric oxide synthase pathway in generation of NO and its uncoupling mechanisms may serve as fundamental treatment for oxidative stress-induced cardiovascular diseases with or without prophylaxis. 


Keywords: citrulline; cardiovascular; pharmacology; nitric oxide

Published at: Vol 5, No 2 (2018) pages: 72-80

DOI: 10.7454/psr.v5i2.3946


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References:

Balderas-Munoz K, Castillo-Martinez L, Orea-Tajeda A, Infante-Vasquez O, Utrera-Lagunas M, Martinez-Memije R, et al. (2012). Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation. Journal of Cardiology, 19(6), 612-617.

Barr F, Tirona R, Taylor M, Rice G, Arnold J, Cunningham G, et al. (2007). Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: Potential therapy for postoperative pulmonary hypertension. Journal of Thoracic and Cardiovascular Surgery, 134(2), 319-326.

Chen IF, Wu HJ, Chen CY, Chou KM, Chang CK. (2016). Branched-chain amino acids, arginine, citrulline alleviate central fatigue after 3 simulated matches in taekwondo athletes: a randomized controlled trial. Journal of International Society of Sports Nutrition, 13, 28.

Figueroa A, Alvarez-Alvarado S, Jaime SJ, & Kalfon R. (2016). l-Citrulline supplementation attenuates blood pressure, wave reflection and arterial stiffness responses to metaboreflex and cold stress in overweight men. British Journal of Nutrition, 116(2), 279-285.

Frank K, Patel K, Lopez G, & Willis B. (2018). Citrulline Research Analysis. Retrieved from https://examine.com/supplements/citrulline/.

Heidi AB, Smith Jeffrey A, Canter Karla G, Christian, et al. (2007). Nitric oxide precursors and congenital heart surgery: A randomized controlled trial of oral citrulline. Journal of Thoracic and Cardiovascular Surgery, 132(1), 58-65.

Hong M, Hartig N, Kaufman K, Hooshmand S, Figueroa A, & Kern M. (2015). Watermelon consumption improves inflammation and antioxidant capacity in rats fed an atherogenic diet. Nutrition Research, 35(3), 251-258.

Incalza M, D’Oria R, Natalicchio A, Perrini S, Laviola L, & Giorgino F. (2017). Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. PubMed, 100, 1-19

Jiang H, Huang K, & Zhang T. (2017). Characterization of a recombinant arginine deiminase from Enterococcus faecalis SK32.001 for L-citrulline production. Process Biochemistry, 64, 136-142.

Kaore S, & Kaore N. (2014). Citrulline: Pharmacological perspectives and role as a biomarker in diseases and toxicities. Biomarkers in Toxicology, 883-905.

Katzung B, Masters S, & Trevor A. (2015). Pharmacology (3rd ed.). New York: McGraw Hill.

Kurauchi Y, Mokudai K, Mori A, Sakamoto K, Nakahara T, Morita M, et al. (2017). L -Citrulline ameliorates cerebral blood flow during cortical spreading depression in rats: Involvement of nitric oxide- and prostanoids-mediated pathway. Journal of Pharmacological Sciences, 133(3), 146-155.

Lorin J, Zeller M, Guilland JC, Cottin Y, Vergely C, & Rocette L. (2014) Arginine and nitric oxide synthase: regulatory mechanisms and cardiovascular aspects. Molecular and Food Research, 58(1), 101-116.

Loscalzo J, & Harrison T. (2013). Harrison’s cardiovascular medicine (2nd ed.). USA: Mc Graw-Hill.

Moens AL, Ketner EA, Takimoto E, Schmidt TS, O’Neill CA, Wolin MS, et al. (2011). Bi-modal dose-dependent cardiac response to tetrahydrobiopterin in pressure-overload induced hypertrophy and heart failure. Journal of Molecular and Cellular Cardiology, 51(4), 564-569.

Mori A, Morita M, Morishita K, Sakamoto K, Nakahara T, & Ishii K. (2015). L-Citrulline dilates rat retinal arterioles via nitric oxide- and prostaglandin-dependent pathways in vivo. Journal of Pharmacological Sciences, 127(4), 419-423.

Safi M, Mahjoob MP, Nateghi S, Khaheshi I, Akbarzadeh MA, & Naderian M. (2017). The Assessment of short-term effect of L-Citrulline on endothelial function via FMD to NMD ratio in known CAD patients: A randomized, cross-over clinical trial (Clinical trial number: NCT02638727). Journal of Internal Medicine, 55(1), 23-27.

Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, et al. (2008). Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. British Journal of Clinical Pharmacology, 65(1), 51-59.

Sharif Kashani B, Tahmaseb Pour P, Malekmohammad M, Behzadnia, N, Sheybani-Afshar F, & Fakhri M, et al. (2014). Oral l-citrulline malate in patients with idiopathic pulmonary arterial hypertension and Eisenmenger Syndrome: A clinical trial. Journal of Cardiology, 64(3), 231-235.

Suzuki T, Morita M, Hayashi T, & Kamimura A. (2017). The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males. Bioscience, Biotechnology, and Biochemistry, 81(2), 372-275.

Tang L, Wang H, & Ziolo MT. (2014). Targeting NOS as a therapeutic approach for heart failure. Pharmacology & Therapeutics, 143(3), 306-315.

Van Deel ED, Octavia Y, de Boer M, Juni RP, Tempel D, van Haperen R, et al. (2015) Normal and high eNOS levels are detrimental in both mild and severe cardiac pressure-overload. Journal of Molecular and Cellular Cardiology, 88, 145-154.

Van Wijck K, Wijnands KA, Meesters DM, Boonen B, Van Loon LJ, Buurman WA, et al. (2014) L-citrulline improves splanchnic perfusion and reduces gut injury during exercise. Medicine science sport exercise, 46(11), 2039-2046.

Xuan C, Lun LM, & He GW. (2015). L-citrulline for protection of endothelial function from ADMA-induced injury in porcine coronary artery. Scientific Reports, 5, 10987.