A study of acute toxicity for combination of arginine and taurine and its effects on the systemic circulation
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Keywords

arginine
taurine
acute toxicity
systemic circulation parameters

Abstract

Monopreparations of arginine and taurine in various dosage forms are widely used in medical practice and have a long-term use in medicine. Available evidence-based medicine data indicate that L-arginine improves endothelial function in angina pectoris, cardiovascular failure and hypercholester- olemia. These effects are due to both the possible increase in nitric oxide production by endothelial NO synthase and indirect antioxidant effects of arginine combined with decrease in concentration of superoxide anion radical released from the vascular endothelium. Taurine has a wide spectrum of pharmacological effects and it acts as a protective agent in some pathological processes, including nervous system diseases (retinal degeneration, cerebrovascular accident, neurodegenerative diseases), metabolic disorders (diabetes mellitus, stroke-like episodes, mitochondrial disease), inflammatory processes. In addition, taurine delays atherosclerosis progression, lowers blood pres- sure, prevents cardiomyopathy, demonstrates effectiveness in ischemic-reperfusion injury, exhibits antiarrhythmic properties, prevents sudden death, and acts as a cardioprotective agent in congestive heart failure. The combination of arginine and taurine could contribute to their greater effectiveness when used in clinical practice. The combination of these drugs in one pharmaceutical product requires a series of preclinical studies, an important stage of which is a study of its toxicological parameters and effects on the body systems and organs. The aim of thе study – is an experimental research of acute toxicity for the combination of arginine and taurine and its effects on the systemic circulatory parameters in order to justify safety when used this combination in clinical practice. Single intraperitoneal injection in female and male white rats of combination (arginine hydrochloride + taurine) in a dose of 260 mg/5 mL (the maximal dose that technically ensures an administration of the maximum volume of the tested agent to the rat) did not cause the death of the experimental animals, any deviations in appearance and general behavioral reactions, and did not affect the dynamics of body mass. Visual inspection and macroscopic examination of rats of both sexes 14 days after administration of the tested agent showed the absence of pathological changes in the internal organs and brain, no signs of hemocirculatory disorders and inflammation. The absolute and relative mass of the internal organs in rats of both sexes of the experimental group did not differ from those parameters in animals of the control group. The single intravenous administration of the tested pharmacological agent in a therapeutic dose causes a short-term (up to 5 min) hypotensive reaction and a slight decrease in heart rate and does not affect the electrical activity of the heart. The results of the study indicate low acute toxicity of the combination of L-arginine and taurine and virtually no effect on the cardiovascular system.

https://doi.org/10.33250/20.01.059
pdf (Українська)

References

1. Rose W. C.The nutritional significance of the amino acids. Physiol Rev. 1938. V. 18, P. 109–136.
2. Wu G., Morris S. M. Jr. Arginine metabolism: nitric oxide and beyond. Biochem. J. 1998. V. 336. P. 1–17.
3. Moncada S., Higgs A. The L-arginine-nitric oxide pathway. N. Engl. J. Med. 1993. V. 329. P. 2002–2012.
4. Palmer R. M. J, Ferrige A. G., Moncada S. Nitric oxide accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987. V. 327. Р. 524–26.
5. Radomski M. W., Palmer R. M. J., Moncada S. An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc. Natl. Acad. Sci. USA. 1990. V. 87. Р. 5193–5197.
6. Kubes P., Suzuki M., Granger D. N. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc. Natl. Acad. Sci. USA. 1991. V. 88. Р. 4651–4655.
7. Garg U. C., Hassid A. Nitric oxidegenerating vasodilators and 8-bromocyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J. Clin. Invest. 1989. V. 83. Р. 1774–1777.
8. Nitric oxide modulates the expression of monocyte chemoattractant protein-1 in cultured human endothelial cells. A. M. Zeiher, B. Fisslthaler, B. Schray-Utz, R. Busse. Circ. Res. 1995. V. 76. Р. 980–986.
9. Granik V. G. Metabolism of L-arginine. Khim-farm. magazine. 2003. No. 3. P. 3–20.
10. Bode-Boger S. M. Effect of L-arginine supplementation on NO production in man. European Journal of Clinical Pharmacology. 2006. V. 62, Suppl. 13. P. 91–99.
11. Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure. T. S. Rector, A. J. Bank, K. A. Mullen et al. Circulation. 1997. V. 18. P. 1674–1679.
12. Alkholifi F. K., Albers D. S. Attenuation of rotenone toxicity in SY5Y cells by taurine and N-acetyl cysteine alone or in combination. Brain Res. 2015. V. 1622. Р. 409–413.
13. Prevention of epileptic seizures by taurine. A. El Idrissi, J. Messing, J. Scalia, E. Trenkner. Adv. Exp. Med. Biol. 2003. V. 526. Р. 515–525.
14. Effects of taurine treatment on epileptic patients. E. M. Airaksinen, S. S. Oja, K.-M. Marnela et al. Prog. Clin. Biol. 1980. V. 39. P. 157–166.
15. Taurine: the comeback of a neutraceutical in the prevention of retinal degenerations. N. Froger, L. Moutsimilli, L. Cadetti et al. Retin Eye Res. 2014. V. 41. P. 44–63.
16. Albrecht J., Schousboe A. Taurine interaction with neurotransmitter receptors in the CNS: an update. Neurochem. Res. 2005. V. 30. P. 1615–1621.
17. Comparative evaluation of taurine and thiotaurine as protectants against diabetes-induced nephropathy in a rat model. K. G. Pandya, R. Budhram, G. Clark, C. A. Lau-Cam. Adv. Exp. Med. Biol. 2013. V. 775. P. 371–394.
18. Murakami S. Role of taurine in the pathogenesis of obesity. Mol. Nutr. Food Res. 2015. V. 59. P. 1353–1363.
19. Taurine deficiency and MELAS are closely related syndromes. S. W. Schaffer, C. J. Jong, D. Warner et al. Adv. Exp. Med. Biol. 2013. V. 776. P. 153–165.
20. Klamt F., Shacter E. Taurine chloramine: an oxidant derived from neutrophils induces apoptosis in human B lymphoma cells through mitochondrial damage. J. Biol. Chem. 2005. V. 280. P. 21346–21352.
21. Eby G., Halcomb W. W. Elimination of cardiac arrhythmias using oral taurine with L-arginine with case histories: hypothesis for nitric oxide stabilization of the sinus node. Med. Hypotheses. 2006. V. 67. P. 1200–1204.
22. Distribution of twenty-four hour urinary taurine excretion and association with ischemic heart disease mortality in 24 populations of 16 countries: results from the WHO-CARDIAC study. Y. Yamori, L. Liu, K. Ikeda et al. Hypertens. Res. 2001. V. 24. P. 453–457.
23. Azuma J., Sawamura A., Awata N. Usefulness of taurine in chronic congestive heart failure. Jpn. Circ. J. 1992. V. 56. P. 95–99.
24. Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats. M. Katakawa, N. Fukuda, A. Tsunemi et al. Hypertens. Res. 2016. V. 39. P. 848–856.
25. Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial. J. Azuma, A. Sawamura, N. Awata et al. Clinical cаrdiology. 1985. V. 8, Is. 5. P. 276–282.
26. URL: https://web.archive.org/web/20170118214915/http://datasheets.scbt.com/sc-202354.pdf.
27. URL: https://echa.europa.eu/hr/registration-dossier/-/registered-dossier/13725/7/3/1.
28. The effects of an oral taurine dose and supplementation period on endurance exercise performance in humans: a meta-analysis. M. Waldron, S. D. Patterson, J. Tallent et al. Review Sports Med. 2018. V. 48 (5). P. 1247–1253.