The effect of derivatives of sulfur-containing amino acids (ademetionine, taurine and glutathione) on survival of animals with acute kidney injury of various genesis




nephroprotection, acute kidney injury, survival, ademetionine, taurine, glutathione


Aim. To study the nephroprotective effect of sulfur-containing amino acids (ademetionine, taurine and glutathione) on different models of acute kidney injury (AKI) by the integral index of the survival rate of animals.

Materials and methods. The experiments were performed on 105 non-linear mature white laboratory rats and 35 mice. The drugs studied – ademetionine (Geptral, Abbott SpA, Italy) in the dose of 20 mg/kg, glutathione (TAD 600, Biomedica Foscama, Italy) in the dose of 30 mg/kg and taurine (Sigma-Aldrich, USA) in the dose of dose 100 mg/kg – were injected intraperitoneally 3-7 days before AKI modeling. Rhabdomyolysis-induced AKI was modeled by the intramuscular injection of 50 % glycerol solution in the dose of 10 ml/kg, toxic AKI – by the injection of gentamicin solution in the dose of 80 mg/kg and the subcutaneous injection of ethylene glycol in the dose of 10 ml/kg. Simulation of renal ischemia was performed under general anesthesia (ethaminal sodium, 40 mg/kg) by clamping of both renal pedicles for a period of 60 min, followed by reperfusion for 24 h.

Results and discusion. The experimental results show a significant improvement in the survival of animals under the effect of the drugs of derivatives of sulfur-containing amino acids studied in conditions of various models of AKI. Ademetionine, taurine and glutathione reduced the lethality of animals on models of rhabdomyolytic, gentamicin, ischemia-reperfusion AKI. In conditions of ethylene glycol intoxication the highest nephroprotective activity by the survival criterion was shown by glutathione (57.1 % survival at 48 h after administration of ethylene glycol against 100 % of mortality in the control group (p < 0.05).

Conclusions. All derivatives of sulfur-containing amino acids studied (ademetionine, taurine and glutathione) exhibit the nephroprotective activity by the criterion of survival of animals on various models of AKI. Glutathione demonstrates the best survival of animals with acute kidney injury of various genesis, while ademetionine has the lowest survival.

Author Biographies

V. M. Drachuk, Bukovinian State Medical University

Аssistant of the Pharmacology Department

I. I. Zamorskii, Bukovinian State Medical University

Doctor of Medical Sciences, professor, Head of the Pharmacology DepartmentUniversity

T. S. Shchudrova, Bukovinian State Medical University

PhD, associate professor of the Pharmacology Department

Ol. M. Goroshko, Bukovinian State Medical University

associate professor of the Pharmacy Department


Waikar, S. S., Liu, K. D., & Chertow, G. M. (2008). Diagnosis, Epidemiology and Outcomes of Acute Kidney Injury. Clinical Journal

of the American Society of Nephrology, 3 (3), 844–861.

Semidotska, Z. D., Chernyakova, I. A., Pionova, O. M., … Tryfonova, N. S. (2017). Acute kidney injury: modern view of problem.

Shidnoevropejskij Zurnal Vnutrisnoi Ta Simejnoi Medicini, 2017 (1), 10–16.

Acute kidney injury: Current concepts and new insights. (2014). Journal of Injury and Violence Research, 8 (1), 58–62. https://doi.


Kellum, J. A., & Lameire, N. (2013). Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Critical

Care, 17 (1), 204.

Song, C. H., Bae, H. J., Ham, Y. R., Na, K. R., Lee, K. W., & Choi, D. E. (2017). A Case of Ethylene Glycol intoxication with Acute

Renal Injury: Successful Recovery by Fomepizole and Renal Replacement Therapy. Electrolytes & Blood Pressure, 15 (2), 47. https://

Gardner, T. B., Manning, H. L., Beelen, A. P., Cimis, R. J., Cates, J. M., Lewis, L. D. (2004). Ethylene glycol toxicity associated with

ischemia, perforation, and colonic oxalate crystal deposition. J. Clin. Gastroenterol, 38, 435–439.

Rahman, S. S., Kadakia, S., Balsam, L., & Rubinstein, S. (2011). Autonomic Dysfunction as a Delayed Sequelae of Acute Ethylene

Glycol Ingestion. Journal of Medical Toxicology, 8 (2), 124–129.

Hanouneh, M., & Chen, T. K. (2017). Calcium Oxalate Crystals in Ethylene Glycol Toxicity. New England Journal of Medicine, 377 (15),

Liberek, T., Śliwarska, J., Czurak, K., Perkowska-Ptasińska, A., Weber, E., Rutkowski, B. (2013). Prolonged renal failure in the course

of atypical ethylene glycol intoxication. Acta Biochimica Polonica, 4 (60), 661–663.

Zviahyntseva, T. D., Chernobai, A. Y., Hlushchenko, S. V. (2014). Ukrainskyi medychnyi chasopys, 3 (101), 56–59.

Anstee, Q. M., & Day, C. P. (2012). S-adenosylmethionine (SAMe) therapy in liver disease: A review of current evidence and clinical

utility. Journal of Hepatology, 57 (5), 1097–1109.

Ostapiv, R. D., Kystsiv, O. S., Manko, V. V. (2015). Visnyk Lvivskoho universytetu. Seriia Biolohichna, 69, 247–255.

Shimada, K., Jong, C. J., Takahashi, K., & Schaffer, S. W. (2015). Role of ROS Production and Turnover in the Antioxidant Activity of

Taurine. Advances in Experimental Medicine and Biology, 581–596.

Traverso, N., Ricciarelli, R., Nitti, M., Marengo, B., Furfaro, A. L., Pronzato, M. A., … Domenicotti, C. (2013). Role of Glutathione in

Cancer Progression and Chemoresistance. Oxidative Medicine and Cellular Longevity, 2013, 1–10.

Salyha, N. O. (2013). Ukraïns’kij bìofarmacevtičnij žurnal, 85 (4), 40–47.

Horoshko, O. M., Zamorskyi, I. I. (2008). Vìsnik farmacìï, 1 (53), 67–71.

Martynjuk, L. P., Ruzhickaja, O. A., Martynjuk, E. S. (2015). Pochki, 1, 24–32.

Arakelian, N. H., Shtryhol, S. Yu. (2006). Ukraine. Patent No 28140. Patent and Trademark Office.

Shtryhol, S. Yu., Lisovyi, V. M., Zupanets, I. A. (2009). Metody eksperymentalnoho modeliuvannia urazhennia nyrok pry farmakolohichnykh

doslidzhenniakh: Metodychni rekomendatsii DFTs Ukrainy. Kyiv, 9–10.

Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes. (2010).

Official Journal of the European Union, 53 (276), 33–80.






Experimental and Clinical Pharmacology