The effect of the germanium complex with nicotinic acid on oxidative modification of cardiac and hepatic proteins in the experimental chronic intoxication with doxorubicin in rats

Authors

  • V. P. Narokha O.O.Bohomolets National Medical University

DOI:

https://doi.org/10.24959/cphj.16.1381

Keywords:

germanium, nicotinic acid, oxidative modification of proteins, myocardium, liver, doxorubicin

Abstract

Anthracycline antitumor antibiotics are widely used for the treatment of malignancies, but this group of drugs is known for their cytotoxic effects, especially cardiotoxicity. It has been proven that the adverse effect of anthracyclines on tissues is based on formation of the reactive oxygen species that enhance development of the oxidative stress. Among the body biomolecules proteins are the most sensitive to peroxidation; they can be the primary markers in determining this pathological process at the cellular level. To identify and prevent the oxidative stress is important for prevention of further tissue apoptosis and necrosis. The aim of the study was to investigate the effect of nicotinic acid and the complex compound of germanium with nicotinic acid (MIGU-1) on oxidative modification of myocardial and hepatic proteins in the experimental chronic intoxication with doxorubicin (CID) in rats. The pattern of modifications in the content of protein peroxidation products (neutral and basic 2,4-dinitrophenylhydrazine) in cardiomyocytes and hepatocytes in rats has been determined; it shows intensification of the oxidative stress in CID. Nicotinic acid in the dose of 10 mg/kg daily did not exhibit the hepatoprotective effect in CID. It has been proven that the use of the new complex compound of germanium with nicotinic acid in the dose of 10 mg/kg daily provide attenuation of protein peroxidation in rats’ cardiomyocytes and hepatocytes in CID. The results obtained allow considering MIGU-1 as a drug with a possible cytoprotective activity, and its further study may be topical and prospective.

References

Дубинина Е.Е., Бурмистров С.О., Ходов Д.А., Поротов Г.Е. // Вопросы мед. химии. – 1995. – Т. 41, №1. – С. 24-26.

Кресюн В.Й., Сейфулліна І.Й., Годован В.В. // Одеський мед. журн. – 2011. – №1 (123). – С. 31-35.

Лук’янчук В.Д., Сейфулліна І.Й., Літвиненко Д.Ф., Марцинко О.Е. // Фармакол. та лікарська токсикол. – 2016. – №1 (47). – С. 3-13.

Ніженковська І.В., Сейфулліна І.Й., Нароха В.П. та ін. // Фармакол. та лікарська токсикол. – 2016. – №2 (48). – С. 74-79.

Barry E., Alvarez J.A., Scully R.E. et al. // Expert Opin Pharmacother. – 2007. – Vol. 8. – P. 1039-1058.

Cross M.J., Berridge B.R., Clements P.J.M. et al. // Br. J. Pharmacol. – 2015. – Vol. 172 (4). – P. 957-974.

Dalle-Donne I., Rossi R., Colombo R. et al. // Clin. Chem. – 2006. – Vol. 52 (4). – P. 601-623.

Damodar G., Smitha T., Gopinath S. et al. // Ann. Med. Health Sci. Res. – 2014. – Vol. 4 (1). – P. 74-79.

Dunlop R.A., Brunk U.T., Rodgers K.J. // Intern. Union of Biochemistry and Molecular Biol. – 2009. – №61 (5). – P. 522-527.

Kim Y., Ma A., Kitta K. et al. // Mol. Pharmacol. – 2003. – Vol. 63. – P. 368-377.

Lewis W., Kleinerman J., Puszkin S. // Canc. Res. – 1982. – Vol. 50. – P. 547-553.

Li S.Q., Fenq L., Jianq W.D. et al. // Fish Shellfish Immunol. – 2016. – Vol. 55. – P. 212-222.

Lowry O.H., Rosebrough N.J., Farr A.L., Randal R.I. // J. Biol. Chem. – 1951. – Vol. 193, №1. – P. 265-275.

Silva de Paula E., Carneiro M.F., Grotto D. et al. // J. Toxicol. Environ. Health A. – 2016. – Vol. 79 (4). – P. 174-183.

Stadtman E.R., Levine R.L. // Amino Acids. – 2003. – №25 (3-4). – P. 207-218.

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Published

2016-12-12

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Section

Pre-clinical studies of new drugs