BIOCHEMICAL MARKERS OF THE FUNCTIONAL LIVER STATE IN RATS WITH TOXIC HEPATITIS UNDER THE CONDITIONS OF GERMANIUM CITRATE ADMINISTRATION

Bìol. Tvarin, 2017, Volume 19, Issue 1, pp. 59–64

http://doi.org/10.15407/animbiol19.01.059

biochemical markers of the functional liver state in rats with toxic hepatitis under the conditions OF germanium citrate administration

G. P. Kopylchuk, O. M. Voloshchuk, O. V. Balandyuk

o.voloschuk@chnu.edu.ua

Chernovtsi national university named after Yurii Fedkovych,
Institute of Biology, Chemistry and Bioresources,
Biochemistry and biotechnology department,
2 Kotsyubynskogo str., Chernivtsi 58000, Ukraine

Activity of rats’ liver marker enzymes under the conditions of acetaminophen-induced toxic liver injury and influence of germanium citrate was studied. Hepatitis was modeled in these rats by per os acetaminophen administration (1 g/kg in 2 % starch suspension for 2 days using a special catheter). Serum sorbitol dehydrogenase activity was determined by the kinetic method in the reaction of NADH-dependent reduction of D-fructose to D-sorbitol. Serum alanine aminotransferase (ALT) activity and aspartate aminotransferase (AST) was evaluated using a kit of reagents (Filicit-Diagnostica,Ukraine). It is shown that under the conditions of modeled toxic liver injury an increase of the enzymatic activity of sorbitol dehydrogenase, alanine transaminase and aspartate transaminase along with the elevation of De Ritis ratio was observed.

Administration of germanium citrate to the intact animals have shown that studied compound is devoid of hepatotoxic properties since the activity of the enzymatic markers of liver state (sorbitol dehydrogenase, AST, ALT) and De Ritis ratio remains on the control level.

Study of the hepatoprotector properties of the germanium citrate have shown that in animals with the previously modeled toxic liver injury and administration of germanium citrate a decrease by 2.5times of sorbitol dehydrogenase activity along with the restoration of transaminases activity and De Ritis ratio down to the control values was observed comparing to the animals which weren’t administered with studied compound. Established decrease of the enzymatic activities of marker liver enzymes opens the new perspectives for the study of biochemical mechanisms of the hepatoprotector properties of germanium citrate.

Кeywords: TOXIC LIVER INJURY, GERMANIUM CITRATE, SORBITOL DEHYDROGENASE, ALANINE TRANSAMINASE, ASPARTATE TRANSAMINASE, DE RITIS RATIO

1. Borlak J., Chatterji B., Londhe K. B., Watkins P. B. Serum acute phase reactants hallmark healthy individuals at risk for acetaminophen-induced liver injury. Genome Medicine, 2013, vol. 5, p. 86. https://doi.org/10.1186/gm493

2. Demidov V. I., Nazarenko O. A., Torshun I. Yu., Grishina T. R., Gromova O. A. The effectiveness of progepara in experimental liver damage alcohol and paracetamol: biochemistry and histology. Farmateka, 2011, no. 2, pp. 93–98. (in Russian)

3. Dremza I. K., Cheshchevik V. T., Zabrodskaya S. V., Maksimchik Y. Z., Sudnikovich E. Yu., Lapshina E. A., Zavodnik I. B. Hepatotoxic efects of acetaminophen. Protective properties of tryptophan-derivatives. Biomedical chemistry, 2010, vol. 56, no. 6, pp. 710–718. (in Russian) https://doi.org/10.18097/pbmc20105606710

4. Fisher K., Vuppalanchi R., Saxena R. Drug-Induced Liver Injury. Arch. Pathol. Lab. Med., 2015, vol. 139, pp. 876–887. DOI: 10.5858/ arpa.2014-0214-RA)

5. Fontana R. J. Acute Liver Failure including Acetaminophen Overdose. Med. Clin. North. Am., 2008, vol. 92, no. 4, pp. 761–794. https://doi.org/10.1016/j.mcna.2008.03.005

6. Freitag A. F., Cardia G. F., da Rocha B. A., Aguiar R. P., Silva-Comar F. M., Spironello R. A., Grespan R., Caparroz-Assef S. M., Bersani-Amado C. A., Cuman R. K. Hepatoprotective Effect of Silymarin (Silybum marianum) on Hepatotoxicity Induced by Acetaminophen in Spontaneously Hypertensive Rats. Evid. Based Complement Alternat. Med., 2015, 538317. https://doi.org/10.1155/2015/538317

7. Han D., Dara L., Win S., Than T. A., Yuan L., Abbasi S. Q., Liu Z.-X., Kaplowitz N. Regulation of drug-induced liver injury by signal transduction pathways: critical role of mitochondria. Trends in Pharmacological Sciences, 2013, vol. 34, no. 4, pp. 243–253. https://doi.org/10.1016/j.tips.2013.01.009

8. Kopylchuk G. P., Voloshchuk O. M. Modeling of the acetaminophen-induced disturbances of the bile producing liver function under the conditions of alimentary deprivation of protein. Biomedicine, 2015, no. 2. pp. 30–36. (in Russian)

9. Koroleva M. V. Exogenous toxic hepatitis. Modern look at etiology, pathogenesis, clinical course. Drug J., 2015, vol. 9, no. 2 (58), pp. 18–22. (in Russian)

10. Krecyun V. Y., Seyffulina I. Y., Godovan V. V. Prospects for the development of new drugs based on complex compounds of germanium Odessa Medical Journal, 2011, no. 1 (123), pp. 31–35. (in Ukrainian)

11. Kuvandik G., Duru M., Nacar A. Yonden Z., Helvaci R., Koc A., Kozlu T., Kaya H., Sogüt S. Effects of Erdosteine on Acetaminophen-induced Hepatotoxicity in Rats. Toxicologic Pathology, 2008, vol. 36, pp. 714–719. https://doi.org/10.1177/0192623308320800

12. Lee J. H., Kim K. W., Yoon M. Y., Lee J. Y., Kim C. J., Sim S. S. Anti-inflammatory effect of germaniumconcentrated yeast against paw oedema is related to the inhibition of arachidonic acid release and prostaglandin E production in RBL 2H3 cells. Auton. Autacoid. Pharmacol., 2005, vol. 25, no. 4, pp. 129–134. https://doi.org/10.1111/j.1474-8673.2005.00335.x

13. McGill M. R., Sharpe M. R., Williams C. D., Taha M., Curry S. C., Jaeschke H. The mechanism underlying acetaminopheninduced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. The Journal of Clinical Investigation, 2012, vol. 122, no. 4, pp. 1574–1583. https://doi.org/10.1172/JCI59755

14. Okovity S. V., Sukhanov D. S., Petrov A. Yu., Romantsov M. G. Hepatotropic medicines: current status. Terapevt. Arch., 2012, no. 2, pp. 62–68. (in Ukrainian)

15. Ozer J., Ratner M., Shaw M., Bailey W., Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology, 2008, vol. 245, no. 3, pp. 194–205. https://doi.org/10.1016/j.tox.2007.11.021

16. Rose C. I., Henderson A. R. Reaction rate assay of serum sorbitol dehydrogenase activity at 37 °C. Clin. Chem., 1975, vol. 21, pp. 1619–1624.

17. Singh A., Bhat T. K., Sharma O. P. Clinical Biochemistry of Hepatotoxicity. J. Clinic. Toxicol., 2011, S4:001. https://doi.org/10.4172/2161-0495.S4-001

18. Somanawat K., Thong-Ngam D., Klaikeaw N. Curcumin attenuated paracetamol overdose induced hepatitis. World J. Gastroenterol., 2013, vol. 19, no. 12, pp. 1962–1967. https://doi.org/10.3748/wjg.v19.i12.1962

19. Sumioka I., Matsura T., Yamada K. Acetaminophen-Induced Hepatotoxicity: Still an Important Issue. Yonago Acta medica, 2004, vol. 47, pp. 17–28.

20. Voloshchuk O. N., Kopylchuk G. P., Buchkovskaya I. M. Activity of the marker liver enzymes under the conditions of toxic hepatitis and alimentary deprivation of protein. Experimental & clinical gastroenterology, 2014, vol. 108, 8, pp. 96–100. (in Russian)

21. Zinko G. A., Slivinska L. G. The influence of selenium and germanium on separate links of pathogenesis of gastroenteritis of calves. The Animal Biology, 2015, vol. 17, no. 2, pp. 57–64. (in Ukrainian)

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