Ukr.Biochem.J. 2019; Volume 91, Issue 1, Jan-Feb, pp. 92-99

doi: https://doi.org/10.15407/ubj91.01.092

Evaluation of biochemical indicators in blood plasma of rats with tetracycline-induced hepatosis and their correction by milk phospholipids

V. A. Gryshchenko1, V. V. Musiychuk1, V. O. Chernyshenko2,
O. V. Gornytska2, T. M. Platonova2

1National University of Life and Environmental Sciences of Ukraine, Kyiv;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
е-mail: viktoriya_004@ukr.net

Received: 13 July 2018; Accepted: 13 December  2018

Tetracycline is a drug with direct cytotoxic action on the liver, and therefore it is widely used in pharmaceutical studies of therapeutic effectiveness of hepatoprotective preparations. The aim of the present work was to determine the biochemical indicators in blood plasma of rats with tetracycline-induced hepatosis and correction properties of milk phospholipids under tetracycline-induced hepatosis in rats. To achieve this, Wistar rats were administered 250 mg/kg of 4% tetracycline hydrochloride suspension once a day intragastrically. As the corrective therapy, 1% solution of BAS “FLP-MD” was administered in liposomal form based on milk phospholipids. Under modeled steatohepatitis, significant destructive changes were observed in the cell membranes of hepatocytes in experimental rats. It was confirmed by higher activity of transaminase (in particular, activity of АSТ increased 4 times, that of ALT 1.7 times and the AST/ALT ratio was increased 2.4 times in blood plasma). The synthesis of clotting factors in livers of animals with hepatosis was inhibited. The content of fibrinogen in blood plasma decreased by 21%, factor II (prothrombin) by 27.8%, Xa-factor by 27.9%, and protein C by 40.6%. The animals also had hypochromic anemia, azotemia and bilirubinemia. The calcium-phosphor metabolism and hyperkalemia were observed. The liposomal BAS “FLP-MD” based on milk phospholipids diminished harmful effects of tetracycline, in particular supporting blood coagulation factors’ level restoration, and also by the activity of transaminases. According to the results, it may be used in prophylactics and pharmaceutical correction of steatohepatitis.

Keywords: , , , , ,


References:

  1. Okudo J, Anusim N. Hepatotoxicity due to Clindamycin in Combination with Acetaminophen in a 62-Year-Old African American Female: A Case Report and Review of the Literature. Case Reports Hepatol. 2016;2016:2724738.  PubMed, PubMedCentral, CrossRef
  2. Bawany MZ, Bhutto B, Youssef WI, Nawras A, Sodeman T. Acute liver failure: an uncommon complication of commonly used medication. Am J Ther. 2013 Sep-Oct;20(5):566-8. PubMed, CrossRef
  3. Begriche K, Massart J, Robin MA, Borgne-Sanchez A, Fromenty B. Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver. J Hepatol. 2011 Apr;54(4):773-94. PubMed, CrossRef
  4. Teschke R, Schulze J, Schwarzenboeck A, Eickhoff A, Frenzel C. Herbal hepatotoxicity: suspected cases assessed for alternative causes. Eur J Gastroenterol Hepatol. 2013 Sep;25(9):1093-8.  PubMed, CrossRef
  5. Björnsson ES, Hoofnagle JH. Categorization of drugs implicated in causing liver injury: Critical assessment based on published case reports. Hepatology. 2016 Feb;63(2):590-603. PubMed, CrossRef
  6. Fabbrini E, Magkos F. Hepatic Steatosis as a Marker of Metabolic Dysfunction. Nutrients. 2015 Jun 19;7(6):4995-5019. PubMed, PubMedCentral, CrossRef
  7. Kawano Y, Cohen DE. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease. J Gastroenterol. 2013 Apr;48(4):434-41. PubMed, PubMedCentral, CrossRef
  8. Bechmann LP, Hannivoort RA, Gerken G, Hotamisligil GS, Trauner M, Canbay A. The interaction of hepatic lipid and glucose metabolism in liver diseases. J Hepatol. 2012 Apr;56(4):952-64. PubMed, CrossRef
  9. Blas-García A, Apostolova N, Valls-Bellés V, Esplugues JV. Endoplasmic Reticulum and Mitochondria: Independent Roles and Crosstalk in Fatty Liver Diseases and Hepatic Inflammation. Curr Pharm Des. 2016;22(18):2607-18. PubMed, CrossRef
  10. Devbhuti P, Saha A, Sengupta C. Clindamycin: effects on plasma lipid profile and peroxidation parameters in rabbit blood plasma. Acta Pol Pharm. 2015 Mar-Apr;72(2):253-60. PubMed
  11. Rui L. Energy metabolism in the liver. Compr Physiol. 2014 Jan;4(1):177-97. PubMed, PubMedCentral, CrossRef
  12. Rousseau A, Woodhams B, Paunet-Bobo M, Van Dreden P, Bigot D, Leclerc S, Lenormand B, Vasse M. Decreased procoagulant phospholipids in patients treated by vitamin K antagonists. Thromb Res. 2012 Sep;130(3):491-4. PubMed, CrossRef
  13. Hryshchenko VA, Tomchuk VA, Lytvynenko OM, Chernyshenko VO, Gryshchuk VI, Platonova TM. An estimate of protein synthesis in liver under induced hepatitis. Ukr Biokhim Zhurn. 2011 Jan-Feb;83(1):63-8. (In Ukrainian). PubMed
  14. Kopec AK, Joshi N, Luyendyk JP. Role of hemostatic factors in hepatic injury and disease: animal models de-liver. J Thromb Haemost. 2016 Jul;14(7):1337-49. PubMed, PubMedCentral, CrossRef
  15. Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev. 2013 Jan;93(1):327-58. PubMed, CrossRef
  16. Owens AP 3rd, Mackman N. Microparticles in hemostasis and thrombosis. Circ Res. 2011 May 13;108(10):1284-97. PubMed, PubMedCentral, CrossRef
  17. Yu HY, Wang BL, Zhao J, Yao XM, Gu Y, Li Y. Protective effect of bicyclol on tetracycline-induced fatty liver in mice. Toxicology. 2009 Jul 10;261(3):112-8. PubMed, CrossRef
  18. Grattagliano I, Diogo CV, Mastrodonato M, de Bari O, Persichella M, Wang DQ, Liquori A, Ferri D, Carratù MR, Oliveira PJ, Portincasa P. A silybin-phospholipids complex counteracts rat fatty liver degeneration and mitochondrial oxidative changes. World J Gastroenterol. 2013 May 28;19(20):3007-17.
    PubMed, PubMedCentral, CrossRef
  19. Vlizlo VV, Fedoruk RS, Ratych IB. Laboratory methods of investigation in biology, stock-breeding and veterinary. Spolom, Lviv, 2012. 764 p. (In Ukrainian).
  20. Melnychuk DO, Tomchuk VA, Yanchuk PI, Gryshchenko VA, Reshetnyk EM, Synelnyk TB. Research methods of liver and biliar system functional state. Kyiv: NUBiP Ukraine, 2015. 414 p. (In Ukrainian).
  21. Pаt. 86516 UA, ICP 61К 35/20, А23К 1/00. Veterinary bioactive addidition of liposomal form and method of reparative therapy in hepatology / Melnychuk D. O., Gryshchenko V. A., Lytvynenko O. M. Publ. 27.04.2009, Bul. N 8. (In Ukrainian).
  22. Dolgov VV, Svirin PV. Laboratory diagnostics of hemostasis disorders. M.-Tver’: Triada, 2005. 227 s. (In Russian).
  23. Sokolovska AS, Chernyshenko TM, Ivanenko TI. Comparative characteristic of methods for determination of the fibrinogen content in blood plasma. Exp Clin Physiol Biochem. 2002;3:82-86. (In Ukrainian).
  24. Gornitskaya OV, Platonova TN. Purification and characteristic of the protein С activator from Agkistrodon halys halys snake venom. Biomed Khimia. 2003;49(5):470-479 (In Russian).
  25. Forkin KT, Colquhoun DA, Nemergut EC, Huffmyer JL. The Coagulation Profile of End-Stage Liver Disease and Considerations for Intraoperative Management. Anesth Analg. 2018 Jan;126(1):46-61. PubMed, CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.