Rytsyk O. B., Fira L. S., Lyhatskyy P. G.

THE STUDY OF MEMBRANES’ PROTECTIVE PROPERTIES OF RESVERATROL UNDER NEOPLASTIC INTOXICATION IN RATS


About the author:

Rytsyk O. B., Fira L. S., Lyhatskyy P. G.

Heading:

CLINICAL AND EXPERIMENTAL MEDICINE

Type of article:

Scentific article

Annotation:

The prevalence of cancer is rapidly increasing in all countries of the world. Colorectal cancer is the third most common type of cancer in Europe. The severity of the patients with this pathology is often due to a violation of the permeability of the cytoplasmic membranes and the destruction of cells, which leads to a change in the activity of organ-specific enzymes. This may be one of the tests to detect the severity of the oncological process. The aim of this work was to investigate the membrane-protective properties of resveratrol in conditions induced carcinogenesis. The object and methods. Experiments were carried out on white male rats, which modeled colon cancer by weekly subcutaneous administration of 1,2-dimethylhydrazine (DMH) at a dose of 7.2 mg/kg of body weight for 30 weeks. Antioxidant resveratrol was injected intragastrally at a dose of 20 mg/kg daily for 7 months. The state of cytoplasmic membranes was evaluated by activity of gamma-glutamyltransferase (GGT), alanine and aspartate aminotransferase (ALT and AST), erythrocytic index of intoxication (EII). Results. Under conditions of DMH-induced carcinogenesis an increase in the activity of GGT in serum is observed at all times of the experiment (for 7 months, the activity of the enzyme is 2.3 times that of the norm). In the liver homogenate there is a decrease in the activity of GGT and at the 7th month, this figure was twice as low as the intact group. Against the background of the use of resveratrol, the GGT activity in serum was lower by 120% in the corresponding study period, compared to the indicator in animals for which no correction was applied. In the liver of rats, the activity of this enzyme increased and this indicator was higher than the level of affected DMH animals by 52.2% at the 7th month of the experiment. The determination of activity of membrane-dependent enzymes – AST and ALT, which are markers of cytolytic processes in an organism, was also investigated. There was an increase in the activity of ALT in serum under the action of DMH: 3 months – by 119.7%, 5 months – 213.5%, 7 months – 220.8%. In the homogenate of the liver there was a decrease of this indicator by 39.0%, 55.0%, 61.3% compared with intact control in the appropriate time. After resveratrol administration, the activity of ALT in serum in the 3rd month of study was 58.4% lower than in the DMHtreated group, by 97.7% in the 5th month and by 102.8% in the 7th month. A similar dynamics was observed in the study of AST. At the 7th month of study, this indicator was 3.6 times higher than intact control in serum, and 3.5 times lower in liver homogenate. In the group of treated animals, this indicator decreased by 230.0% in serum compared with the group of affected DMH animals, and increased by 63.7% in the liver during the corresponding period of the study. Along with changes in the permeability of hepatocyte membranes, there was a change in the permeability of the erythrocytic membrane, which confirms the increase in the percentage of EII. Thus, in the 3rd month – by 27.4%, the 5th – by 55.2%, and the 7th – by 65.9%, the degree of permeability of the erythrocytic membrane is greater in the group of affected animals than in the group of intact control. The applied antioxidant has led to a decrease in EII (at the 7th month it was lower by 50.7% compared with the group where the correction was not used), which indicates the stabilization of the permeability of erythrocytes membranes under the influence of resveratrol. Conclusions. Under the conditions of neoplastic carcinogenesis, activation of cytolytic processes occurs, which leads to a change in the permeability of plasma membranes of hepatocytes and erythrocytes. The used antioxidant – resveratrol, caused a decrease in the activity of organ-specific enzymes in serum and led to a marked decrease in the erythrocytic index of intoxication. The obtained results confirm the membrane-protective properties of resveratrol, which allows to recommend its inclusion in the complex therapy of oncological diseases.

Tags:

free radicals, neoplastic intoxication, colorectal cancer, cytolysis, endotoxemia, resveratrol.

Bibliography:

  1. Mykhailovych YuY, Zhurbenko AV, Sumkina OV. Praktychni aspekty vprovadzhennia skryninhu kolorektalnoho raku v Ukraini. Sotsialnoekonomichne obgruntuvannia. Klynycheskaia onkolohyia. 2013;3:6-10. [in Ukrainian].
  2. Perse M, Cerar A. The dimethylhydrazine induced colorectal tumours in rat-experimental colorectal carcinogenesis. Radiol. Oncol. 2005;39(1):61-70.
  3. Filinska OM, Yablonska SV, Lynchak OV, Burlaka AP, Ostrovska HV, Rybalchenko TV, ta in. Vplyv pokhidnoho maleimidu na rozvytok okysnoho stresu v pechintsi pry indukovanomu 1,2-dymetylhidrazynom kantserohenezi tovstoho kyshechnyka shchuriv. Dopovidi Natsionalnoi akademii nauk Ukrainy. 2010;8:185-90. [in Ukrainian].
  4.  Beijnen JH, Schellens JH. Drug interactions in oncology. Lancet Oncol. 2004;5(8):489-96.
  5. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat. Rev. Drug Discov. 2006;5:493-506.
  6. Aziz MH, Kumar R, Ahmad N. Cancer chemoprevention by resveratrol: in vitro and in vivo studies and the underlying mechanisms (review). Int J Oncol. 2003;23:17-28.
  7. Bishayee A. Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials. Cancer Prev Res (Phila). 2009;2:409-18.
  8. Britton RG, Kovoor C, Brown K. Direct molecular targets of resveratrol: identifying key interactions to unlock complex mechanisms. Ann N Y Acad Sci. 2015;1348:124-33.
  9. Saud SM, Li W, Morris NL, Matter MS, Colburn NH, Kim YS, et al. Resveratrol prevents tumorigenesis in mouse model of Kras activated sporadic colorectal cancer by suppressing oncogenic Kras expression. Carcinogenesis. 2014;35:2778-86.
  10. Soroka YuV. Sorbtsiina korektsiia zmin imunolohichnoi reaktyvnosti shchuriv za umov eksperymentalnoho kantserohenezu ta zastosuvannia khimioterapevtychnykh chynnykiv. Svit biolohii ta medytsyny. 2013;4:82-6. [in Ukrainian].
  11. Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001 Aug;38(4):263-355.
  12. Kamyshnukov VS. Spravochnyk po klynyko-byokhymycheskoi laboratornoi dyahnostyke: v 2-kh t. Mynsk: Belarus; 2000. 1: 495 s.; 2: 463 s. [in Russian].
  13. Chaplyk VV, Lytvynchuk VH. Do pytannia endohennoi intoksykatsii. Eksperym. ta klinich. fiziolohiia i biokhimiia. 2006;3:66-71. [in Ukrainian].
  14. Gross D, Tolba R. Ethics in Animal-Based Research. Eur. Surg. Res. 2015;55(1-2):43-57. 15.Okeh U. Statistical problems in medical research. East. Afr. J. Public. Health. 2009;6(1):1-7.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 2 Part 1 (150), 2019 year, 187-190 pages, index UDK 599.32.616-006:65.9]-092.4

DOI: