Ukr.Biochem.J. 2013; Volume 85, Issue 3, May-Jun, pp. 74-84

doi: http://dx.doi.org/10.15407/ubj85.03.074

Effect of dihydropyrrol and maleimide derivatives on the state of the liver and colon in normal rats and those with colorectal carcinogenesis induced by dimethylhydrazine

H. M. Kuznietsova, O. V. Lynchak, M. O. Danylov, I. P. Kotlyar, V. K. Rybalchenko

Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: gala_kuznetsova@rambler.ru

No liver and colon alterations in rats, caused by cytostatic compounds 5-amino-4-(1,3-benzothyazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3Н-pyrrol-3-one (D1) and 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrol-2,5-dione (MI-1) when administered over a long time were found, as evidenced by the histopathological data and the data of activity of transaminases, alkaline phosphatase and lactate dehydrogenase in the blood serum. D1 and MI-1 in vivo decrease the total area of DMH-induced colon tumors in rats by 46-60%. Furthermore, D1 and MI-1 partially protect the liver and colon mucosa from toxic effects caused by 1,2-dimethylhydrazine (DMH) reducing DNA oxidative modifications, as evidenced by urine 8-hydroxydeoxyguanosine level. The effects of both compounds are similar, but MI-1 is less toxic for the liver and colon of intact animals possessing more pronounced antitumor activity and protective properties in the setting of chemically induced carcinogenesis.

Keywords: , , , , ,


References:

  1. Oliynichenko PI, Bulkina ZP, Siniboroda TI. Handbook on tumor polychemotherapy.  K.: Zdorov’e, 2000. 301 p.
  2. Teletaeva GM. Prevention and treatment of gastrointestinal complications during drug therapy (nausea and vomiting, mucositis, diarrhea). Practical Oncology. 2009;10(3):158-167.
  3. Dancey J, Sausville EA. Issues and progress with protein kinase inhibitors for cancer treatment. Nat Rev Drug Discov. 2003 Apr;2(4):296-313. Review. PubMedCrossRef
  4. Watters AL, Epstein JB, Agulnik M. Oral complications of targeted cancer therapies: a narrative literature review. Oral Oncol. 2011 Jun;47(6):441-8. Epub 2011 Apr 22. Review. PubMed, CrossRef
  5. Elez E, Macarulla T, Tabernero J. Handling side-effects of targeted therapies: safety of targeted therapies in solid tumours. Ann Oncol. 2008 Sep;19 Suppl 7:vii146-52.  PubMedCrossRef
  6. Pestalozzi BC, Knuth A. New antibodies in cancer treatment. Praxis (Bern 1994). 2004 Sep 22;93(39):1589-92. Review. German. PubMed
  7. Broekman F, Giovannetti E, Peters GJ. Tyrosine kinase inhibitors: Multi-targeted or single-targeted? World J Clin Oncol. 2011 Feb 10;2(2):80-93. PubMed, PubMedCentral, CrossRef
  8. Imyanitov EN. General ideas of targeted therapy. Practical Oncology. 2010;11(3):123-130.
  9. Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer. 2009 Jan;9(1):28-39. Review. PubMed, CrossRef
  10. Krishnamurty R, Maly DJ. Biochemical mechanisms of resistance to small-molecule protein kinase inhibitors. ACS Chem Biol. 2010 Jan 15;5(1):121-38. Review.  PubMed, PubMedCentral, CrossRef
  11. Pat. 22204 (UA), Ab1K31/40. The compound 1,4-substituted 5-amino-1,2-dihydropyrrole-3-on that exhibits anticancer activity /Dubinina G.G., Volovenko Yu.M. – Publ. 25.04.2007, Bull. No 5.
  12.  Garmanchuk LV, Senchylo NV, Nikulina VV, Denis EO, Nepiyvoda KD, Nikolaenko TV, Ostapchenko LI. Determination of cytotoxic/cytostatic effect natural and synthetic agents for cultured cells. Physics Alive. 2011;19(2):51-53.
  13. Perse M, Cerar A.  The dimethylhydrazine induced colorectal tumours in rat – experimental colorectal carcinogenesis. Radiol Oncol. 2005;39(1):61-70.
  14. Zhukov NV, Tjulandin SA. Targeted therapy in the treatment of solid tumors: practice contradicts theory. Biochemistry (Mosc). 2008 May;73(5):605-18. PubMedCrossRef
  15. Piñeiro-Carrero VM, Piñeiro EO. Liver. Pediatrics. 2004 Apr;113(4 Suppl):1097-106. Review. PubMed
  16. Afzal S, Jensen SA, Sørensen JB, Henriksen T, Weimann A, Poulsen HE. Oxidative damage to guanine nucleosides following combination chemotherapy with 5-fluorouracil and oxaliplatin. Cancer Chemother Pharmacol. 2012 Feb;69(2):301-7. PubMedCrossRef
  17. Wang T, Leng YF, Zhang Y, Xue X, Kang YQ, Zhang Y. Oxidative stress and hypoxia-induced factor 1α expression in gastric ischemia. World J Gastroenterol. 2011 Apr 14;17(14):1915-22. PubMed, PubMedCentral, CrossRef
  18. Perry G, Nunomura A, Hirai K, Zhu X, Pérez M, Avila J, Castellani RJ, Atwood CS, Aliev G, Sayre LM, Takeda A, Smith MA. Is oxidative damage the fundamental pathogenic mechanism of Alzheimer’s and other neurodegenerative diseases? Free Radic Biol Med. 2002 Dec 1;33(11):1475-9. Review. PubMed, CrossRef
  19. Cohen RA, Tong X. Vascular oxidative stress: the common link in hypertensive and diabetic vascular disease. J Cardiovasc Pharmacol. 2010 Apr;55(4):308-16. Review. PubMed, PubMedCentral, CrossRef
  20. Burlaka EA. Disorders induced by oxidation upon arterial hypertension in children and adolescents and their correction: Avtoref. dis. …kand.med.nauk. Kyiv, 2009. 28 p.
  21. Maynard S, Schurman SH, Harboe C, de Souza-Pinto NC, Bohr VA. Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis. 2009 Jan;30(1):2-10. Review. PubMed, PubMedCentral, CrossRef
  22. Mizutani H, Tada-Oikawa S, Hiraku Y, Kojima M, Kawanishi S. Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide. Life Sci. 2005 Feb 11;76(13):1439-53. PubMed, CrossRef
  23. Burlaka AP, Sidorik EP. The reactive oxygen/nitrogen species in the process of tumor growth.  K.: Nauk. Dumka, 2006. 228 p.
  24. Sova H, Jukkola-Vuorinen A, Puistola U, Kauppila S, Karihtala P. 8-Hydroxydeoxyguanosine: a new potential independent prognostic factor in breast cancer. Br J Cancer. 2010 Mar 16;102(6):1018-23. PubMed, PubMedCentral, CrossRef
  25. Joseph EK, Chen X, Bogen O, Levine JD. Oxaliplatin acts on IB4-positive nociceptors to induce an oxidative stress-dependent acute painful peripheral neuropathy. J Pain. 2008 May;9(5):463-72. PubMedCrossRef
  26. Obtulowicz T, Swoboda M, Speina E, Gackowski D, Rozalski R, Siomek A, Janik J, Janowska B, Ciesla JM, Jawien A, Banaszkiewicz Z, Guz J, Dziaman T, Szpila A, Olinski R, Tudek B. Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients. Mutagenesis. 2010 Sep;25(5):463-71. PubMed, CrossRef
  27. Filinska OM, Yablonska SV, Lynchak OV, Burlaka AP, Ostrovska GV, Rybalchenko TV, Lukyanchuk EV. The influence of maleimide derivative on the development oxidative stress of liver in 1,2-dimethylhydrazine-induced colon cancer in rats.  Dopovidi Nats Akad Nauk Ukrainy. 2010;(8):185-190.
  28. Goralskii LP, Khomich VT, Kononskii OI. Fundamentals of histological techniques and morphofunctional methods of research in health and diesease, Zhitomir: Polissya, 2005. 228 p.
  29. Yablonska SV, Filinska OM, Ostrovska GV, Rybalchenko VK. Evaluation of hepatotoxisity of novel maleimide derivative with cytostatic activity and its influense on peroxidation process and antioxidant system in liver. Ukr Biokhim Zhurn. 2009 Sep-Oct;81(5):83-92. PubMed
  30.  Zaitsev VM, Liflyandskii VG, Marinkin VI. Applied medical statistics. M.:Foliant, 2006. 432 p.
  31. Aruin LI, Kapuller LP, Isakov VA. Morphological diagnostics of diseases of the stomach and intestines. M., 1998. 496 p.
  32. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005 Feb 1;172(3):367-79. Review. PubMed, PubMedCentral, CrossRef
  33. Preston TJ, Henderson JT, McCallum GP, Wells PG. Base excision repair of reactive oxygen species-initiated 7,8-dihydro-8-oxo-2′-deoxyguanosine inhibits the cytotoxicity of platinum anticancer drugs. Mol Cancer Ther. 2009 Jul;8(7):2015-26. PubMed, PubMedCentral, CrossRef
  34. Onose J, Imai T, Hasumura M, Ueda M, Hirose M. Rapid induction of colorectal tumors in rats initiated with 1,2-dimethylhydrazine followed by dextran sodium sulfate treatment. Cancer Lett. 2003 Aug 20;198(2):145-52. PubMed
  35. Guidelines for preclinical study of the specific activity of anticancer drugs suggested for testing in the clinic. M.: Ministry of Health of the Russian Federation, 2000.
  36. Baskar AA, Ignacimuthu S, Paulraj GM, Al Numair KS. Chemopreventive potential of beta-Sitosterol in experimental colon cancer model–an in vitro and In vivo study. BMC Complement Altern Med. 2010 Jun 4;10:24. PubMedPubMedCentral, CrossRef
  37. Kaneko T, Tahara S, Takabayashi F. Inhibitory effect of natural coumarin compounds, esculetin and esculin, on oxidative DNA damage and formation of aberrant crypt foci and tumors induced by 1,2-dimethylhydrazine in rat colons. Biol Pharm Bull. 2007 Nov;30(11):2052-7. PubMed
  38. Kuznyetsova GM, Volovnenko TA, Ostrovska GV, Volovenko YuM, Rybalchenko VK. The influence of cytostatic compound dihydropyrrol derivative on rat bowel tunica mucosa under oxidative stress condition. Dopovidi Nats Akad Nauk Ukrainy. 2012;(2):174-179.

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