DOI: http://dx.doi.org/10.18203/issn.2454-2156.IntJSciRep20150200

Toxicity profile of anticancer drugs in acute lymphoblastic leukemia and protective role of vitamin E on these toxicities in albino rats

Regina Roy, Hema CG, Geetha N

Abstract


Background: Objectives: (1) To study the spectrum of toxicity due to chemotherapy as per MCP841 protocol during the acute phase of treatment of patients with Acute Lymphoblastic Leukemia (ALL). (2) To study the same toxicities in albino rats and the protective role of vitamin E on these toxicities.

Methods: This was a prospective clinical study for one year, in the department of medical oncology and paediatric oncology which was augmented by experimental animal study for 5 months using albino rats. For clinical study, patients diagnosed as ALL taking treatment as per MCP841 protocol were taken. Patients were followed up every day to detect the development of any type of adverse reactions or toxicity symptoms. Laboratory tests done during the course of chemotherapy were reviewed for any abnormality. Animal study involved 18 albino rats; rats were divided into 3 Groups; Group 1 - control (n=6), Group 2 - antileukaemic treated rats (n=6), Group 3 - antileukaemic drugs and vitamin-E treated rats (n=6). 

Results: In the clinical study major toxicities observed were haematological, metabolic, gastrointestinal, general infection, neurotoxicity, pancreatitis, pneumonitis and jaundice. Neurosensory toxicity presented as numbness in the extremities and hyperalgesia and myalgia. Histopathological examination of the internal organs of albino rats studied showed protection of vitamin E for the gastric toxicity, pancreatitis, cardiac toxicity, neuro toxicity and hepatic toxicity whereas there was no reduction in splenic and renal toxicities. In the case of haematological toxicity, protection was only minimal.

Conclusions: The animal study revealed the protective role of vitamin E on cytostatic drug induced toxicities. 

Keywords: Acute lymphoblastic leukaemia (ALL), Antileukaemic drugs, Vitamin E (Vit. E), MCP841 protocol

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References


Charlotte M, Niemeyer, Stephen E, Sallan. Acute lymphoblastic leukemic. Nathan, Oski’s Haematol Infancy Childhood. 1998;2:1246-69.

Spiegel RJ. The acute toxicities of chemotherapy. Cancer Treat. 1981;8:197.

Judith F. Margolin, David G. Poplack. acute lymphoblastic leukemia. Philip A. Pizzo, David G. Poplack, eds. Principles and Practice of Paediatric Oncology. 3rd ed. Philadelphia: Lippincott Raven; 1997: 409-446.

Klaas Hoekman, Wim JF, van der Vijgh, Jan B. Vermorken. Clinical and preclinical modulation of chemotherapy induced toxicity in patients with cancer. Drugs. 1999 Feb;57(2):133-5.

Banimir I. Sikic. The rational basis of cancer chemotherapy. In: Charles R. Craig, Robert E. Stitzel, eds. Modern Pharmacology. 3rd ed. Boston: Little, Brown and Company (Medical Division); 1990: 778-782.

Bruce A. Chabner, Carmen J. Allegra, Gregory A. Curt, Paul Calabresi. Antineoplastic agents. In: Bruce A. Chabner, Carmen J. Allegra, Gregory A. Curt, Paul Calabresi, eds. Goodman and Gilman. The Pharmacological Basis of Therapeutics. 9th ed. New York: McGraw-Hill Professional; 1996: 1233-1287.

Cirillo R, Sacco G, Venturella S, Bright Well J, Giachetti A, Manzini S. Comparison of Doxorubicin and MEN 10755 - induced long term progressive cardiotoxicity in the rat. J Cardiovasc Pharmacol. 2000 Jan;35(1):100-8.

Wahab MH, Akoul KS, Abdul Aziz AA. Modulatory effects of melatonin and Vit.E on ADR induced cardiotoxicity in Ehrlich ascitis carcinoma bearing mice. Tumori. 2000 Mar-Apr;86(2):357-62.

Frank M. Balis, John S. Holcenberg, David G. Poplack. Corticosteroids. In: Philip A. Pizzo, David G. Poplack, eds. General Principles of Chemotherapy: Principles and Practice of Paediatric Oncology. 3rd ed. Philadelphia: Lippincott-Raven; 1997: 215-260.

Smeland E, Fuskevag OM, Nymann K, Svendesn JS, Olsen R, Lindal S, et al. High dose 7 - hydroxymethotrexate : acute toxicity and lethality in a rat model. Cancer Chemother Pharmacol. 1996;37(5):415-22.

Weiji NI, Cleton, FJ, Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treat Rev. 1997;23:209-40.

Keizer HG, Pinedo HM, Schuurhuis GJ, Joenje H. Doxorubicin: a critical review of free radical dependent mechanism of cytotoxicity. Pharmacol Ther. 1990;47:219-31.

Canturk NZ, Canturk Z, Ozbilim G, Yenisey C. Protective effect of Vit.E on gastric mucosal injury in rats with biliary obstruction. Can J Gastroenterol. 2000 Jun;14(6):499.

Peter A. Mayes. Structure and function of the lipid soluble vitamins. In: Peter A. Mayes, eds. Harper’s Biochemistry. 23rd ed. UK: Appleton & Lange; 1993: 592.

Houba PH, Leenders RG, Boven E, Scheeren JW, Pinedo HM, Haisma HJ. Characterization of novel anthracycline prodrugs activated by human β glucuronidase for use in antibody directed enzyme prodrug therapy. Biochem Pharmacol. 1996;52:455-63.