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

Author(s):  
Regina Roy ◽  
Hema CG ◽  
Geetha N

<p class="abstract"><strong>Background:</strong> Objectives:<strong> </strong>(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).<strong> </strong>(2) To study the same toxicities in albino rats and the protective role of vitamin E on these toxicities.<strong></strong></p><p class="abstract"><strong>Methods:</strong> 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). </p><p class="abstract"><strong>Results:</strong> 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<strong> </strong>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.</p><p class="abstract"><strong>Conclusions:</strong> The animal study revealed the protective role of vitamin E on cytostatic drug induced toxicities. </p><strong>Keywords: </strong>Acute lymphoblastic leukaemia (ALL), Antileukaemic drugs, Vitamin E (Vit. E), MCP841 protocol

2020 ◽  
Vol 26 (6) ◽  
pp. 1397-1406 ◽  
Author(s):  
Adel A Hagag ◽  
Ibrahim M Badraia ◽  
Walid A El-Shehaby ◽  
Maaly M Mabrouk

Background Leukemia is the most common pediatric malignancy. It affects bone marrow cells especially lymphoid cell precursor. Leukemia is treated mainly by chemotherapy. Doxorubicin is a well-established chemotherapeutic agent included in treatment protocols of acute lymphoblastic leukemia. Its efficacy is often limited by its cardiotoxic side effects. Many studies are directed to overcome this problem. Black seed oil was found to have a potent cardioprotective effect. Aim of the study: To assess the protective role of black seed oil against doxorubicin-induced cardiotoxicity in children with acute lymphoblastic leukemia. Subjects and methods This study was carried out on 40 children with acute lymphoblastic leukemia including 20 patients under doxorubicin therapy and black seed oil 80 mg/kg/dose divided into 3 doses starting at the same moment of beginning of doxorubicin infusion therapy and continued for 1 week after each doxorubicin dose [group I] and 20 patients under doxorubicin and placebo for 1 week after each doxorubicin dose [group II]. They underwent conventional echo-Doppler measures of left ventricular systolic and diastolic functions and pulsed wave tissue Doppler of lateral mitral annulus. Results No significant differences were found in parameters of electrocardiograph including S-T segment and Q-T interval either before or after doxorubicin therapy. No significant differences in echocardiographic parameters were found between group I and group II before therapy. Non-significant changes in parameters of diastolic function [E/A ratio or e/a ratio] were found after doxorubicin therapy in group I and II, but there were significant reduction in parameters of systolic function [EF, FS and s wave] after doxorubicin therapy more in group II than group I. Conclusion and recommendation: From this study, we concluded that: Black seed oil improves some cardiac side effects of doxorubicin as shown by better systolic functions in children with acute lymphoblastic leukemia who were treated with Doxorubicin and black seed (group I) than in children with acute lymphoblastic leukemia who were treated with doxorubicin alone with no black seeds (group II), and therefore multi center studies is recommended to be done before we can recommend the use of black seed oil as an adjuvant therapy in patients with acute lymphoblastic leukemia under doxorubicin-based treatment protocol.


2014 ◽  
Vol 37 (3) ◽  
pp. 442-452 ◽  
Author(s):  
Shereen A. Elkhateeb ◽  
Nehad F. Mazen ◽  
Osama Y. Ibrahim ◽  
Nermeen R. Abdel-Fattah

Blood ◽  
2004 ◽  
Vol 103 (1) ◽  
pp. 252-257 ◽  
Author(s):  
Maja Krajinovic ◽  
Stéphanie Lamothe ◽  
Damian Labuda ◽  
Émilie Lemieux-Blanchard ◽  
Yves Théorêt ◽  
...  

Abstract The central role of methylenetetrahydrofolate reductase (MTHFR) in the folate metabolism renders MTHFR gene polymorphisms (C677T and A1298C) potential modulators of a variety of disorders whose development depends on folate/homocysteine imbalance. Here, we provide additional evidence on the protective role of these polymorphisms in acute lymphoblastic leukemia (ALL), the most common pediatric cancer. A case-control study was conducted in 270 ALL patients and 300 healthy controls of French-Canadian origin. The TT677/AA1298 and CC677/CC1298 individuals were associated with reduced risk of ALL (crude odds ratio [OR] = 0.4; 95% confidence interval [CI], 0.2-0.9; and OR = 0.3; 95% CI, 0.1-0.6; respectively). Further stratification in patients born before and after January 1996 (approximate time of Health Canada recommendation for folic acid supplement in pregnancy) revealed that the protective effect of MTHFR variants is accentuated and present only in children born before 1996. Similar results were obtained when a transmission disequilibrium test was performed on a subset of children (n = 95) in a family-based study. This finding suggests gene-environment interaction and its role in the susceptibility to childhood ALL, which is consistent with previous findings associating either folate deficiency or MTHFR polymorphisms with risk of leukemia.


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