Protective role of black seed oil in doxorubicin-induced cardiac toxicity in children with acute lymphoblastic leukemia

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.

2021 ◽  
Author(s):  
Amany Mohamed Shalaby ◽  
Adel Mohamed Aboregela ◽  
Mohamed Ali Alabiad ◽  
Mona Tayssir Sadek

Abstract Diabetes mellitus (DM) represents a widespread metabolic disease with a well-known neurotoxicity in both central and peripheral nervous systems. Oxymatrine is a traditional Chinese herbal medicine that has various pharmacological activities including; anti-oxidant, anti-apoptotic and anti-inflammatory potentials. The present work aimed to study the impact of diabetes mellitus on the cerebellar cortex of adult male albino rat and to evaluate the potential protective role of oxymatrine using different histological methods. Fifty-five adult male rats were randomly divided into three groups: group I served as control, group II was given oxymatrine (80 mg/kg/day) orally for 8 weeks and group III was given a single dose of streptozotocin (50mg/kg) intaperitoneally to induce diabetes. Then diabetic rats were subdivided into two subgroups: subgroup IIIa that received no additional treatment and subgroup IIIb that received oxymatrine similar to group II. The diabetic group revealed numerous changes in the Purkinje cell layer in the form of multilayer arrangement of Purkinje cells, shrunken cells with deeply stained nuclei as well as focal loss of the Purkinje cells. A significant increment in GFAP and synaptophysin expression was reported. Transmission electron microscopy showed irregularity and splitting of myelin sheaths in the molecular layer, dark shrunken Purkinje cells with ill-defined nuclei, dilated Golgi saccules and dense granule cells with irregular nuclear outlines in the granular layer. In contrast, these changes were less evident in diabetic rats that received oxymatrine. In conclusion, Oxymatrine could protect the cerebellar cortex against changes induced by DM.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1631-1631
Author(s):  
Stefan Kuhle ◽  
Maria Spavour ◽  
Jacqueline Halton ◽  
Patricia Massicotte ◽  
Irene Cherrick ◽  
...  

Abstract BACKGROUND: Asymptomatic deep venous thrombosis (DVT) are well-known complications of treatment of acute lymphoblastic leukemia (ALL) in children. However, the clinical significance of radiographically detected, asymptomatic DVT is unclear and controversial, as there are no studies on long-term outcome of asymptomatic DVT in children available. There are two likely reasons for the studies not being done in this area. First, there is a lack of defined cohorts of pediatric patients screened for DVT and secondly, there is a great deal of difficulty in following patients over many years. The study, Prophylaxis with Antithrombin Replacement in Kids with ALL treated with L-Asparaginase (PARKAA) was a multicentre randomized controlled trial in which children with ALL were screened for DVT. As survivors of childhood cancer, the PARKAA cohort continues to be followed in their respective centers. Therefore, establishment of the PARKAA cohort (1997–99) and the ability to locate these patients provided a unique opportunity to study the long-term outcome of asymptomatic DVT. OBJECTIVE: To assess the incidence of PTS in children with ALL who previously had an asymptomatic DVT. The objective were approached in two ways. Firstly, to assess the outcome of asymptomatic DVT by determining the prevalence of PTS in children with a history of ALL with radiographically diagnosed DVT (PARKAA cohort); secondly, to corroborate the findings by determining the prevalence of PTS in an unselected group of survivors of childhood ALL. METHODS: Cross-sectional study in two separate populations: Group I comprised of children enrolled in the PARKAA multicentre study who had been screened for, and diagnosed with, DVT in the upper venous system. Group II consisted of non-selected patients < 21 years with a history of ALL followed at Stollery Children’s Hospital, Edmonton. Patients were invited for a follow-up at their treatment centre (Group I) or were assessed for PTS childhood cancer survivor clinic (Group II). PTS was assessed by two of the investigators (Group I) or by the attending oncologist (Group II), respectively, using a standardized scoring sheet. RESULTS: Group I: 13 PARKAA patients with a history of ALL and objectively diagnosed DVT were assessed for PTS (4 males; median age 11.9 years; median age at diagnosis of ALL 4.4 years). 7/13 patients had PTS (54%, 95%CI 25;81). All patients with PTS had collaterals on examination, 3 also had increased arm circumference. Group II: 41 patients with a history of ALL were enrolled (61% males; median age at diagnosis 3.0 years; 28% high-risk, 67% standard risk). Mean length of follow-up since diagnosis was 9.5 years. PTS was diagnosed in 10/41 (24%; 95%CI 11–38) patients. All patients with PTS had collaterals on examination, 5 (50%) also had increased arm circumference. CONCLUSIONS: There is a clinically significant prevalence of PTS in children with a history of ALL and radiographically diagnosed DVT. A significant proportion of survivors of ALL develop PTS, indicating previously undiagnosed DVT in this population.


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


Author(s):  
Arul Daniel J ◽  
Susmita Das ◽  
Neethu Jayan ◽  
Asha Devi S

Objectives: Various clinically available drugs along with the beneficial action also have drastic side effects due to chronic exposure. In liver, these resulting side effects can be over production of reactive oxygen species, which will further lead to oxidative stress and hepatotoxicity. Therefore, as a preventive measure, the protective role of herbal extracts is being evaluated because of its high success rate and low toxic effects. The primary aim of this study was to evaluate the efficiency of the protective role of Asparagus racemosus is evaluated and studied against methotrexate (MTX)-induced hepatic damage in male Wistar albino rats.Methods: The course of the study was for 14 days. During this experimental study, the animals were categorized into four groups with six rats per group. Group I (positive control) which was treated with normal saline, Group II (negative control) with MTX 20 mg/kg of body weight on 12th day, Group III with A. racemosus 300 mg/kg of body weight + MTX 20 mg/kg on 12th day, and Group IV with A. racemosus 100 mg/kg of body weight + MTX 20 mg/kg on 12th day. On 14th day, the animals were sacrificed, and histopathological as well as antioxidant assays were performed.Results and Conclusion: Assays revealed high lipid peroxidation level and low antioxidant levels in Group II. Meanwhile, in Group III and IV, the levels were restored near to control, which supported the protective role of A. racemosus against MTX-induced hepatic damage. Histopathology evaluation also supported the above-mentioned findings.


2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Agnieszka Mizia-Malarz ◽  
Grażyna Sobol-Milejska

Deficiency or impaired function natural killer (NK) cells might result in the development of serious infections and promote the development of malignancies. The aim of our study was to assess the prognostic role of NK cell percentage in bone marrow on the day of acute lymphoblastic leukemia (ALL) diagnosis. 84 children (49 males=58%; median age 5 yrs) with ALL were enrolled. The NK cell percentage was assessed using flow cytometry with antibodies against the cluster of differentiation (CD): CD3, CD56, and CD16. We evaluated two groups: group I (NK+), patients with NK cells in the bone marrow (n=74), and group II (NK-), patients without NK cells in the bone marrow (n=10) (cut-off value of negative <1%). In the patients from group I, the prednisone good response on day 8 and the remission on day 15 of treatment were observed significantly more often (p=.01, p=.03). The children from group I had significantly better survival as compared to those from group II (p=.02) (HR 2.59; 95% CI: 1.38-4.85). The presence of NK cells in the bone marrow at diagnosis can be a prognostic factor in children with ALL. The presented results should be the basis for further research.


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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