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العنوان
immunotoxicological study on effect of two alkylating agents in albino rats/
الناشر
ragya mahmoud m hegazy,
المؤلف
hegazy , ragya mahmoud m
هيئة الاعداد
باحث / ragya mahmoud m hegazy
مشرف / mohamed kamel ahmed
مناقش / olagaber haggag
مناقش / mohamed kamel ahmed
الموضوع
fornesic toxicoloo
تاريخ النشر
1999 .
عدد الصفحات
130p:.
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
علم الأمراض والطب الشرعي
تاريخ الإجازة
1/1/1999
مكان الإجازة
جامعة بنها - كلية طب بشري - طب شعى
الفهرس
Only 14 pages are availabe for public view

from 140

from 140

Abstract

SUMMARY AND CONCLUSION
SUMMARY AND CONCLUSION
Anticancer drugs are well known immunotoxic agents. To assess
the effects of these drugs on the immune system: Immunofunctional
assays using rats are needed for the drugs assumed to be immunotoxic at
a dose level which is not overtly toxic. The immunofunctional test used in
our study is the plaque forming cell (PFC) assay which is the most
popular assay to assess the humoral function.
In our study: different doses of both single and 7 days
administration were used to study the immunotoxic, cytotoxics
haematotoxic and systemic toxic effects of two of the a1kylating agents
which are: cyclophosphamide which has well known immunosuppressive
effective and melphalan which widely used with chemotherapy and
compare between the toxic effects of both drugs.
The study included 120 adult albino rats that divided into 4 groups,
each group divided into 3 subgroups:
Group I: Included 30 animals treated as follow:
• 10 rats were injected with Cy. at dose of 10 mg/kg LV. (single).
• 10 rats were injected with Cy. at dose of30 mg/kg LV. (single).
• 10 rats were injected with saline IV. (single) i.e, control group.
Group II: Included 30 animals treated as follows:
• 10 rats were treated with melphalan at dose 6 mg/kg oral (single).
• 10 rats were treated with melphalan at dose 20 mg/kg oral (single).
• 10 rats were treated with 1% carboxymethyl cellulose oral (single)
i.e., control group.
SUMMARY AND CONCLUSION
Group III: Included 30 animals treated as follows:
• Ten animals were injected daily for 7 days with cyclophosphamide
at dose 3 mg/kg 1.V.
• Ten animals were injected daily for 7 days with cyclophosphamide
at dose 10 mg/kg 1.V.
• Ten animals were injection daily for 7 days with saline LV.
(control).
Group IV: Included 30 animals treated as follows:
• Ten animals were treated daily for 7 days with melphalan at dose (2
mg/kg) oral.
• Ten animals were treated daily for 7 days with melphalan at dose (6
mg/kg) oral.
• Ten animals were treated daily for 7 days with I% carboxymethyl
cellulose oral (control).
Each rat subjected to:
• Rough estimation of systemic toxicity by body weight gain,
• Cytotoxicity of the drug by quantitating the number of spleen cells
per 106 spleen cells.
• Immunotoxicity of the drugs by assessing the humoral immunity
using the plaque forming cell (PFC) assay to determine PFC response
per 106 cells.
• Haematotoxic effect of the drugs by estimation ofW.B.Cs. count
(total and differential) and platelet count.
I I
SUMMARY AND CONCLUSION
Our results showed that:
Witlr single administration:
Cyclophosphamide suppressed PFC at dose lower than that causing
decrease in body weight gain, spleen weight and spleen cellularity while
in melphalan: body weight gain, spleen weight and cellularity tended to
decreased at dose lower than that causing reduction of PFC response also
leukopenia and thrombocytopenia was dose related which was more with
melphalan than Cy.
Comparison of the toxic effects of both drugs resulted into: the
melphalan caused more toxic effects (in all the measured parameters)
than cyclophosphamide especially the single high dose while the toxic
effects of both drugs nearly equal in the single low dose.
Witi, 7 days administration:
The spleen weight, spleen cellularity and PFC response tended to
decrease at the same dose with (Cy.) while body weight gain, spleen
weight and cellularity tended to decreased at dose lower than that causing
reduction ofPFC with melphalan. Leukopenia and thrombocytopenia was
dose related comparison of the toxic effects indicated that melphalan
induced more toxic effects (in all the measured parameters) than
cyclophosphamide especially the multiple high dose while there is nearly
equal toxic effects with the low daily dose.
from tire results of this study we concluded tlrat:
• Although PFC assay is well known old method but considered
highly sensitive indicator for humoral immunity assessment.
• Although, the melphalan is widely used in therapeutics, its toxic
effects especially on the immune system have to be more studied, our
SUMMARY AND CONCLUSION
work showed that melphalan especially in high doses is more
immunotoxic, cycotoxic and haemotoxic in comparison to Cy.
Recommendation:
• In case of ovarian carcinoma we recommended using Cy. Because
melphalan is more immunotoxic, cytotoxic and hematotoxic effects.
• The repeated daily doses has to be recommended because the single
high dose is more immunotoxic, cytotoxic and hematotoxic than the
repeated daily doses.
• Immunofunctional assays and C.B.C. has to be recommended in
patients receiving Cy. Or melphalan.