Document Details
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Document Type |
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Thesis |
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Document Title |
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Studies on Protective Role of Camel Milk Against the Cytotoxic , Cytogenotoxic and Genotoxic Effects of Cisplatin In Albino Mice دراسات على الدور الوقائي لألبان الإبل ضد السمية الخلوية والخلوية الوراثية والوراثية لعقار السيسبلاتين في الفئران البيضاء . |
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Subject |
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Studies on Protective Role of Camel Milk Against the Cytotoxic , Cytogenotoxic and Genotoxic Effects of Cisplatin In Albino Mice |
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Document Language |
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Arabic |
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Abstract |
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The majority of anticancer "antineoplastic" drugs are especially designed to interfere with DNA synthesis , cellular metabolism and cell division . Genotoxicity of anticancer "antineoplastic" drugs has been established in several experimental test system .The majority of these drugs are extremely cytotoxic and many of them are mutagenic and carcinogenic . The high mutagenic potency of these drugs raises the concern that its use in cancer chemotherapy may be responsible for secondary malignancies which have been observed in some cured patients treated with these drugs . Therefore , anticancer drugs are used as mutagens . Cisplatin is widely used antineoplastic agent,the mutagenic and carcinogenic potentials of this agent were established and the drug was used in this study essentially as a reference mutagen .
During recent years , considerable effort have been focused on using antimutagens to modulate the genotoxic effects of the mutagenic antineoplastic drugs . Therefore , much attention has been paid to the research of naturally occurring agents (especially in diet) that are able to stimulate defense mechanisms of the organism .
Therefore, the aim of the present study is to evaluate the possible protective ( antimutagenic ) role of Camel milk against the cytotoxic , cytogenotoxic and genotoxic effects of a widely used antineoplastic drug "cisplatin " in somatic and gametic cells of male mice in vivo .
Male MFI mice were used as the experimental animals . Cisplatin was injected sub-acutely (20 mg /kg) in daily intrapertoneally (i.p.) doses over a five day peroid and acutely (100 mg /kg) in a single i.p. injection , sacrifiting the animals 24hr both after sub-acute and acute treatments .\ Two types of experiments were carried out, the first to check the rate of mitotic index , micronuclei formation and dominant lethal induction by sub-acute and acute treatments of medical doses (20 mg /kg) and (100 mg /kg) respectively and to determine the effect of the sub-acute treatment of (33 ml /kg) of camel milk . The second type of experiments was to check the protective effect of pre & simultaneous sub-acute treatments of camel milk (33 ml /kg(
The experimental animals were divided into seven categories as follows :
(A) includes 10 male mice orally and intrapertoneally (i.p.) sub-acutely treated
with distilled water in daily doses over a five day period and considered as
a control group .
(B) includes 10 male mice orally sub-acutely treated with camel milk
(33 ml/kg) in daily doses over a five day period .
(C) includes 10 male mice (i.p.) sub-acutely treated with the therapeutic dose
(20 mg /kg) of cisplatin in daily doses over a five day period .
(D) includes 10 male mice orally pre-sub-acutely treated with the camel milk
and followed by (i.p.) sub-acutely treated with the therapeutic dose
(20 mg /kg) of cisplatin in daily doses over a five day period .
(E) includes 10 male mice orally simultaneously sub-acutely treated with
camel milk and (i.p.) treated with the therapeutic dose (20 mg /kg) of
cisplatin in daily doses over a five day period .
(F) includes 10 male mice(i.p.) acutely treated with the therapeutic dose
(100 mg /kg) of cisplatin .
(G) includes 10 male mice orally pre-sub-acutely treated with camel milk in
daily doses over a five day period and followed by (i.p.) acute treatment
with the therapeutic dose (100 mg /kg) of cisplatin in the fifth day .
The results showed that the frequencies of mitotic index (MI) , micronuclei (MN) and dominant lethality (DL) in camel milk treated mice were not significantly different from those of control mice .
The study showed that the treatment with therapeutic doses (20 mg /kg & 100 mg /kg) of cisplatin resulted in highly significant inhibition of the mitotic activity (MI) of bone marrow cells .
On the other hand all treatments with camel milk, Either pre-subacuely treatment with both sub-acute and acute treatments of the therapeutic doses (20 mg /kg & 100 mg /kg) of cisplatin respectively or simultaneous sub-cutely treatment with (20 mg /kg) dose of cisplatin , caused a very highly significant enhancement in bone marrow activity (when compared with mice received the therapeutic doses of cisplatin alone) that had been suprresed by the antineoplastic drug .
Sub-acutely and acutely treatments with the two therapeutic doses of cisplatin resulted in a very highly increased in the number of micronuclei in polychromatid erythrocytes in bone marrow cells .On the other hand, the oral administration of camel milk were found to be effective in reducing the clastogenic effect (micronuclei) induced by cisplatin . This reduction was very highly significant as a result of pre-sub-acutely treatment with camel milk either followed by sub-acute treatment with (20 mg /kg) or acute treatment with (100 mg /kg) of cisplatin , whereas it was highly significant as a result of simultaneous treatment of milk and the therapeutic dose (20 mg /kg) of cisplatin .
The analysis of data obtained from the dominant lethal assay revealed that the drug was highly effective in inducing dominant lethality after sub-acute treatment with (20mg /kg) of cisplatin, especially in the first, second and fifth weeks . This implies that the spermatozoa , late spermatid and primary spermatocytes respectively were the most sensitive and highly affected stages by this treatment , while the most sensitive and highly affected stages were the early and late spermatids i.e. the highly dominant lethal value was observed in the second and third weeks .
On the other hand , pre & simultaneous sub-acutely treatments with camel milk and sub-acutely treatment with (20 mg /kg) of cisplatin registered a noticeable decrease in the dominant lethal values in the same stages affected by cisplatin treatment only . It is obviously that the pre-sub-acutely treatment with camel milk and followed by (20 mg /kg) of the drug was the more effective treatment in reducing the dominant lethal values than the simultaneous sub-acutely treatment observed in the majority of examined weeks . Also the sub-acute treatment with camel milk and followed by acute treatment with (100 mg /kg) showed a noticeable decrease in the dominant lethal values in the same stages affected by acute treatment with cisplatin only i.e. the early and late spermatides .
The present study shows the importance of using short-term tests for evaluating the potential antimutagenic effect of certain compound against the cytotoxic and genotoxic effects of chemical compound including the antineoplastic drugs . camel milk administration prior or at the same time to cisplatin were found to be effective in reducing cytotoxic and genotoxic effects in induced by this drug in both cell types studied.This protective effect of camel milk could be attributed to the scavening ability to trap free redicals of some of its components like vitamins and minerals (N.B. cisplatin upon hydrolysis in aqueous solution forms various reactive hydroxyl species) which are known as cells damaging agents .
The findings , therefore , suggest that camel milk may reduce the cytotoxic & genotoxic effects inducing during therapy with cisplatin . Additionally , caml milk also markedly restored the bone marrow cell mitosis, which had been suppressed by this drug .
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Supervisor |
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Dr.Abla Sharaf |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1426 AH
2005 AD |
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Co-Supervisor |
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Dr.Salwa Qitta |
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Added Date |
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Monday, March 9, 2015 |
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Researchers
| لينا عبدالفتاح كردي | Kurdi, Lina Abdul-fattah | Investigator | Doctorate | |
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