الفهرس 
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Abstract
The present study was conducted to investigate the possible utilization of fruit waste represented in seeds of peach and orange as source of bioactive compounds extracted with methanol and assess their capability to reduce and alleviate the cytogenetic, DNA damages and histological side effects induced by the anticancer drug cyclophosphamide in mice.
The studies included the following investigations:
Mice bone marrow cells were investigated for DNA damage after treatment with the test compounds, by the analysis of formation of micronuclei in the PE and the frequency of PEs in bone marrow cells, also the aneugenic/ clastogenic damage was examined using chromosomal aberrations test, and liver damage was investigated histologically.
Cyclophosphamide (CP) at 75 mg/ kg b. wt. was used as a positive control and it induced a high and statistically significant percentage of polychromatic erythrocytes (PEs) in bone marrow cells after 24 h.
Peach seeds extract oral treatment of animals for five days with 500 mg/ kg b. wt. induced a significant increase in polychromatic erythrocytes (PEs) in bone marrow cells nearly 2-folds to the negative control after 1 day of the last treatment. Although the significancy of the treatment with Peach seeds extract only on the PEs induction which was due to its toxic components as hydrogen cyanide compounds, it can be used depending on its fast elimination from the body. That demonstration was noticed after 14 days of treatment.
Peach seeds extract oral treatment of animals for five days with 500 and 250 mg/ kg b. wt. given after CP in a trial to ameliorate its effect, showed a decrease in PEs induction in bone marrow cells after 1, 2, 7, and 14 days after the last treatment in a time dependent manner. The high dose of peach was more efficient in treating CP effects than the low one.
On the other hand oral treatment of animals with 600 mg/ kg b. wt. of orange seeds extract for five days induced a non-significant increase in the PEs in bone marrow cells after 1 day of the last treatment.
Orange seeds extract at the dose of 600 and 300 mg/ kg b. wt. given for five days after receiving a single dose of CP showed a decrease in PEs induction in bone marrow cells after 1, 2, 7, and 14 days after the last treatment in a time dependent manner. Worthy to mention that the high dose of extract gave better results in reducing PEs.
The study also proved that CP-treatment was able to induce highly significant increase in micronucleated PEs. As previously mentioned that the Oral treatment of animals with 500 mg/ kg b. wt. of peach seeds extract for five days significantly induced PEs due to its cytotoxic components similarly, it was found to induce a significant increase in micronucleated PEs in bone marrow cells nearly 5-folds to the negative control after 1 day of the last treatment.
Oral treatment of animals with 500 and 250 mg/ kg b. wt. of peach seeds extract for five days after receiving a single dose of CP showed a decrease in micronucleated PEs induction in bone marrow cells after 1, 2, 7, and 14 days after the last treatment in a time dependent manner. Higher significance was in case of the dose 500 mg.
Orange seeds extract at the dose of 600 mg/ kg b. wt. given for five days induced a significant increase in the micronucleated PEs in bone marrow cells demonstrated 6-folds to the negative control after 1 day of the last treatment. Although the significancy of the treatment with orange extract alone on the micronucleated PEs induction which was due to its cytotoxic components, it can be used depending on its fast elimination from the body. As it was noticed by the depletion of its toxicity after 14 days of treatment.
Similarly orange seeds extract treatment for five days with 600 and 300 mg/ kg b. wt. after receiving a single dose of CP showed a decrease in micronucleated PEs induction in bone marrow cells after 1, 2, 7, and 14 days after the last treatment in a time dependent manner but the dose of 600 mg was more efficient in decreasing micronucleated PEs induction in bone marrow cells.
Structural and numerical chromosomal aberrations (CAs) were significantly elevated in percentage due to Cyclophosphamide treatment.
Oral treatment of animals with 500 mg/ kg b. wt. of peach seeds extract for five days induced a significant increase in percentage of CAs in bone marrow cells compared to the negative control after 1 day of the last treatment. This high percentage can almost reach the value of the control group after excluding the chromosome and chromatid gaps.
The peach seeds extract given at the dose of 500 and 250 mg/ kg b. wt. for five days after receiving a single dose of CP showed a decrease in CAs formation in bone marrow cells after 1, 2, 7, and 14 days after the last treatment in a time dependent manner.
Oral treatment of animals with 600 mg/ kg b. wt. of orange extract for five days induced a significant increase in the CAs percentage in bone marrow cells in comparison of the negative control after 1 day of the last treatment. This high percentage can be similar to the control group after excluding the chromosome and chromatid gaps.
In the same pattern treatment of animals with 600 and 300 mg/ kg b. wt. of orange seeds extract for five days after receiving a single dose of CP showed a decrease in CAs percentage in bone marrow cells after 1, 2, 7, and 14 days after the last treatment in a time dependent manner. Also as peach the results of orange seeds extract at high dose demonstrated higher efficiency.
The present histological investigation of mice liver showed that CP treatment induced marked morphological changes in liver of tested animals, mostly represented in infiltration of different types of inflammatory cells, excessive increase in active Kupffer cells, fibroplasia in portal area around portal veins, appearance of necrotic areas, macro and microvesicular fatty degeneration, and hydropic degeneration after 24 h.
Peach seeds and orange seeds extracts given only to the animals for five days showed nearly normal histological pattern except for minor changes as slight inflammatory cells infiltration and slight dilation of blood sinusoids after 1 day of the last treatment.
Oral treatment of animals with 500 and 250 mg/ kg b. wt. of peach seeds extract for five days after receiving a single dose of CP showed a noticeable improvement in liver histology after 1, 2, 7, and 14 days of the last treatment compared to the case of CP-treatment. The histological study confirmed the cytogenetics findings in which also it was found that the high dose of peach seeds extract was more efficient in treating CP effects than the low one. Also it was noticed that the low dose treatment showed slight changes such as increase of active Kupffer cells especially after 48 h. and 7 days and slight microvesicular fatty degeneration after 7 days.
Like peach, orange seeds extract treatment with 600 and 300 mg/ kg b. wt. of orange extract for five days after receiving a single dose of CP showed a noticeable amelioration in liver histology compared to CP effect after 1, 2, 7, and 14 days of the last treatment in a time dependent manner, except for minor changes such as marked increase of active Kupffer cells especially after 48 h. and 7 days and slight microvesicular fatty degeneration after 7 days in both doses.