الفهرس 
Cancer
Ehrlich ascites carcinomaOnly 14 pages are availabe for public view
 |  | from | 188 |  |  |
| | | from | 188 | | |
Abstract
Ehrlich ascites carcinoma (EAC) is an undifferentiated tumor that has a high capacity for transplant in transplantation, absence of regression, shorter life span, assured malignancy, originally hyperdiploid, quick proliferation and described by the absence of TSTA (tumor-specific transplantation antigen). However, two forms of Ehrlich models are used and they are solid tumors produced by injection subcutaneous for tumor cells or ascetic tumor formation by injection intraperitoneal for these cells. Vitamin B17 (VB17) is termed as (amygdalin and laetrile) it is a type of carbohydrate occurring naturally in plants and it is a cyanogenic diglucoside that mostly found in the fruit of kernels such as apricot, bitter almond, macadamias, and peach. Many research reported that VB17 is typical bioactive components in apricot kernels oil and in addition to VB17 has numerous activities including antitussive, antiasthmatic, antiatherogenic, inhibition/prevention of fibrosis, anticancer, anti-inflammation, and anti-ulcer activities Therefore, the present study aimed to demonstrate the hepatic and renal ameliorative role of vitamin B17 against Ehrlich ascites carcinoma induced liver and kidney toxicity. The mice were divided into five equal groups: Group1 (control): mice were injected with physiological saline; group2 (VB17): mice injected intramuscularly (im) with VB17 (100 mg/Kg body weight/ day) in the hind limb daily for 14 days; group3 (EAC): mice injected once intraperitoneal (ip) with 2.5x106 (EAC) cell; group4 (Pre-treated): mice injected (im) with VB17 daily for 14 days before implanted intraperitoneally with EAC cells; group; (Co-treated): mice were implanted with EAC cells on the first day and then injected intramuscularly with VB17 daily for 14 days. Ehrlich ascites carcinoma (EAC) cells collected from donor mice (Swiss albino) of 20-25 g body weight obtained and suspended in sterile isotonic saline. A fixed number of viable cells (usually 2.5x106 cells/20 g body weight) were transferred to healthy animals by intraperitoneal (ip) transplantation of each recipient mouse. When experimental period finish; fasting overnight and anesthetized with sodium pentobarbital and sacrificed. Blood samples were collected by cardiac puncture from anesthetized mice into the heparinized tube and mixed well to prevent clot formation, blood specimens were stored refrigerated (at 4oC) until used. The rest of the blood was collected in glass tubes for coagulation and serum formation, blood was allowed to sit for 30 min at 4oC to clot and then centrifuged for 10 minutes at 3000 rpm at room temperature; serum was separated and kept in clean stopper vial at -20ºC until assay. After the anesthetized, the liver and kidney were removed and cleaned by using cold saline and then separate the connective tissues and the adhering fat. Weigh 0.8 gm of the liver and kidney were used for comet assay for the assessment of DNA damage and the rest part was immersed immediately in 10% neutral buffered formalin for the estimation of histopathological immunohistochemical examinations. The obtained results can be summarized as follow: 1- Data showed that tumor cells, cellular alterations and mitotic cells from ascites fluid in mice after inoculation with Ehrlich cells were increased in EAC untreated group, while reduced the volume fluid, tumor cells, cellular alterations, and mitotic cells when treated with VB17, the reduction in cellular alterations was more pronounced in the pre-treated group. 2- Inoculated mice with Ehrlich cells showed proliferation of liver and kidney DNA damage in the tail (length, DNA% and moment) when compared to the control. Whereas, the presence of VB17 in the pretreated and co-treated groups induced inhibition in DNA damages when compared to the EAC group. 3- data showed changes in microsomal protein, cytochrome b5 (cyt b5), cytochrome P450 (CYP450), amidopyrine N-demethylase, aniline 4-hydroxylase, and NADPH-cytochrome c reductase were detected in liver tissues in EAC group as compared with control. In contrast, the treated with VB17 in the pre-treated and co-treated group revealed ameliorate in mixed-function monooxygenase systems. 4- Levels of alpha-fetoprotein (AFP) in the EAC group were significantly (p<0.05) increased as compared with control. While treatment of mice with VB17 in the pre-treated and co-treated group revealed enhance in serum AFB levels compared to the EAC group. This reduction was more observed in the pre-treatment group. 5- Serum AST, ALT, ALP and globulin levels were significantly (p<0.05) increased while total protein and albumin were significantly (p<0.05) decreased in EAC as compared with control mice. However, the treated with VB17 in the pre-treated and cotreated group revealed ameliorate in liver enzymes activity compared to the EAC group. The ameliorative effect of vitamin B17 was more pronounced in the pre-treated group 6- Serum urea, creatinine and potassium ions (K+) levels were significantly (p<0.05) increased while sodium ions (Na+) were significantly (p<0.05) decreased in EAC as compared with control mice. In contrast, the treated with VB17 in the pre-treated and cotreated revealed ameliorate in renal function parameters compared to the EAC group. 7- Inoculated mice with Ehrlich cells showed significant changes in hematological parameters (RBC, WBCs, HGB, HCT, MCV, MCH, MCHC, and PLT) when compared to the control group, while the treated with VB17 in the pre-treated and co-treated groups revealed ameliorate in hematological parameters compared to the EAC group. 8- The histopathological examinations of control and VB17 group of mice liver revealed a normal histological section. Liver sections in inoculated mice with Ehrlich cells exhibited marked degeneration in hepatic cords, fibrosis, and marked diffuse necrosis of hepatic tissue, marked inflammatory cells and congested blood sinusoids were observed in the EAC group. While the treated with VB17 in the pre-treated and co-treated groups exhibited improvement and moderate cellular infiltrations in hepatocytes when compared to the EAC group. 9- The histopathological examinations in mice kidney sections in control and VB17 groups showed the entirely normal architecture of the characteristic of the glomeruli and renal tubules. While mice inoculated with Ehrlich cells induced marked damage and degenerated in glomeruli and renal tubules. While the kidney sections in the pre-treated and co-treated groups revealed improvement and arrangement in the kidney histological structure compared to the EAC group. 10- Immunohistochemical examinations of P53 protein expressions in liver and kidney sections showed a negative or weak reactivity for P53 protein in the control and VB17 groups. While a strong expression for p53 protein was observed in nuclei of hepatocytes, glomeruli and renal tubules in the EAC group when compared with the normal control group. Furthermore, the intensity of p53 protein was significantly decreasing in liver and kidney sections in treated mice with VB17 (Pre-treated and Co-treated) groups when compared to the EAC group. 11- Proliferating cell nuclear antigen immunoreactivity (PCNA-ir) expressions in the liver and kidney tissues showed negative or weak reactivity in the control and VB17 groups. In contrast; a strong positive reaction for PCNA was observed in nuclei of hepatocytes, glomeruli and renal tubules in the EAC group when compared with the normal control group. On the other hand, the intensity of PCNA was significantly decreased in liver and kidney sections in treated mice with VB17 (Pre-treated and Co-treated) groups when compared to the EAC group.