Ehrlich Ascites Carcinoma Group Research Articles

Chitosan and Grifola Frondosa nanoparticles insulate liver dysfunction in EAC-bearing mice.

Ehrlich ascites carcinoma (EAC) is a rapidly growing and undifferentiated tumor that can prompt oxidative stress and liver toxicity, whereas chitosan and Grifola Frondosa have widely recognized biological qualities. Therefore, our study designed to assess the potential ameliorative ability of chitosan nanoparticles (CS NPs) and Grifola Frondosa nanoparticles (GF-loaded casein NPs) on EAC-induced hepatic injury in mice. A total of 60 female albino mice were segregated into 6 groups (10 mice each), G1, control group; G2, CS NPs group; G3, GF-loaded casein NPs group; G4, EAC group; G5, EAC treated with CS NPs; G6, EAC treated with GF-loaded casein NPs. According to the findings, EAC considerably increased serum activities of ALT, AST, ALP as well as LDL, cholesterol, and triglycerides levels coincided with marked decrease in albumin and total protein content in liver tissue. At the same time, it drastically lowered GSH levels and catalase activity while significantly elevating MDA levels. In addition, EAC caused DNA damage and apoptosis by decreasing Bcl-2 while increasing p53 expressions. However, either CS NPs or GF-loaded casein NPs therapy improved liver architecture and functioning, increased antioxidant parameters, and prevented hepatocyte death in EAC mice. Our findings concluded that CS NPs and GF-loaded casein NPs have insulating functions against EAC-induced hepatic damage in mice.

Evaluation of antioxidant, anti-inflammatory, anticancer activities and molecular docking of Moringa oleifera seed oil extract against experimental model of Ehrlich ascites carcinoma in Swiss female albino mice

The current research intended to evaluate the antitumor properties of Moringa oleifera oil extract (MOE). Fifty-six female Swiss albino mice were employed in this study. Animals were assigned into four groups: control (C) group, moringa oil extract (MOE) group administered (500 mg/kg b. wt) MOE daily via gavage, Ehrlich ascites carcinoma (EAC) group and EAC group administered daily with (500 mg/kg b.wt) MOE for two weeks (EAC/MOE). The results showed that MOE significantly ameliorated the EAC increase in body weight and reduced the EAC cell viability. In addition, they upgraded the levels of hepatic and renal functions, inflammatory cytokines, oxidative stress markers and EAC-induced hepatic and renal histopathological changes. Treatment of EAC with MOE induced antitumor, anti-inflammatory and antioxidant effects and normalized most of the tested parameters besides the histopathological alterations in both renal and hepatic tissues. HPLC for the MOE identified Cinnamic acid, Ellagic acid, Quercetin, Gallic acid, Vanillin and Hesperidin as major compounds. The molecular docking study highlighted the virtual binding of the identified compounds inside the GSH and SOD proteins, especially for Quercetin which exhibited promising binding affinity with good interactive binding mode with the key amino acids. These results demonstrate that the antitumor constituents of MOE against EAC induced oxidative stress and inflammation by preventing oxidative damage and controlling EAC increase.

Anti-proliferative and immunomodulatory potencies of cinnamon oil on Ehrlich ascites carcinoma bearing mice

Cinnamon is a well-known natural spice and flavoring substance used worldwide. The objective of the present work is to explore the possible antitumor and immunomodulatory potencies of cinnamon essential oil (Cinn) on Ehrlich ascites carcinoma (EAC). A total of fifty female Swiss albino mice were sub-grouped into five groups (n = 10), namely, normal (a non-tumorized and non-treated) group; EAC-tumorized and non-treated group; Cinn (non-tumorized mice received Cinn, 50 mg/kg per body weight daily) group; a group of EAC-tumorized mice treated with Cinn and the final positive control group of EAC-tumorized mice received cisplatin. Eight compounds were identified from Cinn using UPLC-MS-Qtof and NMR analysis. Compared to EAC untreated group, Cinn successfully (P < 0.05) inhibited tumor growth by reducing tumor cell count (45%), viability (53%) and, proliferation accompanied by the inhibition of tumor growth rate. Moreover, a significant (P < 0.05) arrest in the cell cycle at G0/G1 phase was noticed following Cinn treatments (~ 24.5%) compared to EAC group. Moreover, Cinn markedly evoked an antitumor immune response by elevating the percentage of splenic T helper (CD3+CD4+) and T cytotoxic (CD3+CD8+) cells. It is noteworthy that Cinn treatments significantly restored different hematological alterations as well as liver and kidney functions in EAC-tumorized mice. In conclusion, results suggest that Cinn has a good antitumor and immunostimulatory potencies against Ehrlich ascites carcinoma in vivo. The mechanism underlying its antitumor activity may be attributed to its immunostimulatory effects which increase its potential as a promising anticancer candidate.

Anti-proliferative effects of the combination of Sulfamethoxazole and Quercetin via caspase3 and NFkB gene regulation: an in vitro and in vivo study.

Combination therapy comprising natural polyphenols and anticancer drugs has been used to decrease the adverse effects and increase the effectiveness and antioxidant activities of the drugs. The antioxidant and anticancer effects of quercetin (Q), a nutritive polyphenol, have been observed both in vitro and in vivo. Likewise, the anticancer activity of sulfamethoxazole (S) has been demonstrated in vitro and in vivo. This study aimed to investigate the in vitro and in vivo anticancer effects of Q alone and in combination with S. The in vitro effects of S, Q, and S + Q on HCT-116, HepG2, MCF-7, and PC3 cell lines were examined. Additionally, the in vivo effects of these drugs were evaluated using Ehrlich ascites carcinoma (EAC) tumor-bearing mice. The in vitro data revealed the potent anticancer activity of S + Q through the induction of apoptosis and cell cycle arrest. The EAC-inoculated mice treated with S + Q presented with elevated SOD, GSH, CAT, and TAC levels and decreased malondialdehyde levels compared with the untreated EAC group, thus revealing the antioxidant and protective actions of S + Q against EAC cell invasion. Furthermore, the downregulation of NFkB and upregulation of the caspase3 gene in the EAC-inoculated mice treated with the S + Q indicated the induction of the apoptotic pathway and decrease in both cell proliferation and metastasis. In conclusion, the combination of S and Q might exert anticancer effects by inducing apoptosis and exhibiting selective toxicity against the cancer cells and thereby protecting the vital organs.

Indole glucosinolates exhibit anti-inflammatory effects on Ehrlich ascites carcinoma cells through modulation of inflammatory markers and miRNAs.

Nuclear factor-κB (NF-κB) has been identified as the major link between inflammation and cancer. Natural agents that inhibit this pathway are essential in attenuating inflammation induced by cancer or chemotherapeutic drugs. High intake of Brassicaceae vegetables has been determined to modulate essential pathways related to chronic diseases. In this study, we investigated the anti-proliferative and anti-inflammatory effects of the indole glucosinolates; indole-3-carbinol (I3C) and its metabolite 3,3-diindolylmethane (DIM) on the inflammatory biomarkers and miRNAs controlling the NF-κB pathway. In our study, we inoculated Ehrlich ascites carcinoma (EAC) cells in female albino mice, which increased their packed cell volume and induced a significant increase in the levels of several cytokines and inflammatory biomarkers (NF-κB IL-6, IL-1b, TNF-α, and NO). A significant elevation in inflammatory-medicated miRNAs (miR-31 and miR-21) was also noted. Treatment with 5-fluorouracil (5-FU) significantly reduced packed cell volume and viable cell count. However, it was accompanied by a significant increase in the levels of inflammatory markers and expression of miR-31 and miR-21. Nevertheless, although treatment with indoles (I3C and DIM) significantly reduced the packed cell volume and viable cell count, their prominent effect was the marked reduction of all inflammatory biomarkers compared to both the EAC untreated group and the EAC group treated with 5-FU. Moreover, the anti-inflammatory effect of I3C or DIM was accompanied by a significant decrease in the expression of miR-31 and miR-21. Our findings have; therefore, revealed that I3C and DIM have strong anti-inflammatory effects, implying that their use as a co-treatment with chemotherapeutic drugs can effectively improve the anti-tumor effect of chemotherapeutic drugs.

Evaluation of the antitumor effect of trehalose in experimental models: PhD Thesis Abstract

PhD Thesis Abstract Background: Cancer continues to represent the main cause of mortality in the world, the second leading cause of death worldwide next to cardiovascular disease. Therefore, it is important to find effective non-toxic, inexpensive, and suitable neoadjuvant therapy with methotrexate (MTX) to decrease its dosage without lowering its chemotherapeutic efficacy. Aim: This study aimed to investigate the antitumor effect of trehalose (TRE) on mice bearing Ehrlich ascites carcinoma (EAC) and to test whether it can enhance the anticancer potential of MTX. Materials and Methods: In this experiment, mice were assigned into 8 groups were used for assessment of antitumor activity of TRE. The antitumor activity of TRE was assessed by measuring the survival time, counting tumor cells, monitoring autophagic activity at the cellular level by flow cytometry, monitoring autophagic and apoptotic regulated genes (Caspase 3, Bec1, and Bcl2 genes ) by real-time PCR, as well as the biochemical parameters, oxidative stress markers in liver homogenate, complete blood picture (CBC) and histological studies of all groups. Results: Treatment of EAC mice with TRE or MTX alone or in combination resulted in a significant decrease in total, viable, and non-viable tumor cells count as well as the tumor volume in comparison with EAC mice. Treatment with TRE alone or in combination MTX induced a significant increase in the hepatic antioxidant status, a significant upregulation in the gene expression of caspase 3, with the highest expression in the combined group, as compared to the non-treated EAC group. On the other hand, the same treatments resulted in a significant downregulation of Bcl2 and Bec1 genes, with the lowest expression in the combined group. These results showed a significant decrease in autophagic activities in both TRE- and TRE+MTX -treated groups as compared to the non-treated EAC group. Histopathological examination revealed normal lobular architecture with central vein and radiating hepatic cell cords in normal control mice. Conclusion: TRE is considered as an autophagic inhibitor for cancer cells which could be used as a potential neoadjuvant for the antitumor drug, MTX, and probably other chemotherapeutic compounds. This new role of TRE coupled with its apoptotic induction property on tumor cells and lack of toxicity on normal cells increases the efficacy of an antitumor drug for treating a spectrum of cancers. (This Ph.D. thesis was approved by the Faculty of Science, Tanta University, Egypt by March 31, 2018).

Anti-cancer activity of two novel heterocyclic compounds through modulation of VEGFR and miR-122 in mice bearing Ehrlich ascites carcinoma

Metastasis in breast cancer is a leading cause of mortality among women in many countries. This study investigated the anti-cancer role of benzoimidazoquinazoline and benzimidazotriazin; two novel compounds that were designed, synthesized, structurally elucidated, and biologically evaluated as potent anti-angiogenic agents that act through inhibition of vascular endothelial growth factor receptor-2 (VEGFR2). Breast cancer was induced by inoculation of Ehrlich Ascites Carcinoma (EAC) cells. Seventy swiss albino mice were randomly divided into 7 groups, 10 animals each: (1) normal, (2) control EAC group, (3) cisplatin treated group, (4&5) benzoimidazoquinazoline treated (5 mg/kg and 10 mg/kg), (6&7) benzimidazotriazin treated (5 mg/kg and 10 mg/kg). The expression of miR-122 was assessed in the tumor tissue by quantitative PCR, and the VEGF level was determined in serum by ELISA. VEGFR2 and cluster of differentiation (CD)34 were assessed by immunohistochemistry. Serum ALT, AST, creatinine, and urea were measured. Treatment with benzoimidazoquinazoline and benzimidazotriazin decreased tumor weight and serum levels of VEGF, and down-regulated expression of VEGFR2 and CD34 in the tumor tissue. miR-122 was upregulated, particularly in the benzimidazotriazin (10 mg/kg) group. Relative to cisplatin, the novel compounds were less toxic to kidneys. Benzoimidazoquinazoline and benzimidazotriazin are promising anti-cancer agents that act through inhibition of angiogenesis and thus provide a new strategy for advancement of chemotherapy.

Ehrlich ascites carcinoma as model for studying the cardiac protective effects of curcumin nanoparticles against cardiac damage in female mice.

While clinical innovation has improved, cancer or malignant growth stays a genuine medical issue and has been perceived as a significant factor in mortality and morbidity. Current work aimed to define the cardiac defensive effects of curcumin nanoparticles (Cur Nps) against EAC induced cardiac toxicity, injury, and alterations in apoptosis, proliferation, and cytokines immunoreactivity. Forty female mice were aimlessly and equally divided into four groups [Gp1, Control; Gp2, Cur NPs; Gp3, Ehrlich ascites carcinoma (EAC); Gp4, Co-treatment of EAC with Cur NPs (Cur NPs + EAC)]. Serum lactate dehydrogenase (LDH), phosphocreatine kinase (CPK), creatine kinase myoglobin (CK-MB), alkaline phosphatase (ALP), glutamic oxaloacetic transaminase (GOT), cholesterol, triglycerides, potassium ions, cardiac injury, P53, vascular endothelial growth factor protein (VEGF), Bax, and tumor necrosis factor alpha (TNFα) expressions were significantly elevated while sodium ions levels were significantly depleted in EAC when compared to control. Co-treatment of EAC with Cur NPs (Cur NPs + EAC) improved these parameters as compared with EAC group. So, our results indicate that; Cur NPs induced protection to the blood and heart tissue during Ehrlich ascites carcinoma.

Dual inhibition of glycolysis and autophagy as a therapeutic strategy in the treatment of Ehrlich ascites carcinoma.

Cancer cells have extra biosynthetic demands to sustain cell growth and redox homeostasis. Glycolysis and autophagy are crucial to fuel and recycle these biosynthetic demands. This plasticity of cancer cell metabolism participates in therapy resistances. The current study was designed to assess the therapeutic efficacy of dual targeting of glycolysis and autophagy in cancer. Using 3-bromopyruvate (3-BP; antiglycolytic inhibitor) and hydroxychloroquine (HCQ; autophagy inhibitor), we demonstrate their antitumor activity in Ehrlich ascites carcinoma (EAC)-bearing mice. A combination of 3-BP and HCQ significantly decreases tumor ascitic volume and cell count as compared with the EAC group and individual treatment groups. The enhanced antitumor activity is accompanied by hexokinase inactivation, inhibition of cellular protective autophagy, elevated antioxidant activity, and reduced oxidative stress levels. Together, these results suggest targeting both pathways in cancer as an effective therapeutic strategy. Further studies are required to validate this strategy in different cancer models and preclinical trials.

Hepatic ameliorative role of vitamin B17 against Ehrlich ascites carcinoma-induced liver toxicity.

Vitamin B17 (VB17), also known as amygdalin and laetrile, is a type of carbohydrate occurring naturally in many plants, such as apricot kernels which have obtained a great interest in cancer therapy. This study aimed to investigate the hepatic protective potential of VB17 against Ehrlich ascites carcinoma (EAC)-bearing mice-induced liver injury, DNA damage, apoptotic P53, and PCNA alterations. A total of 100 female mice were divided into 5 groups (1st group, control group; 2nd group, VB17 group; 3rd group, EAC group; 4th group, pre-treated EAC with VB17; 5th group, co-treated EAC with VB17). Results showed that the presence of VB17 in pre-treated and co-treated groups lead to decreased DNA damage, microsomal protein, NADPH cytochrome c reductase, alpha-fetoprotein (AFP), AST, ALT, and ALP while showed increased cytochrome b5, cytochrome P450 amidopyrine N-demethylase, and aniline 4-hydroxylase compared with the EAC group. Many histopathological changes were observed in liver sections in EAC as moderate fibrosis and marked diffuse necrosis of hepatic tissue, marked inflammatory cells, and congested blood sinusoids. On the other hand, there was a moderate degree of improvement in hepatocytes in liver sections in pre-treated VB17+EAC, while a mild degree of improvement in hepatocytes, moderate cellular infiltrations, and moderate cytoplasmic vacuolization of hepatocytes in liver sections in co-treated EAC+VB17. In addition, there was a depletion in hepatic P53 and PCNA protein expression compared with the EAC group. It could be concluded that VB17 has a potential hepatoprotective effect against EAC cell-induced liver toxicity.

Alterations in hematological and biochemical parameters and DNA status in mice bearing Ehrlich ascites carcinoma cells and treated with cisplatin and cyclophosphamide

Chemotherapy medicates cancer via killing cells. It may destroy both cancer and normal cells. This research was performed to investigate the influences of cisplatin and cyclophosphamide on Ehrlich ascites carcinoma (EAC) bearing mice through some hematological, biochemical, molecular, and pathological studies. A total of 80 healthy female Swiss mice were equally divided into four groups. Group 1 was kept as the negative control. Groups 2 to 4 were injected intraperitoneally (IP) with 2.5 × 106 EAC where mice in group 2 were kept as the positive control without treatment. Groups 3 and 4 were injected IP daily for 12 days with cisplatin and cyclophosphamide with 10-mg/kg and 100-mg/kg body weight respectively. Blood and tissue samples were collected after 12 days post treatment. Erythrogram revealed macrocytic normochromic anemia in the EAC group. Group 3 showed normocytic normochromic anemia. Group 4 proved macrocytic hypochromic anemia. Thrombocytopenia was detected in gps. 3 and 4. Leukogram revealed significant accretion in total leukocytic, granulocytic, and monocytic counts in gp. 2. On the contrary, gps. 3 and 4 clarify significant drop in these parameters with granulocytosis. A significant perquisite in the liver markers (ALP, AST,and ALT), uric acid, creatinine, and blood urea nitrogen levels were seen all over the experimental periods in all groups. On the other side, total proteins and albumin levels manifested significant dwindling in gp. 2 followed by gp. 4 then gp. 3, where globulin level elucidates significant diminution in gps. 3 and 4, and non-significant decrease was recorded in gp. 2. These results were confirmed by damage in liver and kidney tissues monitored by pathological examination and comet assay.

Ameliorative effects of vitamin B17 on the kidney against Ehrlich ascites carcinoma induced renal toxicity in mice.

Cancer is the major cause of death and many factors that lead to its occurrences, such as environmental pollution and pesticides and other factors. Ehrlich carcinoma development depends on many things associated with the environment, nutrition, personal habits, and family history. The present study aimed to evaluate the potential protective effects of vitamin B17 (VB17) against Ehrlich ascites carcinoma (EAC) that induced kidney toxicity in female mice. The mice were divided into five groups (first group, control group; second group, VB17 group; third group, EAC group; fourth group, pretreated EAC with VB17; fifth group, cotreated EAC with VB17). Results showed the VB17 in pretreated (G4) and cotreated (G5) groups lead to an improvement in DNA damage and cytological examination, in addition significantly (P < .05) increase in Na+ , red blood cell, hemoglobin, hematocrit value, mean corpuscular hemoglobin (MCH), and MCH concentration, whereas significantly (P < .05) decrease in urea, creatinine, K+ , platelets, and white blood cells while insignificant (P < .05) changes in mean corpuscular volume when compared to the EAC group. Many histopathological changes were observed in kidney sections in EAC as marked damage and degenerated, glomerular atrophy, the Malpighian corpuscles that lost their characteristic configuration. On the other hand, a moderate improvement and arrangement in the kidney histological structure in pretreated VB17 + EAC, while a mild enhancement and arrangement of the kidney structure in cotreated EAC + VB17. In addition, depletion in renal P53 and PCNA protein expression compared with the EAC group. It could be concluded that VB17 has a potential renal protective effect against EAC cells induced kidney injury.

Evaluation of Antitumor Activity and Hepatoprotective Effect of Mitomycin C Solubilized in Chamomile Oil Nanoemulsion.

The present study aimed to investigate the antitumor activity and hepatoprotective effect of the MTC, when combined with CHAM oil nanoemulsion (NE), (CHAM-MTC) on the tumor growth. The in vitro study assessed the antineoplastic effect of CHAM-MTC on the MCF-7 breast cancer cells while the in vivo therapeutic effectiveness and toxicities of CHAM-MTC were evaluated in Ehrlich Ascites Carcinoma (EAC) bearing mice. One hundred female Swiss albino mice, divided equally into non-EAC group (negative control), untreated EAC group (positive control) and three EAC groups received once intraperitoneal injection of 0.2ml CHAM-NE, 0.2ml Normal Saline (NS) contained MTC (1mg/kg) and 0.2ml CHAM-NE mixed with MTC (1mg/kg), respectively. The in vitro results indicated that CHAM-NE could potentiate the effect of MTC in sub-effective concentrations since the half-maximal inhibitory concentration (IC50) was reduced by a factor of 21.94 when compared to the MTC-NS. The in vivo study revealed that mice treated with CHAM-MTC showed a significant increase in the median survival time (MST= 37 days) when compared to the MTC-NS treated group (MST= 29.50 days). In addition, CHAM-MTC showed protective ability against the oxidative stress and hepatic damage induced by EAC and MTC treatment. The combination of MTC with CHAM-NE could be valuable in enhancing the therapeutic efficacy of MTC against EAC and in eliminating MTC-induced hepatotoxicity.

Assessment of Autophagy as Possible Mechanism of the Antitumor Effects of Arsenic Trioxide and/or Cisplatin on Ehrlich Ascites Carcinoma Model

Arsenic trioxide (As2O3) (ATO) and cisplatin (CIS) have potent antineoplastic effects in several types of cancer. Autophagy is important for normal cell function and survival, it is also used by tumor cells so, we studied it's role as possible mechanism of ATO and/or CIS antitumor effect on mice bearing Ehrlich ascites carcinoma (EAC) and checked whether ATO can enhance the antitumor potential of CIS. The study was carried out on eight groups of female mice; GP1 (negative control), GP2 (Erlich tumor only), GP3 (Normal +ATO), GP4 (Normal + CIS), GP5 (Normal + ATO+CIS), GP6 (EAC+ATO), GP7 (EAC+CIS) and GP8 (EAC +ATO+ CIS). In this study, viable cells were counted, percentage of viability (%) was calculated. Flowcytometry of autophagosome was appointed. Glutathione S-transferase (GST) and catalase (CAT) enzymes activities, total thiol and malondialdehyde (MDA) concentrations in liver tissues were determined to evaluate the effects of these drugs. Treatment with ATO (GP6) induced a significant decrease in tumor volume and percentage of viability with best result in combination of ATO with low dose of CIS (GP8) against EAC. Our results showed that a reduction in flourscence intensity of autophagosome marker that determined by flowcytometry especially in combination treated group (GP8). CAT, GST enzymes activities and total thiol level were decreased, while MDA level was increased in ATO treated group (GP6) and CIS treated group (GP7) as compared to EAC group. On other hand, combining both ATO and CIS in EAC treated group (GP8) decreased MDA level and augmented the level of total thiol and activities of CAT and GST enzymes. Therefore, our result revealed that combination of ATO and CIS have anti-tumor effects against EAC better than each one alone. So, we recommended the combination of ATO with CIS treatment due to their synergetic effect on cancer

Synthesis and characterization of ruthenium(III) complex containing 2-aminomethyl benzimidazole, and its anticancer activity of in vitro and in vivo models

A novel ruthenium(III) complex with 2-aminomethyl benzimidazole (AMBI) has been synthesized and characterized by elemental analysis, spectroscopic (FTIR, UV–Vis and XRD), thermal, magnetic and electrochemical techniques. Characterization shown that the ruthenium ion is octahedral coordinated by three H2O molecules, one chloride ion and a bidentate AMBI. The calf thymus DNA binding activity of complex was studied by absorption spectra and viscosity measurements. The strong interaction between Ru(III) complex and CT-DNA was investigated and the Kb value equals 8.3 × 10−5. The cytotoxicity effect of water soluble [RuCl(AMBI)(H2O)3]Cl2 complex on breast adenocarcinoma (MCF-7) and human colon carcinoma (HCT-116) cell lines (in vitro) was investigated by the MTT method. The Ru(III) complex shows good cytotoxic activity and the IC50 values are 57.20 and 18.08 μg/mL toward MCF-7 and HCT-116, respectively. The antiproliferative effect of Ru(III) complex on HCT-116 cells was nearly as the cisplatin value; that indicates its efficiency as anticancer agents. Apoptosis was studied by AO/EB staining and the Ru(III) complex shows apoptotic effect against the two cancer cell lines by percent to 23.1 and 33.1%. DNA damage assay by gel electrophoresis was done and the DNA fragmentation that appears in the two treated lanes indicates that there was destruction in the nuclear DNA. The cell cycle arrest by flow cytometry showed that the Ru(III) complex stops the two cancer cell lines proliferation by decrease the S and G0/G1 phases and increase in G2/M indicates that the interactions of our complex with DNA prevents the entry of cells into the DNA synthesis phase as well as into a new cell cycle. Moreover, the Ru(III) complex stops the proliferation of Ehrlich ascites carcinoma (EAC) bearing female mice (in vivo study) with low toxicity to the kidney. In addition, the antioxidant enzymes' activity in the treated and untreated groups' blood samples were also investigated. The decrease in topoisomerase I (Top I) levels in treated mice groups than the EAC group indicates the effect of our compound as topoisomerase I inhibitor.

AMELIORATIVE EFFECTS OF GARLIC EXTRACT AGAINST ADRIAMYCIN INDUCED NEPHROTOXICITY IN EHRLICH ASCITES CARCINOMA BEARING MALE MICE

The present study aimed to assess the protective role of garlic extract against adrymicin (ADR) induced nephrotoxicity in healthy and Ehrlich ascites carcinoma (EAC) bearing male mice. Sixty four Swiss albino male mice, (22 ± 2g) 6-8 weeks old were used and divided into eight groups each one consisted of 8 male mice as follows: 1st control group, 2nd garlic group, 3rd ADR group, 4th garlic/ADR group, 5th EAC group, 6th EAC/garlic, 7th EAC/ADR group and 8th EAC/garlic/ADR group. Serum creatinine, blood urea nitrogen (BNU) and histopathological changes in the kidney tissue were studied by light and electron microscopes. The results of this study revealed many toxicity symptoms such as elevation in serum creatnine and BUN levels in ADR or/and EAC bearing mice comparing with control and all garlic groups. Also, many histopathological lesions as inflammation, vacuolation, apoptosis, necrosis, fibrosis of the renal tubule cells, were recorded in ADR or/and EAC groups. Glomeruli had luminal deformity leading to an increase in the plasma viscosity. Podocytes were recognized with irregular pyknotic nuclei fused foot processes or effacement of pedicles and irregular thickness basement membrane. Degenerated proximal and distal tubules cells were seen with interrupted tubule contours. Swollen endoplasmic reticulum profiles and/or deteriorated mitochondria were also seen. In contrast, the treatment with garlic aqueous extract decreased creatnine, BUN as well as the lesions of most previous histopathological alterations. This study revealed that garlic extract may ameliorate the cytotoxic effect of ADR in normal and EAC bearing mice as indicated by biochemical and histological results.

Some genetic profiles in liver of Ehrlich ascites tumor-bearing mice under the stress of irradiation

Radiation therapy aims to kill cancer cells with a minimum of normal tissue exposure. In an attempt to define the molecular and biochemical changes associated with exposure to radiotherapy, the objective of the present study is to explore the effect of gamma (γ) irradiation on nuclear factor, erythroid 2 (NFE2), P53, stromelysin-1 (matrix metalloproteinase-3) (MMP3), BCL-2 and BAX genes expression in Ehrlich ascites carcinoma (EAC) bearing mice. Various biochemical parameters such as liver function, H2O2, B% and T% lymphocytes, total antioxidants and MDA were investigated to evaluate their usefulness as possible during cancer treatment with radiotherapy. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 0.5Gy. Sixty-four female mice, weighing 20–25g were used in this study and divided into three main groups. The first group served as control group, while the second were injected intraperitoneally with EAC then was subdivided into two groups, II A and II B. The latter one (group II B), the animals were exposed to a single dose of 0.5Gy whole body γ irradiation. The third main group, were irradiated with a single dose of 0.5Gy whole body γ irradiation. Blood and liver tissue samples were collected at 4, 24 and 96h post-irradiation. The gene expression levels in the livers of animals from each exposure group were compared individually with that of pooled sham-irradiated animals. MMP3 and NFE2 were overexpressed in liver samples of EAC group post 4, 24 and 96h of γ irradiation (IIB). On the other hand, P53 and BCL-2 genes were downregulated by using RT-PCR analysis post 4, 24 and 96h of γ irradiation (IIB). As well as, liver function and MDA were increased significantly in the γ - irradiation group (3rd group) when compared to control mice (1st group). Gamma irradiation 3rd group revealed increase in the level of T% and B% lymphocytes. According to the obtained results, both γ rays and time period alter the genes expression and most of the investigated biochemical parameters.

The antitumor effects of tetrodotoxin and/or doxorubicin on Ehrlich ascites carcinoma-bearing female mice

The study aimed to investigate the antitumor effect of tetrodotoxin (TTX) and/or doxorubicin (DOX) on Ehrlich ascites carcinoma (EAC)-bearing mice through the investigated biochemical parameters. TTX and/or DOX with or without N-acetylcystiene were administrated after 10days into EAC-female mice for a period of 2weeks in six equal doses. Treatment with TTX or DOX caused a significant decrease in the mean tumor weight and an increase in the cumulative mean survival time when compared with EAC group. All the treatments reduced the elevated liver tumor markers and increased liver antioxidant enzymes under investigation in comparison with EAC. Hepatic cells, suffered severely from degeneration and karriolysis in EAC group, revealed some improvement as appearance of healthy hepatocytes by TTX treatment. The present results suggested that TTX had a more powerful inhibitor effect on EAC growth than DOX and TTX plus DOX treatments reflected by antitumor biochemical and histological studies.