Anti-radiation effect of MRN-100: a hydro-ferrate fluid, in vivo.

Ionizing radiation (IR) severely harms many organs, especially the hematopoietic tissue, mandating the development of protective nutraceuticals. MRN-100, a hydro-ferrate fluid, has been shown to protect γ-radiated fish against hematopoietic tissue damage and lethality. The current study aimed to examine MRN-100's protective effect against irradiated mice and explore the mechanisms underlying its effect. Mice received a single acute, sub-lethal, 5 Gy, whole body dose of X-ray IR. MRN-100 treatment was administered daily for 2-weeks pre-irradiation until 1-week post-irradiation. Spleen and blood were analysed for oxidative stress, hematological, histological and biochemical parameters. Radiation exposure markedly decreased complete blood count (CBC) parameters including hemoglobin, hematocrit, red blood cells, platelets, white blood cells and lymphocytes, and significantly increased neutrophils. In contrast, MRN-100 supplementation to irradiated mice ameliorated all CBC parameters and protected against DNA damage in both splenic cells and serum. It also had an antioxidant effect, increasing the levels of glutathione, superoxide dismutase, catalase and total antioxidant capacity, which were otherwise decreased by irradiation. MRN-100 intake reduced the oxidative stress biomarker levels of nitric oxide, protein carbonyl, malondialdehyde, reactive oxygen species and 8-hydroxydeoxyguanosine, a marker specific to DNA damage. Furthermore, MRN-100 enhanced serum iron and reversed the radiation-induced elevations of liver enzymes. Finally, MRN-100 protected splenic tissue from irradiation as observed by histology. We conclude that MRN-100 consumption may protect against oxidative stress generated by radiation exposure, suggesting that it may be employed as an adjuvant treatment to prevent radiation's severe damage to important organs.

Anticancer potential of Marina Crystal Minerals (MCM) against the growth of murine mammary adenocarcinoma cells in vivo.

In vitro studies have shown that Marina Crystal Minerals (MCM), a crystallized mixture of minerals and trace elements from sea water, possesses apoptotic and immune modulatory effects in human breast cancer cells MDA-MB-231. The current study aimed to evaluate MCM's anticancer effect in vivo against murine mammary adenocarcinoma cells and to explore its underlying mechanisms. Mice were inoculated intramuscularly with Ehrlich ascites carcinoma (EAC) cells, a breast adenocarcinoma. Tumors became palpable within 9 days. Tumor-bearing mice were injected with MCM intraperitoneally (IP) or intratumorally (IT) at a dose of 40 mg/kg BW for 6 days/week until day 28 post-inoculation. Tumor growth, cell cycle progression, cell cycle regulatory proteins, apoptosis, apoptotic regulatory markers, mitochondrial membrane potential (MMP), natural killer (NK) cell activity, and histopathological effects were investigated. Treatment with MCM reduced tumor volume by 49.4% for IP and 59.5% for IT injection. MCM induced cancer cell apoptosis, as indicated by a sub-G1 peak and confirmed by Annexin V/PI assay and histopathological examination. This was mediated by increased Bax expression, caspase-3 activation, decreased Bcl-2 expression, and MMP disruption. Furthermore, MCM treatment induced G1 cell cycle arrest, mediated through significantly increased expression of p53, p21, and p27 and decreased expression of cyclin D1 and PCNA in cancer cells. Finally, MCM treatment markedly enhanced NK cell cytotoxicity. MCM possesses chemopreventive potential to reduce tumor growth by suppressing cell proliferation, inducing apoptosis in EAC cells via a mitochondrial dependent pathway, and activating the immune system. Our results suggest MCM's beneficial potential for treating breast adenocarcinoma.

Thymax, a gross thymic extract, exerts cell cycle arrest and apoptosis in Ehrlich ascites carcinoma in vivo.

Thymax is a gross thymic extract that has been shown to induce apoptosis in vitro for human breast cancer cells. Here we examine Thymax's ability to induce apoptosis in animals bearing Ehrlich ascites carcinoma (EAC). Thymax was administered six days/week orally to mice (5.45 mg/kg body weight) beginning either 14 days prior to EAC inoculation or 9 days post inoculation; treatment continued for 30 days post inoculation. Pretreatment of mice with Thymax markedly delayed tumor growth and reduced tumor incidence by 38.9%, and tumor volumes relative to untreated controls were suppressed by 90.5% and 55.0% for pre- and post-inoculation groups, respectively. Treatment with Thymax inhibited cellular proliferation by decreasing the expression of tumor markers Ki-67, PCNA, and Cyclin D1 in cancer cells and increasing the expression of p21 and p27. This was associated with the ability of Thymax to arrest the cell cycle of EAC cells in the G0/G1 phase and to induce apoptosis, as indicated by a significant increase in the sub-G1 phase's percentage of hypodiploid cells and further affirmed by DNA fragmentation and Annexin V/propidium iodide staining. In addition, Thymax exerted its apoptotic effect in EAC cancer cells through a mitochondrial-dependent pathway, as evidenced by an increased Bax/Bcl-2 ratio, up-regulation of p53 expression, and activation of caspase-3. We conclude that Thymax supplementation enhances tumor cell demise by arresting the cell cycle and inducing apoptosis. These data suggest that Thymax could be a new adjuvant for breast cancer treatment.

A novel kefir product (PFT) inhibits Ehrlich ascites carcinoma in mice via induction of apoptosis and immunomodulation.

BACKGROUND: The popularity of fermented foods such as kefir, kuniss, and tofu has been greatly increasing over the past several decades, and the ability of probiotic bacteria to exert anticancer effects has recently become the focus of research. While we have recently demonstrated the ability of the novel kefir product PFT (Probiotics Fermentation Technology) to exert anticancer effects in vitro, here we demonstrate its ability to inhibit Ehrlich ascites carcinoma (EAC) in mice. METHODS: Mice were inoculated intramuscularly with EAC cells to develop solid tumors. PFT was administered orally (2 g/kg/day) to mice 6 days/week, either 2 days before tumor cell inoculation or 9 days after inoculation to mice bearing solid tumors. Tumor growth, blood lymphocyte levels, cell cycle progression, apoptosis, apoptotic regulator expression, TNF-α expression, changes in mitochondrial membrane potential (MMP), PCNA, and CD4+ and CD8+ T cells in tumor cells were quantitatively evaluated by flow cytometry or RT-PCR. Further studies in vitro were carried out where EAC cells along with several other human cancer cell lines were cultured in the presence of PFT (0-5 mg/mL). Percent cell viability and IC50 was estimated by MTT assay. RESULTS: Our data shows that PFT exerts the following: 1) inhibition of tumor incidence and tumor growth; 2) inhibition of cellular proliferation via a marked decrease in the expression of tumor marker PCNA; 3) arrest of the tumor cell cycle in the sub-G0/G1 phase, signifying apoptosis; 4) induction of apoptosis in cancer cells via a mitochondrial-dependent pathway as indicated by the up-regulation of p53 expression, increased Bax/Bcl-2 ratio, decrease in the polarization of MMP, and caspase-3 activation; and 5) immunomodulation with an increase in the number of infiltrating CD4+ and CD8+ T cells and an enhancement of TNF-α expression within the tumor. CONCLUSIONS: PFT reduces tumor incidence and tumor growth in mice with EAC by inducing apoptosis in EAC cells via the mitochondrial-dependent pathway, suppressing cancer cell proliferation, and stimulating the immune system. PFT may be a useful agent for cancer prevention.

Chemopreventive role of arabinoxylan rice bran, MGN-3/Biobran, on liver carcinogenesis in rats.

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and one of the most lethal. MGN-3/Biobran is a natural product derived from rice bran hemicelluloses and has been reported to possess a potent anticancer effect in a clinical study of patients with HCC. The current study examines the mechanisms by which Biobran protects against chemically induced hepatocarcinogenesis in rats. The chemical carcinogen used in this study is N-nitrosodiethylamine (NDEA) plus carbon tetrachloride (CCl4). Rats were treated with this carcinogen, and the animals were pretreated or posttreated with Biobran via intraperitoneal injections until the end of the experiment. Treatment with Biobran resulted in: 1) significant alleviation of liver preneoplastic lesions towards normal hepatocellular architecture in association with inhibition of collagen fiber deposition; 2) arrest of cancer cells in the sub-G1 phase of the cell cycle; 3) increased DNA fragmentation in cancer cells; 4) down-regulated expression of Bcl-2 and up-regulated expression of p53, Bax, and caspase-3; and 5) protection against carcinogen-induced suppression of IkappaB-alpha (IκB-α) mRNA expression and inhibition of nuclear factor kappa-B (NF-κB/p65) expression. Additionally, the effect of Biobran treatment was found to be more significant when supplemented prior to carcinogen-induced hepatocarcinogenesis as compared to posttreatment. We conclude that Biobran inhibits hepatocarcinogenesis in rats by mechanisms that include induction of apoptosis, inhibition of inflammation, and suppression of cancer cell proliferation. Biobran may be a promising chemopreventive and chemotherapeutic agent for liver carcinogenesis.

Arabinoxylan rice bran (MGN-3/Biobran) enhances radiotherapy in animals bearing Ehrlich ascites carcinoma†.

This study examines the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the anti-cancer effects of fractionated X-ray irradiation of Ehrlich solid tumor-bearing mice. Swiss albino mice bearing tumors were exposed to the following: (i) Biobran treatment (40 mg/kg/day, intraperitoneal injections) beginning on day 11 post-tumor cell inoculation until day 30; (ii) ionizing radiation (Rad) 2 Gy at three consecutive doses on days 12, 14 and 16; or (iii) Biobran + Rad. Final tumor weight was suppressed by 46% for Biobran, 31% for Rad and 57% for the combined treatment (Biobran + Rad) relative to control untreated mice. Biobran and Rad also arrested the hypodiploid cells in the sub-G1-phase, signifying apoptosis by +102% and +85%, respectively, while the combined treatment induced apoptosis by +123%, with similar results in the degree of DNA fragmentation. Furthermore, Biobran + Rad upregulated the relative gene expression and protein level of p53 and Bax in tumor cells, down-regulated Bcl-2 expression, and increased the Bax/Bcl-2 ratio and caspase-3 activity, with the combined treatment greater than for either treatment alone. Additionally, the combined treatment modulated the decrease in body weight, the increase in liver and spleen weight, and the elevation of liver enzymes aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase to be within normal values. We conclude that Biobran enhances radiation therapy-induced tumor regression by potentiating apoptosis and minimizing toxicities related to radiation therapy, suggesting that Biobran may be useful in human cancer patients undergoing radiotherapy and warranting clinical trials.

Dietary baker's yeast sensitizes Ehrlich mammary adenocarcinoma to paclitaxel in mice bearing tumor.

Baker's yeast, Saccharomyces cerevisiae, has been shown to sensitize a variety of breast cancer cell (BCC) lines to paclitaxel chemotherapy in vitro. The present study evaluated the ability of S. cerevisiae to sensitize BCCs to paclitaxel in animals bearing Ehrlich ascites carcinoma (EAC). Mice bearing EAC were intratumorally injected with dead S. cerevisiae (1x107 cells/ml) in the presence or absence of low- and high-dose paclitaxel [paclitaxel-L, 2 mg/kg body weight (BW) and paclitaxel-H, 10 mg/kg BW, respectively]. At 30 days post tumor inoculation, co-treatment with yeast plus paclitaxel-L showed improvements over paclitaxel-H alone, as measured by tumor weight (-64 vs. -53%), DNA damage (+79 vs. +62%), tumor cell apoptosis (+217 vs. +177%), cell proliferation (-56 vs. -42%) and Ki-67 marker (+95 vs. +40%). Histopathology and ultra-structural examinations showed that yeast plus paclitaxel-L enhanced apoptosis in EAC more than paclitaxel-H alone and caused comparable tumor necrosis. We conclude that baker's yeast may be used with low-dose chemotherapy to achieve the same potency as high-dose chemotherapy in mice bearing EAC. This suggests that baker's yeast may be an anticancer adjuvant and may have clinical implications for the treatment of breast cancer.

Grape seeds and skin induce tumor growth inhibition via G1-phase arrest and apoptosis in mice inoculated with Ehrlich ascites carcinoma.

OBJECTIVES: Chemoprevention or intervention of cancer by means of natural dietary components has shown great promise in controlling malignancy. This study was conducted to investigate the chemopreventive effects of grape seeds (GSE) combined with grape skin (GSK) in mice that were inoculated with Ehrlich ascites carcinoma, and to elucidate the underlying mechanisms. METHODS: GSE + GSK were mixed with the standard diet and supplemented to mice 14 d before Ehrlich ascites carcinoma cell inoculation and continued throughout the experiment. Tumor growth was monitored and cell cycle progression and apoptotic effect of GSE + GSK on tumor cells were evaluated. RESULTS: GSE + GSK intake prevented tumor development in 47% of the animals. Tumor volume and weight were markedly reduced by 93.9 % and 86.3 %, respectively, compared with tumor-bearing mice that were untreated with these agents. GSE + GSK treatment caused a marked increase in the percentage of apoptotic tumor cells as evaluated by flow cytometry and confirmed by histopathologic and electron microscopy examinations. GSE + GSK also caused significant cell cycle arrest at the G1 phase, activation of caspase-3, increase in p53 and Bax expression, and decrease in B-cell lymphoma 2 expression and B-cell lymphoma 2:Bax ratio in tumor cells. Furthermore, the induction of apoptosis and cell proliferation inhibition was indicated immunohistochemically as shown by modulating p53 and Ki67 expression. CONCLUSIONS: The results of this study clearly showed that the combination of GSE and GSK represents a potent chemopreventive and anticancer agent in a mice model of Ehrlich carcinoma. The mechanisms that underlie the effects of these agents include cell cycle arrest, induction of apoptosis, and inhibition of cell proliferation. These findings suggest that GSE + GSK may represent a natural, novel, adjuvant therapeutic strategy for chemoprevention of the growth of solid tumors.

Baker's Yeast Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro.

Our earlier studies have demonstrated that phagocytosis of baker's yeast ( Saccharomyces cerevisiae) induces apoptosis in different cancer cell lines in vitro and in vivo. This study aimed to examine how baker's yeast sensitizes murine and human breast cancer cells (BCC) to paclitaxel in vitro. This sensitizing effect makes lower concentrations of chemotherapy more effective at killing cancer cells, thereby enhancing the capacity of treatment. Three BCC lines were used: the metastatic murine 4T1 line, the murine Ehrlich ascites carcinoma (EAC) line, and the human breast cancer MCF-7 line. Cells were cultured with different concentrations of paclitaxel in the presence or absence of baker's yeast. Cell survival and the IC50 values were determined by MTT assay and trypan blue exclusion method. Percent of DNA damage, apoptosis, and cell proliferation were examined by flow cytometry. Yeast alone and paclitaxel alone significantly decreased 4T1 cell viability postculture (24 and 48 hours), caused DNA damage, increased apoptosis, and suppressed cell proliferation. Baker's yeast in the presence of paclitaxel increased the sensitivity of 4T1 cells to chemotherapy and caused effects that were greater than either treatment alone. The chemosensitizing effect of yeast was also observed with murine EAC cells and human MCF-7 cells, but to a lesser extent. These data suggest that dietary baker's yeast is an effective chemosensitizer and can enhance the apoptotic capacity of paclitaxel against breast cancer cells in vitro. Baker's yeast may represent a novel adjuvant for chemotherapy treatment.

Enhancing the Apoptotic Effect of a Low Dose of Paclitaxel on Tumor Cells in Mice by Arabinoxylan Rice Bran (MGN-3/Biobran).

In this study, we examine the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the apoptotic effect of paclitaxel (Taxol) at low concentration [2 mg/kg body weight (BW)] in animals bearing Ehrlich ascites carcinoma (EAC) cells and elucidate its mechanisms of action. On Day 8 following tumor cells inoculation, mice bearing tumors were administered MGN-3 alone (40 mg/kg BW), paclitaxel alone, or MGN-3 plus paclitaxel. On Day 30 post-tumor inoculation, we observed significant suppression of tumor volume (TV) with paclitaxel alone (59%), MGN-3 alone (77%), and MGN-3 plus paclitaxel (88%). Inhibition of tumor growth post-treatment with both agents, as compared with either treatment alone, was associated with a decrease in cell proliferation, a marked increase in the sub-G0/G1 population, an increase in DNA damage and apoptosis of tumor cells, and a significant maximization of the apoptosis index (AI)/proliferation index (PrI) ratio. Histopathological and electron microscopy examination of the combined treatment group showed an increase in the degenerative regions of the solid tumor tissue and abundant apoptotic cells. These data suggest that MGN-3 supplementation enhances tumor cell demise in the presence of a low dose of chemotherapeutic agent via apoptotic mechanism.

Chemopreventive Activity of MGN-3/Biobran Against Chemical Induction of Glandular Stomach Carcinogenesis in Rats and Its Apoptotic Effect in Gastric Cancer Cells.

In the current study, we investigated the chemopreventive activity of arabinoxylan rice bran, MGN-3/Biobran, against chemical induction of glandular stomach carcinogenesis in rats. Gastric cancer was induced by carcinogen methylnitronitrosoguanidine (MNNG), and rats received MNNG alone or MNNG plus Biobran (40 mg/kg body weight) for a total of 8 months. Averaged results from 2 separate readings showed that exposure to MNNG plus Biobran caused gastric dysplasia and cancer (adenocarcinoma) in 4.5/12 rats (9/24 readings, 37.5%), with 3.5/12 rats (7/24 readings, 29.2%) showing dysplasia and 1/12 rats (8.3%) developing adenocarcinoma. In contrast, in rats treated with MNNG alone, 8/10 (80%) developed dysplasia and adenocarcinoma, with 6/10 rats (60%) showing dysplasia and 2/10 rats (20%) developing adenocarcinoma. The effect of combining both agents was also associated with significant suppression of the expression of the tumor marker Ki-67 and remarkable induction in the apoptotic gastric cancer cells via mitochondrial-dependent pathway as indicated by the upregulation in p53 expression, Bax expression, downregulation in Bcl-2 expression, an increase in Bax/Bcl-2 ratio, and an activation of caspase-3. In addition, Biobran treatment induced cell-cycle arrest in the subG1 phase, where the hypodiploid cell population was markedly increased. Moreover, Biobran treatment protected rats against MNNG-induced significant decrease in lymphocyte levels. We conclude that Biobran provides protection against chemical induction of glandular stomach carcinogenesis in rats and may be useful for the treatment of human patients with gastric cancer.

Biochemical and histopathological changes in liver of the Nile tilapia from Egyptian polluted lakes.

The aim of the present study was to analyze the impact of environmental contamination on oxidative stress and histopathologic biomarkers in liver of the Nile tilapia, Oreochromis niloticus, collected from four sites that differ in their extent of pollution load, including heavy metals: the southeast basin (SEB), main basin (MB), and northwest basin (NWB) of Lake Mariut as well as Boughaz El-Maadiya, a channel in Lake Edku. The SEB was the less-impacted site, and thus considered as a reference. High concentrations of heavy metals (cadmium, copper, iron, lead, zinc, and manganese) were detected in fish liver at sites with anthropogenic pressure. All biomarkers, lipid peroxidation (in the MB, NWB, and Lake Edku), superoxide dismutase (in the MB and NWB), and glutathione peroxidase, and reduced glutathione (in the NWB) were found to be significantly higher compared to the reference values. Catalase, glutathione reductase, and glucose-6-phosphate dehydrogenase showed a varied response and displayed significantly lower activities in the polluted sites. Certain hepatic lesions, detected microscopically, were stimulated in fish from the MB and NWB, reflecting the high contamination of these areas. These included foci of necrosis, melanomacrophage infiltration, congestion, nuclear pyknosis, and extensive vacuolation corresponding to relatively higher lipid content. Overall, our results suggest that the selected biomarkers are useful for the assessment of pollution impacts in natural aquatic environments influenced by multiple pollution sources. The existence of chronic background pollution of the test sites implies that the observed biomarker responses cannot be solely attributed to heavy metals.

Hydroferrate fluid, MRN-100, provides protection against chemical-induced gastric and esophageal cancer in Wistar rats.

In the current study, we examined the protective effect of hydroferrate fluid MRN-100 against the carcinogen methylnitronitrosoguanidine (MNNG)-induced gastric and esophageal cancer in rats. MRN-100 is an iron-based compound composed of bivalent and trivalent ferrates. At 33 weeks post treatment with MNNG, rats were killed and examined for the histopathology of esophagus and stomach; liver, spleen, and total body weight; and antioxidant levels in the blood and stomach tissues. Results showed that 17/20 (85%) gastroesophageal tissues from carcinogen MNNG-treated rats developed dysplasia and cancer, as compared to 8/20 (40%) rats treated with MNNG plus MRN-100. In addition, MRN-100 exerted an antioxidant effect in both the blood and stomach tissues by increasing levels of GSH, antioxidant enzymes SOD, CAT, and GPx, and total antioxidant capacity (TAC) level. This was accompanied by a reduction in the total free-radical and malondialdehyde levels. Furthermore, MRN-100 protected against body and organ weight loss. Thus, MRN-100 exhibited significant cancer chemopreventive activity by protecting tissues against oxidative damage in rats, which may suggest its effectiveness as an adjuvant for the treatment of gastric/esophageal carcinoma.

Modified arabinoxylan from rice bran, MGN-3/biobran, sensitizes metastatic breast cancer cells to paclitaxel in vitro.

BACKGROUND: There is an increased interest in alternative treatments that reduce the toxicity of chemotherapy by lowering the drug concentration, whilst maintaining potency against cancer cells. Previous studies have demonstrated that arabinoxylan from rice bran, MGN-3/Biobran, sensitizes human breast cancer cells (BCC) to daunorubicin (DNR). In the present study, we further evaluated the ability of MGN-3 to sensitize cells to another chemotherapy agent, paclitaxel. MATERIALS AND METHODS: Non-metastatic MCF-7 (human BCC) and metastatic 4T1 (murine BCC) cells were cultured with different concentrations of paclitaxel in the presence or absence of MGN-3. Cell survival, DNA damage, and cell proliferation were examined. RESULTS: MGN-3 increased the susceptibility of both types of cancer cells to paclitaxel by over 100-fold. Mechanistically, MGN-3 works synergistically with paclitaxel by causing DNA damage, enhancing apoptosis, and inhibiting cell proliferation in 4T1 cells. CONCLUSION: Our data demonstrate that MGN-3 is an effective chemosensitizer and may represent a novel adjuvant for the treatment of metastatic breast cancer.

Arabinoxylan rice bran (MGN-3/Biobran) provides protection against whole-body γ-irradiation in mice via restoration of hematopoietic tissues.

The aim of the current study is to examine the protective effect of MGN-3 on overall maintenance of hematopoietic tissue after γ-irradiation. MGN-3 is an arabinoxylan from rice bran that has been shown to be a powerful antioxidant and immune modulator. Swiss albino mice were treated with MGN-3 prior to irradiation and continued to receive MGN-3 for 1 or 4 weeks. Results were compared with mice that received radiation (5 Gy γ rays) only, MGN-3 (40 mg/kg) only and control mice (receiving neither radiation nor MGN-3). At 1 and 4 weeks post-irradiation, different hematological, histopathological and biochemical parameters were examined. Mice exposed to irradiation alone showed significant depression in their complete blood count (CBC) except for neutrophilia. Additionally, histopathological studies showed hypocellularity of their bone marrow, as well as a remarkable decrease in splenic weight/relative size and in number of megakaryocytes. In contrast, pre-treatment with MGN-3 resulted in protection against irradiation-induced damage to the CBC parameters associated with complete bone marrow cellularity, as well as protection of the aforementioned splenic changes. Furthermore, MGN-3 exerted antioxidative activity in whole-body irradiated mice, and provided protection from irradiation-induced loss of body and organ weight. In conclusion, MGN-3 has the potential to protect progenitor cells in the bone marrow, which suggests the possible use of MGN-3/Biobran as an adjuvant treatment to counteract the severe adverse side effects associated with radiation therapy.

Sodium nitrite therapy rescues ischemia-induced neovascularization and blood flow recovery in hypertension.

Arterial hypertension is a major risk factor that can lead to complication of peripheral vascular disease due, in part, to endothelial dysfunction. Because sodium nitrite (SN) can be converted to nitric oxide (NO), which counteracts endothelial dysfunction, we explored the effect of nitrite on neovascularization following hind limb ischemia in different models of hypertension (HT). Chronic delivery of angiotensin II (Ang II, 400 ng/kg/min) or N(omega)-nitro-L-arginine-methyl-ester (L-NAME, 0.1 g/L) was used for a 2-week period to induce hypertension. Mice were subjected to femoral artery ligation-induced ischemia in the hind limb followed by treatment with SN (50 mg/L) for 2 weeks. SN significantly reduced systolic arterial blood pressure in mice receiving Ang II and L-NAME but had no effect in sham animals. After 2 weeks, blood flow and microangiography showed 60 % ± 1.0 recovery in sham compared with 40 % ± 1.3 in HT mice. Importantly, sham and HT mice treated with SN showed a 100 % blood flow recovery associated with normalization in capillary density. The inhibition of xanthine-oxido-reductase (allopurinol) or VEGFR (SU-5416) prevented the neovascularization in HT mice treated with SN. Cyclic GMP (cGMP) content in the hind limb was significantly increased in mice treated with SN compared with non-treated mice. Nitrite/nitrate content was only increased in the sham group treated with SN. Immunoprecipitation and Western blot analysis revealed an increase in eNOS/Akt/VEGFR phosphorylation in skeletal muscle from mice treated with SN compared with non-treated mice. Our findings indicate that SN therapy rescues the neovascularization and blood flow recovery in the ischemic hind limb of sham and HT mice likely through the Akt/NO/cGMP and VEGFR pathways.

Assessment of matrix metalloproteinase-1 for marking liver cirrhosis in chronic hepatitis C patients.

Our objective in the present study was to observe the change in the serum MMP-1 concentration using ELISA in 129 chronic hepatitis C (CHC) (78 non-cirrhotic and 51 with cirrhotic liver) and 50 healthy controls. The values of MMP-1 concentration increased in patients with CHC according to the stage of liver fibrosis. An area under the ROC curves (AUC) of the MMP-1 was 0.98 for discriminating patients with cirrhotic liver from healthy individuals and was 0.78 for discriminating patients with cirrhotic liver from non cirrhotic patients. The diagnostic potential of MMP-1 for discriminating cirrhosis from healthy individuals was very high with 98% sensitivity and 97% efficiency. MMP-1 detected cirrhosis in CHC with 71% sensitivity and 73% efficiency. In Conclusion, measurement of serum MMP-1 is useful for diagnosing liver cirrhosis in CHC patients.

Reversal of age-associated oxidative stress in rats by MRN-100, a hydro-ferrate fluid.

Aging is associated with an increase in the level of reactive oxygen species (ROS), which cause cellular damage. This study examined the protective effects of MRN-100, an iron-based hydro-ferrate fluid, against age-associated oxidative stress using young (4 months old) and aged (22 months old) rats. The effect of MRN-100 intake on lipid peroxidation, protein oxidation, and antioxidant status was studied in the blood, liver, and brain. Aged rats were treated with tap water or MRN-100 (100%) orally daily for 40 days. Results revealed that in aged rats treated with MRN-100 (100%) there was: (i) an inhibition of the levels of oxidative stress biomarkers: malondialdehyde, nitric oxide, protein carbonyl groups and total free radicals; (ii) an augmentation in glutathione and total thiol contents; (iii) an enhancement in the activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase; and (iv) an enhancement in plasma iron and ferritin concentrations, and in transferrin saturation. MRN-100 reversed age-related oxidative changes, bringing levels to within the limits of the young control rats in the blood, liver and brain. MRN-100 showed effectiveness in modulating age-associated oxidative stress in rats, and it may therefore be useful to reduce age-associated disorders where free radicals and oxidative stress are the major cause.

Cytokine gene polymorphisms in egyptian cases with brain tumors.

BACKGROUND: Cytokines are proposed to play important roles in brain tumor biology as well as neurodegeneration or impaired neuronal function. OBJECTIVES: This work aimed to check the association of polymorphisms of cytokine genes in Egyptian cases with brain tumors. METHODS: This work included 45 cases affected by brain tumors diagnosed as 24 benign and 21 malignant. Their median age was 45 years, and they were 20 males and 25 females. These cases were taken randomly from the Neurosurgery Department of Mansoura University Hospital, Egypt. Case genotypes were compared to 98 healthy unrelated controls from the same locality. DNA was amplified using PCR utilizing sequence specific primers (SSP) for detection of polymorphisms related to TNF-a-308 (G/A), IL-10-1082 (G/A), IL-6-174 (G/C) and IL-1Ra (VNTR) genes. RESULTS: Cases affected with benign brain tumors showed a significant higher frequency of IL-10-1082 A/A [odds ratio (OR=8.0), p<0.001] and IL-6-174 C/C (OR=6.3, p=0.002) homozygous genotypes as compared to controls. Malignant cases, on the other hand, showed significantly higher frequency of IL-6-174 C/C (OR =4.8, p=0.002) homozygous genotype and TNF-a-308 A/A (OR=4.9, p<0.001) homozygous genotype when compared to controls. In the meantime, all cases showed no significant difference regarding the distribution of IL-1Ra VNTR genotype polymorphism compared to controls. CONCLUSIONS: Cytokine gene polymorphisms showed a pattern of association with brain tumors which may have potential impact on family counseling and disease management.

Antioxidant potential by arabinoxylan rice bran, MGN-3/biobran, represents a mechanism for its oncostatic effect against murine solid Ehrlich carcinoma.

We have recently examined the oncolytic effect of arabinoxylan rice bran, MGN-3/biobran, against solid Ehrlich carcinoma (SEC)-bearing mice via immune-modulation and apoptosis [N.K. Badr El-din, E. Noaman, M. Ghoneum, In vivo tumor inhibitory effects of nutritional rice bran supplement MGN-3/biobran on Ehrlich carcinoma-bearing mice, Nutr. Cancer 60 (2) (2008) 235-244]. In the present study, we examined the antioxidant system as another possible mechanism through which MGN-3 exerts its oncostatic potential. Female albino mice were inoculated intramuscularly in the right thigh with Ehrlich ascites carcinoma (EAC) cells. MGN-3 (25 mg/kg body weight) was injected intraperitoneally (i.p.) six times a week for 25 days into mice at either day 4 or day 11 post-EAC cell inoculation. Tumor growth, lipid peroxidation (LPx), glutathione (GSH) contents, the activity of the antioxidant scavenger enzymes, and alterations in gene expression were examined. MGN-3 efficiently suppressed the growth of tumors, which was associated with normalization of the LPx levels and augmentation of GSH contents. MGN-3 enhanced the activity of the endogenous antioxidant scavenging enzymes -- superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione-S-transferase (GST) -- in blood, liver, and tumor tissue. Similarly it up-regulated the expression of GPx, SOD1 and CAT mRNA in the liver. The effect of MGN-3 was more pronounced when treated early, at day 4 of tumor cell inoculation, as compared to later treatment at 11 days. In conclusion, MGN-3-induced oncostatic activity by modulating lipid peroxidation, augmenting the antioxidant defense system and protecting against oxidative stress.