Tumor-educated macrophages facilitate tumor metastasis and angiogenesis. We discovered that granu... more Tumor-educated macrophages facilitate tumor metastasis and angiogenesis. We discovered that granulocyte macrophage colony-stimulating factor (GM-CSF) blocked macrophages vascular endothelial growth factor (VEGF) activity by producing soluble VEGF receptor-1 (sVEGFR-1) and determined the effect on tumor-associated macrophage behavior and tumor growth. We show GM-CSF treatment of murine mammary tumors slowed tumor growth and slowed metastasis. These tumors had more macrophages, fewer blood vessels, and lower oxygen concentrations. This effect was sVEGFR-1 dependent. In situ hybridization and flow cytometry identified macrophages as the primary source of sVEGFR-1. These data suggest that GM-CSF can re-educate macrophages to reduce angiogenesis and metastases in murine breast cancer.
Purpose: Cisplatin (CP)-induced nephrotoxicity is associated with the increased generation of rea... more Purpose: Cisplatin (CP)-induced nephrotoxicity is associated with the increased generation of reactive oxygen metabolites and lipid peroxidation in kidney, caused by the decreased levels of antioxidants and antioxidant enzymes. The purpose of this study was to evaluate the role of Spirulina, blue–green alga with antioxidant properties, in the protection of cisplatin-induced nephrotoxicity in rat. Methods: Rats were treated with CP (6 mg/kg bw, single dose, intraperitoneally). Spirulina (1,000 mg/kg) was administered orally for 8 days and CP treatment was given on day 4. Nephrotoxicity was assessed, 6 days after the CP treatment, by measuring plasma urea, creatinine, urinary N-acetyl-(d-glucose-aminidase) (β-NAG) and histopathology of kidney. Results: Rats treated with CP showed marked nephrotoxicity as evidenced from the significant elevation in plasma urea, creatinine and urinary β-NAG. Histological assessment revealed marked proximal tubular necrosis and extensive epithelial vacuolization in the kidney of CP-treated rats. Superoxide dismutase, catalase and glutathione peroxidase were decreased and lipid peroxidation was increased in kidney tissue. Pretreatment with Spirulina protected the rats from CP-induced nephrotoxicity. The rise in plasma urea, creatinine, urinary β-NAG, plasma and kidney tissue MDA and histomorphological changes were significantly attenuated by Spirulina. In vitro studies using human ovarian cancer cells revealed that Spirulina did not interfere with the cytotoxic effects of CP on tumor cells. Conclusions: In summary, Spirulina significantly protected the CP-induced nephrotoxicity through its antioxidant properties.
Myocardial function is dependent on a constant supply of oxygen from the coronary circulation. A ... more Myocardial function is dependent on a constant supply of oxygen from the coronary circulation. A reduction of oxygen supply due to coronary obstruction results in myocardial ischemia, which leads to cardiac dysfunction. Reperfusion of the ischemic myocardium is required for tissue survival. Thrombolytic therapy, coronary artery bypass surgery and coronary angioplasty are some of the treatments available for the restoration of blood flow to the ischemic myocardium. However, the restoration of blood flow may also lead to reperfusion injury, resulting in myocyte death. Thus, any imbalance between oxygen supply and metabolic demand leads to functional, metabolic, morphologic, and electrophysiologic alterations, causing cell death. Myocardial ischemia reperfusion (IR) injury is a multifactorial process that is mediated by oxygen free radicals, neutrophil activation and infiltration, calcium overload, and apoptosis. Controlled reperfusion of the ischemic myocardium has been advocated to prevent the IR injury. Studies have shown that reperfusion injury and postischemic cardiac function are related to the quantity and delivery of oxygen during reperfusion. Substantial evidence suggests that controlled reoxygenation may ameliorate postischemic organ dysfunction. In this review, we discuss the role of oxygenation during reperfusion and subsequent biochemical and pathologic alterations in reperfused myocardium and recovery of heart function.
Doxorubicin (DOX), a potent antineoplastic agent, poses limitations for its therapeutic use due t... more Doxorubicin (DOX), a potent antineoplastic agent, poses limitations for its therapeutic use due to the associated risk of developing cardiomyopathy and congestive heart failure. The cardiotoxicity of doxorubicin is associated with oxidative stress and apoptosis. We have recently shown that Spirulina, a blue-green alga with potent antioxidant properties, offered significant protection against doxorubicin-induced cardiotoxicity in mice. The aim of the present study was to establish the possible protective role of C-phycocyanin, one of the active ingredients of Spirulina, against doxorubicin-induced oxidative stress and apoptosis. The study was carried out using cardiomyocytes isolated from adult rat hearts. Doxorubicin significantly enhanced the formation of reactive oxygen species (ROS) in cells as measured by the 2',7'-dichlorodihydrofluorescein diacetate and dihydroethidium fluorescence. The doxorubicin-induced reactive oxygen species formation was significantly attenuated in cells pretreated with C-phycocyanin. It was further observed that the doxorubicin-induced DNA fragmentation and apoptosis, as assayed by TUNEL assay and flow cytometry coupled with BrdU-FITC/propidium iodide staining, were markedly attenuated by C-phycocyanin. C-phycocyanin also significantly attenuated the doxorubicin-induced increase in the expression of Bax protein, release of cytochrome c, and increase in the activity of caspase-3 in cells. In summary, C-phycocyanin ameliorated doxorubicin-induced oxidative stress and apoptosis in cardiomyocytes. This study further supports the crucial role of the antioxidant nature of C-phycocyanin in its cardioprotection against doxorubicin-induced oxidative stress and apoptosis.
Tumor-educated macrophages facilitate tumor metastasis and angiogenesis. We discovered that granu... more Tumor-educated macrophages facilitate tumor metastasis and angiogenesis. We discovered that granulocyte macrophage colony-stimulating factor (GM-CSF) blocked macrophages vascular endothelial growth factor (VEGF) activity by producing soluble VEGF receptor-1 (sVEGFR-1) and determined the effect on tumor-associated macrophage behavior and tumor growth. We show GM-CSF treatment of murine mammary tumors slowed tumor growth and slowed metastasis. These tumors had more macrophages, fewer blood vessels, and lower oxygen concentrations. This effect was sVEGFR-1 dependent. In situ hybridization and flow cytometry identified macrophages as the primary source of sVEGFR-1. These data suggest that GM-CSF can re-educate macrophages to reduce angiogenesis and metastases in murine breast cancer.
Purpose: Cisplatin (CP)-induced nephrotoxicity is associated with the increased generation of rea... more Purpose: Cisplatin (CP)-induced nephrotoxicity is associated with the increased generation of reactive oxygen metabolites and lipid peroxidation in kidney, caused by the decreased levels of antioxidants and antioxidant enzymes. The purpose of this study was to evaluate the role of Spirulina, blue–green alga with antioxidant properties, in the protection of cisplatin-induced nephrotoxicity in rat. Methods: Rats were treated with CP (6 mg/kg bw, single dose, intraperitoneally). Spirulina (1,000 mg/kg) was administered orally for 8 days and CP treatment was given on day 4. Nephrotoxicity was assessed, 6 days after the CP treatment, by measuring plasma urea, creatinine, urinary N-acetyl-(d-glucose-aminidase) (β-NAG) and histopathology of kidney. Results: Rats treated with CP showed marked nephrotoxicity as evidenced from the significant elevation in plasma urea, creatinine and urinary β-NAG. Histological assessment revealed marked proximal tubular necrosis and extensive epithelial vacuolization in the kidney of CP-treated rats. Superoxide dismutase, catalase and glutathione peroxidase were decreased and lipid peroxidation was increased in kidney tissue. Pretreatment with Spirulina protected the rats from CP-induced nephrotoxicity. The rise in plasma urea, creatinine, urinary β-NAG, plasma and kidney tissue MDA and histomorphological changes were significantly attenuated by Spirulina. In vitro studies using human ovarian cancer cells revealed that Spirulina did not interfere with the cytotoxic effects of CP on tumor cells. Conclusions: In summary, Spirulina significantly protected the CP-induced nephrotoxicity through its antioxidant properties.
Myocardial function is dependent on a constant supply of oxygen from the coronary circulation. A ... more Myocardial function is dependent on a constant supply of oxygen from the coronary circulation. A reduction of oxygen supply due to coronary obstruction results in myocardial ischemia, which leads to cardiac dysfunction. Reperfusion of the ischemic myocardium is required for tissue survival. Thrombolytic therapy, coronary artery bypass surgery and coronary angioplasty are some of the treatments available for the restoration of blood flow to the ischemic myocardium. However, the restoration of blood flow may also lead to reperfusion injury, resulting in myocyte death. Thus, any imbalance between oxygen supply and metabolic demand leads to functional, metabolic, morphologic, and electrophysiologic alterations, causing cell death. Myocardial ischemia reperfusion (IR) injury is a multifactorial process that is mediated by oxygen free radicals, neutrophil activation and infiltration, calcium overload, and apoptosis. Controlled reperfusion of the ischemic myocardium has been advocated to prevent the IR injury. Studies have shown that reperfusion injury and postischemic cardiac function are related to the quantity and delivery of oxygen during reperfusion. Substantial evidence suggests that controlled reoxygenation may ameliorate postischemic organ dysfunction. In this review, we discuss the role of oxygenation during reperfusion and subsequent biochemical and pathologic alterations in reperfused myocardium and recovery of heart function.
Doxorubicin (DOX), a potent antineoplastic agent, poses limitations for its therapeutic use due t... more Doxorubicin (DOX), a potent antineoplastic agent, poses limitations for its therapeutic use due to the associated risk of developing cardiomyopathy and congestive heart failure. The cardiotoxicity of doxorubicin is associated with oxidative stress and apoptosis. We have recently shown that Spirulina, a blue-green alga with potent antioxidant properties, offered significant protection against doxorubicin-induced cardiotoxicity in mice. The aim of the present study was to establish the possible protective role of C-phycocyanin, one of the active ingredients of Spirulina, against doxorubicin-induced oxidative stress and apoptosis. The study was carried out using cardiomyocytes isolated from adult rat hearts. Doxorubicin significantly enhanced the formation of reactive oxygen species (ROS) in cells as measured by the 2',7'-dichlorodihydrofluorescein diacetate and dihydroethidium fluorescence. The doxorubicin-induced reactive oxygen species formation was significantly attenuated in cells pretreated with C-phycocyanin. It was further observed that the doxorubicin-induced DNA fragmentation and apoptosis, as assayed by TUNEL assay and flow cytometry coupled with BrdU-FITC/propidium iodide staining, were markedly attenuated by C-phycocyanin. C-phycocyanin also significantly attenuated the doxorubicin-induced increase in the expression of Bax protein, release of cytochrome c, and increase in the activity of caspase-3 in cells. In summary, C-phycocyanin ameliorated doxorubicin-induced oxidative stress and apoptosis in cardiomyocytes. This study further supports the crucial role of the antioxidant nature of C-phycocyanin in its cardioprotection against doxorubicin-induced oxidative stress and apoptosis.
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