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1.
Immunol Cell Biol ; 86(3): 277-88, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18268518

RESUMO

Bovine lactoferrin (bLf), an iron-containing natural defence protein found in bodily secretions, has been reported to inhibit carcinogenesis and the growth of tumours. Here, we investigated whether natural bLf and iron-saturated forms of bLf differ in their ability to augment cancer chemotherapy. bLf was supplemented into the diet of C57BL/6 mice that were subsequently challenged subcutaneously with tumour cells, and treated by chemotherapy. Chemotherapy eradicated large (0.6 cm diameter) EL-4 lymphomas in mice that had been fed iron-saturated bLf (here designated Lf(+)) for 6 weeks prior to chemotherapy, but surprisingly not in mice that were fed lesser iron-saturated forms of bLf, including apo-bLf (4% iron saturated), natural bLf (approximately 15% iron saturated) and 50% iron-saturated bLf. Lf(+)-fed mice bearing either EL-4, Lewis lung carcinoma or B16 melanoma tumours completely rejected their tumours within 3 weeks following a single injection of either paclitaxel, doxorubicin, epirubicin or fluorouracil, whereas mice fed the control diet were resistant to chemotherapy. Lf(+) had to be fed to mice for more than 2 weeks prior to chemotherapy to be wholly effective in eradicating tumours from all mice, suggesting that it acts as a competence factor. It significantly reduced tumour vascularity and blood flow, and increased antitumour cytotoxicity, tumour apoptosis and the infiltration of tumours by leukocytes. Lf(+) bound to the intestinal epithelium and was preferentially taken up within Peyer's patches. It increased the production of Th1 and Th2 cytokines within the intestine and tumour, including TNF, IFN-gamma, as well as nitric oxide that have been reported to sensitize tumours to chemotherapy. Importantly, it restored both red and white peripheral blood cell numbers depleted by chemotherapy, potentially fortifying the mice against cancer. In summary, bLf is a potent natural adjuvant and fortifying agent for augmenting cancer chemotherapy, but needs to be saturated with iron to be effective.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Lactoferrina/administração & dosagem , Linfoma/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Farmacêuticos/administração & dosagem , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/imunologia , Carcinoma Pulmonar de Lewis/irrigação sanguínea , Carcinoma Pulmonar de Lewis/dietoterapia , Carcinoma Pulmonar de Lewis/imunologia , Bovinos , Citotoxicidade Imunológica/efeitos dos fármacos , Suplementos Nutricionais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Imuno-Histoquímica , Ferro/química , Lactoferrina/química , Lactoferrina/imunologia , Linfoma/dietoterapia , Linfoma/imunologia , Melanoma Experimental/irrigação sanguínea , Melanoma Experimental/dietoterapia , Melanoma Experimental/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neovascularização Patológica/tratamento farmacológico
2.
Br J Nutr ; 94(2): 244-52, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16115359

RESUMO

Bovine milk has been shown to contain bioactive components with bone-protective properties. Earlier studies on bovine milk whey protein showed that it suppressed bone resorption in the female ovariectomised rat. A new osteotropic component was subsequently identified in the whey basic protein fraction, but bone bioactivity may also be associated with other whey fractions. In the present study, we investigated whether acidic protein fractions isolated from bovine milk whey could prevent bone loss in mature ovariectomised female rats. Six-month-old female rats were ovariectomised (OVX) or left intact (sham). The OVX rats were randomised into four groups. One group remained the control (OVX), whereas three groups were fed various whey acidic protein fractions from milk whey as 3 g/kg diet for 4 months. Outcomes were bone mineral density, bone biomechanics and markers of bone turnover. Bone mineral density of the femurs indicated that one of the whey AF over time caused a recovery of bone lost from OVX. Plasma C-telopeptide of type I collagen decreased significantly in all groups except OVX control over time, indicating an anti-resorptive effect of whey acidic protein. Biomechanical data showed that the AF may affect bone architecture as elasticity was increased by one of the whey AF. The femurs of AF-supplemented rats all showed an increase in organic matter. This is the first report of an acidic whey protein fraction isolated from milk whey that may support the recovery of bone loss in vivo.


Assuntos
Reabsorção Óssea/prevenção & controle , Suplementos Nutricionais , Proteínas do Leite/administração & dosagem , Osteoporose/prevenção & controle , Animais , Biomarcadores/análise , Fenômenos Biomecânicos , Peso Corporal/fisiologia , Densidade Óssea/fisiologia , Reabsorção Óssea/fisiopatologia , Feminino , Fêmur/fisiopatologia , Vértebras Lombares/fisiopatologia , Tamanho do Órgão/fisiologia , Osteocalcina/análise , Osteoporose/fisiopatologia , Ovariectomia/métodos , Inibidores de Proteases/administração & dosagem , Ratos , Ratos Sprague-Dawley , Útero/fisiopatologia
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