The effect of probiotic microorganisms and bioactive compounds on chemically induced carcinogenesis in rats.

Diet interventions and natural bioactive supplements have now been extensively studied to reduce risks of colon cancer, which is one of the major public health problem throughout the world. The objective of our investigation was to study the effects of probiotic, prebiotic, nutritional plant extract, and plant oil on selected biochemical and immunological parameters in rats with colon cancer induced by N,N dimethylhydrazine (DMH). Male and female Wistar albino rats were were fed by a high-fat (HF) diet (10% fat in the diet) and were divided into 9 groups: Control group; PRO group - HF diet supplemented with probiotic Lactobacillus plantarum to provide 3 x 109 c.f.u. of strain/1 ml of medium; PRE group - HF diet supplemented with inulin enriched with oligofructose (2% of HF diet); HES group - HF diet supplemented with plant extract of Aesculus hippocastanum L. (1% of HF diet); OIL group - HF diet comprised Linioleum virginale (2% of HF diet); and combination of probiotic microorganisms and bioactive compounds in the groups - PRO-PRE, PRO-HES, PRO-OIL, PRE-OIL. Carcinogenesis was initiated with subcutaneous injection of DMH (20 mg/kg) two times at week interval and dietary treatments were continued for the six weeks. Application of probiotic microorganisms and bioactive compounds in all treated groups significantly decreased the activities of bacterial enzymes (p<0.001), the fecal bile acids concentration (p<0.01; p<0.001) and significantly increased serum TNFalpha level (p<0.001) in comparison to the control rats. The number of coliforms was reduced in PRO, PRO-PRE, PRO-OIL and PRE-OIL groups and significantly higher count of lactobacilli (p<0.05) was observed in PRO-PRE, PRO-OIL and PRE-OIL groups in compare with the controls. In conclusion, the results of this study indicate that probiotic microorganisms and bioactive compounds could exert a preventive effect on colon carcinogenesis induced by DMH.

Antiangogenic effect of selected phytochemicals.

Angiogenesis, the formation of new blood vessels from a preexisting vascular network is considered a key step in tumour growth, invasion, and metastasis. Recent studies show that several natural compounds inhibit angiogenesis and nowadays numerous bioactive plant compounds are tested for their antiangiogenic potential. This review examines current knowledge regarding the antiangiogenic potential of several phytochemicals, including polyphenols resveratrol and curcumin as well as miscellaneous compounds from garlic, Hypericum perforatum, Panax ginseng, Coptis chinensis and Rheum palmatum.

In vitro antiproliferative and antiangiogenic effects of Flavin7.

Flavin7 (F7) is a nutritional supplement often taken by cancer patients in Central Europe during chemo- and radiation therapy. In this study, investigation of the antiproliferative and antiangiogenic activities of this supplement were performed. Flavin7 showed antiproliferative activity in Jurkat as well as in HeLa cells. It significantly reduced the growth of both cancer cell lines at the doses of 200 microg/ml to 20 microg/ml (p<0.001 and p<0.01, respectively). In F7-treated Jurkat cells we found a significant increase in the fraction of cells with sub-G(0)/G(1) DNA content, which is considered to be a marker of apoptotic cell death. Apoptosis was also confirmed by annexin V staining and DNA fragmentation. Furthermore, F7 at the doses of 100 microg/ml to 4 microg/ml inhibited endothelial cell migration and capillary tube formation what indicates its potential antiangiogenic properties. Flavin7 also inhibited the activity of matrix metalloproteinases (MMPs), preferentially MMP-9, at the doses of 100 microg/ml to 4 microg/ml. Our data suggest that F7 possesses marked antiproliferative and antiangiogenic properties in vitro. Further research is needed to elucidate also its in vivo activities.

Antiangiogenic effects of flavonoids and chalcones.

Angiogenesis, the development of new blood vessels from the existing vasculature, is essential in normal developmental processes. Uncontrolled angiogenesis is a major contributor to a number of disease states such as inflammatory disorders, obesity, asthma, diabetes, cirrhosis, multiple sclerosis, endometriosis, AIDS, bacterial infections and autoimmune disease. It is also considered a key step in tumour growth, invasion, and metastasis. Angiogenesis is required for proper nourishment and removal of metabolic wastes from tumour sites. Therefore, modulation of angiogenesis is considered as therapeutic strategies of great importance for human health. Numerous bioactive plant compounds are recently tested for their antiangiogenic potential. Among the most frequently studied are polyphenols present in fruits and vegetables. Plant polyphenols inhibit angiogenesis and metastasis through regulation of multiple signalling pathways. Specifically, flavonoids and chalcones regulate expression of VEGF, matrix metalloproteinases (MMPs), EGFR and inhibit NFkappaB, PI3-K/Akt, ERK1/2 signalling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of flavonoids and chalcones and examines underlying mechanisms.

Protective effect of selected flavonoids on in vitro daunorubicin-induced cardiotoxicity.

Flavonoids are an ubiquitous group of polyphenolic substances with varied chemical structures present in foods of plant origin and act as free radical scavenging and chelating agents with a variety of biological activities. Using a model of spontaneously beating, cultured adult rat cardiomyocytes, this study examined the cardioprotective role of quercetin, naringenin, pycnogenol and a model antioxidant, trolox, against daunorubicin-induced toxicity. Cardiomyocyte protection was assessed by MTT test and extracellular lactate dehydrogenase detection. Protection of cardiomyocytes was concentration/dose dependent for quercetin > naringenin > pycnogenol > trolox. Quercetin (10(-4)-10(-6) mol/L) after 24 h of co-incubation with daunorubicin significantly increased the cardiomyocyte survival in all tested concentrations (p < 0.001). The cytoprotective effect of naringenin (10(-4)-10(-6) mol/L) was similar to those of quercetin (p < 0.001 and p < 0.01, respectively). Pycnogenol was the least effective of the flavonoids studied. On the other hand, all tested flavonoids had significantly better protective effects than trolox. The leakage of lactate dehydrogenase induced by daunorubicin was also prevented by the studied compounds and was in accordance with their cytoprotective activity.

Effect of quercetin on daunorubicin-induced heart mitochondria changes in rats.

Cancer therapy with daunorubicin is limited by its cardiotoxicity. It has been suggested that daunorubicin-induced free radical generation can be involved. The precise molecular mechanism of daunorubicin-induced cardiotoxicity is still not well understood but it is believed that mitochondria play an important role in this process. It has been reported that flavonoids with antioxidant properties may prevent anthracycline-induced cardiotoxicity. In this work, we investigated the effects of daunorubicin and quercetin on mitochondrial enzyme activities such as ATPase, glutathione peroxidase (GPx) and glutathione reductase (GR). Moreover, we also studied the changes of outer mitochondrial membrane using synchronous fluorescence spectra. The activity of ATPase and GR were significantly increased after daunorubicin application. Pretreatment with quercetin significantly alleviated this increase. On the other hand, GPx activity was significantly decreased and quercetin prevented this decrease. Treatment with quercetin alone had no significant effect on the enzyme activity studied. Quercetin also completely prevented daunorubicin-induced changes in fluorescence of the outer mitochondrial membrane. In conclusion, our data indicate that quercetin may be useful in mitigating daunorubicin-induced cardiotoxicity.

Dietary flavonoids and risk of coronary heart disease.

Flavonoids, a group of phenolic compounds found naturally in fruit, vegetables, nuts, flowers, seeds and bark are an integral part of the human diet. They have been reported to exhibit a wide range of biological effects, including antiischemic, antiplatelet, antineoplastic, antiinflammatory, antiallergic, antilipoperoxidant or gastroprotective actions. Furthermore, flavonoids are potent antioxidants, free radical scavengers and metal chelators, and inhibit lipid peroxidation. Oxidative modification of low-density lipoproteins (LDLs) is believed to play a crucial role in atherogenesis. Epidemiological studies have shown that the consumption of fruits and vegetables, and regular red wine consumption is related with a reduced risk of cardiovascular diseases.