In vitro and in vivo antioxidant potentials of an ethanolic extract of Ganoderma lucidum in rat mammary carcinogenesis.

AIM: Considering the importance of diet in the prevention of cellular damage caused by reactive oxygen species which has been implicated for several diseases, this present study was undertaken to evaluate the in vitro and in vivo antioxidant potential of the ethanolic extract of the fruiting bodies of Ganoderma lucidum on 7, 12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis in Sprague Dawley rats. METHODS: Ganoderma lucidum extract was tested for in vitro antioxidant and radical scavenging assays, such as (ABTS(+)) radical cation decolorization assay, DPPH radical scavenging, hydroxyl radical, and superoxide radical scavenging assays. The in vivo antioxidant potentials were analyzed by SOD, CAT, and GPx in plasma, mammary, and liver tissues. RESULTS: In all the in vitro antioxidant and radical scavenging assays the extract exhibited good scavenging activity. In vivo enzymatic antioxidant levels, such as SOD, CAT, and GPx were decreased in DMBA-induced animals. Moreover, pretreatment with G. lucidum (500 mg · kg(-1) bw) to DMBA-induced animals significantly (P < 0.05) increased the levels of SOD, CAT, and GPx in plasma, mammary, and liver tissues compared to DMBA induced animals. CONCLUSIONS: From these findings, it is suggested that G. lucidum extract could be considered as a potential source of natural antioxidants and can be used as an effective chemopreventive agent against mammary cancer.

Ellagic acid encapsulated chitosan nanoparticles for drug delivery system in human oral cancer cell line (KB).

Ellagic acid (EA), a naturally occurring polyphenolic compound is well documented for its anticancer property in numerous pre-clinical models. The properties like poor water solubility and limited oral bio-availability of ellagic acid has hampered its clinical applications. The present study, reports the preparation of ellagic acid encapsulated chitosan nanoparticles (EA@CS-NP) by ionic gelation method as an effective drug delivery for oral cancer treatment. The synthesized ellagic acid nanoparticle is spherical shaped with an average particle size of 176nm. The drug-encapsulation and loading-efficiency of the nanoparticles were 94±1.03% and 33±2.15% respectively. The in vitro drug release profile in the PBS medium shows sustained release of EA from EA@CS-NP. Further, this study evaluates the therapeutic efficacy of EA@CS-NP in human oral cancer cell line (KB) using MTT and DNA fragmentation analysis. EA@CS-NP exhibit significant cytotoxicity in KB cells in a dose-dependent manner with a very low IC50 value compared to the free EA. The results of the present study strengthen our hypothesis and hope that this novel formulation could possibly overcome the current limitations of ellagic acid and can open a new avenue for oral cancer therapy.

Solution conformation of alpha, beta or gamma-methylglutamyl-containing derivatives as probes of vitamin K-dependent carboxylase using molecular modelling and nuclear magnetic resonance.

In the present study, the conformational behaviour of methyl substituted N-BOC glutamic acid methyl esters (2M, 3T, 3E, 4T, 4E) has been completely characterized through combined NMR and molecular modeling studies. Hetero- and homonuclear coupling constants were measured in order to assign the remaining diastereotopic methylene protons at C(3) and/or C(4), and used for comparison with theoretical data. In parallel, the complete conformational analysis of these analogues has been achieved using molecular mechanics and molecular dynamics (MD) methods. The conformation of the glutamyl residue is established by the excellent agreement between the experimental and calculated side chain scalar coupling constants. The theoretical NMR data were calculated taking into account all the accessible conformations and using the averaging methods appropriate for internal motions. There is a significant influence of the methyl group on the conformational behaviour and on the biological relevance of these structures. Steric effect or electrostatic interaction may also have a considerable influence in stabilizing a conformational population in D2O solution. The conformational preferences of those different analogues in aqueous and methanol solution are discussed in the light of biological results obtained on the vitamin K-dependent carboxylase system.

The effect of a pulsed magnetic field and that of methyl-silane triol on galactosamine induced hepatitis among rats.

Liver cell necrosis was induced in rats by a galactosamine injection. Cell death was due to an increase of Ca++ intracellular levels and was also under the control of genes. Rats were then either exposed or not to a 6 mT 100 HZ pulsed magnetic field (PMF) and they either received or not methylsilane-triol injections. Animals were sacrificed twenty-seven hours after a galactosamine injection. On the one hand it appeared from transaminase levels that the PMF increased the number of animals which were sensitized to galactosamine but decreased transaminase levels. On the other hand PMF decreased the protective effect of MST against galactosamine. We may suggest that PMF should be considered as an additional cellular signal received through genes which would determine the evolution towards or against apoptosis according to the age of the cell itself but also the Ca++ intracellular level.

Proton magnetic relaxation studies in normal and cancerous breast tissues.

Proton magnetic resonance (PMR) relaxation times were measured for dissected malignant and normal tissue derived from breast cancer patients. Relaxation time measurements (T1, T2) were carried out at a RF frequency of 20 MHz and at a temperature of 27 degrees C with a Brucker PC 120 NMR Process analyser. The tissue types were confirmed by histopathological examination. In general T1 values were found to be longer for malignant tissues as compared to normal tissues which is in agreement with the earlier observations. The measured T2 values do not exhibit the malignant tissues above. The percentage of water content was also measured in both normal and malignant tissue and was found to be considerably larger in tumour tissue as compared to normal tissue. These results are discussed on the basis of two fraction fast exchange models of water molecules and confirm that PMR relaxation time measurement plays an important role in the differentiation of cancerous tissues from that of normal.