A new, simplified model for the estimation of polyphenol oxidation potentials based on the number of OH groups.

We present a new and simpler regression model for the estimation of the first oxidation potentials (Ep1) of flavonoids based on the number of phenolic, alcoholic, and carboxylic OH groups. In the regression we included the Ep1 of 12 polyphenols (mostly flavonols and catechins) that were measured in our laboratory at pH 3. The model yielded r=0.986 and SE=0.040. Later successive inclusions of previously reported Ep values into the regression model, 7 at pH 3, the model (N=19) yielded r=0.980, SE=0.046 and 19 at pH 7 the model (N=38), yielded r=0.985, SE=0.044.

Melittin induced cytogenetic damage, oxidative stress and changes in gene expression in human peripheral blood lymphocytes.

Melittin (MEL) is the main constituent and principal toxin of bee venom. It is a small basic peptide, consisting of a known amino acid sequence, with powerful haemolytic activity. Since MEL is a nonspecific cytolytic peptide that attacks lipid membranes thus leading to toxicity, the presumption is that it could have significant therapeutic benefits. The aim was to evaluate the cyto/genotoxic effects of MEL in human peripheral blood lymphocytes (HPBLs) and the molecular mechanisms involved using a multi-biomarker approach. We found that MEL was cytotoxic for HPBLs in a dose- and time-dependent manner. It also induced morphological changes in the cell membrane, granulation and lysis of exposed cells. After treating HPBLs with non-cytotoxic concentrations of MEL, we observed increased DNA damage including oxidative DNA damage as well as increased formation of micronuclei and nuclear buds, and decreased lymphocyte proliferation determined by comet and micronucleus assays. The observed genotoxicity coincided with increased formation of reactive oxygen species, reduction of glutathione level, increased lipid peroxidation and phospholipase C activity, showing the induction of oxidative stress. MEL also modulated the expression of selected genes involved in DNA damage response (TP53, CDKN1A, GADD45α, MDM), oxidative stress (CAT, SOD1, GPX1, GSR and GCLC) and apoptosis (BAX, BCL-2, CAS-3 and CAS-7). Results indicate that MEL is genotoxic to HPBLs and provide evidence that oxidative stress is involved in its DNA damaging effects. MEL toxicity towards normal cells has to be considered if used for potential therapeutic purposes.

In vitro genotoxicity of mycotoxins ochratoxin A and fumonisin B(1) could be prevented by sodium copper chlorophyllin--implication to their genotoxic mechanism.

The aim of this study was to investigate the possible protective effect of sodium copper chlorophyllin (CHL) against cytotoxicity and DNA damage induced by mycotoxins ochratoxin A (OTA) and fumonisin B1 (FB1). CHL (0.1-100 µg/ml) alone had no impact on cell viability and genome damage in the primary human peripheral blood lymphocytes (HPBLs) and exhibited free radical scavenging activity in the DPPH assay. Both mycotoxins, OTA (4 µmol/l) and FB1 (20 µg/ml), induced DNA damage in HPBLs already after 1 h exposure. When the HPBLs were co-exposed to CHL (10 and 100 µg/ml) and OTA (4 µmol/l) or FB1 (20 µg/ml) for 1 h, CHL protected against cell and DNA damage induced by both mycotoxins, implying that OTA and FB1 cytogenotoxicity mechanisms function at least partially through oxidative stress. Therefore, CHL could be a perfect candidate for possible use as an antioxidant.