Evaluation of intraperitoneal ozone application effects to rat’s antioxidant enzymes, superoxide dismutase and glutathione peroxidase.

Ozone is a powerful oxidant that presents dual activity: either as a therapeutic or as a toxic agent. The aim of this study was to investigate the effects of intraperitoneal (i.p.) application of ozone on the endogenous antioxidant enzymes of Wistar rats compared with the amendment of the total antioxidant capacity in blood and urine. Rats were divided randomly into two groups: the control group (CG) which was injected with placebo (NaCl 0.9%) and the ozone group (OG) which was administrated daily for 10 consecutive days with ozone at a concentration of 6.3μg/Kg body weight. Blood and urine samples were collected at the beginning, after the administration period and 22 days after the initiation of the experiment. Intraperitoneal application of ozone leads to a potent Increase to glutathione peroxidase (GPx) levels with no effect to Superoxide dismutase (SOD) levels. Total antioxidant capacity (TAC) was significantly decreased in plasma, red blood cells (RBCs) and urine of the rats. Malondialdehyde (MDA) concentration in urine remained stable. To our knowledge these are the first experimental results showing that repeated i.p. application of ozone in low doses produce severe changes to the whole antioxidant capacity of the blood and indications of toxicity, as the organism exert efforts to adapt to oxidative stress.

Resveratrol diminishes platelet aggregation and increases susceptibility of K562 tumor cells to natural killer cells.

Platelet aggregation around migrating cancer cells protects them against the activity of natural killer cells (NKCs). The inability of immune system to response results in the progression of malignant diseases. This study was designed to evaluate the effects of resveratrol (3, 4', 5-trihydroxystilbene) on platelet aggregation and NKCs activity. Experiments were designed to evaluate the platelet aggregation, production of thromboxane B2 (TXB2), estimation of expression of the platelet receptor GpIIb/IIIa (major biological markers for platelet aggregation) and functional activity of the NKCs against the K562 cancer cell line after incubation with various concentrations of reveratrol. Resveratrol at a concentration of 3 × 10-3Μ completely inhibited platelet aggregation (p<0.05), decreased TXB2 levels (p<0.05) and inhibited the expression of receptor GpIIb/IIIa in non-stimulated platelets (p<0.05). At the same concentration, it increased the NKCs cytotoxic activity at an average rate of 319 ± 34, 450 ± 34 and 62 ± 2.4% (p<0.05) in the NKC/targets cells ratios of 12.5:1, 25:1 and 50:1, respectively. Thus, resveratrol not only completely inhibited platelet aggregation and reduced TXB2 levels and expression of receptor GpIIb/IIIa, but also increased the cytotoxic activity of NKCs in vitro and thus increased the susceptibility of tumor cells to NKCs. Thus, resveratrol can be used as an additional supplement to modulate the immune system and to inhibit platelet aggregation in thromboembolic episodes. Further clinical investigation in vivo could lead to specific concentrations that may maximize the beneficial effect of resveratrol.

Inhibition of platelet aggregation and immunomodulation of NK lymphocytes by administration of ascorbic acid.

Platelets aggregation around migrating tumor cells offers protection against the cytotoxic activity of the natural killers cells (NKC). The ascorbic acid in 3X10-3Μ concentration completely inhibited platelet aggregation, decreased thromboxane B2 levels, and inhibited the expression of platelet membranic receptor GpIIb/IIIa in non stimulated platelets, and increased the NKC cytotoxicity in an average rate of 105, 61, and 285% in the NKC/targets cells ratios 12.5:1, 25:1 and 50:1 respectively. The results suggest the role of ascorbic acid in increasing the susceptibility of tumor cells to NKC; the ascorbic acid could be used as part of a multidrug therapy to treat diseases which up to now have been treated only through chemotherapy.