Oenothera paradoxa defatted seeds extract containing pentagalloylglucose and procyanidins potentiates the cytotoxicity of vincristine.

The purpose of the study was a comparison of Oenothera paradoxa Hudziok defatted seeds extract (EPE) effect with the activity of individual constituents of the extract: pentagalloylglucose (PGG), gallic acid, (+)-catechin and the procyanidin fraction, as well as an assessment of the combined effect of EPE and vincristine (VCR) in the absence or presence of MRP1 (indomethacin) and P-glycoprotein (verapamil) inhibitors, on two human cancer cell lines, metastatic melanoma (HTB-140) and hepatoma (HepG2). The presence of EPE, PGG and procyanidins caused a marked reduction in viability (MTT assay) and rise in mortality (LDH release assay) of HTB-140 cells. The combined use of EPE (25 µg/mL) and VCR (1 µM) in HTB-140 and HepG2 cells produced an increased cytotoxicity as compared to vincristine alone - by more than 4 and 1.5 times, respectively. In HTB-140 cells, the level of intracellular ATP (measured by bioluminescence) was lowered over 7-fold as a result of exposure to the combination of EPE and VCR, while the addition of MRP-1 inhibitor did not cause an increased cytotoxicity or further lowering of the ATP level. Our results demonstrate that EPE, containing PGG and procyanidins, significantly increased the sensitivity of cancer cells, particularly the melanoma cells, to the action of vincristine.

Effects of novel plant antioxidants on platelet superoxide production and aggregation in atherosclerosis.

Superoxide anion is produced in human platelets predominantly by Nox2-dependent NADPH oxidases. In vitro experiments have shown that it might play a role in modulating platelet functions. The relationship between platelet superoxide production and aggregation remains poorly defined. Accordingly, we aimed to study superoxide production and aggregation in platelets from subjects with significant cardiovascular risk factors (hypertension, hypercholesterolemia, smoking and diabetes mellitus) and from control individuals. Moreover, we studied the effects of novel polyphenol-rich extracts of Aronia melanocarpa (chokeberry) berries on platelet function in vitro. Superoxide production was significantly increased in patients with cardiovascular risk profile when compared to controls, while platelet aggregation in response to either collagen or thrombin were borderline higher, and did not reach statistical significance. Interestingly, no relationship was observed between platelet aggregation ex vivo and platelet superoxide production in either of studied groups. No correlation was found between endothelial function (measured by FMD) and platelet aggregation ex vivo either. Polyphenol-rich extracts of A. melanocarpa berries caused a significant concentration dependent decrease in superoxide production only in patients with cardiovascular risk factors, while no effect was observed in the control group. A. melanocarpa extracts abolished the difference in superoxide production between risk factor patients and controls. A. melanocarpa extracts exerted significant concentration dependent anti-aggregatory effects in both studied groups, which indicated that these effects may be independent of it's ability to modulate superoxide production. The anti-aggregatory effects of chokeberry extracts were similar irrespective of aggregation inducing agent (collagen or thrombin). Moreover, they appear to be independent of platelet NO release as NOS inhibition by L-NAME did not lead to their abrogation.

Homocysteine, fibrinogen, and lipoprotein(a) levels are simultaneously reduced in patients with chronic renal failure treated with folic acid, pyridoxine, and cyanocobalamin.

Ischemic heart disease and other complications of atherosclerosis are the usual cause of death in patients with chronic renal failure. Important factors associated with early onset of atherosclerosis in these patients are hyperhomocysteinemia, hyperfibrinogenemia, and elevated levels of lipoprotein(a) (Lp(a)). Folic acid (15 mg/d), pyridoxine (150 mg/d), and cyanocobalamin (1 mg/wk) were administered for 4 weeks in 21 patients receiving dialysis, and a simultaneous, statistically significant reduction in the concentration of homocysteine, fibrinogen, and Lp(a) was found. A positive correlation between decreasing homocysteine and fibrinogen levels was also noted. The parameters studied approached presupplementation values 6 months after vitamins were discontinued. The results suggest that vitamin supplementation has a favorable effect on risk factors of atherosclerosis in patients with renal failure and that interactions may exist between homocysteine, fibrinogen, and Lp(a).

Influence of probucol on enhanced LDL oxidation after fish oil treatment of hypertriglyceridemic patients.

The susceptibility of low-density lipoprotein (LDL) to oxidation was studied in hypertriglyceridemic men (5 with type III and 5 with type IV) at baseline on a low-saturated-fat, low-cholesterol diet, after 6 weeks of dietary supplementation with fish oil (Promega, 12 g/d), and after 6 weeks of fish oil combined with probucol (500 mg BID). The relative content of n-3 polyunsaturated fatty acids in plasma and LDL was increased during the two treatment periods, and a low alpha-tocopherol to n-3 polyunsaturated fatty acids ratio was observed. Plasma thiobarbituric acid-reactive substances (TBARS) levels were unchanged after 6 weeks of fish oil, but the ratio of lipid peroxides to the reduced triglyceride (TG) levels (MDA:TG) was significantly higher (P < .01). Addition of probucol lowered both absolute levels of TBARS (P < .01) and the MDA to TG ratio (P < .001). The susceptibility of LDL to Cu(2+)-catalyzed oxidation was evaluated over a 5-hour time course by determining TBARS formation, free amino group levels, and changes in LDL electrophoretic mobility. TBARS levels that were higher in native LDL (1.019 < d < 1.050 g/mL) after 6 weeks of fish oil than at baseline (P < .01) were reduced 52.3 +/- 11.3% by the addition of probucol (P < .001). With fish oil alone, TBARS production after exposure of LDL to Cu2+ for 5 hours was increased 17.0 +/- 5.8% compared with corresponding baseline values (P < .001), whereas a 64.1 +/- 14.3% reduction from the previous period was observed with fish oil + probucol (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of thermally oxidized soya bean oil on metabolism of chylomicrons. Increased uptake and degradation of oxidized chylomicrons in cultured mouse macrophages.

Oral administration of thermally oxidized soya bean oil (TO) increased the level of lipid peroxides in human plasma, mainly in chylomicrons. No changes were observed after fresh oil (FO) intake. Human chylomicrons obtained after TO ingestion were rich in lipid peroxides and degraded more rapidly by cultured mouse macrophages than chylomicrons after FO. The uptake of TO chylomicrons by macrophages occurred via a saturable process and was partially inhibited by beta-very low density lipoprotein as well as by acetyl-low density lipoprotein and fucoidin. A 48-h incubation of macrophages with TO chylomicrons caused a 10-fold higher accumulation of cholesterol ester mass in the cells than the incubation with FO chylomicrons. These studies suggest that chylomicrons containing lipid peroxides may be taken up by mouse macrophages by mediation of beta-VLDL receptor as well as by acetyl-LDL receptor, and show a potential pathway by which chylomicrons obtained after ingestion of heated oil could contribute to accumulation of cholesterol esters in macrophages.