Toxic effects of single animal hormones and their mixtures on the growth of Chlorella vulgaris and Scenedesmus armatus.

In their environments, aquatic organisms are simultaneously exposed to mixtures of several endocrine disrupting compounds, including hormones. However, most of the toxicity studies so far focused on effects of single contaminants. The available information on the potential toxicity of combined hormones on microalgae is extremely limited. For these reasons the aim of this study was to evaluate the individual and mixture effect of estrone (E1), ß-estradiol (E2), estriol (E3), 17-α-ethinylestradiol (EE2), progesterone (PRO), 5-pregnen-3ß-ol-20-one (PRE), levonorgestrel (LG) and testosterone (TST) on Chlorella vulgaris and Scenedesmus armatus. Green algae cells were exposed to different concentrations (0.1-100 mg L-1) of hormones for 14 days. Biomass in the form of dry weight and chlorophyll a was examined. The decreasing order of toxicity (based on EC50, 14d) to Chlorella vulgaris and Scenedesmus armatus was: EE2>PRO > E2>PRE > TST > E3>LG > E1 and EE2>PRO > TST > E2>PRE > LG > E1>E3, respectively. Chlorella vulgaris was more sensitive to the effects of hormones than Scenedesmus armatus. Although mixed hormones were more toxic to green algae than single hormones, in the ecosystem mixtures can pose higher ecological risk than single pollutants. Therefore, data on the toxicology of both single and mixed hormones is very valuable for assessment of the possibility of adverse ecological effects caused by these pollutants. Furthermore, these results suggest that environmental exposure to hormone mixtures may cause toxicity levels different to the sum of those of the single hormones and provides a basic understanding of their toxic effect on algae.

Extralipid effects of micronized fenofibrate in dyslipidemic patients.

The aim of this study was to evaluate the levels of lipid and extralipid parameters in patients with atherogenic dyslipidemia. We investigated the lipid-lowering therapeutic efficacy of fenofibrate and its extralipid influence on oxidized low-density lipoprotein (oxLDL), C-reactive protein (CRP), Fibrinogen, factor VII and plasminogen activator type 1 (PAI-1) during 1-month treatment. Fourteen individuals with HLPIIb were treated with micronized fenofibrate (267 mg/d) for 1 month. The control group included twelve volunteers. Lipidograms were determined with enzymatic kits. ELISA method was used to measure oxLDL and PAI-1. Plasma CRP levels were measured spectrophotometrically. Fibrinogen and factor VII serum levels were evaluated with automatic coagulometer. After 1-month therapy with micronized fenofibrate, we observed a significant reduction of total cholesterol (TC) (277.2 to 217.8 mg/dl, p < 0.05), LDL (183.6 to 129.4 mg/dl, p < 0.05), trigliceryde (TG) (316.7 to 220.6 mg/dl, p < 0.05), oxLDL (68.7 +/- 5.5 to 39.7 +/- 3.7 U/l, p < 0.001) and increase in high-density lipoprotein (HDL) (35.1 to 41.9 mg/dl, p < 0.05). Fibrate treatment also decreased CRP(5.81 +/- 0.26 to 5.08 +/- 0.06 mg/l, p < 0.001), PAI-1 (120.4 +/- 9.7 to 84.7 +/- 5.9 ng/ml; p < 0.05), fibrinogen (3.65 +/- 0.17 to 3.44 +/- 0.16 g/l, ns) and factor VII (159.7% +/- 56.7 to 141% +/- 42.4, ns). The micronized fenofibrate at a daily dose of 267 mg demonstrated a highly beneficial effect on all lipid parameters and advantageous influence on inflammatory and thrombogenic plasma risk factors in patients with dyslipidemia HLPIIb.

Monocyte release of tumor necrosis factor-alpha and interleukin-1beta in primary type IIa and IIb dyslipidemic patients treated with statins or fibrates.

Both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as well as peroxisome proliferator-activated receptor (PPAR)alpha activators (fibrates) proved to be effective in the primary and secondary prevention of cardiovascular diseases. The benefits of hypolipemic therapy in cardiovascular diseases cannot be explained only by the lipid-lowering potential of these agents. The aim of this study was to clarify the effect of hypolipemic agents on proinflammatory cytokine release from human monocytes in relationship with their action on plasma levels of sensitive systemic marker of low-grade vascular inflammation. Plasma lipid and high-sensitivity C-reactive protein (hsCRP) levels, and the release of tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta from monocytes were assessed at baseline and 30 and 90 days following randomization of IIa dyslipidemic patients into fluvastatin or simvastatin groups and randomization of type IIb dyslipidemic patients to the micronized form of either ciprofibrate or fenofibrate. Lipopolysaccharide-stimulated monocytes from dyslipidemic patients released significantly more TNFalpha (types IIa and IIb dyslipidemias) and interleukin-1beta (type IIa dyslipidemia) in comparison with monocytes in 59 age-, sex-, and weight-matched control subjects. Their baseline hsCRP levels were also higher. Both statins and fibrates reduced the release of TNFalpha and interleukin-1beta, and lowered plasma hsCRP levels. The effects of hypolipemic agents on cytokine release and plasma hsCRP were unrelated to their lipid-lowering action. Our results have demonstrated that type IIa and IIb dyslipidemic patients exhibit the abnormal pattern of TNFalpha and interleukin-1beta production by activated monocytes. Both HMG-CoA reductase inhibitors and PPARalpha activators normalize monocytic secretion of these cytokines, and this action may partially contribute to the systemic antiinflammatory effect of hypolipemic agents. The statin- and fibrate-induced suppression of proinflammatory cytokine release from monocytes seems to play a role in their beneficial effect on the incidence of cardiovascular events.

Monocyte suppressing action of fenofibrate.

Since atherosclerosis has been proven to be an inflammatory disease, it is obvious that the proper treatment for dyslipidemia should not only correct lipid parameters but also inhibit inflammation. Monocytes and monocyte-derived proinflammatory cytokines are widely known to be involved in the formation and rupture of the atherosclerotic plaque. The aim of our study was to assess the effect of fenofibrate, a commonly used hypolipidemic drug, on the release of interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) by monocytes from patients with combined hyperlipidemia. Fourteen patients with biochemically confirmed type IIb dyslipidemia who did not respond to a low-fat diet were treated with micronized fenofibrate for 1 month. The control group included 12 healthy, normolipidemic, age-matched subjects. To accurately evaluate the levels of the inflammatory cytokines, we excluded patients with any inflammatory disease. Monocytes were isolated from peripheral blood before and after the treatment. IL-1beta, IL-6 and MCP-1 release was measured by enzyme-linked immunosorbent assay (ELISA) after lipopolysaccharide stimulation. IL-1beta, IL-6 and MCP-1 levels were significantly higher in hyperlipidemic patients compared to the control (143.9 +/- 6.5 vs. 74.4 +/- 4.4 pg/ml; 8212 +/- 285 vs. 6110 +/- 170 pg/ml; 19.6 +/- 0.9 vs. 12.3 +/- 0.6 ng/ml, respectively). Thirty-day fenofibrate treatment decreased the release of IL-1beta by 43% (143.9 +/- 6.5 vs. 86.2 +/- 5.9 pg/ml), of IL-6 by 22% (8212 +/- 285 vs. 6330 +/- 234 pg/ml), and of MCP-1 by 29% (19.6 +/- 0.9 vs. 14.0 +/- 0.8 ng/ml). The evaluated cytokines were markedly elevated in patients with type IIb dyslipidemia. Effective fenofibrate therapy had a significant inhibitory effect on the release of monocyte-derived inflammatory cytokines.

[Pleiotropic effects of micronized fenofibrate in patients with combined hyperlipidemia]. / Plejotropowe dzialanie fenofibratu mikronizowanego u chorych z hiperlipidemia mieszana.

More and more recent studies demonstrate the pleiotropic effects of fibrates. Except lowering plasma lipid levels they can influence blood coagulation abnormalities and stabilise atherosclerotic lesions--a frequent result of the activation of inflammatory cells within the vascular wall. The anti-inflammatory action of fibrates includes inhibiting the release of many cytokines, such as Tumor Necrosis Factor e (TNF-alpha) by these cells. The aim of this study was to evaluate the effect of fenofibrate on the plasma levels of Plasminogen Activator Inhibitor type 1 (PAI-1) and fibrinogen in patients with combined dyslipidemia. Moreover, we assessed the amount of TNF-alpha released by peripheral blood isolated monocytes before and after therapy. Fourteen patients (8 women and 6 men) with hyperlipidemia IIb were treated with micronized fenofibrate (Lipanthyl 200 m, Fournier) in a daily dose of 200 mg for one month. The control group consisted of 12 individuals matched for age with biochemical confirmation of normolipemia. Plasma PAI-1 and TNF-alpha levels were measured by the ELISA method. Fibrinogen levels were measured according to the commonly used Clauss method. Before treatment the haemostatic compounds and TNF-alpha studied were significantly higher in the group with hyperlipidaemia IIb compared to the control group. One-month therapy with fenofibrate resulted in significant decrease of triglycerides and total cholesterol. After treatment, PAI-1 and fibrinogen levels also decreased significantly: PAI-1 from 101.18 +/- 9.74 ng/mL to 81.22 +/- 6.68 ng/mL, p < 0.01 and fibrinogen from 364.5 +/- 29.6 mg/dL to 294.7 +/- 19.3 mg/dL, p < 0.01. The study also revealed that the level of produced TNF-alpha decreased significantly from 2136.0 +/- 250.8 pg/mL to 1336.8 +/- 132.0 pg/mL, p < 0.05. These results may confirm new pathways of fibrates action.