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The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate. Control normolipidaemic and hyperlipidaemic rats were receiving saline. Simvastatin, fenofibrate, and saline were administered by gavage for three weeks. In normolipidaemic rats simvastatin and fenofibrate showed similar and dose-independent effects on plasma and brain MDA and GSH concentrations. Generally, plasma and brain MDA decreased, while brain GSH concentration increased. In hyperlipidaemic rats simvastatin did not affect plasma and brain MDA and GSH concentrations but significantly decreased liver GSH. Fenofibrate decreased plasma and liver MDA but increased brain MDA. In both rat strains fenofibrate significantly decreased liver GSH concentrations, most likely because fenofibrate metabolites bind to GSH. Our findings suggest that simvastatin acts as an antioxidant only in normolipidaemic rats, whereas fenofibrate acts as an antioxidant in both rat strains., Cilj ovog istraživanja bio je istražiti učinke različitih doza simvastatina i fenofibrata na malondialdehid (MDA) i reducirani glutation (GSH) u plazmi, jetri i mozgu mužjaka normolipidemičnih (Wistar) i hiperlipidemičnih (Zucker) štakora. Na prvim dvjema eksperimentalnim skupinama normolipidemičnih štakora simvastatin je primijenjen u dozama 10 ili 50 mg/kg dnevno, a fenofibrat na trećoj i četvrtoj skupini u dozama od 30 i 50 mg/kg/dan. Prva eksperimentalna skupina hiperlipidemičnih štakora primala je simvastatin 50 mg/kg/dan, a druga fenofibrat 30 mg/kg/dan. Kontrolne skupine normolipidemičnih i hiperlipidemičnih štakora primale su fiziološku otopinu. Simvastatin, fenofibrat i fiziološka otopina primjenjivani su oralno tijekom tri tjedna. U plazmi i mozgu normolipidemičnih štakora simvastatin I fenofibrat pokazali su slične i o dozi neovisne učinke na koncentracije MDA i GSH. Općenito, MDA je bio smanjen, a koncentracija GSH bila je povećana. U hiperlipidemičnih štakora simvastatin nije utjecao na koncentraciju MDA i GSH, ali je prouzročio značajno smanjenje GSH u jetri. Fenofibrat je smanjio MDA u plazmi i jetri te povećao MDA u mozgu. U oba soja štakora fenofibrat je značajno smanjio koncentraciju GSH u jetri, vjerojatno zbog konjugacije GSH s nekim metabolitima fenofibrata. Prema našim rezultatima, simvastatin djeluje antioksidacijski samo u normolipidemičnih štakora, a antioksidacijski učinak fenofibrata prisutan je u oba soja.

Pseudokolinesteraza (PChE), osim što ima značajnu farmakološku ulogu, zajedno s acetilkolinesterazom sudjeluje u hidrolizi acetilkolina. Nova saznanja su da je acetilkolin protuupalna molekula, da postoji kolinergički protuupalni put i da PChE može predstavljati upalni biljeg kod sistemskih upala blažeg stupnja. Zato je važno poznavati lijekove koji mijenjaju aktivnost PChE. U ovom istraživanju su ispitivani učinci simvastatina, rosuvastatina i fenofibrata na aktivnost PChE i parametre oksidacijskog stresa kod normolipemičkih i hiperlipemičkih štakora, budući da je u patološkim stanjima, kao što su upala i hiperlipidemija prisutan i oksidacijski stres. Svi istraživani antilipidni lijekovi značajno su povećali aktivnost PChE u plazmi oba soja štakora. U mozgu normolipemičnih štakora porast aktivnosti PChE dokazan je nakon primjene statina, dok je u mozgu hiperlipemičnih štakora na porast aktivnosti utjecao i fenofibrat. U jetrima je porast aktivnosti bio izraženiji kod hiperlipemičnih štakora. Rezultati ispitivanja učinaka antilipidnih lijekova na parametre oksidacijskog stresa pokazuju da simvastatin i fenofibrat u plazmi i mozgu normolipemičnih štakora pokazuju antioksidacijski učinak, za razliku od rosuvastatina koji može djelovati prooksidacijski. U plazmi i mozgu hiperlipemičnih štakora simvastatin ne djeluje na parametre oksidacijskog stresa, dok fenofibrat u plazmi istog soja štakora djeluje antioksidacijski, a u mozgu prooksidacijski. U jetrima oba soja štakora fenofibrat djeluje izrazito prooksidacijski. Rezultati pokazuju da sva tri antilipidna lijeka utječu na aktivnost PChE i parametre oksidacijskog stresa u normalnim i patološkim uvjetima, te stoga mogu utjecati kako na farmakološku ulogu PChE tako i na tijek nekih patofizioloških procesa., Beside significant pharmacological role pseudocolinesterase (PChE) is involved in hydrolysis of acetylcholine, an anti-inflammatory molecule. Drugs can alter PChE activity. Since oxidative stress is present in pathological conditions such as inflammation and hyperlipemia in this study the effects of simvastatin, rosuvastatin, and fenofibrate on PChE activity and parameters of oxidative stress in normolipemic and hyperlipemic rats were investigated. All investigated drugs significantly increased plasma PChE activity in both strains of rats. In the brain of normolipemic rats, increase in PChE activity was demonstrated after statin administration, whereas in hyperlipemic rat brain, an increase in activity was also after fenofibrate. In the liver, increase in activity was more pronounced in hyperlipemic rats. Unlike rosuvastatin, simvastatin and fenofibrate showed antioxidant effect in plasma and brain of normolipemic rats. In plasma of hyperlipemic rats fenofibrate showed antioxidant effects, and in brain pro-oxidant. In the liver of both strains of rats, the effects of fenofibrate were pro-oxidant, and effect of simvastatin was antioxidant in the liver of normolipemic and pro-oxidant in hyperlipemic rats. Investigated drugs influenced PChE activity and oxidative stress under normal and pathological conditions. The consequences could be change in pharmacological role of PChE and change in course of some pathophysiological processes.

Introduction: Statins have been shown to possess antioxidant effects and our previous results showed that simvastatin significantly decrease malondialdehyde (MDA) levels in plasma and tissue of rats. Here we wanted to investigate the influence of rosuvastatin (ROSU) on MDA level and superoxide dismutase (SOD) activity in plasma and liver of rats, both considered to be markers of oxidative stress. Material and Methods: Thirty-six male Wistar rats were divided in one control group (saline) and two experimental groups (ROSU 5 mg/kg/day and 10 mg/kg/day). Drug and saline were given orally for period of 3 weeks. Animals were sacrificed with ether 24 hours after last dose. Blood samples were obtained directly from heart and liver tissue was rinsed with saline. MDA in plasma was measured with high performance liquid chromatography using commercially HPLC kits, while in liver using Drury method. SOD activity was measured in plasma with sensitive spectrophotometric assay and in liver using Flohé and Ötting method. Data were analyzed using ANOVA test. Results are expressed as the means and SDs. Results: ROSU in both doses decreased MDA level in liver but decrease was significant (p

Statins are drugs widely used to treat hypercholesterolemia and reduce the risk of cardiovascular morbidity and mortality in patients with coronary heart disease. The mechanism of their action may be the inhibition of oxidant formation and blocking the effects of reactive oxygen species (ROS). As reported in recent studies, rosuvastatin has a beneficial effect on the plasma lipid profile and can reduce serum cholesterol and ROS formation in diabetic patients. The aim of this work was to determine the influence of rosuvastatin on the prooxidant- antioxidant balance in rat kidneys. This study was performed on male normolipidemic Wistar rats (N=36) divided into two control (treated with saline 5 mg kg-1 per day) and two experimental rosuvastatin-treated (5 and 10 mg kg-1 per day) groups. Animals were treated orally for 21 days. Malondialdehyde (MDA) – parameter of lipid peroxidation was measured in the kidney tissue homogenate of control and treated animals using the method by Drury et al. (1997). Data were analysed using t-test. Results are expressed as Mean±STD. MDA concentration was significantly lower in both experimental groups compared to controls: 0.41±0.05 vs. 0.62±0.08 µmol g-1 tissue (5 mg kg-1 per day vs. control ; p

Background: It was suggested that statins exerted their protective effect against Alzheimer disease (AD) due to inhibition of cholinesterase (ChE) activity. Results of some nonclinical and clinical studies have shown that statins either do not influence or decrease enzyme catalytic activity. Our previous studies showed that simvastatin increased plasma and liver ChE activity in normolipidemic rats. In respect to these findings we studied influence of simvastatin (SIMV) and fenofibrate (FENO) on ChE activity in hyperlipidemic rats. Methods: Twenty-one male hyperlipidemic Zucker rats were divided into one control and two experimental groups. One experimental group was on SIMV treatment (50 mg/kg/day) and another on FENO treatment (30 mg/kg/day). Both agents were given orally for 3 weeks, as well as saline for control group. Animals were sacrificed 24 hours after the last dose. Blood samples were obtained directly from heart. Liver and brain tissue were rinsed with saline. ChE activity was determined by Ellman’s spectrophotometric method using butyrylthiocholine and acetylthiocholine as substrates. In liver tissue the ChE activity was measured with and without ethopropazine hydrochloride. Enzyme activities were expressed as μmol of substrate hydrolysed per min per ml of serum or g of tissue. Data were analyzed using ANOVA and Dunnett's test. Results were considered as significant with p

Ovaj rad razmatra sigurnosna pitanja bežičnih mesh mreža. Sigurnosni zahtjevi bežičnih mesh mreža uglavnom su identični sigurnosnim zahtjevima bilo kojeg drugog komunikacijskog sustava. U drugom poglavlju su detaljno opisani napadi na fizičkom, MAC i mrežnom sloju budući da oni čine jezgru mreže.

Inhibitors of acetylcholinesterase and butyrylcholinesterase are used for treatment of Alzheimer's disease. Because interaction between cholinergic system and drugs is important, it was investigated the influence of fenofibrate on cholinesterase activity in brain, plasma and liver of rats. The results have shown that fenofibrate causes increase of cholinesterase activity, which may be specially important for cholinergic function in central nervous system.

Introduction: Our previous results showed that simvastatin (SIMV), rosuvastatin (ROSU) and fenofibrate (FENO) decrease malondialdehyde (MDA) level in brain of normolipidemic rats. Now we have decided to investigate the influence of SIMV, ROSU and FENO on glutathione level in brain of rats, that is a marker of oxidative stress as well. Material and Methods. Male Wistar rats were divided in six control groups (saline) and six experimental groups. Two experimental groups were on SIMV treatment (10 and 50 mg/kg/day), two experimental groups on ROSU (5 and 10 mg/kg/day) and remaining groups on FENO treatment (30 and 50 mg/day). Agents and saline were given orally for the period of 3 weeks. Animals were sacrificed with ether 24 hours after last dose. Brain samples were rinsed with saline. Concentration (μg/ml) of reduced glutathione (GSH) was measured in supernatants of brain using Ellman’s method (1958). Data were analysed using two-group t-test. Results are expressed as the means, SDs and 95% confidence intervals for the difference between means. Results: SIMV in both doses and higher dose of FENO caused significant increase (p

Introduction. Statins have many independent or “pleiotropic” effects beyond cholesterol lowering. Epidemiological reports have demonstrated that statins protect against Alzheimer disease (AD). It’s known that the most striking neurochemical disturbance in AD is a deficiency of acetylcholine. Since acetylcholinesterase (AChE) and plasma cholinesterase (PChE) are involved in cholinergic transmission, cholinesterase inhibitors are used for treatment of AD. According to the some experimental data statins can protect against AD by inhibition of both enzymes. The results of some other nonclinical and clinical studies have shown that statins do not influence the AChE and PChE activities. Our previous results have shown the increase of plasma and liver PChE activity in normolipidemic rats after simvastatin and atorvastatin treatment during 3 weeks. Because of opposite literature data, we decided to investigate the influence of rosuvastatin (ROSU) on plasma and liver PChE activity of normolipidemic rats and to repeat the experiment with simvastatin (SIMV). Material and Methods. Forthy six male normolipidemic Wistar rats were divided into four control groups and four experimental groups. Two experimental groups were on SIMV treatment (10 and 50 mg/kg/day) and the remaining two groups on ROSU treatment (5 and 10 mg/kg/day). Both agents were given orally for the period of 3 weeks, as well as the saline for the control groups. Animals were sacrificed with ether 24 hours after the last dose. Blood samples were obtained directly from heart and liver tissue was rinsed with saline. The PChE activity in plasma and liver was determined by Ellman’s spectrophotometric method using butyrylthiocholine and acetylthiocholine as substrates. In liver tissue, the PChE assay was carried out with and without ethopropazine hydrochloride. Enzyme activities are expressed as μmol of substrate hydrolysed per min per ml of plasma or g of tissue. Data were analysed by Dunn’s Multiple Comparison Test. Results were considered as significant with p

Free radicals can be involved in pathogenesis of Alzheimer disease (AD). While the literature data have shown that antilipemic drugs either decrease or have not influence on malondialdehyide (MDA) level, our previous unpublished results have shown that simvastatin (SIMV) reduce MDA in rat’s brain. We decided to compare the influence of rosuvastatin (ROSU) and fenofibrate (FENO) on MDA level in the brain of normolipidemic rats and to repeat the experiment with (SIMV). Ninety male Wistar rats were divided into five control groups (saline) and five experimental groups. One experimental group was on SIMV treatment (10 mg/kg/day), two groups on ROSU treatment (5 and 10 mg/kg/day) and remaining groups on FENO treatment (30 and 50 mg/kg/day). Agents and saline were given orally for the period of 3 weeks. Animals were sacrificed with ether 24 hours after the last dose and brain samples were rinsed with saline. MDA levels were measured by HPLC-MS method (Drury JA et al, 1997). Data were analysed by Dunn’s Multiple Comparison Test. ROSU and SIMV in dose of 10 mg/kg/day decreased significantly MDA level (μmol/L) in brain of normolipidemic rats for 10% and 58% vs. control (p

U radu se hrvatski pridjevi svrstavaju u nekoliko tipova prema naglasnome ponašanju u sklonidbi. Pokazuje se i plodnost pojedinoga naglasnoga tipa.