Cholesterol oxides inhibit cholesterol esterification by lecithin:cholesterol acyl transferase

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Cholesterol oxides are atherogenic and can affect the activity of diverse important enzymes for the lipidic metabolism. The effect of 7 beta-hydroxycholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestan-3 beta.5 alpha.6 beta-trol,5,6 beta-cpoxycholesterol, 5,6 alpha-cpoxycholesterol and 7 alpha-hydroxycholesterol on esterification of cholesterol by lecithin cholesterol acyl transferase (LCAT, EC 2.3.1 43) and the transfer of esters of cholesterol oxides from high density lipoprotein (HDL) to low density lipoproteins (LDL) and very low density lipoporteins (VLDL) by cholesteryl ester transfer protin (CETP) was investigated HDL enriched with increasing concentrations of cholesterol oxides was incubated with fresh plasma as source of LCAT. Cholesterol and cholesterol oxides esterification was followed by measuring the consumption of respective free sterol and oxysterols. Measurements of cholesterol and cholesterol oxides were done by gas-chromatography. (14)C-cholesterol oxides were incorporated into HDL(2) and HDL(3) subfractions and then incubated with fresh plasma containing LCAT and CETP. The transfer of cholesterol oxide esters was followed by measuring the (14)C-cholesterol oxide-derived esters transferred to LDL and VLDL. All the cholesterol oxides studied were esterified by LCAT after incorporation into HDL particles, competing with cholesterol by LCAT. Cholesterol esterification by LCAT was inversely related to the cholesterol oxide concentration. The esterification of (14)C-cholesterol oxides was higher in HDL(3) and the transfer of the derived esters was greater from HDL(2) to LDL and VLDL. The results suggest that cholesterol oxides may exert part of their atherogenic effect by inhibiting cholesterol esterification on the HDL surface and therby disturbing reverse cholesterol transport.453429435Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [96/12164-0

Oxidized lipoproteins and antioxidants in hypertension and hypercholesterolemia

USP, FCF, São Paulo, BrazilUNIFESP, São Paulo, BrazilInst Dante Pazzanese Cardiol, São Paulo, BrazilUNIFESP, São Paulo, BrazilWeb of Scienc

Superoxide dismutase, glutathione peroxidase activities and the hydroperoxide concentration are modified in the hippocampus of epileptic rats

The relationship between free radical and scavenger enzymes has been found in the epileptic phenomena and reactive oxygen species have been implicated in seizure-induced neurodegeneration. Using the epilepsy model obtained by systemic administration of pilocarpine (PILO) in rats, we investigated the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities as well as the hydroperoxide (HPx) concentration in the hippocampus of rats during status epilepticus (SE). silent and chronic periods. the enzyme activities as well as the HPx concentration were measured using spectrophotometric methods and the results compared to values obtained from saline-treated animals. the SOD activity decreased after long-lasting SE period and during the chronic phase. in addition, FIN levels increased in same periods whereas the GPx activity increased only in the hippocampus of animals submitted to I h of SE. Animals presenting partial seizures, those submitted to 5 h of SE and animals from the silent period (seizure free) showed normal levels of SOD, GPx and HPx. These results show a direct evidence of lipid peroxidation during seizure activity that could be responsible for neuronal damage in the hippocampus of rats, during the establishment of PILO model of epilepsy. (C) 2001 Elsevier Science B.V. All rights reserved.Universidade Federal de São Paulo, UNIFESP, Escola Paulista Med, Disciplinas Bioquim, BR-04023900 São Paulo, SP, BrazilUniversidade Federal de São Paulo, UNIFESP, Escola Paulista Med, Disciplinas Neurol, BR-04023900 São Paulo, SP, BrazilUniv São Paulo, Dept Analises Clin & Toxicol, BR-05508900 São Paulo, SP, BrazilUniversidade Federal de São Paulo, UNIFESP, Escola Paulista Med, Disciplinas Bioquim, BR-04023900 São Paulo, SP, BrazilUniversidade Federal de São Paulo, UNIFESP, Escola Paulista Med, Disciplinas Neurol, BR-04023900 São Paulo, SP, BrazilWeb of Scienc

Circadian and ultradian rhythms of superoxide-dismutase in the pineal-gland

UNIV São Paulo,INST CIENCIAS BIOMED,BR-05508 São Paulo,BRAZILUNIV São Paulo,FAC CIENCIAS FARMACEUT,BR-30768 São Paulo,BRAZILESCOLA PAULISTA MED,BR-04023 São Paulo,SP,BRAZILESCOLA PAULISTA MED,BR-04023 São Paulo,SP,BRAZILWeb of Scienc

Antioxidants and endothelium-dependent relaxation (EDR) impairment in hypertension and hypercholesterolemia

Univ São Paulo, Fac Ciencias Farmaceut, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilInst Dante Pazzanese Cardiol, São Paulo, BrazilUniversidade Federal de São Paulo, EPM, São Paulo, BrazilWeb of Scienc

Oral administration of S-nitroso-N-acetylcysteine prevents the onset of non alcoholic fatty liver disease in rats

AIM: To evaluate the potential of 5-nitroso-N-acetylcysteine (SNAC) in inhibition of lipid peroxidation and the effect of oral SNAC administration in the prevention of nonalcoholic fatty liver disease (NAFLD) in an animal model. METHODS: NAFLD was induced in Wistar male rats by choline-deficient diet for 4 wk. SNAC-treated animals (n=6) (1.4 mg/kg/day of SNAC, orally) were compared to 2 control groups: one (n=6) received PBS solution and the other (n=6) received NAC solution (7 mg/kg/d). Histological variables were semiquantitated with respect to macro and microvacuolar fat changes, its zonal distribution, foci of necrosis, portal and perivenular fibrosis, and inflammatory infiltrate with zonal distribution. LOOHs from samples of liver homogenates were quantified by HPLC. Nitrate levels in plasma of portal vein were assessed by chemiluminescence. Aqueous low-density lipoprotein (LDL) suspensions (200 mu g protein/mL) were incubated with CuCl(2) (300 mu mol/L) in the absence and presence of SNAC (300 mu mol/L) for 15 h at 37 degrees C. Extent of LDL oxidation was assessed by fluorimetry. Linoleic acid (LA) (18.8 mu mol/L) oxidation was induced by soybean lipoxygenase (SLO) (0.056 mu mol/L) at 37 degrees C in the presence and absence of N-acetylcysteine (NAC) and SNAC (56 and 560 mu mol/L) and monitored at 234 nm. RESULTS: Animals in the control, group developed moderate macro and microvesicular fatty changes in periportal area. SNAC-treated animals displayed only discrete histological alterations with absence of fatty changes and did not develop liver steatosis. The absence of NAFLD in the SNAC-treated group was positively correlated with a decrease in the concentration of LOOH in liver homogenate, compared to the control group (0.7+/-0.2 nmol/mg vs 3.2+/-0.4 nmol/mg protein, respectively, P<0.05), while serum levels of aminotransferases were unaltered. The ability of SNAC in preventing lipid peroxidation was confirmed in in vitro experiments using LA and LDL as model substrates. CONCLUSION: Oral administration of SNAC prevents the onset of NAFLD in Wistar rats fed with choline-deficient diet. This effect is correlated with the ability of SNAC to block the propagation of lipid peroxidation in vitro and in vitro. (C) 2006 The WJG Press. All rights reserved.12121905191