Liliana Oliveros

Lipid metabolism in liver of rat exposed to cadmium.

We investigated the effect of exposition to cadmium (Cd, 15ppm for 8 weeks) through drinking water on liver lipid metabolism in adult male Wistar rats. As compared to metal non-exposed (control) rats, the serum triglycerides, cholesterol and LDL+VLDL cholesterol concentrations increased. This was associated to a decrease of lipoprotein lipase activity in post heparinic plasma. The VLDL secretion from liver was not modified. Cd treatment increased triglycerides and decreased esterified cholesterol contents in liver. The high triglyceride mass was related to the increased glycerol-3-phosphate acyltransferase mRNA expression. In addition, the liver fatty acids synthesis increased, as determined by an increment of fatty acid synthetase and isocitrate dehydrogenase activities, and [(14)C]-acetate incorporation into saponifiable lipid fraction. The relative percentage of palmitic acid (16:0) and total saturated fatty acids were increased compared with control. Hepatic glucose-6-phosphate dehydrogenase, malic dehydrogenase and cholesteryl ester hydrolase activities were unchanged. In liver, the Cd treatment decreased triglyceride and cholesterol in mitochondria, also increased triglyceride in cytosol, and cholesterol and phospholipid contents in nuclei, compared with control. In addition, an increase of nuclei phosphatidylcholine synthesis was observed. Cd exposure alters directly or indirectly the serum lipid content and liver lipid metabolism.

Polymorphisms in cytokines and growth factor genes and their association with acute rejection and recurrence of hepatitis C virus disease in liver transplantation

Acute rejection (AR) and recurrence of hepatitis C virus (HCV) infection are complications after liver transplantation (LTx). Genetic factors play a role in cytokine production as a consequence of polymorphisms within cytokine genes. Our goal was to identify genetic factors that might be associated with AR and recurrence of HCV in liver transplant recipients (LTxRs). We studied 77 Caucasian LTxRs and 100 Caucasian healthy individuals. We studied single‐nucleotide polymorphisms (SNPs) in tumor necrosis factor‐α[TNF‐α, interleukin‐6 (IL‐6), IL‐10, transforming growth factor‐β1, and angiotensin‐converting enzyme genes by SNaPSHOT™ Multiplex assay. SNPs were classified as high producers (HP), intermediate producers (IP), or low producers (LP), and their association with AR and recurrence of HCV were studied. The frequency of TNF‐α IP and HP genotypes was significantly higher in LTxRs with AR in comparison to patients without AR (TNF‐α HP −238: 63 vs 20%, p < 0.001; TNF‐α HP −308: 47.4 vs 20%, p = 0.02). The frequency of IL‐6 IP and HP genotypes was higher in patients with AR episodes, but the difference was not statistically significant (p = 0.14). However, when we analyzed the simultaneous presence of pro‐inflammatory genotypes in the same patient, we found a significant difference between patients with and without AR, respectively (42.1 vs 14.6%, p = 0.012). Moreover, the frequency of the IL‐10 LP genotype was higher in LTx patients with AR (p = 0.001) compared to patients without AR. There was an association between pro‐inflammatory genotypes and HCV recurrence. Our data suggest that cytokine gene polymorphisms might play a role in AR and HCV recurrence in LTxRs.

Vitamin A deficiency modifies lipid metabolism in rat liver

Liver fatty acid metabolism of male rats fed on a vitamin A-deficient diet for 3 months from 21 d of age was evaluated. Vitamin A restriction produced subclinical plasma and negligible liver retinol concentrations, compared with the control group receiving the same diet with 4000 IU vitamin A (8 mg retinol as retinyl palmitate)/kg diet. Vitamin A deficiency induced a hypolipidaemic effect by decreasing serum triacylglycerol, cholesterol and HDL-cholesterol levels. The decrease of liver total phospholipid was associated with low phosphatidylcholine synthesis observed by lower [14C]choline incorporation into phosphatidylcholine, compared with control. Also, liver fatty acid synthesis decreased, as was indicated by activity and mRNA expression of acetyl-CoA carboxylase (ACC), and incorporation of [14C]acetate into saponified lipids. A decrease of the PPARalpha mRNA expression was observed. Liver mitochondria of vitamin A-deficient rats showed a lower total phospholipid concentration coinciding with a decrease of the cardiolipin proportion, without changes in the other phospholipid fractions determined. The mitochondria fatty acid oxidation increased by 30 % of the control value and it was attributed to a high activity and mRNA expression of carnitine palmitoyltransferase-I (CPT-I). An increase in serum beta-hydroxybutyrate levels was observed in vitamin A-deficient rats. Vitamin A deficiency alters the mitochondria lipid composition and also enhances fatty acid oxidation by modifying the production of malonyl-CoA, the endogenous inhibitor of CPT-I, due to decreased activity of liver ACC. The incorporation of vitamin A into the diet of vitamin A-deficient rats reverted all the changes observed.

Alterations in the Lipid Metabolism of Rat Aorta: Effects of Vitamin A Deficiency

Antioxidants are known to reduce cardiovascular disease by reducing the concentration of free radicals in the vessel wall and by preventing the oxidative modification of low-density lipoproteins. The prooxidative effect of a vitamin-A-deficient diet on the aorta has previously been demonstrated by us. In this study, the lipid metabolism in the aorta of rats fed on a vitamin-A-deficient diet was evaluated. Vitamin A deficiency induced a hypolipidemic effect (lower serum triglyceride and cholesterol levels) and a decreased serum paraoxonase 1/arylesterase activity. The concentrations of triglycerides, total cholesterol, free and esterified cholesterol, and phospholipids were increased in the aorta of vitamin-A-deficient rats. The phospholipid compositions showed an increase in phosphatidylcholine (PC), phosphatidylinositol plus phosphatidylserine and phosphatidylethanolamine, a decrease in sphingomyelin, and no change in phosphatidylglycerol. In the aorta, the increase in triglycerides was associated with an increased fatty acid synthesis and mRNA expression of diacylglycerol acyltransferase 1. The increased PC content was attributed to an increased synthesis, as measured by [methyl-14C]choline incorporation into PC and high CTP:phosphocholine cytidylyltransferase-α mRNA expression. The cholesterol synthesis, evaluated by [1-14C]acetate incorporated into cholesterol and mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, did not change. The lipoprotein lipase and lectin-like oxidized low-density lipoprotein receptor 1 mRNA expression levels increased in the aorta of vitamin-A-deficient animals. The incorporation of vitamin A into the diet of vitamin-A-deficient rats reverted all the changes observed. These results indicate that a vitamin-A-deficient diet,in addition to having a prooxidative effect, alters the aorta lipid metabolism.

Alterations in the lipid content of pituitary gland and serum prolactin and growth hormone in cadmium treated rats.

The present study was undertaken to assess whether chronic exposition to cadmium (Cd, 0.133 mM per liter for 2 months) through drinking water may affect the lipid contents in the pituitary anterior lobe (PAL) of adult male Wistar rats. As compared to metal non-exposed controls, PALs exposed to cadmium showed an increase in total phospholipid contents, which was associated to an increase of the incorporation of [1−14C]-methyl choline into phosphatidylcholine and of [U−14C]-glucose into total phospholipids. The incorporation of [1−14C]-methyl choline into sphingomyelin was not changed. Incorporation of [1−14C]-acetate into total fatty acids also increased but incorporation of [1−14C]-acetate into cholesterol did not change. The activity of phospholipase D decreased both in PALs from Cd exposed rats and in PAL dispersed cells treated with Cd in the culture medium from Cd non-exposed rats. In PALS from Cd exposed rats, a decrease of serum prolactin and growth hormone concentrations was determined. The results shown that cadmium modifies the lipid contents of pituitary gland and directly or indirectly the levels of prolactin and growth hormone in serum.

Effect of nutritional vitamin A deficiency on lipid metabolism in the rat heart: Its relation to PPAR gene expression.

OBJECTIVE We studied the effect of dietary vitamin A deprivation on lipid composition and mRNA expression of regulatory enzymes involved in rat heart energetic lipid metabolism and its relation to the expression of peroxisome proliferator-activated receptor (PPAR) and retinoid X receptor (RXR) genes. METHODS Male Wistar 21-d-old rats were fed for 3 mo with a vitamin A-free diet (vitamin A-deficient group) and the same diet plus 8 mg of retinol palmitate per kilogram of diet (control group). One group of deficient animals received the control diet 15 d before sacrifice (vitamin A-refed group). Heart ventricular and mitochondrial lipid contents were determined. Lipid synthesis was measured using radioactive precursors and acetyl-coenzyme A carboxylase and mitochondrial carnitine palmitoyltransferase-I (CPT-I) activities using radioactive substrates. Fatty acid composition of mitochondrial phospholipids was analyzed by gas-liquid chromatography. Heart expression of acetyl-coenzyme A carboxylase, CPT-I, PPAR-alpha, PPAR-beta, RXR-alpha, and RXR-beta was assessed by reverse transcriptase polymerase chain reaction, and CPT-I expression was also measured by real-time polymerase chain reaction. RESULTS Vitamin A deficiency induced changes in heart ventricular lipid content and synthesis. Mitochondrial cardiolipin decreased and the proportion of phospholipids/saturated fatty acids increased. Heart activity and mRNA levels of CPT-I and expression of PPAR-alpha and PPAR-beta genes were enhanced, whereas acetyl-coenzyme A carboxylase activity diminished. Furthermore, vitamin A deficiency decreased heart mRNA levels of RXRs. Vitamin A refeeding reverted most of the observed changes. CONCLUSION Lipid metabolism is significantly modified in hearts of vitamin A-deficient rats. Alteration of mitochondrial energetic processes by modifying the activity and gene expressions of the regulatory enzymes is associated with a high PPAR expression induced by vitamin A deprivation.

Vitamin A deficiency induces prooxidant environment and inflammation in rat aorta

We evaluated whether nutritional vitamin A deficiency generates oxidative stress and inflammation in aorta. Wistar male rats (21 days old) were given free access to a control (8 mg retinol as retinyl palmitate/kg) or a vitamin A- deficient diet for three months. One group of deficient animals was fed with the control diet fifteen days before sacrifice. Thiobarbituric acid-reactive substances (TBARS) and nitrite concentration where both analyzed in serum and aorta. Aorta Copper–Zinc Superoxide dismutase (CuZnSOD), Glutathion peroxidase (GPx) and Catalase (CAT) activities were measured. In addition, binding activity of the nuclear factor- kB (NF-kB), inducible and endothelial Nitric Oxide synthase (iNOS and eNOS, respectively) and Ciclooxygenase-2 (COX-2) expressions were determinated in aorta. Rats fed the vitamin A- deficient diet were characterized by sub-clinical plasma retinol concentration and showed increased serum and aorta concentrations of TBARS compared to controls. Lower than control activities of CuZnSOD, GPx, and CAT were observed in aorta of the vitamin A- deficient group. The binding activity of NF- kB was higher in vitamin A- deficient animals than controls. In addition, NO production evaluated as nitrite concentration increased in aorta and serum, associated with a higher expression of iNOS, eNOS and COX-2 in aorta of vitamin A-deficient rats. The incorporation of vitamin A into the diet of vitamin A-deficient rats reverted the changes observed in TBARS level, CuZnSOD and GPx activities, nitrite concentration and also, iNOS, eNOS and COX-2 expression. Prooxidant environment and inflammation are induced by vitamin A deficiency in rat aorta.

Vitamin a deficiency modifies antioxidant defenses and essential element contents in rat heart

Abstract Oxidative stress in the heart of male rats fed on a vitamin A-deficient diet for three months from 21 days of age was evaluated. Vitamin A restriction produced subclinical plasma retinol concentration (0.7 μmol/l), negligible liver retinol stores and a significant decrease of heart retinol concentration, as determined by HPLC, compared with the control group receiving the same diet with 4000 IU of vitamin A (8 mg retinol as retinyl palmitate) per kg of diet. Vitamin A-deficient rats had lower body weight than control rats. No change in the heart weights was observed. In serum of rats fed the vitamin A-deficient diet the concentrations of thiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH) increased by ∼65% and 60%, respectively, compared with those fed on the control diet. In hearts of vitamin A-deficient rats the concentration of TBARS and the glutathione peroxidase activity significantly increased. The activity of catalase decreased by ∼30%, while the superoxide dismutase did not change. Additionally, vitamin A-deficient rats showed lower heart concentrations of the trace elements selenium, manganese and chromium. Heart iron, copper and zinc concentrations were not affected. Vitamin A deprivation for 3 months decreased the plasma and heart retinol concentrations associated with changes in non-enzymatic and enzymatic antioxidant defense system components.

Nutritional vitamin A deficiency alters antioxidant defenses and modifies the liver histoarchitecture in rat.

Oxidative stress and morphologic changes in the liver of female rats fed on a vitamin A-deficient diet for 3 months from 21 days of age were evaluated. Vitamin A restriction produced subclinical plasma retinol concentration (0.6 μmol–L) and negligible liver retinol stores, as determined by high-performance liquid chromatography, compared to the control group, which received the same diet with 4000 IU of vitamin A (8 mg retinol as retinyl palmitate) per kg of diet. Vitamin A-deficient rats had lower body weight than control rats. No change in the liver weights was observed. In the liver of rats fed the vitamin A-deficient diet, the concentrations of thiobarbituric acid-reactive substances increased by ∼50%, and the activities of catalase and glutathione peroxidase increased by 30% and 40%, respectively, compared with those fed on the control diet. Liver superoxide dismutase activity did not change. Additionally, vitamin A-deficient rats showed higher liver concentrations (μg/g tissue) of iron (316.03 ± 12.1 vs 203.12 ± 9.5) and lower concentrations of the antioxidant trace elements zinc (15.50 ± 1.03 vs 26.63 ± 0.25) and copper (2.27 ± 0.22 vs 4.25 ± 0.37) than those of control. Liver selenium concentration was not affected. Morphologically, livers from vitamin A-deficient rats showed a partial hepatic cord disarrangement and an increased number of hepatocytes in process of involution with piknotic nuclei and condensed cytoplasm. A reduced number of fat-hepatocytes distributed at random was observed. Portal spaces showed evidence of edema and a marked infiltration by mononuclear as well as polimorphonuclear cells. Loose portal connective tissue increased, as did the number of fibroblast-like cells in portal spaces. Vitamin A deprivation for 3 months decreased the liver retinol concentration associated with marked histological alterations in the organ, which could be due, at least in part, to the increase in oxidative stress. J. Trace Elem. Exp. Med. 13:343–357, 2000.

Nutritional Deficiencies and Phospholipid Metabolism

Phospholipids are important components of the cell membranes of all living species. They contribute to the physicochemical properties of the membrane and thus influence the conformation and function of membrane-bound proteins, such as receptors, ion channels, and transporters and also influence cell function by serving as precursors for prostaglandins and other signaling molecules and modulating gene expression through the transcription activation. The components of the diet are determinant for cell functionality. In this review, the effects of macro and micronutrients deficiency on the quality, quantity and metabolism of different phospholipids and their distribution in cells of different organs is presented. Alterations in the amount of both saturated and polyunsaturated fatty acids, vitamins A, E and folate, and other micronutrients, such as zinc and magnesium, are discussed. In all cases we observe alterations in the pattern of phospholipids, the more affected ones being phosphatidylcholine, phosphatidylethanolamine and sphingomyelin. The deficiency of certain nutrients, such as essential fatty acids, fat-soluble vitamins and some metals may contribute to a variety of diseases that can be irreversible even after replacement with normal amount of the nutrients. Usually, the sequelae are more important when the deficiency is present at an early age.