Oxide In Rats Research Articles

Free Radical Oxidation in Rats in the Delayed Period after Combined Exposure to Dust and Radiation

We studied the intensity of free radical processes in organs (liver, spleen, thymus, lymph nodes of the small intestine, and adrenal glands) and cells (lymphocytes) in the delayed period after combined exposure to a sublethal dose of γ-radiation (6 Gy) and asbestos dust particles. Combined exposure was followed by accumulation of LPO metabolites (diene conjugates and malonic dialdehyde) in homogenates of the studied organs and resulted in antioxidant defense failure in experimental animals. Ionizing radiation have a pivotal role in these processes.

Antioxidant potential of barley extract in rats subjected to a high-fat diet

Antioxidants have the ability to neutralize free radicals produced in the body during lipid oxidation. The objective in this article was to study the effect of the barley extract on lipid oxidation in rats subjected to a high-fat diet. The experiment lasted 67 days. The animals were separated into three experimental groups: standard (P), high-fat diet group (L), and group with high-fat diet supplemented with barley extract (C). The feed intake of L and C groups was the lowest (p < 0.05). The treatments did not influence weight gain, organ weight, and the blood parameters measured. However, the levels of malondialdehyde present in the liver tissue were higher in the L group and lower in the P and C groups. Therefore, the results indicated an increased level of lipid peroxidation in the liver of rats subjected to high-fat diet, which was reduced by the consumption of barley.

Triheptanoin-enriched diet attenuates hypertrophy and preserves diastolic function and cardiac glucose oxidation in rats with pressure overload

Triheptanoin-enriched diet attenuates hypertrophy and preserves diastolic function and cardiac glucose oxidation in rats with pressure overload

Comparative study and histomorphometric analysis of bone allografts lyophilized and sterilized by autoclaving, gamma irradiation and ethylene oxide in rats

To compare three sterilization methods (autoclave, gamma irradiation and ethylene oxide) over non demineralized lyophilized bone allografts. Bone allografts were implanted on paravertebral muscles of 21 rats. After 30 days animals were sacrificed and grafts underwent comparative analysis regarding histomorphometric and macroscopic parameters. Allografts that underwent the three sterilization methods presents similar weight gain, cortical thickness similar to control group, and less fibrosis than the control group. Grafts that underwent sterilization in autoclave presented less presence of multinucleated giant cells, although not statistically significant. There was also no statistically significant difference regarding mineralization on the three groups. The three sterilization methods cause similar effects on bone allografts regarding macroscopic and histomorphometric parameters.

Citrus Flavanones Affect Hepatic Fatty Acid Oxidation in Rats by Acting as Prooxidant Agents

Citrus flavonoids have a wide range of biological activities and positive health effects on mammalian cells because of their antioxidant properties. However, they also act as prooxidants and thus may interfere with metabolic pathways. The purpose of this work was to evaluate the effects of three citrus flavanones, hesperidin, hesperetin, and naringenin, on several parameters linked to fatty acid oxidation in mitochondria, peroxisomes, and perfused livers of rats. When exogenous octanoate was used as substrate, hesperetin and naringenin reduced the mitochondrial NADH/NAD+ ratio and stimulated the citric acid cycle without significant changes on oxygen uptake or ketogenesis. When fatty acid oxidation from endogenous sources was evaluated, hesperetin and naringenin strongly reduced the mitochondrial NADH/NAD+ ratio. They also inhibited both oxygen uptake and ketogenesis and stimulated the citric acid cycle. Hesperidin, on the other hand, had little to no effect on these parameters. These results confirm the hypothesis that citrus flavanones are able to induce a more oxidised state in liver cells, altering parameters related to hepatic fatty acid oxidation. The prooxidant effect is most likely a consequence of the ability of these substances to oxidise NADH upon production of phenoxyl radicals in the presence of peroxidases and hydrogen peroxide.

Vitamin C Supplementation Does not Improve Hypoxia-Induced Erythropoiesis

Hypoxia induces reactive oxygen species production. Supplements with antioxidant mixtures can compensate for the decline in red cell membrane stability following intermittent hypobaric hypoxia by decreasing protein and lipid oxidation. We aimed to determine whether supplementation with vitamin C is implicated in the regulation of erythropoiesis and in the oxygen-carrying capacity of the blood, and also whether antioxidant supplementation prevents the oxidative stress associated to intermittent hypoxia. Twenty-four male Wistar rats were randomly divided into four experimental groups: normoxia control (n=6), normoxia + vitamin C (n=6), hypoxia control (12 h pO(2) 12%/12 h pO(2) 21%) (n=6), and hypoxia + vitamin C (n=6). Animals were supplemented with vitamin C at a dose of 250 mg·kg(-1)·day(-1) for 21 days. Red blood cell count, hemoglobin, hematocrit, reticulocytes, erythropoietin, and oxidative stress parameters such as malondialdehyde and protein oxidation in plasma were analyzed at two different time points: basal sample (day zero) and final sample (day 21). Similar RBC, Hb, Hct, and Epo increments were observed in both hypoxic groups regardless of the vitamin C supplementation. There was no change on MDA levels after intermittent hypoxic exposure in any experimental group. However, we found an increase in plasma protein oxidation in both hypoxic groups. Vitamin C does not affect erythropoiesis and protein oxidation in rats submitted to intermittent hypoxic exposure.

Iron Excess Disturbs Metabolic Status and Relative Gonad Mass in Rats on High Fat, Fructose, and Salt Diets

The aim of this study was to assess the metabolic and physiological changes in rats fed a diet high in fat, fructose, and salt, and with excess iron level. Mineral status was also estimated. Wistar rats were assigned to groups fed either a standard control diet (C) or a diet high in fat, fructose, and salt. The noncontrol diets contained either normal (M) or high level (MFe) of iron. After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized. The kidneys and gonads were collected, and blood samples were taken. Serum levels of insulin, nitric oxide, and iron were measured. The iron, zinc, copper, and calcium concentrations of tissues were determined. It was found that the M diet led to a significant increase in the relative kidney mass of the rats compared with the control group. Among the rats fed the M diet, markedly higher serum level of iron and lower levels of zinc and copper were observed in tissues, while significantly higher calcium levels were found in the gonads. The MFe diet resulted in decreased obesity index, insulin level, and nitric oxide serum concentration in the rats, when compared with both the M and C diets. The high iron level in the modified diet increased the relative mass of the gonads. The excess iron level in the diet disturbed the zinc, copper, and calcium status of tissues. The decrease in insulin and nitric oxide in rats fed the diet high in iron, fat, fructose, and salt was associated with disorders of zinc, copper, and calcium status, as well as with an increase in the relative mass of the gonads.

Comparative study of genotoxicity and tissue distribution of nano and micron sized iron oxide in rats after acute oral treatment

Though nanomaterials (NMs) are being utilized worldwide, increasing use of NMs have raised concerns over their safety to human health and environment. Iron oxide (Fe2O3) NMs have important applications. The aim of this study was to assess the genotoxicity of Fe2O3-30nm and Fe2O3-bulk in female Wistar rats. Fe2O3-30nm was characterized by using transmission electron microscopy, dynamic light scattering, laser Doppler velocimetry and surface area analysis. The rats were treated orally with the single doses of 500, 1000, 2000mg/kg bw of Fe2O3-30nm and Fe2O3 –bulk. The genotoxicity was evaluated at 6, 24, 48 and 72h by the comet assay in leucocytes, 48 and 72h by micronucleus test (MNT) in peripheral blood cells, 18 and 24h by chromosomal aberration (CA) assay and 24 and 48h by MNT in bone marrow cells. The biodistribution of iron (Fe) was carried out at 6, 24, 48 and 72h after treatment in liver, spleen, kidney, heart, brain, bone marrow, urine and feces by using atomic absorption spectrophotometry.The % tail DNA, frequencies of micronuclei and CAs were statistically insignificant (p>0.05) at all doses. These results suggest that Fe2O3-30nm and Fe2O3-bulk was not genotoxic at the doses tested.Bioavailability of Fe was size and dose dependent in all the tissues from the groups exposed to Fe2O3-30nm. Fe2O3 NMs were able to enter in the organs and the rats are biocompatible with much higher concentration of Fe. However, the accumulated Fe did not cause significant genotoxicity. This study provides additional knowledge about the toxicology of Fe2O3 NMs.

Interrelated effects of dihomo-γ-linolenic and arachidonic acids, and sesamin on hepatic fatty acid synthesis and oxidation in rats

Interrelated effects of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (ARA), and sesamin, a sesame lignan, on hepatic fatty acid synthesis and oxidation were examined in rats. Rats were fed experimental diets supplemented with 0 or 2g/kg sesamin (1:1 mixture of sesamin and episesamin), containing 100g/kg of maize oil or fungal oil rich in DGLA or ARA for 16d. Among the groups fed sesamin-free diets, oils rich in DGLA or ARA, especially the latter, compared with maize oil strongly reduced the activity and mRNA levels of various lipogenic enzymes. Sesamin, irrespective of the type of fat, reduced the parameters of lipogenic enzymes except for malic enzyme. The type of dietary fat was rather irrelevant in affecting hepatic fatty acid oxidation among rats fed the sesamin-free diets. Sesamin increased the activities of enzymes involved in fatty acid oxidation in all groups of rats given different fats. The extent of the increase depended on the dietary fat type, and the values became much higher with a diet containing sesamin and oil rich in ARA in combination than with a diet containing lignan and maize oil. Analyses of mRNA levels revealed that the combination of sesamin and oil rich in ARA compared with the combination of lignan and maize oil markedly increased the gene expression of various peroxisomal fatty acid oxidation enzymes but not mitochondrial enzymes. The enhancement of sesamin action on hepatic fatty acid oxidation was also confirmed with oil rich in DGLA but to a lesser extent.

GLP-1 improves survival and preserves diastolic function and cardiac glucose oxidation in rats with pressure overload

Objectives: The incretin hormone GLP-1 has been associated with protective effects in diabetes and ischemic heart disease. We investigated the role of GLP-1 treatment in rats subjected to chronic pressure overload (PO) with the aim to detect a novel metabolic mechanism to improve ventricular function.

Fish oil at low dietary levels enhances physiological activity of sesamin to increase hepatic fatty acid oxidation in rats

We previously demonstrated that a diet containing fish oil at a level of 80 g/kg strongly stimulated the physiological activity of a sesame sesamin preparation containing sesamin and episesamin at equal amounts to increase hepatic fatty acid oxidation. This study was conducted to clarify whether fish oil at lower dietary levels enhances the physiological activity of sesamin to increase hepatic fatty acid oxidation. Rats were fed experimental diets supplemented with 0 or 2 g sesamin/kg, and containing 0, 15 or 30 g fish oil/kg for 15 days. Among rats fed sesamin-free diets, diets containing 15 and 30 g fish oil/kg slightly increased the activity of enzymes involved in hepatic fatty acid oxidation. Sesamin increased these values irrespective of the presence or absence of fish oil in diets; however, the extent of the increase of many parameters was much greater in rats given fish oil-containing diets than in those fed a fish oil-free diet. Diets simultaneously containing sesamin and fish oil increased the gene expression of various peroxisomal fatty acid oxidation enzymes in a synergistic manner; but they were ineffective in causing a synergistic increase in mRNA levels of mitochondrial fatty acid oxidation enzymes. The extent of the synergistic increase in the activity of hepatic fatty acid oxidation enzymes and mRNA levels of the peroxisomal enzymes was indistinguishable between diets containing 15 and 30 g fish oil/kg and appeared comparable to that observed previously with a diet containing 80 g fish oil/kg.

Relationships between Lipophilicity and Biological Activities in a Series of Indoline-based Anti-oxidative Acyl-CoA:Cholesterol Acyltransferase (ACAT) Inhibitors

A novel series of 1-alkyl-7-amido-indoline-based anti-oxidative acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors have been reported and are expected to lower plasma cholesterol levels due to the inhibition of intestinal and hepatic ACAT, and to inhibit cholesterol accumulation in macrophages due to the inhibition of low density lipoprotein (LDL) oxidation. In the present study, relationships between lipophilicity and biological activities were examined in 13 derivatives. Lipophilicity (logP) increased and water solubility decreased with dependence on the number of carbons in the 1-alkyl chain. Inhibitory activity against both in vitro intestinal ACAT and LDL oxidation positively correlated with logP; however, the optimum logP, at which the level of activity is maximal, differed between these two effects. Inhibitory activity against in vitro plasma oxidation was weakly dependent on logP. Plasma concentrations of the derivatives after oral administration at 10 mg/kg correlated negatively with logP and positively with water solubility. Hypocholesterolemic activity in rats fed a high-cholesterol diet, and the ratio of Cmax and IC50 values for ACAT inhibition, an index of effective plasma concentration, positively and highly correlated with logP, while ex vivo inhibitory activity against plasma oxidation in rats, and the ratio of Cmax and IC50 values for the inhibition of plasma oxidation negatively correlated with logP. In conclusion, in vitro ACAT inhibitory and anti-oxidative activity were differently dependent on logP, and intestinal absorption was inversely dependent on lipophilicity in indoline-based anti-oxidative ACAT inhibitors. The hypocholesterolemic effect positively correlated and the ex vivo anti-oxidative effect negatively correlated with lipophilicity. Optimum logP as a bioavailable dual inhibitor against in vivo ACAT and lipid peroxidation was estimated to be 3.8 (1-pentyl and 1-isopentyl derivatives) in the present series of derivatives.

Effect of Dietary Tocotrienols on Antioxidant Status and Low Density Lipoprotein Oxidation in Rats, Exposed to Cigarette Smoke

Effect of Dietary Tocotrienols on Antioxidant Status and Low Density Lipoprotein Oxidation in Rats, Exposed to Cigarette Smoke

Clofibrate‐Induced Reduction of Plasma Branched‐Chain Amino Acid Concentrations Impairs Glucose Tolerance in Rats

It has been reported that branched-chain amino acid (BCAA) administration stimulates glucose uptake into muscles and whole body glucose oxidation in rats. The authors examined the effect of decreased plasma BCAA concentrations induced by clofibrate treatment on glucose tolerance in rats. Since clofibrate, a drug for hyperlipidemia (high serum triglyceride concentration), is a potent inhibitor of the branched-chain α-keto acid dehydrogenase kinase, clofibrate treatment (0.2 g/kg body weight) activated the hepatic branched-chain α-keto acid dehydrogenase complex, resulting in decreased plasma BCAA concentrations by 30% to 50% from the normal level. An intraperitoneal glucose tolerance test was conducted after clofibrate administration, and the results showed that peak plasma glucose concentration and the area under the curve of glucose concentration during the intraperitoneal glucose tolerance test were significantly higher in clofibrate-treated rats than in control rats. This impaired glucose tolerance in the clofibrate-treated rats was ameliorated by administration of BCAAs (0.45 g/kg body weight, leucine:isoleucine:valine = 2:1:1), which kept plasma BCAA concentrations at normal levels during the intraperitoneal glucose tolerance test. These results suggest that plasma BCAAs play an important role in maintaining normal glucose tolerance in rats.

SIRT3 Deficiency and Mitochondrial Protein Hyperacetylation Accelerate the Development of the Metabolic Syndrome

Acetylation is increasingly recognized as an important metabolic regulatory posttranslational protein modification, yet the metabolic consequence of mitochondrial protein hyperacetylation is unknown. We find that high-fat diet (HFD) feeding induces hepatic mitochondrial protein hyperacetylation in mice and downregulation of the major mitochondrial protein deacetylase SIRT3. Mice lacking SIRT3 (SIRT3KO) placed on a HFD show accelerated obesity, insulin resistance, hyperlipidemia, and steatohepatitis compared to wild-type (WT) mice. The lipogenic enzyme stearoyl-CoA desaturase 1 is highly induced in SIRT3KO mice, and its deletion rescues both WT and SIRT3KO mice from HFD-induced hepatic steatosis and insulin resistance. We further identify a single nucleotide polymorphism in the human SIRT3 gene that is suggestive of a genetic association with the metabolic syndrome. This polymorphism encodes a point mutation in the SIRT3 protein, which reduces its overall enzymatic efficiency. Our findings show that loss of SIRT3 and dysregulation of mitochondrial protein acetylation contribute to the metabolic syndrome.

ラット脂肪細胞のインスリン受容体, グルコース摂取, グルコース酸化におよぼす高脂肪食の影響

ラット脂肪細胞のインスリン受容体, グルコース摂取, グルコース酸化におよぼす高脂肪食の影響

Vasodilator efficiency of endogenous prostanoids, Ca2+-activated K+ channels and nitric oxide in rats with spontaneous, salt-dependent or NO-deficient hypertension

Hypertension is associated with the imbalance of vasoconstrictor and vasodilator systems. Vasodilation is usually evaluated in isolated blood vessels, but except for nitric oxide (NO), relatively little attention is given to the in vivo efficiency of particular vasodilator mechanisms. The aim of our study was to evaluate the contribution of endogenous vasodilator prostanoids, Ca(2+)-activated K(+) channels and NO to blood pressure (BP) maintenance in rats with three different forms of experimental hypertension. Both principal vasopressor systems (the renin-angiotensin system and the sympathetic nervous system) were blocked by captopril and pentolinium in conscious spontaneously hypertensive rats (SHRs), Dahl salt-hypertensive (DS-HS) rats and rats with NO-deficient hypertension, as well as in their normotensive controls. Thereafter, we monitored BP changes in rats subjected to either a sequential or an isolated blockade of prostanoid synthesis by the non-selective cyclooxygenase inhibitor, indomethacin, of Ca(2+)-activated K(+) channels by tetraethylammonium and of NO formation by N(G)-nitro-L-arginine methyl ester. All three forms of experimental hypertension were characterized by augmented sympathetic vasoconstriction. The vasodilatation exerted by endogenous prostanoids and Ca(2+)-activated K(+) channels was enhanced in all forms of hypertension, almost proportionally to BP elevation. On the contrary, NO-dependent vasodilatation was not enhanced in any form of experimental hypertension, and there was a severe relative NO deficiency in both, SHRs and DS-HS rats. In conclusion, our data suggested that there is a compensatory activation of vasodilator prostanoids and Ca(2+)-activated K(+) channels in rats with experimental hypertension, whereas NO-dependent vasodilatation is not augmented. Thus, the overall activity of vasodilator systems failed to compensate for augmented sympathetic vasoconstriction in hypertensive animals.

Mild hypothermia induced cardioprotection against ischemia/reperfusion injury mediated by nitric oxide in rat isolated heart model

Mild hypothermia induced cardioprotection against ischemia/reperfusion injury mediated by nitric oxide in rat isolated heart model

Inhalation Carcinogenicity and Chronic Toxicity of Indium‐tin Oxide in Rats and Mice

Carcinogenicity and chronic toxicity of indium-tin oxide (ITO) were examined by inhalation exposure of rats and mice to ITO aerosol. Fifty mice of both sexes were exposed to ITO at 0 (control), 0.01, 0.03 or 0.1 mg/m(3) for 6 h/day, 5 day/wk for 104 wk, and 50 rats of both sexes were exposed to 0, 0.01 or 0.03 mg/m(3) ITO for the same time period. The repeated exposure of 50 rats of both sexes to 0.1 mg/m(3) ITO was discontinued at the 26th wk, followed by clean air exposure for the remaining 78 wk. In rats, incidences of bronchiolo-alveolar adenomas and carcinomas, bronchiolo-alveolar hyperplasia, alveolar wall fibrosis and thickened pleural wall, alveolar proteinosis and infiltrations of alveolar macrophages and inflammatory cells were significantly increased. Combined incidences of malignant lung tumors in male rats and total lung tumors in male and female rats were significantly increased at exposure to 0.01 mg/m(3) ITO. In mice, no carcinogenic response occurred, but thickened pleural wall, alveolar proteinosis and alveolar macrophage infiltration were induced. Mice were less susceptible to ITO than rats. The lung content of indium was the greatest, followed by the spleen, kidney and liver. Blood indium levels increased dose-dependently. There was clear evidence of carcinogenicity of inhaled ITO in male and female rats but not clear evidence in mice, together with occurrence of the chronic pulmonary lesions in both rats and mice.

Regulation of hepatic fat and glucose oxidation in rats with lipid-induced hepatic insulin resistance

Pyruvate dehydrogenase plays a critical role in the regulation of hepatic glucose and fatty acid oxidation; however, surprisingly little is known about its regulation in vivo. In this study we examined the individual effects of insulin and substrate availability on the regulation of pyruvate dehydrogenase flux (V(PDH) ) to tricarboxylic acid flux (V(TCA) ) in livers of awake rats with lipid-induced hepatic insulin resistance. V(PDH) /V(TCA) flux was estimated from the [4-(13) C]glutamate/[3-(13) C]alanine enrichments in liver extracts and assessed under conditions of fasting and during a hyperinsulinemic-euglycemic clamp, whereas the effects of increased plasma glucose concentration on V(PDH) /V(TCA) flux was assessed during a hyperglycemic clamp in conjunction with infusions of somatostatin and insulin to maintain basal concentrations of insulin. The effects of increases in both glucose and insulin on V(PDH) /V(TCA) were examined during a hyperinsulinemic-hyperglycemic clamp. The effects of chronic lipid-induced hepatic insulin resistance on this flux were also examined by performing these measurements in rats fed a high-fat diet for 3 weeks. Using this approach we found that fasting V(PDH) /V(TCA) was reduced by 95% in rats with hepatic insulin resistance (from 17.2 ± 1.5% to 1.3 ± 0.7%, P < 0.00001). Surprisingly, neither hyperinsulinemia per se or hyperglycemia per se were sufficient to increase V(PDH) /V(TCA) flux. Only under conditions of combined hyperglycemia and hyperinsulinemia did V(PDH) /V(TCA) flux increase (44.6 ± 3.2%, P < 0.0001 versus basal) in low-fat fed animals but not in rats with chronic lipid-induced hepatic insulin resistance. These studies demonstrate that the combination of both hyperinsulinemia and hyperglycemia are required to increase V(PDH) /V(TCA) flux in vivo and that this flux is severely diminished in rats with chronic lipid-induced hepatic insulin resistance.