Beneficial effects of dietary copper supplementation on serum lipids and antioxidant defenses in rats.

BACKGROUND: A nutrition experiment was utilized to investigate the effects of two levels of dietary copper (Cu) supplementation on lipid profile and antioxidant defenses in serum of rats. METHODS: Male Wistar rats (180-200 g; n = 10) were divided into three groups: control group (A), fed a basal diet with 6 microg Cu/g, and rats fed a basal diet with Cu (CuSO4) supplementation from aqueous solutions, for 4 weeks at the final concentrations of 2 mg Cu/rat (B) and 3 mg Cu/rat (C). RESULTS: No significant changes were observed in final body weight, body weight gain, food consumption, total serum protein and high-density lipoprotein. Cu supplementation reduced the triacylglycerol (TG), total cholesterol and low-density lipoprotein (LDL-C). The LDL-C/TG ratio and total antioxidant substances (TAS) were higher in (B) and (C) groups than in (A) group. There was a positive correlation between Cu supplementation and ceruloplasmin levels. The markers of oxidative stress, lipid hydroperoxide and lipoperoxide were decreased with Cu supplementation. No alterations were observed in superoxide dismutase, indicating saturation of Cu enzyme site. The glutathione peroxidase activities (GSH-Px) were increased in both Cu-supplemented groups. Considering that a copper-selenium interaction can affect mineral availability of both elements, the effects of Cu on TAS and GSH-Px activities were associated with increased selenium disposal. CONCLUSIONS: Dietary Cu supplementation had beneficial effects on lipid profile by improving endogenous antioxidant defenses and decreasing the oxidative stress in vivo.

Antioxidant effect of saponin: potential action of a soybean flavonoid on glucose tolerance and risk factors for atherosclerosis.

At the present time, much attention is being paid to antioxidant substances because many pathological conditions are associated with oxidative stress. The purpose of the present study was to discover the potency of saponin (2-phenyl-benzopyrane), a soybean flavonoid, with respect to its hypoglycaemic and hypolipidaemic action, and the association of these effects with oxidative stress. Male Wistar rats were divided into two groups (n = 6): control group and saponin-treated group (60 mg/kg) during 30 days. Saponin had no effects on glucose tolerance. Although no changes had been observed in low-density lipoprotein-cholesterol, saponin-treated animals had increased low-density lipoprotein-cholesterol/triacylglycerol ratio and decreased triacylglycerol, very low-density lipoprotein-cholesterol and total/high-density lipoprotein-cholesterol ratio than the control group. Saponin-treated rats showed lower lipid hydroperoxide than control rats, indicating decreased potential to atherosclerosis. No alterations were observed in antioxidant enzymes, superoxide dismutase and glutathione peroxidase, while lipid hydroperoxide were decreased in saponin-treated rats. In conclusion, the beneficial effects of saponin on serum lipids were related to a direct saponin antioxidant activity.

Toxicity of dietary restriction of fat enriched diets on cardiac tissue.

The present study examines the effects of caloric restriction in cardiac tissue evaluation markers of oxidative stress. High-fat dietary restrictions can have a long-term impact on cardiac health. Dietary restriction of control diet increased myocardial superoxide dismutase (SOD) and catalase activities. Dietary restriction of fatty acid-enriched diets increased myocardial lipoperoxide concentrations, while SOD activity was decreased in cardiac tissue of rats with dietary restriction of fatty acid-enriched diets. Dietary restriction of unsaturated fatty acid-enriched diet induced the highest lipoperoxide concentration and the lowest myocardial SOD activity. Dietary restriction of unsaturated fatty acid decreased myocardial glycogen, and increased the lactate dehydrogenase/citrate synthase ratio. Dietary restriction of fatty acid-enriched diets were more deleterious to cardiac tissue than normal ad lib.-fed diet. In conclusion, the effects of caloric restriction on myocardial oxidative stress is dependent on which nutrient is restricted. Dietary restriction of fatty acid-enriched diets is deleterious relative to ad lib.-fed chow diet.

The use of the oxidative stress responses as biomarkers in Nile tilapia (Oreochromis niloticus) exposed to in vivo cadmium contamination.

Water contaminants have a high potential risk for the health of populations. Protection from toxic effects of environmental water pollutants primarily involves considering the mechanism of low level toxicity and likely biological effects in organisms who live in these polluted waters. The biomarkers assessment of oxidative stress and metabolic alterations to cadmium exposure were evaluated in Nile tilapia, Oreochromis niloticus. The fish were exposed to 0.35, 0.75, 1.5, and 3.0 mg/l concentrations of Cd2+ (CdCl2) in water for 60 days. Fish that survived cadmium exposure showed a metabolic shift and a compensatory development for maintenance of the body weight gain. We observed a decreased glycogen content and decreased glucose uptake in white muscle. Lactate dehydrogenase (LDH) and creatine phosphokinase (CK) activities were also decreased, indicating that the glycolytic capacity was decreased in this tissue. No alterations were observed in total protein content in white muscle due to cadmium exposure suggesting a metabolic shift of carbohydrate metabolism to maintenance of the muscle protein reserve. There was an increase in glucose uptake, CK increased activity, and a clear increase of LDH activity in red muscle of fish with cadmium exposure. Since no alterations were observed in lipoperoxide concentration, while antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were changed in the liver and the red and white muscle of fish with cadmium exposure, we can conclude that oxygen free radicals are produced as a mediator of cadmium toxicity. Resistance development is related with increased activities of antioxidant enzymes, which were important in the protection against cadmium damage, inhibiting lipoperoxide formation.

Toxicity of ad lib. overfeeding: effects on cardiac tissue.

The aim of the present study was to determine the effects of ad lib. overfeeding and of dietary restriction (DR) on oxidative stress in cardiac tissue. Lipoperoxide concentrations were decreased and antioxidant enzymes were increased in moderate-DR-fed rats. Severe-DR induced increased lipoperoxide concentrations. Overfeeding increased lipoperoxide levels in cardiac tissue. Total superoxide dismutase (SOD) and Cu-Zn superoxide dismutase (Cu-Zn SOD) activities were decreased in cardiac tissue at 35 days of overfeeding. As no changes in glutathione peroxidase (GSH-Px) were observed in overfed rats, while SOD and Cu-Zn SOD activities were decreased in these animals, it is assumed that superoxide anion is an important intermediate in the toxicity of ad lib. overfeeding. Overfeeding induced alterations in markers of oxidative stress in cardiac tissue.

Risk assessment of cadmium toxicity on hepatic and renal tissues of rats.

Pollution and industrial practices result in concentrations of metals and other environmental agents that are related to environmental toxicity. A rat bioassay was utilized for the identification of toxic effects of cadmium intake. This demonstrated increased total urinary proteins and increased kidney weights in rats exposed to CdCl2 for 7 days, in drinking water (100 mg/L). Serum creatinine, total and direct bilirubin concentrations and alanine transaminase activity were increased in Cd-exposed rats, indicating renal and hepatic toxicity. It was also observed that lipoperoxide concentrations were increased, while Cu-Zn superoxide dismutase activity was decreased in rats treated with cadmium. This indicated that the renal and hepatic toxicity induced by cadmium involved superoxide radicals.

Toxicity of chronic ethanol ingestion and superoxide radical formation on seminal vesicle of rats.

The toxic effects of chronic ethanol ingestion were evaluated in male adult rats for 300 days. The animals were divided into three groups: the controls received only tap water as liquid diet; the chronic ethanol ingestion group received only ethanol solution (30%) in semivoluntary research; and the withdrawal group received the same treatment as chronic ethanol-treated rats until 240 days, after which they reverted to drinking water. Chronic ethanol ingestion induced increased lipoperoxide levels and acid phosphatase activities in seminal vesicles. Cu-Zn superoxide dismutase (SOD) decreased from its basal level 70.8 +/- 3.5 to 50.4 +/- 1.6 U/mg protein at 60 days of chronic ethanol ingestion. As changes in GSH-PX activity were observed in rats after chronic ethanol ingestion, while SOD activities were decreased in these animals, it is assumed that superoxide anion elicits lipoperoxide formation and induces cell damage before being converted to hydrogen peroxide by SOD. Ethanol withdrawal induced increased SOD activity and reduced seminal vesicle damage, indicating that the toxic effects were reversible, since increased SOD activity was adequate to scavenge superoxide radical formation. Superoxide radical is an important intermediate in the toxicity of chronic ethanol ingestion.

Superoxide radical and toxicity of environmental nickel exposure.

Three nickel compounds were tested for pancreatic, hepatic and osteogenic damage in rats by a single i.m. injection Ni++ (7 mg kg-1). The nickel induced biochemical alterations included significantly increased levels of serum alkaline phosphatase in rats with NiS (75%) and NiO (50%). Amylase and aspartate transaminase were also increased, and lipoperoxide was increased in rats with NiO (5.6-fold) and NiS (3.4-fold). No serum changes were observed with NiCl2. Daily injection of Cu-Zn superoxide dismutase (SOD) conjugated with polyethylene glycol prevented the serum level changes, indicating that superoxide radical is an important intermediate in toxicity of nickel insoluble compounds.

Increased oxygen radical and high-dietary-carbohydrate pancreatic damage.

These data suggest that an improved understanding of the relationship between high dietary carbohydrate and the rate of lipid peroxidation may give some insight into possible treatment modalities for pancreatic damages and may shed light on molecular mechanisms underlying certain pathological processes. High dietary carbohydrate lesions are age related and induced alterations on ceruloplasmin, phospholipids, total proteins, copper and zinc serum levels. Significantly increased serum and pancreatic amylase, and lipoperoxide determinations were observed in 20 month old rats. Cu-Zn superoxide dismutase was decreased in these animals. Daily injection of Cu-Zn superoxide dismutase conjugated with polyethylene glycol (SOD-PEG) prevented the serum and pancreatic changes, indicating that superoxide radical is an important intermediate to high dietary carbohydrate lesion.

Protective effect of nickel chloride on superoxide damage: enhancement of CuZn superoxide dismutase affinity to the oxygen free radical.

The effect of nickel from soluble NiCl2 on Cu-Zn superoxide dismutase (SOD) activity, as well as on rate of nitro blue tetrazolium reduction, was studied in vitro since lipid peroxidation has been implicated in cell damage by nickel insoluble compounds, whose toxicity and carcinogenicity are well established. The physical and chemical nature of nickel compounds is one of the key determinations of its toxicity. Soluble nickel freely enter cells, but is just as readily excreted reducing the opportunity for production of lipid damage. Nickel from NiCl2 strongly activated SOD activity. In vitro addition of nickel chloride to a crude lung preparation altered the KM for SOD without changing the Vmax. Nickel chloride produced increased enzyme affinity to the substrate, because decreased (O2-) concentration that yields half-maximal velocity. The combination of nickel and SOD may contribute to stabilization of the particular conformation of SOD responsible for maximal catalytically activity.

High dietary carbohydrate and pancreatic lesion.

The ability of high dietary carbohydrate to induce acute pancreatitis was investigated in groups of 16, 21-day and 15-month old rats fed different carbohydrate diets for 30 days. Significantly increased levels of serum amylase (2-fold), phospholipids (50%), phosphorus (2-fold), and lipoperoxides (8-fold) were observed in 15-month old rats fed a high-carbohydrate diet, compared to rats fed a diet with normal carbohydrate levels, indicating peroxidation of membrane lipids which caused final cell death and pancreatic lesion. Serum Cu-Zn superoxide dismutase activity was not altered. Daily administration of bovine Cu-Zn superoxide dismutase conjugated with polyethylene glycol prevented the serum level alterations and pancreatic lesions, indicating that the superoxide radical has a role in dietary carbohydrate-induced acute pancreatitis. No biochemical changes were observed in rats in which treatment was initiated on the 21st day of life indicating that this is an age-related lesion.

High dietary carbohydrate and pancreatic lesion

The ability of high dietary carbohydrate to induce acute pancreatitis was investigated in groups of 16, 21-day and 15-month old rats fed different carbohydrate diets for 30 days. Significantly increased levels of serum amylase (2-fold), phospholipids (50 per cent ), phosphorus (2-fold), and lipoperoxides (8-fold) were observed in 15-month old rats fed a high-carbohydrate diet, compared to rats fed a diet with normal carbohydrate levels, indicating peroxidation of membrane lipids which caused final cell death and pancreatic lesion. Serum Cu-Zn superoxide dismutase activity was not altered. Daily administration of bovine Cu-Zn superoxide dismutase conjugated with polyethylene glycol prevented the serum level alterations and pancreatic lesions, indicating that the superoxide radical has a role in dietary carbohydrate-induced acute pancreatitis. No biochemical changes were observed in rats in which treatment was initiated on the 21st day of life indicating that this is an age-related lesion

Intratracheal injection of nickel chloride and copper-zinc superoxide dismutase activity in lung of rats.

Superoxide radical (O2-) is a free radical that may be involved in various toxic processes. Cu--Zn superoxide dismutase catalyses the dismutation of the superoxide free radical and protects cells from oxidative damage, and it has been used clinically. The concentration of Ni2+ and Cu--Zn superoxide dismutase activity were measured in lungs of rats at time intervals of 5, 12, 19, 26, 33, and 40 days following an intratracheal injection of 127 nmol of NiCl2. Nickel chloride increased nickel content and resulted in a significant increase of Cu--Zn superoxide dismutase activity in lungs. This elevation of Cu--Zn superoxide dismutase activity was highest on the 12th day (approximately threefold) and is at levels comparable to controls rats on day 40 onwards. Since Cu--Zn superoxide dismutase activity was increased in lung throughout our experimental period without corresponding increases of Cu2+ and Zn2+, we speculate that the elevation of Cu--Zn superoxide dismutase activity might be due to an increased half-life of the enzyme, induced by nickel.

Pancreas damage and intratracheal NiCl2 administration. Effects of nickel chloride.

Changes in activities of Cu-Zn superoxide dismutase (SOD- E.C.1.15.1.1.) and lactate dehydrogenase (LDH- E.C.1.1.1.27.) and levels of copper, total protein, triglycerides, phospholipids and total lipids were investigated in pancreas of rats after intratracheal administration of NiCl2 (8.4 mumol/kg). Nickel chloride induced increased SOD activity in pancreas and erythrocytes. This elevation was related to increased copper and decreased phospholipid content in pancreas of these animals. In conclusion, the ability of an animal to tolerate nickel chloride induced damage was governed by a delicate balance between the generation of cytotoxic agents and the various pancreas defense capabilities.

Nickel chloride effects on erythrocyte generation of superoxide radical.

The superoxide anion (O2-) is an extremely potent free radical which is produced during the metabolism of aerobic living cells. (O2-) may be involved in lipid peroxidation reactions which occur in a variety of systems. Cu-Zn superoxide dismutase, a metalloprotein, catalyzes the dismutation of the superoxide free radical and protects cells against superoxide damage. The ability of NiCl2 to prevent lysis of erythrocytes was tested in rats. NiCl2 administered by intratracheal route prevented hemolysis and decreased total lipids, phospholipids and bilirubin in serum. The protective effect of NiCl2 was linked to an increase in the erythrocyte activity of superoxide dismutase.

Nickel chloride effects on erythrocyte generation of superoxide radical

The superoxide anion (O2) is an extremely potent free radical which is produced during the metabolism of aerobic linving cells. (O2) may be involved in lipid peroxidation reactions which occur in a variety of systems. Cu-Zn speroxide dimutase, a metalloprotein, catalyzes the dismutation of the superoxide free radical and protects cells aginst superoxide damage. The ability of NiCl2 to prevent lysis of erythrocytes was tested in rats. NiCl2 administered by intratracheal rouyte prevented hemolysis and decreased total lipids, phospholipids and bilirubin in serum. The protective effect of NiCl2 was linked to an increase in the erytrocyte activity of superoxide dismutase

Influence of nickel chloride on iron-deficiency in rats.

The present study was designed to investigate the effects of nickel chloride on dietary iron deficiency in rats. The degree of iron deficiency was relatively moderate, but a more generalized anemia occurred in iron deficiency, in absence of nickel chloride. Moderate iron deficiency anemia induced increased lactate-dehydrogenase activity of serum and bone marrow, perhaps related to the decreased production of energy by oxidative means. Nickel chloride, perhaps for its ability to change iron absorption, for the maintenance of bone marrow metabolism and for to increase ceruloplasmin activity, inhibited the alteration on hemoglobin synthesis. Furthermore, nickel chloride possibly for its action on copper content and Cu-Zn superoxide-dismutase activity, inhibits the shortening of the red cell life span, caused by superoxide radicals.

Effect of nickel chloride on streptozotocin-induced diabetes in rats.

The potential of nickel chloride to prevent streptozotocin-induced hyperglycemia was tested in rats in vivo. To induce diabetes, streptozotocin (100 mg/kg body weight) was injected as a single dose. Streptozotocin treatment resulted in a significant decrease in plasma insulin and ceruloplasmin, and pancreatic Cu, protein, and Cu-Zn superoxide dismutase activity. In rats treated with nickel chloride (10 mg/kg body weight) and streptozotocin, these values were comparable with those observed in control rats. The results indicate that nickel chloride injected before streptozotocin prevented streptozotocin-induced hyperglycemia, and suggest that the protective effect was related to Cu-Zn superoxide dismutase activity, mediated by copper.

Nickel chloride protection against alloxan- and streptozotocin-induced diabetes.

The ability of NiCl2 to prevent alloxan- and streptozotocin-induced hyperglycemia was tested in rats. NiCl2 injected before alloxan and streptozotocin prevented the hyperglycemic response to the drugs. The protective effect of NiCl2 was linked to an increase in the specific activity of Cu-Zn superoxide dismutase (SOD). The effect of NiCl2 on SOD activity might be related to the effect of nickel on calcium, copper and zinc concentrations.