Effects of Copper and/or Cholesterol Overload on Mitochondrial Function in a Rat Model of Incipient Neurodegeneration.

Copper (Cu) and cholesterol (Cho) are both associated with neurodegenerative illnesses in humans and animals models. We studied the effect in Wistar rats of oral supplementation with trace amounts of Cu (3 ppm) and/or Cho (2%) in drinking water for 2 months. Increased amounts of nonceruloplasmin-bound Cu were observed in plasma and brain hippocampus together with a higher concentration of ceruloplasmin in plasma, cortex, and hippocampus.

Role of copper and cholesterol association in the neurodegenerative process.

Age is one of the main factors involved in the development of neurological illnesses, in particular, Alzheimer, and it is widely held that the rapid aging of the world population is accompanied by a rise in the prevalence and incidence of Alzheimer disease. However, evidence from recent decades indicates that Cu and Cho overload are emerging causative factors in neurodegeneration, a hypothesis that has been partially investigated in experimental models. The link between these two variables and the onset of Alzheimer disease has opened up interesting new possibilities requiring more in-depth analysis.

Pesticide-induced decrease in rat testicular steroidogenesis is differentially prevented by lipoate and tocopherol.

We have previously demonstrated that the sub-chronic administration of low doses of Toc or α-Toc, glyphosate and zineb to rats (i.p. 1/250 LD50, three times a week for 5 weeks) provoked severe oxidative stress (OS) in testicles.

Dietary lipid-induced changes in enzymes of hepatic lipid metabolism.

Objective: To investigate the effect of different dietary oils on the main hepatic enzymes involved in metabolism and their impact on oxidative stress status.

Methods: Twenty-four male Wistar rats were fed for 60 d on the same basal diet plus different lipid sources from commercial oils: soybean (S), olive (O), coconut (C), and grape seed (G). After sacrifice, the liver lipid fatty acid composition, enzymatic and non-enzymatic components of the antioxidant defense system, and the activity of enzymes involved in lipid metabolism were determined.

The oxidative damage and inflammation caused by pesticides are reverted by lipoic acid in rat brain.

We have previously demonstrated that the administration of low doses of dimethoate, glyphosate and zineb to rats (i.p. 1/250 LD50, three times a week for 5weeks) provokes severe oxidative stress (OS) in specific brain regions: substantia nigra, cortex and hippocampus.

Exogenous arachidonate restores the dimethoate-induced inhibition of steroidogenesis in rat interstitial cells.

The present work studies the potential restorative effect of polyunsaturated fatty acids (PUFA, 5 μM/24 h) on the dimethoate (DMT)-induced inhibition of testosterone biosynthesis in Leydig cells isolated from rat testes. Various fatty acids (FA) from the n-6 (18:2, 20:3, 20:4, 22:4 and 22:5) and n-3 (18.3, 20:5, 22:5, 22:6) series were assayed in Leydig cells, alone (as delipidated BSA complexes) and in combination with DMT (1 ppm).

Cytotoxic effects of copper overload on human-derived lung and liver cells in culture.

Background: Copper (Cu) is an essential trace metal used as a catalytic cofactor for many enzymes. However, it can have nocive effects when it participates in the Fenton reaction, producing reactive oxygen species (ROS). Excess Cu is present in the plasma of patients with diseases in which cell survival is crucial.

Peripheral markers in neurodegenerative patients and their first-degree relatives.

We have determined various biomarkers in the peripheral blood of Alzheimer, Parkinson and vascular dementia patients by comparing the samples with those of first-degree relatives and control subjects. Our results, together with correlation studies using data from the Mini-Mental State Examination (MMSE), suggest that the clinical evaluation of the nitrite (NOx) concentration in Alzheimer patients should be complemented by assays of protein carbonyls (PCs) levels, the ratio of reduced to oxidized glutathione (GSH/GSSG) in plasma, PCs in erythrocytes and PCs and calcium content in leukocytes. For Parkinson patients it would be useful to determine NOx, thiobarbituric-acid reactive substances (TBARS) and PCs in erythrocytes, and NOx and TBARS en leukocytes.

Occupational exposure characterization in professional sprayers: clinical utility of oxidative stress biomarkers.

The impact of involuntary exposure to pesticides was studied in a group of professional sprayers (S) (25±5 years old) exposed to various agrochemicals for about 10 years. The results were compared with a group of non exposed people (C). S group showed hematological, renal, pancreatic and hepatic biomarkers within the reference values established for the general population, including cholinesterase activity.

Clinical parameters and biomarkers of oxidative stress in agricultural workers who applied copper-based pesticides.

Copper based-pesticides are widely used in agricultural practice throughout the world. We studied the (i) concentration of Cu and proteins involved in Cu homeostasis, (ii) plasma redox status, and (iii) biomarkers of exposure in Cu-based pesticide applicators in order to compare them with clinical biochemical tests. Thirty-one professional applicators and 32 control subjects were recruited.

Carnosine and neocuproine as neutralizing agents for copper overload-induced damages in cultured human cells.

Copper is dangerous when it is present in excess, mainly because it can participate in the Fenton reaction, which produces radical species. As a consequence of copper pollution, people are involuntarily exposed to a copper overload under sub-clinical and sub-symptomatological conditions, which may be very difficult to detect. Thus, we investigated (i) the possible use of the chelator molecules carnosine and neocuproine to prevent the Cu overload-induced damage on cellular lipids and proteins, as tested in human cell culture systems, and (ii) the differential response of these two chelating agents in relation to their protective action, and the type of copper ion involved in the process, by using two types of human cultured cells (HepG2 and A-549).

Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives.

The concentration of plasma copper, ceruloplasmin (CRP), non-ceruloplasmin-bound Cu (NCBC), and metallothioneins (MTs) were studied as putative biomarkers for neurodegenerative diseases in patients and in their first-degree relatives. We found increased levels of Cu in the plasma of Alzheimer's disease (AD), Parkinson's disease (PD), and vascular dementia (VD) patients, and the increase observed in VD group was linked to the evolution of the disease. CRP was also elevated in response to the inflammatory component of the diseases, however, a correlation with illness progression was only observed in VD patients.

Alterations in copper homeostasis and oxidative stress biomarkers in women using the intrauterine device TCu380A.

Copper ions participate in the Häber-Weiss reaction to produce ROS, which can be toxic when in excess. The purpose of this study was to measure the copper concentration (Cu) in the plasma of women using Cu-IUDs and determine (i) the effect of Cu on oxidative stress biomarkers, (ii) the levels of copper transport proteins in the plasma and (iii) the status of some liver damage markers in relation to the length of the intrauterine device use. Thirty-nine controls and 35 T380-IUD users were recruited.

Antioxidant defense system in rats simultaneously intoxicated with agrochemicals.

The effect of dimethoate, zineb and glyphosate administered alone or in combination on liver, kidney, brain and plasma antioxidant defense system was investigated. Lipid peroxidation, and RNS production were increased in all tissues studied, especially in those groups that received a combination of drugs. Intoxicated rats exhibited lower antioxidant ability, higher oxidized protein and glutathione levels in plasma with a decreased concentration of α-tocopherol in brain and liver, between 30% and 60% of control.

[Fatty acid composition of human milk from mothers of preterm and full-term infants].

Introduction: Human milk is an essential food for newborns and affects life in the long or short terms. Its composition is modified by nutritional status and maternal diet as well as by gestational age of the newborn. It provides human milk-fed infants with the medium-chain fatty acids which are a source of energy, and essential fatty acids and their metabolic derivatives which have been involved in the neural maturation.

Alteration and recovery of the antioxidant system induced by sub-chronic exposure to microcystin-LR in mice: its relation to liver lipid composition.

The effects of MC-LR on antioxidant system in liver and kidney and its effects on hepatic lipid composition after prolonged exposure to sublethal doses of microcystins (MCs) were studied in mice. Mice were treated i.p.

Involvement of lipids in dimethoate-induced inhibition of testosterone biosynthesis in rat interstitial cells.

The mechanism involved in the inhibition of testosterone (Te) biosynthesis after a sub-chronic exposure to low doses of dimethoate (D) was studied in rat interstitial cells (IC). Expression of COX-2 in IC isolated from D-treated rats increased by 44% over C data, while transcription of StAR decreased by approx. 50% and the expression of this protein was diminished by approximately 40%.

Effect of pesticides on cell survival in liver and brain rat tissues.

Pesticides are the main environmental factor associated with the etiology of human neurodegenerative disorders such as Parkinson's disease. Our laboratory has previously demonstrated that the treatment of rats with low doses of dimethoate, zineb or glyphosate alone or in combination induces oxidative stress (OS) in liver and brain. The aim of the present work was to investigate if the pesticide-induced OS was able to affect brain and liver cell survival.

Microtubule depolymerization modifies the incorporation of fatty acids into glycerolipids.

Background: The influence of cytoskeletal integrity on fatty-acid (FA) metabolism is an almost unexplored field of biochemical research. This study therefore investigated the influence of cytoskeletal integrity on the incorporation of palmitate and eicosa-8,11,14-trienoate into glycerolipids of Hep G2 human hepatoma cells.

Material/methods: Attached cultures and suspended cells were exposed to colchicine (COL, 10 microM) or dihydrocytochalasin B (DHCB, 20 microM) and supplemented with [14C]FAs bound to delipidated BSA or [14C]glycerol during 0-300 min of incubation.

Influence of commercial dietary oils on lipid composition and testosterone production in interstitial cells isolated from rat testis.

The aim of this study was to examine the influence of dietary fat on lipid composition, as well as on the steroidogenic function of interstitial cells isolated from Wistar rats that had been fed semi-synthetic diets containing four different commercial oils (S soybean, O olive, C coconut, and G grape seed). Steroidogenic enzyme activities, lipid composition, and androgen production were measured in testicular interstitial cells. Lipid analysis included measurement of the contents of major lipid subclasses (neutral lipids, polar lipids, free and esterified cholesterol), as well as principal polar and neutral lipid fatty acyl compositions.

Dietary lipids modify redox homeostasis and steroidogenic status in rat testis.

Objective: The present study explored the effect of dietary oils on lipid composition, antioxidant status, and the activity of the main steroidogenic enzymes in the testis.

Methods: Forty Wistar rats were randomly assigned to one of four groups (n = 10) fed for 60 d on the same basal diet plus different lipid sources as commercial oils: soybean, olive, coconut, or grapeseed. After sacrifice, testicular lipids and fatty acid composition, free radical biomarkers, antioxidant levels, hormones, and steroidogenic enzymes were determined.

Hepatic recovery after damage produced by sub-chronic intoxication with the cyanotoxin microcystin LR.

The effect of sub-chronic exposure of intraperitoneal (i.p.) injections of microcystin-LR (MC-LR) on microscopic tissue architecture, hepatic function and lipid peroxidation has been studied in liver and kidney of mice.

A reliable biomarker derived from plasmalogens to evaluate malignancy and metastatic capacity of human cancers.

Antigen tumor markers employed in monitoring therapeutical approaches are limited by their specificity (Sp) and sensitivity (Se). The aim of this study was to investigate the suitability of a lipid tumor marker derived from ether-linked phospholipids and to compare it with others usually assayed in clinical practice. Complex lipids from normal and pathological breast, lung, and prostate tissue were isolated and analyzed by TLC and c-GLC methods.

Oxidative stress biomarkers and hormonal profile in human patients undergoing varicocelectomy.

The aetiology of varicocele is multifactorial although hormonal imbalance and oxidative stress play a key role in the progression of illness. No conclusive evidence has been presented previously, describing the changes in these two factors and the evolution of patients after varicocelectomy. Semen characteristics and hormonal profile were analysed in 36 infertile men with unilateral left varicocele and 33 age-paired controls (proved to be fertile men), after careful inclusion/exclusion selection criteria.

Lipid metabolism in rats is modified by nitric oxide availability through a Ca++-dependent mechanism.

We studied lipid metabolism and the antioxidant defense system in plasma and liver of rats fed diets supplemented with L(omega)-nitro-L-arginine methyl ester (L-NAME), isosorbide dinitrate (DIS), L-arginine (Arg), or the associations of these drugs. Liver hydroperoxide and thiobarbituric-acid-reactive substance (TBARS) levels were decreased by Arg and increased by L-NAME or DIS treatments. Oxidized glutathione and conjugated dienes were increased by DIS.