Virginia Berlanga Campos Junqueira

Oxidative stress in gill, erythrocytes, liver and kidney of Nile tilapia (Oreochromis niloticus) from a polluted site

Abstract A comparison between some pro- and antioxidant parameters in erythrocyte, gill, liver and kidney of Nile tilapia, O. niloticus from a fish farm (Control group) and from a polluted site in the Billings Reservoir (Reservoir group) was done. No hematological alterations were observed in blood of Billings fish. The erythrocyte oxidative stress was characterized by increased oxygen uptake and decreased induction time (induced by t-butyl hydroperoxide, t-BHP) evidencing a higher susceptibility to oxidative damage. Moreover, beside the augmented erythrocyte superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PDH) and glutathione peroxidase activities, a decrease in both catalase (CAT) activity and total glutathione content (GSH), in erythrocytes of Reservoir fish was observed. The higher cytochrome b5 levels observed in the gill microsomal fraction is likely to be the cause of the enhanced oxyradical production. This fact, associated with the diminished CAT and G6PDH activities, accounts for a gill oxidative stress of Reservoir fish. Except for the NADPH-cytochrome P-450 (c) reductase activity, the other liver pro-oxidant parameters were greatly increased in the Reservoir fish. These results together with the increase in SOD activity and decrease in CAT, glutathione reductase (GR) and G6PDH activities indicated a liver oxidative stress status. The observed increases in kidney NADH cytochrome c reductase and in both cytochromes P-450 and b5 contents were not reflected in enhanced oxyradical production, suggesting a well coupled P-450 catalytic cycle in this tissue. However, the antioxidant enzymes had a similar pattern in liver. The decrease in GSH observed in kidney is probably associated with conjugation reactions for subsequent excretion. All these results furnish useful data for future investigations of polluted aquatic sites in order to provide a data base relating the presence of pollutants to biological effects at a molecular level.

Lindane-induced liver oxidative stress.

The development of an oxidative stress condition in the liver by lindane intoxication is discussed as a possible hepatotoxic mechanism of the insecticide. Lindane is metabolized by liver microsomal enzymes to a variety of metabolites, which are susceptible of conjugation for proper elimination. In addition, the interaction of lindane with the liver tissue results in the induction of the microsomal cytochrome P-450 system, together with enhanced rates of superoxide radical generation and a significant increase in indicators of lipid peroxidation. Concomitantly, lindane intoxication induces a derangement of some antioxidant mechanisms of the liver cell, including decreased superoxide dismutase and catalase activities and alterations in reduced glutathione content leading to depressed GSH/GSSG ratios. The time course study of the changes in hepatic lipid peroxidation and antioxidant parameters are closely interrelated and coincide with the onset and progression of morphological lesions.

Dose-dependent study of the effects of acute lindane administration on rat liver superoxide anion production, antiooidant enzyme activities and lipid peroxidation

The administration of single i.p. doses of lindane (20, 40, 60 and 80 mg/kg) to rats produced a progressive increase in the liver microsomal content of cytochrome P-450 and in the rate of superoxide anion generation, as measured by adrenochrome formation. A dose-dependent increase in lipid peroxidation of liver homogenates, assessed by measuring thiobarbituric acid reactants, was also found. Lindane treatment did not alter the activity of liver glucose-6-phosphate dehydrogenase, glutathione reductase or glutathione peroxidase, while that of superoxide dismutase and catalase was significantly reduced. These changes were accompanied by a progressive liver steatosis. The collected metabolic data were interpreted in terms of a causal relationship between an increase in superoxide radical generation, secondary to cytochrome P-450 induction and a resulting increase in lipid peroxidation. The decrease in superoxide dismutase and catalase activities is likely to contribute to the increased levels of lipid peroxidation in view of their antioxidant properties.

Lindane-Induced Oxidative Stress. I. Time Course of Changes in Hepatic Microsomal Parameters, Antioxidant Enzymes, Lipid Peroxidative Indices and Morphological Characteristics

1. Lindane (60 mg/kg) administered orally to rats increased liver cytochrome P-450 content and superoxide radical (O2-.) generation 24 h after treatment, while formation of thiobarbituric acid reactants and NADPH/ADP-supported microsomal chemiluminescence were significantly increased 4 h after treatment. 2. Hepatic superoxide dismutase (SOD) and catalase decreased 6 h after lindane treatment and SOD/O2-. ratio progressively decreased during 4 to 24 h after lindane treatment. 3. Morphological evidence of hepatic cell injury after lindane treatment was seen at all times studied, and appeared to increase with time. 4. Lindane administration results in time-dependent oxidative stress in liver which involves an early component (4-6 h) related to the reductive metabolism of lindane, and a late component (24 h) associated with the induction of cytochrome P-450; the biochemical changes correlated with the observed morphological lesions.

Desigualdades no acesso e utilização dos serviços de saúde na Região Metropolitana de São Paulo

This paper presents case study findings in five municipalities in the Sao Paulo Metropolitan Region. Inequalities in access to health care services and their utilization were described through advanced tabulation data from the 1998 SEADE Life Conditions Survey. The variables analyzed were: owning or not owning private health care insurance, income and age brackets. The health care service attributes studied were: health care services coverage by a health insurance plan, health services demands and average waiting time to receive health care. Compared with other studies, using the 1998 IBGE PNAD, the results allowed us to confirm interregional imbalances which can only be detected in shorter special scale studies: the municipalities. Despite showing the high private health insurances coverage the Sao Paulo Metropolitan Region has a great inner heterogeneity. The inequalities in private health care insurance, access, waiting time, and type of insurance coverage were observed through income quintiles and age classes analyses. Findings suggest that an expansion of the States regulation capacity is necessary in order to empower the Brazilian Health Care System principles of universality and equity to be qualified to offer Brazilians the right to access health care services.

Absence of oxidative stress following paradoxical sleep deprivation in rats

Paradoxical sleep deprivation was performed on rats using platform technique to investigate the oxidative process associated with it. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total glutathione (GSH) and malondialdehyde production were measured in brain of rats under control conditions (C) and those on single large platforms (SLP), multiple large platforms (MLP), single small platforms (SSP) and multiple small platforms (MSP) groups. SOD, CAT and GPx brain activity and malondialdehyde production were not modified by any of the procedures. Brain GSH, however, was significantly reduced in both SSP and SLP groups. These results suggest that paradoxical sleep deprivation per se is not associated with oxidative damage. The observed alterations could be attributed to factors such as immobilization and social isolation present in the single platform techniques.

FUNCTIONAL ACTIVITY OF BLOOD POLYMORPHONUCLEAR LEUKOCYTES AS AN OXIDATIVE STRESS BIOMARKER IN HUMAN SUBJECTS

In the present work, we studied the role of polymorphonuclear leukocytes (PMN) in aged individuals and coronary heart disease (CHD)-bearing patients, two physiopathological processes associated with overproduction of reactive oxygen species (ROS). The effects of antioxidant supplementation on the functional activity of PMN from CHD patients were also determined. The function of PMNs was evaluated by measuring of phagocytosis, killing activity, and ROS production. Luminol amplified chemiluminescence (CL) was used to estimate ROS production by stimulated PMNs. Total cholesterol and the LDL-cholesterol fraction from CHD patients were found to be higher than those recommended, returning to normal levels after antioxidant therapy. PMN CL of CHD patients was found to be higher than the associated control groups. Antioxidant therapy administrated to CHD patients lead to an increase in the killing activity accompanied by a decrease in PMN CL of these subjects. The study also showed that killing activity of PMN from human subjects over 60 years was significantly lower than the activity measured in younger subjects. PMN CL produced after stimulation was found to be positively correlated with the increasing age of human subjects (r=.946, p < .01).

Regression of morphological alterations and oxidative stress-related parameters after acute lindane-induced hepatotoxicity in rats

Changes in rat liver oxidative stress-related parameters, morphological alterations, as well as circulating and tissue levels of lindane were studied 1-7 days after the administration of a single dose of 60 mg of lindane/kg. One day after lindane treatment, a significant enhancement in the oxidative stress status of the liver was observed, characterized by an increase in thiobarbituric acid reactants production and in the microsomal generation of superoxide radical (O.-2) coupled to cytochrome P450 induction, and a decrement in the activity of superoxide dismutase (SOD) and catalase. Consequently, the O.-2 production/SOD activity ratio was enhanced two-fold. In this condition, light microscopy studies revealed the incidence of liver lesions in periportal areas, together with significant changes at the mitochondrial level observed by electron microscopy, which coincide with the maximal levels of lindane in the liver, adipose tissue, plasma and whole blood. Changes in oxidative stress-related parameters observed after 1 day of lindane treatment regressed to normal from the third day and thereafter, together with the decrement in circulating and tissue levels of the insecticide. It is concluded that morphological and oxidative stress-related changes induced in the liver by acute lindane intoxication are readily reversible, depend on the hepatic content of the insecticide, and seem to be conditioned by the changes in O.-2 generation.

Lindane-Induced Oxidative Stress. II. Time Course of Changes in Hepatic Glutathione Status

1. Four hours after treatment of rats with lindane (60 mg/kg), hepatic GSH content was decreased (22%) and GSSG was increased (20%), while biliary concentration and excretion of both GSH and GSSG and bile flow were diminished. These changes coincide with the onset of hepatic lipid peroxidation. 2. The changes induced by lindane at 4 h disappeared at 6 h after treatment, but liver GSSG content (91%), biliary GSSG excretion (133%) and bile flow (42%) were enhanced at 24 h. 3. The data indicate that lindane treatment elicits marked changes in hepatocyte glutathione status, with a decrease in the GSH/GSSG ratio at early (2-4 h) and late (24 h) periods of poisoning.

High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients

Abnormal riboflavin status in the absence of a dietary deficiency was detected in 31 consecutive outpatients with Parkinsons disease (PD), while the classical determinants of homocysteine levels (B6, folic acid, and B12) were usually within normal limits. In contrast, only 3 of 10 consecutive outpatients with dementia without previous stroke had abnormal riboflavin status. The data for 12 patients who did not complete 6 months of therapy or did not comply with the proposed treatment paradigm were excluded from analysis. Nineteen PD patients (8 males and 11 females, mean age +/- SD = 66.2+/-8.6 years; 3, 3, 2, 5, and 6 patients in Hoehn and Yahr stages I to V) received riboflavin orally (30 mg every 8 h) plus their usual symptomatic medications and all red meat was eliminated from their diet. After 1 month the riboflavin status of the patients was normalized from 106.4+/-34.9 to 179.2+/-23 ng/ml (N = 9). Motor capacity was measured by a modification of the scoring system of Hoehn and Yahr, which reports motor capacity as percent. All 19 patients who completed 6 months of treatment showed improved motor capacity during the first three months and most reached a plateau while 5/19 continued to improve in the 3- to 6-month interval. Their average motor capacity increased from 44 to 71% after 6 months, increasing significantly every month compared with their own pretreatment status (P < 0.001, Wilcoxon signed rank test). Discontinuation of riboflavin for several days did not impair motor capacity and yellowish urine was the only side effect observed. The data show that the proposed treatment improves the clinical condition of PD patients. Riboflavin-sensitive mechanisms involved in PD may include glutathione depletion, cumulative mitochondrial DNA mutations, disturbed mitochondrial protein complexes, and abnormal iron metabolism. More studies are required to identify the mechanisms involved.