Effects of N-acetylcysteine on alcohol abstinence and alcohol-induced adverse effects in rats

Alcoholism is rampant in modern society and some antioxidant compound could perhaps be useful to reduce the damage done by alcohol consumption and abstinence. The present study was undertaken to investigate the association of N-acetylcysteine (NAC) intake, alcoholism, and alcohol abstinence on lipid profile, in vivo low-density lipoprotein (LDL) oxidation, oxidative stress, and antioxidant status in serum and liver of rats. Initially, male Wistar 30 rats were divided into two groups: (C, N = 6) given standard chow and water; (E, N = 24) receiving standard chow and aqueous ethanol solution in semi-voluntary research. After 30 days of ethanol exposure, (E) group was divided into four subgroups (N = 6/group): (E-E) continued drinking 30% ethanol solution; (E-NAC) drinking ethanol solution containing 2 g/L NAC (AB) changed ethanol solution to water; (AB-NAC) changed ethanol to aqueous solution 2 g/L NAC. After 15 days of the E-group division, E-E rats had higher serum alanine transaminase, lower body weight, and surface area, despite higher energy intake than C. E-E rats had also lower feed efficiency, dyslipidemia with enhanced triacyl glycerol, very low-density lipoprotein (VLDL), lipid hydroperoxide (LH) and in vivo oxidized-LDL (ox-LDL). AB, E-NAC, and AB-NAC rats ameliorated serum oxidative stress markers and normalized serum lipids. E-E rats had higher hepatic LH and lower reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio than C, indicating hepatic oxidative stress. AB and E-NAC rats normalized hepatic LH, GSSG, and the GSH/GSSG ratio, compared to E-E. AB-NAC rats had the lowest serum ox-LDL, hepatic LH levels, and the highest GSH reductase activity in hepatic tissue. In conclusion, the present study brought new insights into alcohol consumption, because ethanol exposure enhanced serum in vivo ox-LDL, as well as serum and hepatic oxidative stress. N-acetylcysteine offers promising therapeutic value to inhibit ethanol-induced adverse effects. Ethanol withdrawal had beneficial effects on serum lipids, but was more effective when coupled with NAC supplementation. Ethanol abstinence and NAC intake interact synergistically, improving serum lipids and hepatic antioxidant defenses. (c) 2009 Elsevier B.V. All rights reserved.

The effect of gastric dilatation in rats submitted to gasified water ingestion under the hepatic metabolic function

INTRODUÇÃO: O excesso de peso na população aumentou de forma significante nas últimas décadas e as bebidas gasosas tornaram-se um fator ambiental importante no comportamento alimentar das pessoas, sendo os EUA, México e Brasil, nesta ordem, os três maiores paises produtores e consumidores de refrigerantes. OBJETIVO: Investigar os efeitos da dilatação gástrica em ratos submetidos a ingestão de água gaseificada, veículo uniforme para todos os refrigerantes, sobre parâmetros metabólicos da função hepática. MÉTODOS: Foram constituídos dois grupos de 15 ratos acompanhados por 15 semanas. Ao Grupo-I, foram oferecidos 200 g/dia de ração ad libitum e 100 ml de água não gaseificada em 3 períodos diários, ao Grupo-II, foram oferecidos 200 g/dia de ração ad libitum e 100 ml de água gaseificada em 3 períodos diários; em cada grupo,foram calculados a média (x) e o desvio padrão (s); para todos os atributos estudados foi utilizado o método estatístico de teste t pareado, comparando-se GI com GII, testando-se o efeito dos tipos de água. RESULTADOS: Os resultados identificaram que os animais que foram submetidos ao tratamento com água gaseificada (Grupo-II), apresentaram um aumento de transaminase glutâmica pirúvica (TGP) e fosfatase alcalina p<0,01), tendência de aumento da transaminase glutâmica oxalacética (TGO) (0,10>p>0,05) e aumento da área gástrica com alterações morfológicas macroscópicas como o desaparecimento do pregueamento mucoso característico. CONCLUSÃO: A água gaseificada favoreceu o aumento da área gástrica com conseqüente desaparecimento macroscópico do pregueamento mucoso do órgão, que ocasionou alterações metabólicas da função hepática.

Nutritionally induced changes in endosperm of shrunken-1 and brittle-2 maize kernels grown in vitro

Although mineral nutrition affects maize (Zea mays L.) yield by controlling starch deposition in kernels, the mechanisms involved are largely unknown. Our objectives were to examine this relationship by nutritionally and genetically altering starch production in the endosperm. Kernels of W64A and two starch-deficient mutants, shrunken-1 and brittle-2, were grown in vitro with varying supplies of N (0-50 mM) or P (0-6 mM) to produce different degrees of endosperm starch production, and the levels of enzyme activities and metabolites associated with carbohydrate and N metabolism were examined. In vitro grown kernels exhibited the expected starch phenotypes, and a minimum level of media N (25 mM) and P (2 mM) was required for optimal growth. However, increasing the availability of N or P could not overcome the genetically induced decrease in starch deposition of the mutants. Nitrogen deficiency enhanced sugar accumulation, but decreased amino acid levels, soluble protein, enzyme activity, starch synthesis, and endosperm dry weight. Phosphorous deficiency also decreased starch production and endosperm dry weight, but with only a minimal effect on the activities of ADP-glucose pyrophosphorylase and alanine transaminase. Genotypic differences in endosperm starch, and the increases induced by N and P supply, Here closely associated with the level of endosperm N, but not endosperm P. Thus, while both N and P are crucial for optimal yield of maize grain, they appear to act by different means, and with different importance in governing starch deposition in the endosperm.

Toxic effects of alcohol intake on prostate of rats

BACKGROUND. The present report was carried out to determine whether alcohol intake could induce prostate lesions.METHODS. We tested male rats for 300 days. Animals were divided into three groups: controls received only tap water as liquid diet; the chronic alcohol intake group received only ethanol solution in semivoluntary research; and the withdrawal group received the same treatment as chronic alcohol intake until 240 days, after which they reverted to drinking water.RESULTS. Chronic alcohol intake increased lipoperoxide concentrations and acid phosphatase activities. Cu-Zn superoxide dismutase (SOD) was decreased at 60 days, but approached controls values at 300 days following treatment. The serum increased alkaline phosphatase, and alanine transaminase activities reflected the chronic toxic effect of ethanol.CONCLUSIONS. Since SOD activity was unable to scavenge superoxide radical and lipoperoxide formation, we can conclude that superoxide is an important intermediate in prostate damage of chronic alcohol intake. (C) 1997 Wiley-Liss, Inc.

REACTIVE OXYGEN GENERATION BY AZOMETHINE-H - A NEW ANTIMALARIAL DRUG

Superoxide radical (O-2(-)) is a free radical that may be involved in various toxic processes. Cu-Zn superoxide dismutase catalyzes the dismutation of the superoxide free radical and protects cells from oxidative damage. A rat bioassay validated for the identification of the toxic effects of azomethine H revealed increased serum activities of amylase, alanine transaminase, and alkaline phosphatase. The lipoperoxide and bilirubin concentrations were also increased in animals that received azomethine H (1 g/kg) from ascorbic or hydrochloric acid solutions. Azomethine H increased Cu-Zn superoxide dismutase activity. This elevation of Cu-Zn superoxide dismutase activity was highest on the 7th day and was at levels comparable with those of control rats from day 60 onwards. Superoxide is an important intermediate in the action and toxicity of azomethine H.

Differential/combined effect of water contamination with cadmium and nickel on tissues of rats

The contamination of water by metal compounds is a worldwide environmental problem. Concentrations of metals are widely related to biochemical values which are used in disease diagnosis due to environmental toxicity. The acute combined effects of cadmium and nickel on biochemical parameters were determined and compared with those of Cd2+ or Ni2+ alone in rats. Male adult rats were given drinking solutions of CdCl2 [Cd(II) cation, 100 mg/liter] or NiSO4 [Ni(II) cation, 100 mg/liter]. For the combined treatment, the animals (Ni+Cd) received both Ni(II)) cation (100 mg/liter) and Cd(II) cation (100 mg/liter). Nickel treatment induced increased alanine transaminase (ALT) activity and hepatotoxicity, but not renal injury. In contrast, cadmium exposure produced hepatic, renal and myocardial damage, characterized by increased creatinine, total and direct bilirubin concentrations and increased ALT and lactate dehydrogenase (LDH) activities. The combined effect Ni-Cd is less toxic than cadmium alone, suggesting antagonism between these toxicants. The toxicity of nickel and cadmium, alone and in combination, decreased Cu-Zn superoxide dismutase (SOD) activity and increased lipoperoxide formation. (C) 1998 Elsevier B.V. Ltd. All rights reserved.

Impact of an environmentally realistic intake of water contaminants and superoxide formation on tissues of rats

Water contaminants have a high potential risk for the health of populations and for this reason their toxic effects urgently should be established. The present study was carried out to determine whether an environmentally realistic intake of water contaminants can induce tissue lesions, and to clarify the contribution of superoxide radical (O-2(.-)) formation to this effect. Male Wistar rats were given drinking water from the Tiett River (group A) and from the Capivara River (group B). The increased creatinine, glucose, alanine transaminase and amylase levels in serum reflected the toxic effects of river-water contaminants to renal, pancreatic and hepatic tissues of rats. As changes in lipoperoxide were observed in rats after river-water intake while superoxide dismutase activities decreased in these animals, it is assumed that the superoxide anion elicits lipoperoxide formation and induces tissue damage. There is evidence that oxygen tension reflects water pollution, since river-water with a-low oxygen tension induced more elevated toxicity in rat tissues. (C) 1999 Elsevier B.V. Ltd. All rights reserved.

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.

TOXIC EFFECTS OF WATER EUTROPHICATION ON PANCREATIC, HEPATIC AND OSTEOGENIC TISSUES OF RATS

Pollution, industrial solvents, concentrations of metals and other environmental agents are widely related to biochemicals values which are used in disease diagnosis of environmental toxicity. A rat bioassay validated for the identification of toxic effects of eutrophication revealed increased serum activities of amylase, alanine transaminase (BLT) and alkaline phosphatase (ALP) in rats that received algae, filtered water and nickel or cadmium from drinking water. Serum Cu-Zn superoxide dismutase activity decreased from its basal level of 40.8 +/- 2.3 to 26.4 U/mg protein, at 7 days of algae and at 48 hr of nickel and cadmium water ingestion. The observation that lipoperoxide concentration was not altered in rats treated with filtered water, while amylase, ALT and ALP were increased in these rats and in those treated with nickel or cadmium, indicated that pancreatic, hepatic and osteogenic lesions by eutrophication were not related to superoxide radicals, and might be due to a novel toxic environmental agent found in filtered and non-filtered algae water.

Acute, subchronic and chronic 2,4-dichlorophenoxyacetic acid (2,4-D) intoxication in rats

The acute, subchronic and chronic toxicities of 2,4- dichlorophenoxyacetic acid (2,4-D) were studied in rats. Animals were exposed acutely (600 mg/kg), subchronically (200 ppm for 30 d) and chronically (200 ppm for 180 d) to 2,4-D by the oral route. Clinical, laboratory and histopathological methods were used as indicators of toxicity. After acute exposure, the herbicide decreased locomotor activity and induced ataxia, sedation, muscular weakness (mainly of the hind quarters) and gasping for breath; increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), amylase activities and creatinine levels; decreased total protein (TP) and glucose levels; and increased hematocrit values. Subchronic and chronic 2,4-D exposures did not induce overt clinical signs or symptoms of intoxication. However, subchronic herbicide exposure increased AST activity and albumin and hematocrit values, and chronic exposure increased AST, AP and LDH activities, decreased amylase and glucose levels, but did not change hematocrit values. Chromatographic analysis of the serum of chronically exposed rats showed the presence of the herbicide; the amount found (3.76 ± 1.16 mg/ml) suggested the absence of 2,4-D accumulation within the body. Although macroscopic or histopathological lesions were not observed in acutely, subchronically or chronically 2,4-D exposed rats, the laboratory data obtained suggest tissue injuries after dosing, since the results are considered early indicators of primarily hepatic and muscle tissue damage.

Free radical production by azomethine H: Effects on pancreatic and hepatic tissues

The antimalarial properties of azomethine H represent the basis for its use as a chemotherapeutic agent. This work was carried out in order to verify the biological side effects of azomethine H and to clarify the contribution of reactive oxygen species (ROS) in this process. It was shown that azomethine H increased serum activities of amylase, alanine transaminase (ALT) and the TEARS concentrations, in rats. No changes were observed in glutathione peroxidase and catalase activities. The drug-induced tissue damage might be due to superoxide radicals (O-2(.-)), since Cu-Zn superoxide dismutase activities were increased by azomethine I-I treatment. This study allows tentative conclusions to be drawn regarding which reactive oxygen metabolites play a role in azomethine H activity. We concluded that (O-2(.-)) maybe produced as a mediator of azomethine H action.

Toxic effects of nickel exposure on heart and liver of rats

The role of air pollution as a health risk factor is of special interest. Numerous toxic pollutants, such as nickel, are being released to the environment as a result of combustion of fossil fuels, crude oil, and coal. Nickel in the atmosphere can be combined with other environmental pollutants, producing various nickel compounds, which have varying animal toxicity. A rat biossay validated for the identification of toxic effects of nickel revealed increased serum activities of total lactate dehydrogenase (LDH) and alanine transaminase (ALT) in rats that received intratracheal injection of Ni2+ in .09% saline solution of NiCl2. The total LDH activity was also increased in the heart, and the isoenzyme pattern showed the LDH1/LDH2 ratio elevated to greater than 1. We conclude that intratracheal administration of nickel induced cardiac and hepatic damage. The development of cardiac and hepatic damage and of increased enzymes' activities was only demonstrated when nickel had accumulated in these tissues, indicating that nickel depot is essential to its toxicity. Intratracheal administration of NiCl2 induced changes in LDH and ALT activities.

Long-term toxicity following acute administration of nickel

Nickel compounds have high potential risk for the health of populations and for this reason their toxic effects should be urgently established. To determine the effect of nickel monosulfide in the muscle at the injection site on pancreatic, hepatic, and osteogenic lesions and the potential therapeutic effect of Cu-Zn superoxide dismutase (SOD), male Wistar rats received single intramuscular injections of nickel monosulfide (NiS - 7 mg Ni2+/Kg). A group of these experimental rats were injected intraperitoneally, with a single weekly dose of SOD covalently linked to polyethylene glycol (SOD-PEG). Rats were sacrificed at 2, 4, 6, and 8 months after Ni2+ injection. Nickel monosulfide produced tumors at the injection site. The increased phospholipid, alanine transaminase (ALT), alkaline phosphatase (ALP), and amylase levels in serum, in absence of SOD-PEG, reflected the toxic effects on pancreatic, hepatic, and osteogenic tissues of rats. SOD activity was increased in serum of rats receiving SOD-PEG throughout the experiment, and no significant difference was observed in biochemical parameters of control and experimental rats in presence of SOD- PEG. Superoxide radical generated by Ni2+ is of primary importance in the development of tumors at the injection site. Superoxide anion (O2 -) is also an important toxic intermediate with respect to hepatic, pancreatic, and osteogenic injury, since SOD-PEG has a potential therapeutic effect.

Toxic mechanism of nickel exposure on cardiac tissue

The incidence of cardiovascular disease has increased in the general population, and cardiac damage is indicated as one important cause of mortality. In addition, pollution and metal exposure have increased in recent years. For this reason, toxic effects of metals, such as nickel, and their relation to cardiac damage should be urgently established. Although free radical-mediated cellular damage and reactive oxygen species have been theorized as contributing to the nickel mechanism of toxicity, recent investigations have established that free radicals may be important contributors to cardiac dysfunction. However, there is little information on the effect of nickel exposure on markers of oxidative stress in cardiac tissue. Nickel exposure (Ni2+ 100 mg L-1 from NiSO4) significantly increased lipoperoxide and total lipid concentrations in cardiac tissue. We also observed increased serum levels of cholesterol (59%), lactate dehydrogenase (LDH-64%), and alanine transaminase (ALT-30%) in study animals. The biochemical parameters recovered to the control values with tocopherol intake (0.2 mg 200 g-1). Vitamin E alone significantly decreased the lipoperoxide concentration and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the heart. Since no alterations were observed in catalase and GSH-Px activities by nickel exposure while SOD activities were decreased, we conclude that superoxide radical (O2 -) generated by nickel exposure is of primary importance in the pathogenesis of cardiac damage. Tocopherol, by its antioxidant activity, decreased the toxic effects of nickel exposure on heart of rats.

Toxic mechanism of cadmium exposure on cardiac tissue

The presence of toxic substances in the workplace environment requires systematic evaluation of exposure and health status in exposed subjects. Cadmium is a highly toxic element found in water. Although free mediated cellular damage and reactive oxygen species (ROS), had been theorized as contributing to the cadmium mechanism of toxicity, and recent investigations have established that free radicals may be important contributors to cardiac dysfunction, there is little information on the effect of cadmium exposure on markers of oxidative stress in cardiac tissue. Cadmium exposure (Cd2+ - 100 mg/1-from CdCl2) in drinking water, during 15 days, significantly increased lipoperoxide and decreased the activities of superoxide dismutase and glutathione peroxidase. No alterations were observed in catalase activity in heart of rats with cadmium exposure. We also observed decreased glycogen and glucose concentration and increased total lipid content in cardiac tissue of rats with cadmium exposure. The decreased activities of alanine transaminase and aspartate transaminase reflected decreased metabolic protein degradation, and increased lactate dehydrogenase activity was related with increases in capacity of glycolysis. Since the metabolic pathways were altered by cadmium exposure, we can conclude that Cd2+ exposure induced ROS and initiate some series of events that occur in the heart and resulted in metabolic pathways alterations.