Brain and lungs of rats are differently affected by cigarette smoke exposure: Antioxidant effect of an organoselenium compound

Cigarette smoke exposure has been associated with oxidative stress in several organs. Antioxidant effect of diphenyl diselenide (PhSe)₂, an organoselenium compound, on oxidative damage induced by sub-chronic cigarette smoke exposure in brain and lungs of rats was investigated. Animals were exposed 5 times/week to one, two, three and four cigarettes for exposure periods of 15 min during the first, second, third and fourth weeks. Reactive species (RS) levels, enzymatic antioxidant defenses (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities) and non-enzymatic antioxidant defenses (ascorbic acid and non-protein thiol (NPSH) levels) were examined in brain and lungs of rats. An increase in RS levels induced by cigarette smoke in both tissues of rats was demonstrated. Cigarette smoke altered enzymatic antioxidant defenses (GST, CAT and SOD activities) in both tissues, and reduced the non-enzymatic antioxidant defenses in lungs. (PhSe)₂ (0.5 mg/kg/day, 5 times/week) restored RS levels and antioxidant defenses in brain of rats exposed to cigarette smoke. (PhSe)₂ treatment increased NPSH levels, GST and GR activities per se in lungs of rats. In conclusion, sub-chronic exposure to cigarette smoke caused alterations in antioxidant defense system and a tissue-specific oxidative stress in brain and lungs of rats. (PhSe)₂ restored antioxidant defenses in lungs and brain of rats.     

Chronic fluoride toxicity and myocardial damage: antioxidant offered protection in second generation rats

This experiment was designed to investigate the extent of peroxidative changes and histological alterations in the myocardium of rats exposed to high fluoride for two generations, in addition to ameliorative role of selenium and vitamin E on the above indices. Adult albino Wistar rats were given fluoride through drinking water (200 ppm F) and maintained subsequently for two generations, while they were exposed to fluoride throughout the experiment. Fluoride treatment significantly increased the lipid peroxidation and decreased the activity of antioxidant enzymes, viz., catalase, superoxide dismutase, and glutathione level in auricle and ventricle regions of the heart. Decreased feed and water consumption, organ somatic index and marginal drop in body growth rate were observed. Decreased antioxidant enzymes and increased malondialdehyde levels might be related to oxidative damage that occurs variably in the myocardium of rats. Biochemical changes were supported by the histological observations, which also revealed that chronic exposure to fluoride causes damage to the myocardium. Results of this study can be taken as an index of cardio-toxicity in rats exposed to water fluoridation. Further, oral supplementation of selenium and vitamin E not only inhibited oxidative stress but also enhanced the activities of antioxidant enzymes. Administration of antioxidants during fluoride exposure significantly overcame cardiac fluoride toxicity and therefore may be a therapeutic strategy for fluorotic victims.     

Oxidative stress induced by atrazine in rat erythrocytes: Mitigating effect of vitamin E

The present study investigates the propensity of atrazine to induce oxidative stress and its possible attenuation by vitamin E in rat erythrocytes, which is a convenient model to understand the oxidative damage induced by various xenobiotics. Experimental animals were administered atrazine (300?mg/kg body weight, daily) and/or vitamin E (100?mg/kg body weight, daily) orally for a period of 7, 14, and 21 days. Results indicated that the reduced glutathione (GSH) content of the erythrocytes of atrazine treated rats was significantly decreased as compared to the control group. Co-administration of vitamin E along with atrazine restored the GSH content of erythrocytes nearly to control levels. The activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione-s-transferase were found to be increased significantly in the erythrocytes accompanied by a decrease in the activity of the glucose-6-phosophate dehydrogenase, following atrazine exposure. On the other hand, when vitamin E was co-administered along with atrazine, activities of these enzymes were found to be restored significantly. In conclusion, results of the study demonstrated that atrazine induced oxidative stress in rat erythrocytes, in terms of increased activities of the various antioxidant enzymes, and decreased content of reduced glutathione. However, vitamin E administration ameliorated the effects of atrazine, suggesting that vitamin E is a potential antioxidant against atrazine-induced oxidative stress.     

Vitamin E isoform γ-tocotrienol alleviates cigarette smoke-induced chronic obstructive pulmonary disease

OBJECTIVE Cigarette smoke-induced chronic obstructive pulmonary disease(COPD)is a leading cause of death,where inflammation and oxidative stress are involved in the pathogenesis.Vitamin E isoformγ-tocotrienol possesses both anti-oxidative and anti-inflammatory properties.We hypothesized thatγ-tocotrienol may have protective effects against COPD.METHODS BALB/c mice were exposedto cigarette smoke daily for 2 weeks with oralγ-tocotrienol treatment in the second week.Bronchoalveolar lavage(BAL)fluid was assessed for total and differential cell counts,oxidative damage biomarkers,and cytokine levels.Lung tissues were examined for the expression of antioxidants and pro-inflammatory biomarkers.In order to measure changes in lung functions in COPD,another set of mice was exposed to cigarette smoke for 2 months with oralγ-tocotrienol treatment in the last 2 weeks.RESULTSγ-Tocotrienol dose-dependently abated cigarette smoke-induced elevation of BAL fluid total and neutrophil cell counts,cytokine and chemokine(IL-1β,IL-6,IL-17,LIX,G-CSF,KC,RANTES and VEGF)levels,as well as oxidative/nitrosative damage biomarker(advanced oxidation of protein products,8-isoprostane,8-hydroxy-2-deoxyguanosine and 3-nitrotyrosine)levels.γ-Tocotrienol promoted total lung antioxidant capacity and endogenous antioxidant activities of superoxide dismutase,catalase and glutathione peroxidase.More importantly,γ-tocotrienol markedly restored work of breathing and lung functions(total lung capacity,static compliance and FEV100/FVC)in chronic experimental COPD.Furthermore,γ-tocotrienol demonstrated better anti-oxidative,anti-inflammatory,and restoration of lung functions in COPD than prednisolone.CONCLUSION We have shown for the first time the efficacy of vitamin E isomerγ-tocotrienol in protection against cigarette smoke-induced COPD by direct neutralization of free radicals,abating oxidative damage,and restoring antioxidants activities,coupled with anti-inflammatory actions in the inflamed airways.     

Effect of subchronic administration of antioxidants against cigarette smoke exposure in rats

Effects of subchronic administration of antioxidants against pulmonary damage mediated by cigarette smoke were investigated in rats. Rats were continuously received ascorbic acid,N-acetylcysteine and ginseng extract together drinking water from day 25 after birth. After 30 days of antioxidant supplementation, rats were exposed to cigarette smoke generated from six cigarettes (11 mg tar) for 20 min per day throughout 30 days, and then several biochemical markers related to the redox status in vivo were analyzed in the respiratory system. The cigarette smoke induced mild histological changes in trachea and lungs. The activity of Superoxide dismutase (SOD) in the lung was significantly increased, and catalase and glutathione peroxidase activities were increased less than SOD, but total sulfhydryl compounds (Total-SH) content was decreased by cigarette smoking. In spite of the increase in activities of antioxidant enzymes, the inhibitory capacity of lung preparations on in vitro lipid peroxidation using ox brain homogenates was decreased and the change in the capacity was not related to the changes of these intracellular enzymes activities, but with the content of Total-SH. On the other hand, the content of thiobarbituric acid reactive substances and the ratio of elastase to anti-protease in the lung homogenates were significantly increased. Supplementation of antioxidants, however, effectively attenuated all of such alterations induced by cigarette smoke. These results indicate that although cigarette smoking induces antioxidant enzymes in the lung as a self defense mechanism, it seems to be not sufficient to protect the pulmonary system, and that chronic antioxidant feeding could be effective to reduce pulmonary damage induced by free radicals.     

Protective effects of N-acetylcysteine on peroxidative changes of the fetal rat lungs whose mothers were exposed to cigarette smoke

BACKGROUND: This experimental study investigated the protective effects of N-acetylcysteine (NAC) on peroxidative changes in fetal lungs in the offspring of rats exposed to cigarette smoke. METHODS: Thirty fetal rats used for analysis, were divided into three groups as follows: control group (n = 10), whose mothers were exposed to fresh air; group I (n =10), whose mothers were exposed to cigarette smoke; and group II (n =10), whose mothers were exposed to cigarette smoke and given 10 mg/kg per day NAC. In groups I and II, smoke exposure was started 4 weeks before the pregnancy, and continued to the 14th day of pregnancy, and in Group II, NAC was administered intraperitoneally for 14 days. The mothers and their fetuses were decapitated on the 14th day of pregnancy. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the lung tissues of fetuses to determine the oxidant-antioxidant balance. RESULTS: While tissue MDA levels in Group I were found significantly higher than the control group (129.7+/-65.4 versus 63.4 +/-15.4 nmol/100 mg protein, P <0.05), GSH levels were significantly lower (17.1+/-7.3 versus 45.4 + 8.1 nmol/mg protein, P <0.01). Furthermore, in Group II, MDA levels were significantly lower (56.9+/-20.6 versus 129.7+/-65.4 nmol/100 mg protein, P <0.05), and GSH levels were significantly higher (34.57+/-10.7 versus 17.1+/-7.3 nmol/mg protein, P <0.0001) when compared with Group I. No statistically significant difference was found in tissue MDA and GSH levels between Group II and the control group (P >0.05). CONCLUSIONS: These results suggest that smoke exposure during pregnancy causes oxidative damage in fetal lungs. This smoke-induced damage might be prevented by NAC.     

Protective effects of Sesbania grandiflora on kidney during alcohol and polyunsaturated fatty acid-induced oxidative stress

Context: Kidney is an organ highly vulnerable to damage caused by reactive oxygen species (ROS), due to abundance of polyunsaturated fatty acids in the composition of renal lipids. Oxidative stress plays an important role in the development of alcohol-induced tissue injury. This leads to membrane damage by lipid peroxidation, alteration of enzyme function and formation of acetaldehyde protein adducts. Many alcoholics along with alcohol consume fried foods that are normally made up of polyunsaturated fatty acid (PUFA). The toxic effects of alcohol are further enhanced by the consumption of PUFA.

Objective: In our study, we analyzed the effect of Sesbania grandiflora (S. grandiflora) on alcohol and PUFA-induced oxidative stress in male albino Wistar rats.

Materials and methods: The levels of lipid peroxidative markers (thiobarbutric acid reactive substances [TBARS] and lipid hydroperoxides [HP]), the levels of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) and non-enzymatic (reduced glutathione, vitamin E, vitamin C) antioxidants were analyzed in kidney to evaluate the effects of S. grandiflora.

Results: The levels of TBARS and HP were significantly increased in alcohol + ΔPUFA group, which were found to be reduced on treatment with S. grandiflora. The levels of both enzymatic and non-enzymatic antioxidants were decreased in alcohol + ΔPUFA group, which were found to be restored on treatment with S. grandiflora.

Conclusion: From this, we conclude that S. grandiflora protects the kidney against alcohol and PUFA-induced oxidative stress, which can be attributed to the phenolic compounds and anthocyanins present in the plant.     

Cigarette smoke extract inhibits expression of peroxiredoxin V and increases airway epithelial permeability

Inhaled cigarette smoke induces oxidative stress in the epithelium of airways. Peroxiredoxin V (PRXV) is a potent antioxidant protein, highly expressed in cells of the airway epithelium. The goal of our study was to determine whether cigarette smoke extract (CSE) influenced expression of this protein in airway epithelia in vivo and in vitro. In Sprague-Dawley rats, we determined effects of CSE on airway epithelial permeability, mRNA levels and expression of PRXV protein. Exposure of isolated tracheal segment in vitro to 20% CSE for 4 h resulted in development of increased permeability to albumin, significantly reduced mRNA levels for PRXV, and reduced amounts of PRXV protein in the epithelium. In cultures of the airway epithelial cell lines (Calu-3, JME), primary airway cell culture (cow), and alveolar epithelial cells A549, CSE also significantly decreased transepithelial electrical resistance and expression of PRXV protein, and induced glutathione and protein oxidation. To demonstrate functional importance of PRXV, we exposed clones of HeLa cells with siRNA-downregulated PRXV to hydrogen peroxide, which resulted in increased rate of cell death and protein oxidation. CSE directly downregulates expression of functionally important antioxidant enzyme PRXV in the epithelial cells of airways, which represents one pathophysiological mechanism of cigarette smoke toxicity.     

Cardioprotective effects of subcutaneous ebselen against daunorubicin-induced cardiomyopathy in rats

Daunorubicin is an anthracycline antitumour agent that can cause severe cardiomyopathy leading to a frequently fatal congestive heart failure. Although the exact molecular mechanisms of cardiotoxicity are not well established, oxidative mechanisms involving daunorubicin-induced superoxide anion production have been proposed. In the present study, we showed that ebselen a seleno-organic compound exhibiting glutathione peroxidase-like and antioxidant activities, significantly ameliorated daunorubicin-induced cardiomyopathy. Subcutaneous administration of ebselen to daunorubicin-treated rats showed significant improvement in serum cardiac indices including creatine kinase isoenzyme and lactate dehydrogenase as well as serum glutathione (GSH) peroxidase. Moreover, myocardium of daunorubicin/ebselen-treated rats showed significant improvement in daunorubicin-induced depletion of GSH peroxidase activity and reduced glutathione content, in addition to attenuation of daunorubicin-induced increase in cardiac malondialdehyde production and total nitrate/nitrite concentration levels. These results were confirmed by histopathological examination of ventricles of daunorubicin/ebselen-treated rats that revealed significant improvement of the characteristic cardiomyopathic changes induced by daunorubicin treatment. Interestingly, control rats treated with ebselen showed significant elevation in serum lactate dehydrogenase activity, cardiac malondialdehyde production and total nitrate/nitrite concentration levels compared with the untreated control animals. In conclusion, ebselen treatment significantly alleviates daunorubicin-induced cardiomyopathy.     

Diphenyl diselenide prevents oxidative damage induced by cigarette smoke exposure in lung of rat pups

The effect of cigarette smoke exposure on lungs of rat pups was evaluated. Animals were exposed to passive cigarette smoke during 3 weeks and a number of toxicological parameters in lung of pups were examined, such as lipid peroxidation, δ-aminolevulic acid dehydratase (δ-ALA-D) activity, components of the enzymatic antioxidant defenses (superoxide dismutase (SOD) and catalase activities) and non-enzymatic antioxidant defenses (Vitamin C and non-protein thiol (NPSH) levels). Furthermore, a possible protective effect of diphenyl diselenide, (PhSe)₂, was studied. The results demonstrated an increase in lipid peroxidation, an inhibition of δ-ALA-D activity, a reduction of Vitamin C and NPSH levels induced by cigarette smoke exposure, indicating damage in lungs of rat pups. Oral administration of (PhSe)₂ (0.5 mg/kg) restored TBARS levels, non-enzymatic antioxidant defenses and activity of δ-ALA-D. These results indicated that exposure to cigarette smoke enhanced oxidative stress, thereby disturbing the tissue defense system. (PhSe)₂ protected against oxidative damage induced by cigarette smoke exposure in lung of rat pups.     

Long-term exposure to crotonaldehyde causes heart and kidney dysfunction through induction of inflammatory and oxidative damage in male Wistar rats

Crotonaldehyde is a ubiquitous hazardous pollutant, present in cigarette smoke and automobile exhaust and is endogenously generated by lipid peroxidation. Most of the current studies focus on its lung toxicity. However, there have been few investigations on the cardiac and renal toxicity caused by crotonaldehyde exposure. We hypothesized that oral intake of crotonaldehyde can cause inflammatory and oxidative/nitrosative damage to the heart and kidneys. Therefore, we treated male rats with crotonaldehyde by gavage at 0, 2.5, 4.5, and 8.5?mg/kg/day for 120?d and evaluated the alterations in histological and serological parameters, oxidative state, and inflammation responses to explore the roles of crotonaldehyde-induced oxidative/nitrosative stress and inflammation in the heart and kidney dysfunction and to explore the relationship between heart and kidney dysfunction. We found that body weight increment, as well as heart and kidney coefficients decreased with an increasing crotonaldehyde dosage. Histological examinations indicated that crotonaldehyde exposure led to focal myocardial necrosis, cardiac fibrosis, renal tubular epithelial cell edema, and renal lymphocyte infiltration. We also assessed the impact of crotonaldehyde treatment on oxidative/nitrosative stress markers, antioxidant enzymes, inflammatory biomarkers, heart/kidney functional markers, and angiotensin II-aldosterone-brain natriuretic peptide (AngII-ALD-BNP) levels. Overall, we found that proinflammatory cytokine and malondialdehyde levels increased in a dose-dependent manner. Furthermore, crotonaldehyde treatment (4.5 and 8.5?mg/kg) significantly prevented the upregulation of antioxidant enzyme activity, thereby increasing oxidative/nitrosative stress (p?相似文献   

Protective effect of aqueous Curry leaf (Murraya koenigii) extract against cadmium-induced oxidative stress in rat heart

Treatment of rats with a low dose of cadmium chloride caused a significant damage in the rat cardiac tissue indicated by the increase in the level of serum glutamate oxaloacetate transaminase and lactate dehydrogenase1 activities. Histological studies confirmed the damage due to cadmium. That cadmium-induced tissue damage was caused due to oxidative stress was evident from the changes observed in the levels of lipid peroxidation and reduced glutathione, the protein carbonyl content, and the alterations in the activities of cardiac antioxidant and pro-oxidant enzymes. Treatment of rats with cadmium also caused alterations in the activities of mitochondrial Kreb’s cycle as well as respiratory chain enzymes. All these changes were ameliorated when the rats were pre-treated with an aqueous extract of Curry leaf (Murraya koenigii). The studies indicated that the aqueous extract of Curry leaf protects the rat cardiac tissue against cadmium-induced oxidative stress possibly through its antioxidant activity. As curry leaf is consumed by people as part of their diet in India and South-East Asian and some European countries as well, and, as it has no reported side-effects, the results seem to have relevance at places where humans are exposed to cadmium environmentally or occupationally.     

Lactate dehydrogenase isoenzyme patterns upon chronic exposure to cigarette smoke: Protective effect of bacoside A

Despite a strong association between cigarette smoking and alarming increase in mortality rate from smoking-related diseases, around 35-40% of the world's population continues to smoke and many more are being exposed to environmental tobacco smoke. Since the role of free radicals and oxidative damage in the pathogenesis of smoking-related diseases has been suggested, bacoside A, a potent antioxidant was tested for its ability to protect against cigarette smoking-induced toxicity in terms of lactate dehydrogenase (LDH) and its isoenzymes. Rats were exposed to cigarette smoke and simultaneously administered with bacoside A, for a period of 12 weeks. Total LDH activity was assayed in serum, lung, heart, brain, liver and kidney, and serum LDH isoforms were separated electrophoretically. Cigarette smoke exposure resulted in significant increase in serum LDH and its isoenzymes with a concomitant decrease in these organs. These alterations were prevented by administration of bacoside A. Excessive oxidants from cigarette smoke is known to cause peroxidation of membrane lipids leading to cellular damage, thereby resulting in the leakage of LDH into the circulation. Bacoside A could have rendered protection to the organs by stabilizing their cell membranes and prevented the release of LDH, probably through its free radical scavenging and anti-lipid peroxidative effect.     

Creatine kinase isoenzyme patterns upon chronic exposure to cigarette smoke: protective effect of Bacoside A

Cigarette smoking is implicated as a major risk factor in the development of cardiovascular and cerebrovascular diseases. Creatine kinase (CK) and its isoforms (CK-MM, MB, BB) have been advocated as sensitive markers in the assessment of cardiac and cerebral damage. Therefore, in the present study, we report the isoenzyme patterns of CK in rats upon exposure to cigarette smoke and the protective effect of Bacoside A against chronic smoking induced toxicity. Adult male albino rats were exposed to cigarette smoke and simultaneously administered with Bacoside A, the active constituent from the plant Bacopa monniera, for a period of 12 weeks. The activity of CK was assayed in serum, heart and brain, and its isoenzymes in serum were separated electrophoretically. Rats exposed to cigarette smoke showed significant increase in serum CK activity with concomitant decrease in heart and brain. Also cigarette smoke exposure resulted in a marked increase in all the three isoforms in serum. Administration of Bacoside A prevented these alterations induced by cigarette smoking. Cigarette smoking is known to cause free radical mediated lipid peroxidation leading to increased membrane permeability and cellular damage in the heart and brain resulting in the release of CK into the circulation. The protective effect of Bacoside A on the structural and functional integrity of the membrane prevented the leakage of CK from the respective tissues, which could be attributed to its free radical scavenging and anti-lipid peroxidative effect.     

Oxidative stress in heart tissue of hyperthyroid and iron supplemented rats.

This study was designed to investigate the effect of hyperthyroidism and/or iron supplementation or cardiac oxidative stress parameters--the lipid peroxidation end product glutathione (GSH), glutathione peroxidase (CSH-Px), and superoxide dismutase (CuZnSOD)--in rats. In plasma, ferritin as an indicator of iron status and glutamate oxaloacetate transaminase (GOT) as an indicator of damage to the heart tissue were analyzed. Our findings show that hyperthyroidism increased lipooxidative damage as reflected by higher lipid peroxidation end product levels and elevated antioxidant defense parameters-GSH and GSH-Px. Iron supplementation per se does not affect oxidative stress parameters studied in the euthyroid state. Although iron increased lipid peroxidation in the hyperthyroid state, this effect was less than that seen in euthyroidism. Iron supplementation to hyperthyroid rats significantly lowered plasma ferritin levels, suggesting increased iron elimination with consequently reduced oxidative stress.     

Baicalein Abrogates Reactive Oxygen Species (ROS)‐mediated Mitochondrial Dysfunction during Experimental Pulmonary Carcinogenesis In Vivo

Our current study aimed to evaluate the chemotherapeutic efficacy of baicalein (BE) in Swiss albino mice, which is exposed to benzo(a)pyrene [B(a)P] for its ability to alleviate mitochondrial dysfunction and systolic failure. Here, we report that oral administration of B(a)P (50 mg/kg body weight)‐induced pulmonary genotoxicities in mice was assessed in terms of elevation in reactive oxygen species (ROS) generation and DNA damage in lung mitochondria. MDA‐DNA adducts were formed in immunohistochemical analysis, which confirmed nuclear DNA damage. mRNA expression levels studied by RT‐PCR analysis of voltage‐dependent anion channel (VDAC) and adenine nucleotide translocase (ANT) were found to be significantly decreased and showed a marked increase in membrane permeability transition pore (MPTP) opening. Accompanied by up‐regulated Bcl‐xL and down‐regulated Bid, Bim and Cyt‐c proteins studied by immunoblot were observed in B(a)P‐induced lung cancer–bearing animals. Administration of BE (12 mg/kg body weight) significantly reversed all the above deleterious changes. Moreover, assessment of mitochondrial enzyme system revealed that BE treatment effectively counteracts B(a)P‐induced down‐regulated levels/activities of isocitrate dehydrogenase, α‐ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase, cytochrome‐C‐oxidase and ATP levels. Restoration of mitochondria from oxidative damage was further confirmed by transmission electron microscopic examination. Further analysis of lipid peroxidation, superoxide dismutase, catalase, glutathione peroxidase, glutathione‐S‐transferase, glutathione reductase, reduced glutathione, vitamin E and vitamin C in lung mitochondria was carried out to substantiate the antioxidant effect of BE. The overall data conclude that chemotherapeutic efficacy of BE might have strong mitochondria protective and restoration capacity in sub‐cellular level against lung carcinogenesis in Swiss albino mice.     

Evidence for cigarette smoke-induced oxidative stress in the rat pancreas

Background/aims: Recent findings with a rodent model of cigarette smoke inhalation revealed a causal relationship between chronic exposure to cigarette smoke and the development of pancreatitis. The present study was conducted to ascertain whether cigarette smoke induces oxidative stress in the rat pancreas concurrently with inflammation.

Methodology: Rats (six per treatment group) were treated for 0, 3, 6, 9, or 12 weeks with cigarette smoke (0.7?mg/L). Pancreatic tissues were examined for histological and pathological alterations and serum for changes in interleukin-6 concentration. Pancreatic expression and localization of α-smooth muscle actin, transforming growth factor-β1, and collagen-1 were determined as measures of progressive inflammation/fibrosis. Pancreatic superoxide dismutase and glutathione peroxidase activities and malondialdehyde content were measured as indices of oxidative stress.

Results: Inflammatory cell infiltration and ductal hyperplasia were detected in pancreata after 12 weeks of treatment with cigarette smoke. The serum interleukin-6 concentration increased significantly and pancreatic glutathione peroxidase activity declined significantly after 12 weeks of treatment. No other significant changes were observed.

Conclusions: Pancreata of rats exposed chronically to cigarette smoke exhibit inflammation concurrently with suppression of glutathione peroxidase activity. These observations favor a role for oxidative stress in the induction of pancreatitis associated with chronic cigarette smoke inhalation.     

Pharmacological effect of carvacrol on d-galactosamine-induced mitochondrial enzymes and DNA damage by single-cell gel electrophoresis

The present study aimed at investigating the effect of carvacrol on hepatic mitochondrial enzyme activities and DNA damage in D: -galactosamine (D: -GalN)-induced hepatotoxicity in male albino Wistar rats. The activities of hepatic mitochondrial enzymes such as isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADPH dehydrogenase and cytochrome c oxidase significantly decreased in D: -GalN-hepatotoxic rats, and administration of carvacrol brought these parameters towards normality. In D: -GalN-hepatotoxic rats, the hepatic mitochondrial concentration of thiobarbituric acid reactive substances significantly increased, and administration of carvacrol significantly reduced them towards normality. Furthermore, the activities of enzymatic antioxidants such as superoxide dismutase and glutathione peroxidase and the levels of non-enzymatic antioxidants such as vitamin C, vitamin E and reduced glutathione decreased significantly in the liver mitochondria. Administration of carvacrol returned the enzymatic and non-enzymatic antioxidants towards normality. D: -GalN-hepatotoxic rats had increased DNA damage, which administration of carvacrol significantly decreased. These results suggest that carvacrol has liver mitochondrial antioxidant properties and possesses a defensive effect against mitochondrial enzymes and DNA damage in D: -GalN-induced rats.     

Barium chloride dose‐dependently induced heart and lung injury in Wistar rats

Barium (Ba) is one of the environmental pollutant metals that incite deleterious effects on human health. The present study investigated the effects of exposure to different doses of barium chloride (BaCl₂) on heart and lung of Wistar rats. Rats were exposed to BaCl₂ at 150, 300, and 600 mg/L for seven consecutive days. Results indicated that exposure to Ba caused heart and lung damage evidenced by significant increase in plasma lactate dehydrogenase and creatine kinase activities, total cholesterol, triglyceride, and low‐density lipoprotein‐cholesterol levels, while high‐density lipoprotein‐cholesterol level decreased when compared with control. Moreover, BaCl₂ significantly decreased superoxide dismutase, catalase, and acetylcholinesterase activities as well as glutathione level in heart and lung of the treated rats. Furthermore, the dose‐dependent increase in cardiac and lung lipid peroxidation, advanced oxidative protein product and nitric oxide levels were accompanied by marked increase in metallothionein in the BaCl₂‐treated rats. Administration of BaCl₂ altered hematological parameters and significantly increased concentrations of interleukin‐6 in the treated rats. Histology analysis showed significant alteration in the heart and lung tissues of Ba‐treated rats. In conclusion, BaCl₂‐induced heart and lung damages via disruption of antioxidant defense systems, and activation of inflammatory mediators and alteration in hematological parameters in rats.     

Exposure to alcohol and tobacco smoke causes oxidative stress in rats

BackgroundTobacco smoking and alcohol abuse causes oxidative stress in humans and underlay numerous chronic degenerative diseases. Liver is the main organ exposed to alcohol toxic metabolites, whereas tobacco smoke is chiefly harmful to the lungs.MethodsThe aim of the current study was the assessment and comparison of selected oxidative stress markers, reduced glutatione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase, nitrites and protein nitrosylation and DNA damage in the livers and in the lungs of alcohol-addicted rats exposed to tobacco smoke alone or in combination with a single dose of ethanol.ResultsThe highest levels of GSH were measured in the liver of smoke only exposed animals and in the lungs of rats exposed to smoke and alcohol. In the liver of animals treated with a single dose of alcohol or with smoke and alcohol, GST was significantly higher than in the group exposed to smoke only. SOD and catalase showed the highest activities in the livers of rats receiving a single dose of alcohol. High concentration of nitrites was observed in the lungs of animals treated with smoke and alcohol in combination, which corresponded to elevated protein nitrosylation in this group, whereas in the livers of these animals relatively low level of nitrites was accompanied with the lowest concentration of nitrosylated proteins. In the liver of alcohol only treated rats the highest nitrites corresponded to the highest protein nitrosylation. In the lungs of all treatment groups the range of DNA damage was higher, than the respective values in the livers. Although alcohol is not considered a specific toxicant to the lungs it was found to cause oxidative stress in this organ.ConclusionsThe obtained results suggest that in the ethanol-addicted rats combined exposure to smoke and alcohol differentially modulate endogenous antioxidant defense system and reactions to oxidative stress.