Oxidative Stress and Antioxidant Defense in the Heart, Liver, and Kidney of Bat Species with Different Feeding Habits.

The aim of this study was to compare the oxidative metabolism of four neotropical bat species with different feeding habits and investigate the relationship between their feeding habits and oxidative status. In terms of oxidative damage, our findings revealed major differences among the four bat species. In particular, hematophagous bats had lower levels of oxidative damage in the heart but higher levels in the liver. Nectarivorous bats had lower levels of carbonyl groups in the kidneys compared to insectivorous and hematophagous bats. The activity of various antioxidant and non-antioxidant enzymes in the heart, liver, and kidney also showed significant differences among the bat species. H2O2 consumption was lower in the heart of hematophagous bats, while insectivorous bats exhibited the highest enzymatic activity in the kidney. SOD activity was lower in the heart of hematophagous bats and lower in nectarivorous bats in the liver. Fumarase activity was higher in the heart of frugivorous/insectivorous and lower in nectarivorous/hematophagous bats. GPx activity was higher in the heart of nectarivorous/insectivorous and higher in the kidney of insectivorous bats. GST activity was higher in the heart of nectarivorous and lower in hematophagous bats. The correlation analysis between oxidative markers and enzymatic/non-enzymatic antioxidants in the heart, liver, and kidney exhibited distinct patterns of correlations due to variations in antioxidant defense mechanisms and oxidative stress responses in different organs. The observed differences in oxidative damage, antioxidant enzyme activities, and correlations between oxidative markers and antioxidants highlight the adaptability and complexity of the antioxidant defense systems in these bats. Each organ appears to have specific demands and adaptations to cope with oxidative stress based on its physiological functions and exposure to dietary components. Our results have major significance for the conservation and management of bats, which are threatened species despite being crucial components of ecosystems. Our study's implications go beyond bat biology and offer valuable insights into comparative oxidative physiology.

Oxidative Stress and Antioxidant Defense in the Brain of Bat Species with Different Feeding Habits.

Assessing the levels of oxidative stress markers and antioxidant enzymes in the brain is crucial in evaluating its antioxidant capacity and understanding the influence of various dietary patterns on brain well-being. This study aimed to investigate the antioxidant status and oxidative damage in the brain of bat species with different feeding habits to gain insights into their protective mechanisms against oxidative stress and their interspecific variation. The levels of oxidative damage markers and the activities of antioxidants were measured in the brain of four bat species with different feeding habits, namely insectivorous, frugivorous, nectarivorous, and hematophagous. Insectivorous bats showed higher levels of SOD and fumarase compared to the other groups, while hematophagous bats showed lower levels of these enzymes. On the other hand, the activities of glutathione peroxidase and glutathione S-transferase were higher in hematophagous bats and lower in insectivorous bats. The carbonyl groups and malondialdehyde levels were lower in frugivores, while they were similar in the other feeding guilds. Nitrite and nitrate levels were higher in the hematophagous group and relatively lower in all other groups. The GSSG/GSH ratio was higher in the hematophagous group and lower in frugivores. Overall, our results indicate that the levels of oxidative stress markers and the activities of antioxidant enzymes in the brain vary significantly among bat species with different feeding habitats. The findings suggest that the antioxidant status of the brain is influenced by diet and feeding habits.

Mycotoxin deactivator improves performance, antioxidant status, and reduces oxidative stress in nursery pigs fed diets containing mycotoxins.

Ingestion of mycotoxins can result in many problems, including decreased growth rates and immune suppression. The present study aimed to evaluate the impact of the supplementation of a mycotoxin deactivator composed by adsorbent clay minerals; inactivated fermentation extracts of Saccharomyces cerevisiae; and blend of antioxidants, organic acids, and botanicals in diets containing added mycotoxins for nursery pigs on their performance and antioxidant status. Ninety pigs weaned with 24 d of age (7.12 ± 0.68 kg of BW) were used. Pigs were housed in pens of three animals each according to body weight, litter origin, and sex. The dietary treatments consisted of feeding the pigs with a standard control diet as negative control (NC; mycotoxin levels at accepted regulatory Brazilian Ministry of Agriculture standards; deoxynivalenol (DON): <100 µg/kg; zearalenone (ZEA): <20 µg/kg; fumonisins (FB): <1 mg/kg); the standard diet added with mycotoxins to reach a low contamination level is considered as positive low (PCL-; DON: 900 µg/kg; ZEA: 100 µg/kg; FB: 5,000 µg/kg) without deactivator; a positive low added the deactivator at an inclusion rate of 1 kg/ton (PCL+); the standard diet added with mycotoxins to reach a high contamination level is considered as positive high (PCH-; DON: 4,500 µg/kg; ZEA: 500 µg/kg; FB: 18,000 µg/kg) without the deactivator; and a positive high added the deactivator at an inclusion rate of 5 kg/ton (PCH+). Pigs were individually weighed at the beginning and at the end of each phase and feed intake recorded based on daily pen intake during the experiment. On days 7, 19, 34, and 43 post-weaning, blood samples were drawn for antioxidant analyses. Antioxidant enzymes (glutathione peroxidase [GPx] and total superoxide dismutase [TSOD]), vitamins [Vit A, E, and C], and malondialdehyde [MDA]) were evaluated in erythrocyte and plasma samples. Pigs challenged with mycotoxins presented lower performance traits, decrease in the efficiency of central antioxidant systems (↓GPx, ↓TSOD, ↓Vit A, ↓Vit E, and ↓Vit C), and a higher oxidative damage to lipids (↑MDA) when compared with the control and deactivator-associated treatments. Our findings showed that the use of a mycotoxin deactivator can mitigate the negative impacts on performance and oxidative stress when animals are subjected to diets contaminated by different levels of mycotoxins.

Short leukocyte telomeres predict 25-year Alzheimer's disease incidence in non-APOE ε4-carriers.

BACKGROUND: Leukocyte telomere length (LTL) has been shown to predict Alzheimer's disease (AD), albeit inconsistently. Failing to account for the competing risks between AD, other dementia types, and mortality, can be an explanation for the inconsistent findings in previous time-to-event analyses. Furthermore, previous studies indicate that the association between LTL and AD is non-linear and may differ depending on apolipoprotein E (APOE) ε4 allele carriage, the strongest genetic AD predictor. METHODS: We analyzed whether baseline LTL in interaction with APOE ε4 predicts AD, by following 1306 initially non-demented subjects for 25 years. Gender- and age-residualized LTL (rLTL) was categorized into tertiles of short, medium, and long rLTLs. Two complementary time-to-event models that account for competing risks were used; the Fine-Gray model to estimate the association between the rLTL tertiles and the cumulative incidence of AD, and the cause-specific hazard model to assess whether the cause-specific risk of AD differed between the rLTL groups. Vascular dementia and death were considered competing risk events. Models were adjusted for baseline lifestyle-related risk factors, gender, age, and non-proportional hazards. RESULTS: After follow-up, 149 were diagnosed with AD, 96 were diagnosed with vascular dementia, 465 died without dementia, and 596 remained healthy. Baseline rLTL and other covariates were assessed on average 8 years before AD onset (range 1-24). APOE ε4-carriers had significantly increased incidence of AD, as well as increased cause-specific AD risk. A significant rLTL-APOE interaction indicated that short rLTL at baseline was significantly associated with an increased incidence of AD among non-APOE ε4-carriers (subdistribution hazard ratio = 3.24, CI 1.404-7.462, P = 0.005), as well as borderline associated with increased cause-specific risk of AD (cause-specific hazard ratio = 1.67, CI 0.947-2.964, P = 0.07). Among APOE ε4-carriers, short or long rLTLs were not significantly associated with AD incidence, nor with the cause-specific risk of AD. CONCLUSIONS: Our findings from two complementary competing risk time-to-event models indicate that short rLTL may be a valuable predictor of the AD incidence in non-APOE ε4-carriers, on average 8 years before AD onset. More generally, the findings highlight the importance of accounting for competing risks, as well as the APOE status of participants in AD biomarker research.

Increased IL-8 levels in HIV-infected individuals who initiated ART with CD4+ T cell counts <350 cells/mm3 - A potential hallmark of chronic inflammation.

The identification of inflammatory markers in HIV+ individuals on ART is fundamental since chronic ART-controlled HIV infection is linked to an increased inflammatory state. In this context, we assessed plasma levels of pro-inflammatory cytokines (IL-1ß, IL-8, and IL-12p70) of HIV+ individuals who initiated ART after immunosuppression (CD4+ T cell counts <350 cells/mm3). HIV+ individuals were stratified according to two extreme phenotypes: Slow Progressors (SPs; individuals with at least 8 years of infection before ART initiation) and Rapid Progressors (RPs; individuals who needed to initiate ART within 1-4 years after infection). A control group was composed of HIV-uninfected individuals. We found increased IL-8 levels (median: 5.13 pg/mL; SPs and RPs together) in HIV-infected individuals on ART as compared to controls (median: 3.2 pg/mL; p = 0.04), although no association with the progression profile (slow or rapid progressors) or CD4+ T cell counts at sampling was observed. This result indicates that IL-8 is a general marker of chronic inflammation in HIV+ individuals on ART, independently of CD4+ T cell counts at the beginning of the treatment or of the potential progression profile of the patient. In this sense, IL-8 may be considered a possible target for novel therapies focused on reducing inflammation in chronic HIV infection.

Role of asthma and intolerance to acetylsalicylic acid on the redox profile in nasal polyp tissue.

PURPOSE: Nasal polyposis is a chronic inflammatory disease of the mucosa of the nasal cavity and paranasal sinuses. The etiology of nasal polyposis is unclear; however, it may be associated with asthma and intolerance to acetylsalicylic acid, possibly altering the redox profile. The study intends to compare the redox profile in polyps surgically removed from three clinical groups of patients with nasal polyposis who were divided according to the presence of asthma and intolerance to acetylsalicylic acid. METHODS: Patients were divided into three groups: nasal polyposis only (n = 30); nasal polyposis and asthma (n = 19); and nasal polyposis, asthma and intolerance to acetylsalicylic acid (n = 10). The following redox evaluations were performed: enzymatic antioxidant activity of superoxide dismutase, glutathione peroxidase, hydrogen peroxide consumption and glutathione S-transferase; non-enzymatic antioxidant levels of vitamin C, vitamin E and glutathione; levels of the oxidative damage biomarkers carbonyl groups (measuring protein damage) and malondialdehyde (measuring lipid peroxidation); and nitrite and nitrate levels. RESULTS: Compared with the polyposis only group, hydrogen peroxide consumption, glutathione S-transferase, vitamin E and malondialdehyde were lower in the asthma group. Total glutathione (0.12 ± 0.01 vs. 33.34 ± 10.48 µmol/mg) and nitrite and nitrate (0.06 ± 0.01 vs. 15.95 ± 1.38 nmol/mg) levels were higher in the nasal polyposis, asthma and intolerance to acetylsalicylic acid group. CONCLUSIONS: In patients with nasal polyposis, asthma may alter the redox profile associated with the hydrogen peroxide and lipid damage pathways, whereas asthma and intolerance to acetylsalicylic acid increase nitrite and nitrate and total glutathione levels.

Effects of lipoic acid and n-3 long-chain polyunsaturated fatty acid on the liver ovariectomized rat model of menopause.

BACKGROUND: Bilateral ovariectomy is an experimental model used to analyse the effects of menopause and develop strategies to mitigate the deleterious effects of this condition. Supplementation of the diet with antioxidants has been used to reduce potential oxidative stress caused by menopause. The purpose of the study was to analyse the effects of α-lipoic acid (LA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), dietary supplementation on oxidative stress in the livers of ovariectomized rats. METHODS: In this study, we evaluated the effect of dietary supplementation with LA, DHA and EPA for a period of 16 weeks on oestrogen levels and oxidative stress biomarkers in the livers of ovariectomized 25 three-month-old rats. RESULTS: Serum oestrogen levels were lower after ovariectomy but were not altered by dietary treatments. LA was capable of acting in the liver, recovering the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase, and reducing protein oxidative damage. Moreover, LA supplementation reduced nitrite and nitrate levels. DHA and EPA recovered the antioxidant activity of cytosolic and mitochondrial superoxide dismutase, decreasing protein oxidation. Protection against lipid oxidation differed between treatments. The DHA-treated group showed increased levels of the lipid peroxidation biomarker malondialdehyde compared to the ovariectomized group. However, malondialdehyde levels were not altered by EPA treatment. CONCLUSIONS: The results suggest that the antioxidant response varies among evaluated supplementations and all supplements were able to alter enzymatic and non-enzymatic antioxidants in the livers of ovariectomized rats. DHA presented the most evident antioxidant effect, decreasing protein and lipid damage.

Redox changes in the brains of reproductive female rats during aging.

Reproduction is a critical and demanding phase of an animal's life. In mammals, females usually invest much more in parental care than males, and lactation is the most energetically demanding period of a female's life. Here, we tested whether oxidative stress is a consequence of reproduction in the brains of female Wistar rats. We evaluated the activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase; H2O2 consumption; protein carbonylation; NO2 & NO3 levels; and total glutathione, as well as sex hormone levels in brain tissue of animals at 3, 6, 12, and 24months of age. Animals were grouped according to reproductive experience: breeders or non-breeders. Most of the studied parameters showed a difference between non-breeders and breeders at 12 and 24months. At 24months of age, breeders showed higher superoxide dismutase activity, H2O2 consumption, glutathione peroxidase activity, and carbonyl levels than non-breeders. In 12-month-old non-breeders, we observed a higher level of H2O2 consumption and higher superoxide dismutase and glutathione peroxidase activities than breeders. By evaluating the correlation network, we found that there were a larger number of influential nodes and positive links in breeder animals than in non-breeders, indicating a greater number of redox changes in breeder animals. Here, we also demonstrated that the aging process caused higher oxidative damage and higher antioxidant defenses in the brains of breeder female rats at 24months, suggesting that the reproduction process is costly, at least for the female brain. This study shows that there is a strong potential for a link between the cost of reproduction and oxidative stress.

Relationship between post-cardiac arrest myocardial oxidative stress and myocardial dysfunction in the rat.

BACKGROUND: Reperfusion after resuscitation from cardiac arrest (CA) is an event that increases reactive oxygen species production leading to oxidative stress. More specifically, myocardial oxidative stress may play a role in the severity of post-CA myocardial dysfunction. This study investigated the relationship between myocardial oxidative stress and post-CA myocardial injury and dysfunction in a rat model of CA and cardiopulmonary resuscitation (CPR). Ventricular fibrillation was induced in 26 rats and was untreated for 6 min. CPR, including mechanical chest compression, ventilation, and epinephrine, was then initiated and continued for additional 6 min prior to defibrillations. Resuscitated animals were sacrificed at two h (n = 9), 4 h (n = 6) and 72 h (n = 8) following resuscitation, and plasma collected for assessment of: high sensitivity cardiac troponin T (hs-cTnT), as marker of myocardial injury; isoprostanes (IsoP), as marker of lipid peroxidation; and 8-hydroxyguanosine (8-OHG), as marker of DNA oxidative damage. Hearts were also harvested for measurement of tissue IsoP and 8-OHG. Myocardial function was assessed by echocardiography at the corresponding time points. Additional 8 rats were not subjected to CA and served as baseline controls. RESULTS: Compared to baseline, left ventricular ejection fraction (LVEF) was reduced at 2 and 4 h following resuscitation (p < 0.01), while it was similar at 72 h. Inversely, plasma hs-cTnT increased, compared to baseline, at 2 and 4 h post-CA (p < 0.01), and then recovered at 72 h. Similarly, plasma and myocardial tissue IsoP and 8-OHG levels increased at 2 and 4 h post-resuscitation (p < 0.01 vs. baseline), while returned to baseline 72 h later. Myocardial IsoP were directly related to hs-cTnT levels (r = 0.760, p < 0.01) and inversely related to LVEF (r = -0.770, p < 0.01). Myocardial 8-OHG were also directly related to hs-cTnT levels (r = 0.409, p < 0.05) and inversely related to LVEF (r = -0.548, p < 0.01). CONCLUSIONS: The present study provides evidence that lipid peroxidation and DNA oxidative damage in myocardial tissue are closely related to myocardial injury and LV dysfunction during the initial hours following CA.

Oxidative stress in testis of animals during aging with and without reproductive activity.

The free radical theory of aging postulates that an imbalance between reactive oxygen species (ROS) and reactive nitrogen species (RNS) and antioxidant defenses is important in senescence. To address this issue and gain insight into the aging process, we have evaluated the antioxidant defenses and have assessed oxidative damage in testis tissues in aging male rats. In order to relate aging and reproduction, animals with and without reproductive activity were studied. In reproductive animals the results showed a progressive increase in antioxidant enzyme activity until 12 months of age followed by an abrupt fall at 24 months. In non-reproductive animals, antioxidant activity was stable through 12 months of age, but again, fell abruptly at 24 months of age. In addition, increased aconitase activity and increased testosterone levels were found among reproductively active animals. The data demonstrate the existence of metabolic differences in testis of reproductively experienced animals and reproductively naïve animals.

Oxidative stress in the brain of reproductive male rats during aging.

Reproduction alters the male physiology. We performed a comprehensive study to examine oxidative stress in the brains of male rats with (experienced) or without (naïve) reproductive activity during aging. Oxidative stress was assessed by measuring the activity of catalase, glutathione peroxidase, superoxide dismutase, glutathione S-transferase, aconitase, and aconitase reactivated, and by measuring lipid peroxidation, protein carbonylation, nitrite and nitrate levels, vitamin C levels, and glutathione (total, reduced, oxidized forms) levels in brain tissue, as well as testosterone and estradiol levels in serum. Reproductively active animals exhibited increased testosterone levels and aconitase activity, suggesting an increased metabolism. Increased antioxidant enzyme activities and increased levels of antioxidant compounds were observed, yet damage to biomolecules was also observed in experienced rats. During aging changes in oxidative stress were observed. We found higher activities of antioxidant enzymes, higher amounts of antioxidants, and more damage at six months of age among experienced animals than among naïve animals. Similar antioxidant activities and levels, and damage were found between the groups at twenty-four months of age. These results add comprehensive data regarding changes in oxidative stress during aging, and suggest an explanation for the costs of reproduction.

Inflammatory and oxidative stress markers after intravenous insulin in percutaneous coronary intervention with stent in type 2 diabetes mellitus: a randomized controlled trial.

CONTEXT/OBJECTIVE: The objective of the study was to evaluate the effects of normalizing glycemia through iv insulin per 24 h on markers of oxidative stress and inflammation in patients with diabetes submitted to percutaneous coronary intervention (PCI) with stent. PATIENTS/METHODS: This was a prospective, open-label, randomized controlled trial, comparing continuous iv insulin per 24 h targeting glycemia less than 110 mg/dl iv insulin treatment (IIT; n = 35) to standard treatment (ST; n = 35, regular insulin if glycemia was greater than 200 mg/dl). Blood samples for glycemia, glycated hemoglobin, lipids, inflammatory markers [C-reactive protein (CRP), soluble CD40 ligand, IL-6, and endothelin 1 (ET-1)] and oxidative stress (total antioxidant status, carbonyl) were collected immediately after and 24 h after PCI. RESULTS: Seventy patients were included. Mean age was 60.5 ± 10 yr, 60% were men, glycated hemoglobin was 8.1 ± 1.8 (IIT) vs. 7.6 ± 1.6% (ST) (P = 0.39). The intensive insulin group had lower glycemia (P = 0.006) and higher insulinemia (P < 0.001). Insulin did not change CRP [4.5 (2.1-11.7) vs. 6.8 (2.4-10.3), P = 0.35], soluble CD40 ligand [402 (191-843) vs. 610 (230-1200), P = 0.68], IL-6 [6.21 (3.1.-10.4) vs. 10.37 (5.9-15.3), P = 0.09], and ET-1 [1.02 (0.7-1.8) vs. 1.10 (0.7-1.9), P = 0.657]. CRP, IL-6, and ET-1 increased after PCI in both groups (P < 0.05). No change was observed on protein oxidation (carbonyl, P = 0.70; total antioxidant status, P = 0.33). There was a positive correlation between CRP and glycemia (r = 0.29, P = 0.002). CONCLUSIONS: Continuous iv insulin for 24 h increased insulin levels and prevented hyperglycemia. Insulin infusion did not prevent the rise in inflammatory and oxidative stress markers, and no differences were observed between IIT and ST after PCI with a stent.

Response to oxidative stress in eight pathogenic yeast species of the genus Candida.

In the course of an infection, the formation of reactive oxygen species by phagocytes and the antioxidant defense mechanisms of microorganisms play a crucial role in pathogenesis. In this study, isolates representing 8 pathogenic Candida species-Candida albicans, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida krusei, Candida parapsilosis and Candida tropicalis-were compared with regard to their resistance to oxidative stress in vitro. We evaluated degree of resistance, induction of oxidative damage, capacity to adapt, and induction of antioxidant enzymes. The species showed variable sensitivity to oxidative attack. C. albicans, C. glabrata, and C. krusei were more resistant to oxidative stress under the conditions tested; C. parapsilosis and C. tropicalis presented medium resistance; and C. dubliniensis, C. famata, and C. guilliermondii were more sensitive. The overall greater resistance to oxidative stress of C. albicans and C. glabrata may provide an advantage to these species, which are the major causative agents of candidiasis.

Pulmonary antioxidant defences and protein damage during the ageing process of both sexes.

The free radical theory holds that the senescence is caused by oxidative damage that results from an imbalance between reactive oxygen and nitrogen species (RONS) and antioxidant defences. Hence, it plays an important role in the field of gerontology. We evaluated, in male and female rats, the activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and total superoxide dismutase (tSOD), as well as oxidative protein damage in pulmonary tissue at 3, 6, 12, and 20 months of age. The results show an increase in the activities of all antioxidant enzymes at 12 months of age in female rats, suggesting an association with the reproductive life cycle. Protein damage in female pulmonary tissues did not change significantly throughout the ageing process. In male rats, the activity of GPx in 20 months of age showed an inter-gender increase, while the tSOD and GPx showed higher activities in 20 months of age in the intra-gender analysis. The male lung showed higher protein damage at 6 months of age. These findings suggest that antioxidant enzymatic activity is connected to the reproductive life cycle.