Protein Carbonyl Levels Research Articles

Maternal Obesity Alters Placental and Umbilical Cord Plasma Oxidative Stress, a Cross-Sectional Study.

Maternal obesity has been shown to impair the oxidative status in the placenta and newborns, potentially leading to adverse pregnancy outcomes and long-term effects on the programming of offspring metabolic status. This study aimed to investigate the impact of maternal obesity on maternal and umbilical cord plasma oxidative status, as well as placental oxidative adaptation. Maternal obesity (n = 20), defined as a pre-pregnancy BMI ≥ 25 kg/m2, and maternal leanness (n = 20), defined as a pre-pregnancy BMI < 23 kg/m2, were the group categories used in this study. Both groups were matched according to gestational age at delivery. Maternal blood, umbilical cord blood, and placental tissue were collected to assess nutritional content (cholesterol, triglyceride, and protein), oxidative stress markers (MDA and protein carbonyl), and antioxidant activity (SOD and catalase). Placental protein expression (SOD2, catalase, UCP2, and Nrf2) was evaluated using Western blot analysis. Catalase activity in maternal plasma significantly increased in the maternal obesity group (p = 0.0200), with a trend toward increased MDA and protein carbonyl levels. In umbilical cord plasma, triglyceride, protein carbonyl, and catalase activity were significantly elevated in the maternal obesity group compared with the lean controls (p = 0.0482, 0.0291, and 0.0347, respectively). Placental protein expression analysis revealed significantly decreased SOD2 (p = 0.0011) and catalase (p < 0.0001), along with Nrf2 downregulation (p < 0.0001). An increase in mitochondrial antioxidant UCP2 expression was observed (p = 0.0117). The neonatal protein carbonyl levels positively correlated with placental protein carbonyl (r = 0.7405, p < 0.0001) and negatively correlated with maternal catalase activity (r = -0.4332, p = 0.0052). This study thus provides evidence that maternal obesity is associated with placental and fetal oxidative stress, alongside a concurrent increase in placental antioxidant UCP2 expression.

Lactoferrin modulates oxidative stress and inflammatory cytokines in a murine model of dysbiosis induced by clindamycin.

Antibiotics, specifically clindamycin, cause intestinal dysbiosis, reducing the microbiota with anti-inflammatory properties. Furthermore, clindamycin can induce alterations in the immune responses and oxidative stress. Lactoferrin, among other activities, participates in the maintenance of intestinal homeostasis and reduces dysbiosis induced by antibiotic treatment. The aim of this study was to analyze the effect of native and iron-saturated bovine LF in a murine model of dysbiosis induced by clindamycin. Six groups of male C57BL/6 mice were treated with saline (control), clindamycin (Clin), native lactoferrin (nLF), iron-saturated lactoferrin (sLF), nLF/Clin or sLF/Clin. Oxidation caused in the intestinal cells of the ileum of animals subjected to different treatments was analyzed, focusing on lipid peroxidation and protein carbonyl content. The expression of inflammatory mediators was determined by qRT-PCR. Treatment with clindamycin did not modify lipid peroxidation, but significantly increased protein carbonyl levels up to almost 5-fold respect to the control, an effect that was reversed by orally administering sLF to mice. Furthermore, clindamycin increased the expression of interleukin-6 and TNF-α by 1- and 2-fold change, respectively. This effect was reversed by treatment with nLF and sLF, decreasing the expression to basal levels. In conclusion, this study indicates that lactoferrin can prevent some of the effects of clindamycin on intestinal cells and their associated immune system.

8624 Maternal ZIKV Infection Causes Oxidative Damage in Placenta of Both Female and Male Mice

Abstract Disclosure: V.M. Nascimento: None. I.S. Andrade: None. C.B. Andrade: None. R.S. Alves: None. R.P. Sousa: None. A.C. Valim: None. L.S. Dias: None. K.N. Fontes: None. I.F. Miranda: None. S.A. Coelho: None. L.B. Arruda: None. R.S. Fortunato: None. T.M. Ortiga-Carvalho: None. The placenta is a maternal-fetal organ with nutritional, exchanging, hormonal and protecting functions that are vital for fetal growth and development during gestation. However, these functions can be disturbed by vertically transmitted pathogens such as Zika virus (ZIKV). In 2015, ZIKV was responsible for an increasing number of newborns with congenital abnormalities in Brazil, known as Congenital Zika Syndrome (CZS). Nonetheless, the extension of ZIKV infection in the placenta, leading to CZS, is still unclear. It is known that ZIKV causes oxidative stress in trophoblasts. However, no one has ever studied placental oxidative stress caused by ZIKV infection in vivo. Here, we investigated whether maternal ZIKV infection could cause sex-specific oxidative stress in murine placenta. At gestational day (GD)12.5, pregnant mice (C57BL/6; 8-12 weeks old) were infected with ZIKV-BRPE243 (5x107 PFU; ZIKV group, n=22) or Mock (supernatants of noninfected C6/36 cells; control group, n=28). At GD18.5, c-section was performed and maternal spleens, placentas, fetuses and fetal brains were collected. We measured placental carbonylated protein levels (n=7), by 2D OxyBlot, nitrotyrosine residues (n=5), by immunohistochemistry, reduced thiol content (n=9), total superoxide dismutase (SOD; n=9) and total glutathione peroxidase (GPx; n=9) activities, by spectrophotometry. Data were analyzed by unpaired Student’s t test and Two-Way ANOVA with Tukey’s post test and represented as mean±SEM. ZIKV infection increased maternal spleen weight (p&amp;lt;0.0001) and decreased both female (p=0.0429) and male (p=0.0171) placental weight. Although placental weights were affected by the infection, female and male fetal weight and fetal crown-rump length were not changed. Conversely, maternal ZIKV infection increased only female fetal brain weight (p=0.0028). Moreover, we found that ZIKV infection increased nitrotyrosine residues in the placental labyrinth region of both female (p&amp;lt;0.0001) and male (p=0.0007) fetuses. Meanwhile, nitrotyrosine residues were increased by the infection only in the placental junctional zone of female fetuses (p=0.0131). Although ZIKV increased this oxidative damage biomarker, placental carbonylated protein levels were not changed by the infection in both sexes. Also, reduced thiol content and total SOD and GPx activities were not affected. Together, our data show that maternal ZIKV infection caused oxidative stress in both placental regions of female and male fetuses, as we saw that ZIKV increased oxidative damage, although antioxidant defenses were not changed by the infection, at least at term (GD18.5). ZIKV infection may have disturbed placental growth, as we found that placental weight was decreased in both sexes. Moreover, we believe that the increase in the female fetal brain weight could be a suggestive feature of cerebral edema or hydrocephalus. Presentation: 6/2/2024

8624 Maternal ZIKV Infection Causes Oxidative Damage in Placenta of Both Female and Male Mice

Abstract Disclosure: V.M. Nascimento: None. I.S. Andrade: None. C.B. Andrade: None. R.S. Alves: None. R.P. Sousa: None. A.C. Valim: None. L.S. Dias: None. K.N. Fontes: None. I.F. Miranda: None. S.A. Coelho: None. L.B. Arruda: None. R.S. Fortunato: None. T.M. Ortiga-Carvalho: None. The placenta is a maternal-fetal organ with nutritional, exchanging, hormonal and protecting functions that are vital for fetal growth and development during gestation. However, these functions can be disturbed by vertically transmitted pathogens such as Zika virus (ZIKV). In 2015, ZIKV was responsible for an increasing number of newborns with congenital abnormalities in Brazil, known as Congenital Zika Syndrome (CZS). Nonetheless, the extension of ZIKV infection in the placenta, leading to CZS, is still unclear. It is known that ZIKV causes oxidative stress in trophoblasts. However, no one has ever studied placental oxidative stress caused by ZIKV infection in vivo. Here, we investigated whether maternal ZIKV infection could cause sex-specific oxidative stress in murine placenta. At gestational day (GD)12.5, pregnant mice (C57BL/6; 8-12 weeks old) were infected with ZIKV-BRPE243 (5x107 PFU; ZIKV group, n=22) or Mock (supernatants of noninfected C6/36 cells; control group, n=28). At GD18.5, c-section was performed and maternal spleens, placentas, fetuses and fetal brains were collected. We measured placental carbonylated protein levels (n=7), by 2D OxyBlot, nitrotyrosine residues (n=5), by immunohistochemistry, reduced thiol content (n=9), total superoxide dismutase (SOD; n=9) and total glutathione peroxidase (GPx; n=9) activities, by spectrophotometry. Data were analyzed by unpaired Student’s t test and Two-Way ANOVA with Tukey’s post test and represented as mean±SEM. ZIKV infection increased maternal spleen weight (p&amp;lt;0.0001) and decreased both female (p=0.0429) and male (p=0.0171) placental weight. Although placental weights were affected by the infection, female and male fetal weight and fetal crown-rump length were not changed. Conversely, maternal ZIKV infection increased only female fetal brain weight (p=0.0028). Moreover, we found that ZIKV infection increased nitrotyrosine residues in the placental labyrinth region of both female (p&amp;lt;0.0001) and male (p=0.0007) fetuses. Meanwhile, nitrotyrosine residues were increased by the infection only in the placental junctional zone of female fetuses (p=0.0131). Although ZIKV increased this oxidative damage biomarker, placental carbonylated protein levels were not changed by the infection in both sexes. Also, reduced thiol content and total SOD and GPx activities were not affected. Together, our data show that maternal ZIKV infection caused oxidative stress in both placental regions of female and male fetuses, as we saw that ZIKV increased oxidative damage, although antioxidant defenses were not changed by the infection, at least at term (GD18.5). ZIKV infection may have disturbed placental growth, as we found that placental weight was decreased in both sexes. Moreover, we believe that the increase in the female fetal brain weight could be a suggestive feature of cerebral edema or hydrocephalus. Presentation: 6/2/2024

Oxidative protein damage negatively affects protein-protein interaction: The case of KRAS-cRAF

Protein-protein interactions (PPIs) play crucial roles in cellular signaling, transmitting signals from the cell surface to its interior. One of the most important signaling cascades is the RAS-RAF-MEK-ERK pathway. This pathway is initiated by various upstream signaling reactions, including receptor tyrosine kinase (RTK) activation, and it controls many biological functions like cell proliferation, differentiation, and survival. Once RAS is activated, it binds RAF and relays the signal to downstream proteins. The RAS-binding domain (RBD) in RAF protein plays a crucial role in this process, facilitating the RAS-ERK pathway signaling.In this study, we explored the effect of oxidative stress induced by UV radiation on the KRAS-RBD interaction. Using the Split Intein-Mediated Protein Ligation (SIMPL) method, we assessed the impact of different UV doses on KRAS-RBD interactions and observed a disruption of this interaction at higher doses. UV-treated samples exhibited high levels of protein carbonylation, as detected by Oxime Blot and mass spectrometry (MS) analysis, indicating oxidative damage. The MS results provided detailed insights into specific carbonylation modifications on the KRAS protein.Our study demonstrates that protein oxidation and carbonylation can disrupt protein-protein interactions, specifically the KRAS/c-RAF interaction. These findings highlight the impact of oxidative stress on signaling pathways, such as those triggered by UV irradiation. A deeper understanding of these molecular changes may aid in developing therapies targeting diseases linked to oxidative stress, including cancer.

Brain mitochondrial damage attenuation by quercetin and N-acetyl cysteine: peripheral and central antiemetic effects.

Nausea serves as a protective mechanism in organisms to prevent excessive consumption of toxic substances. Due to the adverse effects of chemical anti-nausea drugs, there is a growing interest in using herbal remedies and natural antioxidants. In this study, we evaluated the neuroprotective effects of quercetin (QU) and N-acetylcysteine (NAC) against oxidative damage induced by nausea. Emesis was induced in chickens using ipecac and copper sulfate (600 and 60mg/kg, orally, respectively). QU and NAC (with doses of 50, 100, 200mg/kg), and their combination were administered, along with a standard therapy (metoclopramide; MET 2mg/kg) for one-time. Mitochondrial function, lipid peroxidation (LPO), protein carbonyl (PC), glutathione level (GSH), and reactive oxygen species (ROS) as oxidative damage biomarkers were evaluated in the chicken's brain mitochondria. QU and NAC significantly reduced emesis induced by copper sulfate and ipecac compared to the control group (P<0.001). Significant differences in oxidative damage were observed in the groups received of copper sulfate and ipecac compared with control group. Levels of LPO, ROS, and PC were significantly decreased after the administration of QU and NAC in emesis induced by copper sulfate and ipecac. While, mitochondrial function and GSH levels were increased after the administration of QU and NAC. Combination therapy with QU and NAC yielded the most effective results. This study suggests that QU and NAC possess antiemetic effects through both peripheral and central mechanisms and exhibit neuroprotective effects against oxidative brain damage induced by emesis by increasing plasma antioxidants or scavenging free radicals.

Biotransformation and oxidative stress markers in yellowfin seabream (Acanthopagrus latus): Interactive impacts of microplastics and florfenicol

This study investigates the combined toxicity of microplastics (MPs) and florfenicol (FLO) on biotransformation enzymes and oxidative stress biomarkers in the liver and kidney of yellowfin seabream (Acanthopagrus latus). Fish were fed 15 mg kg−1 of FLO and 100 or 500 mg kg−1 of MPs for 10 days. Biomarkers, including ethoxyresorufin-O-deethylase, glutathione-S-transferase, superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde (MDA), and protein carbonylation (PC), were measured in both organs at 1, 7, and 14 days post-exposure. FLO levels peaked on day 1 and declined after that. Liver biomarkers were more responsive to pollutants, with the combined exposure of FLO and MPs leading to more pronounced toxicity. By day 14, only the FLO group showed a return to baseline biomarker levels, while MDA and PC levels remained elevated in MPs and co-exposed groups. These findings highlight the importance of considering the interactive effects of multiple pollutants in addressing marine environmental stressors.

Oxidative stress causes liver injury via the damage of redox system and the apoptosis induced by mitochondria of broiler

The aim of this study was conducted to explore the effects of oxidative stress on the redox system, mitochondrial function, and apoptosis in liver of broilers. 144 one-day-old male Ross-308 broilers from the same batch had been prepared in advance and were divided into 3 treatments: normal control group (without intraperitoneal injection), normal saline group (intraperitoneal injection of normal saline), and hydrogen peroxide (H2O2) group (intraperitoneal injection of H2O2) with 6 replicates of 8 chickens each. The experimental period was 42 days. The injection volumes were 1.0 mL/kg of Ross-308 broiler body weight. On the 42nd day of the experimental period, two Ross-308 broilers were randomly selected from each cage, a total of 36 broilers were stunned by electric shock and slaughtered to collect liver samples. The results showed that compared with the non-injection group and the injection of saline group, H2O2 exposure elevated the relative weight of liver and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum of Ross-308 broilers (p < 0.05). Meanwhile, compared with the non-injection group and the injection of saline group, the H2O2 exposure increased the levels of reactive oxygen species (ROS), MDA, lipid peroxide (LPO) and protein carbonyl, decreased the activities of total superoxide dismutase (T-SOD), catalase (CAT), total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) (p < 0.05). Compared with the non-injection group and the injection of saline group, the H2O2 exposure caused microvesicular steatosis and mitochondrial vacuolisation in the liver tissues of broilers. Additionally, after H2O2 exposure, the levels of nuclear factor erythroid 2–related factor 2 (Nrf2) positive cells were reduced and the relative percentage of hepatocyte apoptosis were increased in the liver tissues of broilers (p < 0.05). The conclusion of this study is that the oxidative stress induced by intraperitoneal injection of H2O2 could induce excessive production of ROS in broiler liver, which damage the antioxidant status and mitochondrial function of liver cells, leading to cell apoptosis. HIGHLIGHTS Oxidative stress can cause severe damage to the liver of broilers. Oxidative stress can mainly damage liver antioxidant function Oxidative stress can induce cell apoptosis by damaging mitochondria in the liver of broilers

Comparative Analysis of Oxidative Metabolism in Liver in Different Experimental Models of Hypothyroidism: Low Iodine Diet and Anti-Thyroid drug (Methimazole)

Objectives: On the concept of oxidative stress in hypothyroidism, which still remains ambiguous and controversial, the article emphasizes the issue of the impact of the experimental conditions on the validity of the data obtained in different methods of modeling thyroid dysfunction. Materials and Methods: Experiments were conducted on 112 white nonlinear male rats. Thyroid hormones and biomarkers of oxidative metabolism in the liver tissue were determined in rats kept for 3 months on a low-iodine diet (LID) and in rats with methimazole (MMI)-induced hypothyroidism (2,5 mg/100 g of body weight for 3 weeks). Results: In LID-rats (n=96) total serum T4 amounted 43, total T3 in liver tissue - 73% of the level found in euthyroid animal, p=0.0121 and p=0.0051, respectively), whereas in MMI-rats (n=96) both total and free serum T4 were 67% of control (p=0.0002 for both total and free T4). In LID-rats cytochrome oxidase (CcOX) activity in liver tissue was 68.5, concentration of malondialdehyde (MDA) - 58% of euthyroids (p value - 0.0202 and 0.0127, respectively), while protein carbonyls (PC) level was 116% of the control (p=0.0411). In MMI-rats liver malate dehydrogenase (MDH) activity decreased up to 70.9, but succinate dehydrogenase (SDH) activity and MDA concentration increased up to 163.6 and 154% of the level in euthyroid animals respectively (p˂0.05). Conclusion: LID-model led to the more pronounced inhibition of thyroid function, than that the MMI-hypothyroidism model used. LID-model was accompanied by a decrease in the intensity of oxidative metabolism in liver tissue, whereas MMI-hypothyroidism - by activation of the succinate oxidation pathway and an increase in the concentration of secondary lipid peroxidation products in the liver of experimental animals. The results suggest that the conflicting data obtained from studies of oxidative metabolism in hypothyroidism, among other assumptions, may be due to the different approaches used by researchers to model thyroid dysfunction.

Pharmaceutical Interventions for the Management of Hemorrhagic Shock in Hepatic Surgery: An Experimental Swine Model Outcome.

Introduction During abdominal trauma or major hepatic surgery, the liver can be subjected to hypoxic conditions due to hemorrhage, leading to various degrees of ischemic injury to hepatocytes. Hemorrhagic shock, a critical and life-threatening condition, often complicates hepatic surgery due to massive blood loss, resulting in inadequate tissue perfusion and oxygenation. The challenge in managing hemorrhagic shock in hepatic surgery is heightened by the liver's unique blood supply and its crucial role in coagulation. Effective treatment requires a multifaceted approach, including surgical intervention, blood transfusions, and pharmaceutical therapy to stabilize hemodynamics and promote coagulation. Additionally, reperfusion of the liver after resuscitation can cause severe injury through inflammatory and oxidative pathways, potentially leading to multiple organ dysfunction. This study examines the effectiveness of combining standard fluid therapy with antioxidants (bucillamine and valproic acid) in mitigating oxidative stress and reducing hepatocyte damage in the context of hemorrhagic shock. Method Thirty male swine were randomly divided into four groups as follows: Group A (n=6/control group), Group B (n=8), Group C (n=8), and Group D (n=8). A resection of the left liver lobe was performed, followed by the controlled loss of a specific volume of blood until the mean arterial pressure dropped to between 30 and 40 mmHg. The animals were maintained in this state of hypovolemic shock for 50 minutes, followed by IV administration of fluids. Additionally, pharmaceutical agents were administered to Groups B (bucillamine), C (valproic acid), and D (combination of bucillamine and valproic acid). The experiment lasted six hours in total. Results The study showed that animals treated with pharmaceutical agents like bucillamine and valproic acid and their combination demonstrated significantly reduced serum levels of protein carbonyls (PCs) and thiobarbituric acid reactive substances (TBARS) compared to the control group. Furthermore, histological evaluation of liver tissues revealed that treated animals showed reduced histopathological signs of injury, suggesting that the pharmaceutical agents not only lowered biochemical markers of oxidative stress but also provided a protective effect against liver damage in the context of hemorrhagic shock. Conclusion These findings suggest that incorporating antioxidant therapy into resuscitation protocols may offer substantial benefits in mitigating hepatic damage associated with hemorrhagic shock. This approach could potentially improve outcomes in clinical settings where oxidative stress plays a critical role in injury progression by better understanding the pathophysiology of this complex and dynamic process.

Effects of uric acid on oxidative stress in vascular smooth muscle cells.

Hyperuricemia during hypertension is associated with aberrant vascular functions and increased oxidative stress, which affects endothelial dysfunction. Nevertheless, the molecular mechanisms underlying the effects of uric acid on vascular smooth muscle cells (VSMCs) through oxidative stress remain unclear. The aim of the present study was to investigate the dose- and time-dependent effects of uric acid on oxidative stress and p53 protein expression in VSMCs. VSMCs were incubated with various concentrations of uric acid (0-50 mg/dl) for different time periods (1-24 h). Thiobarbituric acid reactive substances (TBARs), protein carbonylation and nitric oxide (NO) levels were determined using appropriate assay kits. Superoxide anion release was detected using the Görlach method. Western blotting was performed to determine the protein expression levels of p53. The findings demonstrated that the application of uric acid led to an increase in protein carbonylation and superoxide anion levels while causing a decrease in NO levels. Conversely, no significant effect was observed on TBARS levels. Additionally, it was observed that high concentrations of uric acid suppressed p53 expression at 6, 12 and 24 h. The present study provided evidence that the influence of uric acid on oxidative stress was more closely associated with time than dose; however, not all effects observed were strictly time-dependent.

Serum levels of iron, zinc, selenium, copper and oxidative stress in hypertensive patients: A comparative study of age-related changes in the governorate of Basrah, Iraq

Hypertension is the force of blood through blood vessels, where the heart works harder and blood vessels are under more pressure. The relationship between trace element levels and oxidative stress in hypertension is under investigation, with conflicting results. This study aimed to determine the relationship between concentrations of certain antioxidant trace elements (iron, zinc, selenium, and copper) and protein carbonyl concentration as an indicator of oxidative stress in the serum of hypertensive patients compared to the control group in Basra, Iraq, according to age. The study included 100 hypertensive patients (44 males and 56 females) compared to 50 healthy individuals (25 males and 25 females). Patients were divided into three age groups: 35–45, 46–56, and over 57 years. The study showed a significant decrease (p&lt;0.001) in the mean concentration of all selected elements in the patients' serum compared to the control group. Conversely, the mean protein carbonyl level showed a significant increase (p&lt;0.001) in patients compared to the control group. Trace element concentrations decreased in patients with increasing age, while carbonyl protein levels increased, especially in the third age group. The study also showed a significant negative correlation between protein carbonyl level and all trace elements at p&lt;0.001. These results suggest that hypertension is associated with an imbalance in oxidative stress and trace elements. Monitoring trace element intake may help reduce oxidative stress and improve overall health in individuals with hypertension, especially with advancing age, by restoring the balance of essential elements and antioxidants in the body.

Melatonin protects against sarcopenia in middle-aged mice.

Sarcopenia is a common age-related disease. Melatonin (MEL) is an age-related endocrine hormone, which displays a crucial role in resisting oxidative stress during aging. Importantly, the antioxidant properties of MEL can be mediated by mitochondria. Therefore, we wondered whether MEL could mitigate oxidative stress caused by mitochondria in sarcopenia. The middle-aged mice were administered 5 mg/kg/d and 10 mg/kg/d of MEL for 2 months. Young mice were used as the control group. After treatment with MEL, the grip strength of the fore/hind limbs, running time, and distance were elevated, and the weights of the gastrocnemius (GA), tibialis anterior (TA), extensor digitorum longus (EDL), and soleus (SOL) were enhanced in middle-aged mice. Additionally, MEL was observed to alleviate histological damage and increase the cross-sectional area of muscle fibers in GA tissues of middle-aged mice. Furthermore, following MEL treatment, there was an increase in the percentage and size of normal mitochondria as well as mtDNA copy number but a reduction in the levels of malondialdehyde (MDA), protein carbonyl, and reactive oxygen species (ROS) in the GA tissues of middle-aged mice. At the molecular level, MEL repressed the levels of ATROGIN-1, muscle RING-finger protein-1 (MURF-1), and the ratio of p-P38/P38, but elevated the expression of cytochrome c oxidase subunit 4 (COX4), cystatin C (CYTC), nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in the GA tissues of middle-aged mice. Importantly, 10 mg/kg MEL was more efficacious in the treatment of sarcopenia than 5 mg/kg MEL. MEL attenuates sarcopenia in middle-aged mice, and the mechanism may relate to mitochondria-induced oxidative stress and the PGC-1α/TFAM pathway.

Impact of Extremely Low-Frequency Electromagnetic Fields on Skeletal Muscle of Sedentary Adult Mice: A Pilot Study.

Extremely low-frequency electromagnetic fields (ELF-EMFs) are ubiquitous in industrialized environments due to the continuous use of electrical devices. Our previous studies demonstrated that ELF-EMFs affect muscle cells by modulating oxidative stress and enhancing myogenesis. This pilot study investigated these effects on the skeletal muscles of sedentary adult mice, assessing physiological responses to ELF-EMF exposure and potential modulation by antioxidant supplementation. Male C57BL/6 mice were exposed to ELF-EMFs (0.1 or 1.0 mT) for 1 h/day for up to 5 weeks and fed a standard diet without or with N-acetyl-cysteine (NAC). The results showed transient increases in muscle strength (after 2 weeks of exposure at 1.0 mT), potentially linked to muscle fiber recruitment and activation, revealed by higher PAX7 and myosin heavy chain (MyH) expression levels. After ELF-EMF exposure, oxidative status assessment revealed transient increases in the expression levels of SOD1 and catalase enzymes, in total antioxidant capacity, and in protein carbonyl levels, markers of oxidative damage. These effects were partially reduced by NAC. In conclusion, ELF-EMF exposure affects skeletal muscle physiology and NAC supplementation partially mitigates these effects, highlighting the complex interactions between ELF-EMFs and antioxidant pathways in vivo. Further investigations on ELF-EMFs as a therapeutic modality for muscle health are necessary.

Sublethal Effect of Benzo[a]pyrene (B[a]P) on Oxidative Stress and Antioxidant Enzymes in the Mud Crab Scylla serrata

Under various severe environmental conditions, marine organisms can suffer from oxidative stress. In the mud crab, the sub-lethal effect of benzo[a]pyrene (B[a]P) using environmentally realistic concentrations (10 ppb and 20 ppb) on oxidative stress and antioxidant defenses was studied. For oxidative stress, levels of Thiobarbituric Acid (TBARS) and carbonyl protein (CP) were determined. After 30 days of B[a]P exposure, the tissues contained considerably more CP and TBARS. The tissues of crab exposed to sublethal level of B[a]P for 30 days showed decrease in antioxidant defense enzymes, including superoxide dismutase (SOD) and catalase (CAT). Under B[a]P exposure, SOD and CAT activities were decreased considerably in the hepatopancreas. The glutathione S transferase (GST) increased in the hepatopancreas due to B[a]P exposure. The current study found a strong link between oxidative stress and antioxidant defenses in crab exposed to B[a]P. Overall, the results show that hepatopancreas is the most sensitive component to oxidative damage, implying that Scylla serrata could be employed as a bioindicator of organic pollution exposure by evaluating antioxidant enzyme activities.

Analysis of the anti-Candida activity of tricyclic antidepressants in association with amphotericin B and their antifungal mechanisms.

Candida species are among the priority pathogens in the area of research and development. Due to the problems associated with resistance to antifungals, new therapeutic alternatives are necessary. In this regard, drug repositioning has gained prominence. The objective of this study was to evaluate the activity of three tricyclic antidepressants (TCAs) - amitriptyline (AMT), nortriptyline (NOR) and clomipramine (CLO) - isolated or associated with antifungals against strains of Candida spp., as well as to analyze the possible mechanism of action. Among the methods used were broth microdilution tests, tolerance level assessment, checkerboard assays, flow cytometry and fluorescence microscopy. Furthermore, Candida cells were visualized after treatments by scanning electron microscopy (SEM). AMT presented MIC 50% in the range of 16 to 128µg/mL, NOR from 8 to 128µg/mL, and CLO from 8 to 64µg/mL, with all three TCAs having a fungicidal inhibitory action profile. For these TCAs, there was synergism with amphotericin B (AMB) in 100% of the isolates. In association with fluconazole (FLC) and itraconazole (ITR), there were mostly indifferent interactions. TCAs isolated and associated with AMB reduced cell viability, promoted DNA fragmentation and damage, caused mitochondrial depolarization, externalization of phosphatidylserine, produced reactive oxygen species (ROS), decreased reduced glutathione (GSH) and increased carbonyl protein levels, causing morphological changes. The results suggest the antifungal mechanism of the TCAs works via the apoptotic pathway.

Biomonitoring of Heavy Metal Toxicity in Freshwater Canals in Egypt Using Creeping Water Bugs (Ilyocoris cimicoides): Oxidative Stress, Histopathological, and Ultrastructural Investigations.

The abundance of metal pollutants in freshwater habitats poses serious threats to the survival and biodiversity of aquatic organisms and human beings. This study intends for the first time to assess the pernicious influences of heavy metals in Al Marioteya canal freshwater in Egypt, compared to Al Mansoureya canal as a reference site utilizing the creeping water bug (Ilyocoris cimicoides) as an ecotoxicological model. The elemental analysis of the water showed a significantly higher incidence of heavy metals, including cadmium (Cd), cobalt (Co), chromium (Cr), nickel (Ni), and lead (Pb), in addition to the calcium (Ca) element than the World Health Organization's (WHO) permitted levels. The Ca element was measured in the water samples to determine whether exposure to heavy metals-induced oxidative stress engendered Ca deregulation in the midgut tissues of the creeping water bug. Remarkably, increased levels of these heavy metals were linked to an increase in chemical oxygen demand (COD) at the polluted site. Notably, the accumulation of these heavy metals in the midgut tissues resulted in a substantial reduction in antioxidant parameters, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and ascorbate peroxidase (APOX), along with a marked rise in malondialdehyde (MDA), cytochrome P450, and protein carbonyl levels. These results clearly indicate a noticeable disturbance in the antioxidant defense system due to uncontrollable reactive oxygen species (ROS). Notably, the results demonstrated that oxidative stress caused disturbances in Ca levels in the midgut tissue of I. cimicoides from polluted sites. Furthermore, the comet and flow cytometry analyses showed considerable proliferations of comet cells and apoptotic cells in midgut tissues, respectively, exhibiting prominent correlations, with pathophysiological deregulation. Interestingly, histopathological and ultrastructural examinations exposed noticeable anomalies in the midgut, Malpighian tubules, and ovarioles of I. cimicoides, emphasizing our findings. Overall, our findings emphasize the potential use of I. cimicoides as a bioindicator of heavy metal pollution in freshwater to improve sustainable water management in Egypt.

Green tea beverage protects against thiabendazole-induced kidney and liver injury through antioxidant actions in rats in vivo

ABSTRACT Thiabendazole (TBZ) is an important molecule used in several different areas. Two percent of green tea leaf extracts (GTE) obtained by maceration were tested against TBZ-induced liver and kidney toxicity, by using four groups of male Wistar rats controls, control-tea (2%), TBZ-treated, and TBZ+GTE. The results revealed, after 4 weeks of treatment, an increase in nitric oxide (NO), advanced oxidation protein products (AOPP) and protein carbonyl (PC) levels and a decrease in catalase activity in the tissues homogenates on TBZ-treated rats. The administration of GTE to TBZ-treated rats attenuated the increase in NO, AOPP and PC levels and improved activities of catalase and markers. Histological examination demonstrated marked tissue damage in the liver and kidney of TBZ-treated animals. Co-administration of TBZ and green tea reduced tissue damage. Acute exposure to TBZ leads to acute inflammation through oxidant – antioxidant imbalance. GTE could therefore be a useful therapeutic option for reversing TBZ-induced oxidative stress.

Storage causes protein oxidation of soybean meal and affects antioxidant status, digestive performance and meat quality of broilers.

This study investigated the protein oxidation of soybean meal (SBM) stored in a warehouse and the effects of SBM on growth performance, antioxidant status, digestive performance, intestinal morphology, and breast muscle quality of broilers. In total, 160 one-day-old Arbor Acres Plus broilers (half male and half female) were randomly divided into two groups with ten replicates of eight birds each: The control group was served with a basal diet including SBM stored at -20 °C (FSBM), and the experimental group was served with a basal diet including SBM stored in a warehouse at room temperature for 45 days (RSBM). Compared with FSBM, the protein carbonyl level in RSBM was increased, the free and total thiol levels and in vitro digestibility of protein were decreased. The RSBM decreased the serum glutathione (GSH) level and the hepatic total superoxide dismutase (T-SOD) activity at days 21 and 42 when compared with FSBM. Further, RSBM reduced the duodenal T-SOD activity, jejunal catalase (CAT), and T-SOD activities at day 21, and decreased the duodenal CAT and T-SOD activities, jejunal T-SOD activity, and ileal GSH level and T-SOD activity at days 21 and 42 when compared with FSBM. Besides, the trypsin activity and the ratio of villus height (VH) to crypt depth (CD) in small intestines of broilers at days 21 and 42 were reduced when fed with a RSBM-contained diet. Compared with FSBM, the 24-h drip loss, shear force, and 24- and 48-h cooking loss of breast muscle were increased of RSBM group, the opposite result was observed for muscle lightness at 48 h. Room temperature storage for 45 days led a protein oxidation and decreased in vitro digestibility in SBM, and fed RSBM impaired growth performance, antioxidant status, and meat quality, reduced trypsin activity, and affected the small intestine morphologyin broilers.

Curcumin Attenuates Doxorubicin-Induced Cardiac Oxidative Stress and Increases Survival in Mice.

Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat multiple types of cancer, but its clinical application is limited by cardiotoxicity, mainly due to oxidative stress. Curcumin (CUR) is a natural polyphenolic compound with strong antioxidant properties, but its potential protective effects against DOX-induced cardiotoxicity need further investigation. This study aimed to evaluate CUR's efficacy in mitigating DOX-induced oxidative stress in the hearts of BALB/c mice. Mice received a DOX dose of 9 mg/kg or 16 mg/kg; half of the mice received daily doses of 100 mg/kg CUR for 15 days. Survival analysis, histopathological examination, and oxidative stress markers were assessed to determine the cardioprotective effects of CUR. Results showed that CUR significantly reduced oxidative damage and improved survival rates, particularly at the lower DOX dose (9 mg/kg). Mice treated with DOX-9 mg/kg plus CUR showed improved health conditions and reduced levels of reactive oxygen species (ROS), lipid peroxidation, sulfhydryl production, and protein carbonylation. Histopathological analysis confirmed reduced cardiac tissue damage. In conclusion, CUR combined with a lower dose of DOX effectively reduces oxidative stress and cardiac injury, enhancing survival in BALB/c mice. These findings suggest that CUR is a promising adjunct therapy to mitigate DOX-induced cardiotoxicity, potentially improving the DOX therapeutic index in cancer treatment.