Elevated Total Antioxidant Capacity Research Articles

Design and Optimization of Sesamol Nanosuspensions to Potentiate the Anti-Tumor Activity of Epirubicin against Ehrlich Solid Carcinoma-Bearing Mice.

There is a growing interest in discovering natural sources of anti-cancer drugs. Sesamol (SES) is a phenolic compound with antitumor effects. The present study aimed to investigate the anticancer properties of SES and its nano-suspensions (SES-NS) combined with Epirubicin (EPI) in breast cancer (BC) using mice bearing a solid Ehrlich tumor. The study involved 35 female albino mice and investigated the effects of SES and EPI on tumor growth, proliferation, apoptosis, autophagy, angiogenesis, and oxidative stress. Methods including ELISA, qRT-PCR, and immunohistochemistry were utilized. The findings revealed reductions in tumor growth and proliferation using SES either alone or combined and evidenced by decreased AKT (AKT Serine/Threonine kinase1) levels, angiogenesis indicated by lower levels of VEGFR (vascular endothelial growth factor), and apoptosis demonstrated by elevated caspase3 and BAX levels. Furthermore, autophagy increased and was indicated by increased levels of beclin1 and lc3, along with decreased oxidative stress as evidenced by elevated TAC (total antioxidant capacity) and reduced MDA (malondialdehyde) levels. Interestingly, SES-NS demonstrated more significant effects at lower doses. In summary, this study underscores the potential of SES as a promising agent for BC treatment. Moreover, SES-NS potentiated the beneficial effects of EPI while mitigating its adverse effects.

Strategic administration of antioxidant multiminerals and vitamins to transitional buffaloes augments antioxidant and udder defense mechanisms in early lactation

The aim of the study was to examine the effects of repeated administrations of antioxidant multiminerals and vitamins in transition buffaloes on udder defense mechanism, antioxidant activity and occurrence of intramammary infection (IMI) in early lactation period. Forty clinically healthy pregnant buffaloes were enrolled 45 days before expected date of calving and randomly allocated into five different supplementation groups (n = 8): only basal ration (control), vitamin E and selenium (VES), multiminerals (MM), ascorbic acid (AA) and chromium (Cr) picolinate in basal diet. The udder defense mechanism was monitored by measuring phagocytic activity (PA), myeloperoxidase (MPO) and nitric oxide (NO) productions in milk leukocytes, antioxidant activity was evaluated by measuring total antioxidant capacity (TAC) in plasma and occurrence of IMI was assessed by milk cytology, bacterial count in milk and visible clinical signs of udder until day 28 post-calving. The results showed that the VES and MM supplementations exhibited significantly higher PA, MPO and NO productions of milk leukocytes till first week of lactation whereas, elevated mean TAC in plasma was maintained from day −7 to 1 of calving in MM supplementation group as compared to control group. Statistically, no significant difference in occurrences of subclinical or clinical IMI was noted across the groups until four weeks of lactation. Taken together, it is concluded that repeated administrations of VES and MM to transition buffaloes could be an effective strategy to maintain good udder health by augmenting milk leukocyte functions and antioxidant status and preventing incidence of IMI in early lactation.

Combined quercetin and simvastatin attenuate hepatic fibrosis in rats by modulating SphK1/NLRP3 pathways

Liver fibrosis involves several signalling pathways working in concert regulating the deposition of extracellular matrix. In this study, we evaluated the effect of quercetin and simvastatin alone and their combination on the treatment of experimentally induced hepatic fibrosis in rats. To decipher the potential mechanisms involved, liver fibrosis was induced in rats by administration of 40 % carbon tetrachloride (CCl4) (1 μl/g rat, i.p., twice weekly) for 6 weeks. Quercetin (50 mg/kg, orally), simvastatin (40 mg/kg, orally) either individually or combined were administered for another 4 weeks. The three treatment groups ameliorated hepatic dysfunction and altered parameters of sphingolipid and pyroptosis pathways. Yet, the combined group showed a more pronounced effect. Treatments lowered serum levels of GOT, GPT, ALP and elevated albumin and total protein levels. Histopathological and electron microscope examination of liver tissue revealed diminished fibrosis and inflammation. Protein expression levels of α-SMA, IL-1β, PPAR-γ, TGF-β1, caspase-1 and caspase-3 expression in liver tissues were reduced. Additionally, hepatic mRNA levels of SphK1 and NLRP3 decreased after treatment. Furthermore, the three groups lowered MDA levels and elevated total antioxidant capacity, GSH and Nrf2 expression levels. Treatments downregulated sphingolipid pathway and NLRP3-mediated pyroptosis and stimulated an anti-apoptotic, anti-proliferative and antioxidant activity. This suggests that targeting the SphK1/NLRP3 pathway could be a prospective therapeutic strategy against liver fibrosis.

Comparison of the Effects of Rosmarinic Acid and Electromagnetic Radiation-Induced Cardiotoxicity on Rats.

Electromagnetic radiation (EMR) causes stable aggregation of reactive oxygen species (ROS), producing oxidative stress. Rosmarinic acid (RA), a plant-origin antioxidant, has been proposed against the side effects of cell phone and ultrahigh-frequency waves. Forty-two male Wistar rats were randomly divided into 6 groups. Group 1 (controls) received 5 mL of normal saline with the gavage method, Group 2 received 915 MHz radiation, Group 3 received 2450 MHz radiation, Group 4 received RA plus 915 MHz radiation, Group 5 received RA plus 2450MHz radiation, and Group 6 received oral RA (5 mg/kg). Treatment and radiation (1 hour per day) continued for up to 30 days. EMR significantly reduced the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), the content of glutathione (GSH), and the level of total antioxidant capacity (TAC) and significantly increased oxidative stress indices, such as the levels of malondialdehyde (MDA) and nitric oxide (NO), and the content of protein carbonyl (PC). In contrast, RA significantly elevated TAC level (all groups), GSH content (the RA/cell phone radiation group), GPx activity (the RA/ultrahigh-frequency radiation group), SOD activity (all groups), and CAT activity (RA/ultrahigh-frequency radiation group) and conversely reduced MDA level (all groups), NO level (all groups), and PC content (all groups) in the RA/cell phone and RA/ultrahigh-frequency radiation groups compared with the NS/cell phone and NS/ultrahigh-frequency radiation groups, respectively. The administration of RA resulted in a significant reversal of cardiac markers in EMR-intoxicated rats. RA treatment showed a significant protective effect against EMR-induced cardiotoxicity.

Meta-Analysis of Assessment of Total Oxidative Stress and Total Antioxidant Capacity in Patients with Periodontitis.

Periodontitis is intricately linked to oxidative stress-antioxidant (redox) imbalance. The antioxidant system scavenges the oxygen free radicals in biological fluids in patients with periodontitis. However, little is still known about the free radicals mediated oxidative stress and reductive ability of the antioxidant system. Thus, the present meta-analysis aims to quantitatively review the literature that assessed the oxidative stress marker total oxidative stress (TOS) and total antioxidant capacity (TAC) in various biological fluids of patients with periodontitis. Methodology. Electronic databases were searched for studies that assessed TOS and TAC levels in various biological samples of patients with periodontitis. From the 1,812 articles identified, 1,754 were excluded based on title and abstract screening due to irrelevance to the topic of interest. A full-text assessment of the remaining 58 articles led to the selection of 42 articles that satisfied the inclusion criteria. Of these, only 24 studies had consistent data for quantitative analysis. The periodontitis group displayed significantly elevated TOS levels (p < 0.05) in serum, gingival crevicular fluid (GCF), and saliva samples in the studies evaluated. In contrast, the periodontitis group exhibited significantly attenuated TAC levels (p < 0.01) compared to healthy controls in plasma, serum, and GCF samples of the studies evaluated, which was insignificant in salivary samples (p=0.433). At the same time, the periodontitis group displayed insignificantly elevated TAC levels after periodontal therapy (p=0.130). The present meta-analysis showed significantly higher TOS and lower TAC in periodontitis, reflecting the elevated oxidative stress level than the control group. Clinical Relevance. Scientific rationale for the study: The imbalance between oxidants and antioxidants (oxidative stress (OS)) plays a critical role in the onset and progression of periodontitis; the assessment of the relationship between OS-related biomarkers in regional samples and systemic samples of patients with periodontitis helps us to evaluate the periodontal disease progression. The OS biomarker levels can be used to assess periodontal disease and therapeutic efficacy.

Oxidative, Genotoxic and Cytotoxic Damage Potential of Novel Borenium and Borinium Compounds

In this study, the biological properties of novel borenium and borinium compounds in terms of their oxidative, genotoxic, and cytotoxic effects were assessed on cultured human peripheral blood cells, as well as several types of cancer cells. Our results revealed that the borinium compounds yielded the best results in terms of supporting total antioxidant capacity (TAC). In fact, borenium 1, borenium 2, borenium 3, borinium 4, and borinium 5 compounds elevated TAC levels of cultured human blood cells at rates of 42.8%, 101.5%, 69.8%, 33.3%, and 49.2%, respectively. There were no statistically significant differences (p &gt; 0.05) between the negative control and the groups treated with all borinium and borenium concentrations from the micronucleus (MN) and chromosome aberration (CA) assays, demonstrating the non-genotoxic effects. Moreover, borenium 1 (60.7% and 50.7%), borenium 2 (70.4% and 57.2%), borenium 3 (53.1% and 45.2%), borinium 4 (55.1% and 48.1%), and borinium 5 (51.0% and 36.1%) minimized the mitomycin C(MMC)-induced genotoxic damages at different rates as determined using CA and MN assays, respectively. Again, it was found that the borinium compounds exhibited higher cytotoxic activity on cancer cells when compared to borenium compounds. Consequently, in light of our in vitro findings, it was suggested that the novel borinium and borenium compounds could be used safely in pharmacology, cosmetics, and various medical fields due to their antioxidant and non-genotoxic features, as well as their cytotoxicity potential on cancer cells.

Sex-biased response of pollution biomarkers in fish: Insights from the killifish Poecilia vivipara

Copper ions (Cu) are one of the most frequent trace-contaminants found in Brazilian waters and, although considered as an essential element, in high concentrations can accumulate and induce toxicity. Biomarkers are important tools that can be used to assess these impacts, but to be considered trustworthy, they have to be previously tested in target organisms through laboratory studies under controlled conditions. However, many of these experiments are conducted using only males, as it is believed that the hormonal variation of females can bias the results, increasing data variability. Notwithstanding, few studies have actually tested this hypothesis, highlighting the importance of considering and measuring the role of sex in ecotoxicological studies. The aim this study was to evaluate the influence of sex on biomarkers classically used in environmental monitoring programs using the fish Poecilia vivipara as model. For this, females and males were exposed for 96 h to two Cu concentrations (9 and 20 μg/L) and a control group. In liver and gills, Cu accumulation, total antioxidant capacity (TAC) and lipid peroxidation (LPO) were evaluated. In addition, samples of peripheral blood were used for neutrophil to lymphocyte ratio determination, a measure of the onset of secondary stress. Results show that Cu hepatic accumulation did not differ between females and males, but higher levels of this metal were observed in exposed animals compared to control fish. Additionally, interactive effects were observed for hepatic LPO, as males showed elevated oxidative damage in comparison to females. Moreover, Cu exposure elevated hepatic LPO relative to control only in males, but this increase in oxidative damage was not accompanied by changes in liver TAC. On the other hand, differences in branchial Cu accumulation and LPO were not observed. Conversely, control females showed elevated TAC in comparison to control males, but Cu exposure eliminated this difference. Cu exposure also induced an increase in the N:L ratio, indicating the presence of a secondary stress response unrelated to sex. Ultimately, the findings of this study demonstrate that sex can influence the response of biomarkers that are typically used in ecotoxicological investigations in a multifaceted manner. As a result, using animals from a singular sex in such studies may result in consequential outcomes, potentially leading to underestimation or overestimation of results.

Efficacy of clofazimine against acute and chronic Toxoplasma gondii infection in mice

Toxoplasmosis is a zoonotic protozoal disease affecting approximately one-third of the world's population. The lack of current treatment options necessitates the development of drugs with good tolerance and effectiveness on the active and cystic stages of the parasite. The present study was established to investigate, for the first time, the potential potency of clofazimine (CFZ) against acute and chronic experimental toxoplasmosis. For this purpose, the type II T. gondii (Me49 strain) was used for induction acute (20 cysts in each mouse) and chronic (10 cysts in each mouse) experimental toxoplasmosis. The mice were treated with 20 mg/kg of CFZ intraperitoneally and orally. The histopathological changes, brain cyst count, total Antioxidant Capacity (TAC), malondialdehyde (MDA) assay, and the level of INF-γ were also evaluated. In the acute toxoplasmosis, both IP and oral administration of CFZ induced a significant reduction in brain parasite burden by 90.2 and 89%, respectively, and increased the survival rate to 100% compared with 60% in untreated controls. In the chronic infection, cyst burden decreased at 85.71 and 76.18% in CFZ-treated subgroups in comparison to infected untreated controls. In addition, 87.5% and 100% of CFZ-treated subgroups survived versus untreated control 62.5%. Moreover, CFZ significantly increased INF-γ levels in acute and chronic toxoplasmosis. Tissue inflammatory lesions were considerably reduced in the CFZ-treated chronic subgroups. CFZ treatment significantly reduced MDA levels and elevated TAC in both acute and chronic infections. In conclusion, CFZ showed a promising finding regarding the ability to reduce cyst burden in acute and chronic infection. Further studies are needed to investigate the therapeutic role of CFZ on toxoplasmosis using the long-term treatment and more advanced approaches. In addition, clofazimine may need to be accompanied by another drug to augment its effect and prevent the regrowth of parasites.

Cardioprotective role of the coenzyme Q10 and coconut oil in acute aluminum phosphide poisoning: a randomized controlled clinical trial.

Aluminum phosphide (ALP)-induced cardiotoxicity is a major cause of high mortality rates. As there is no specific antidote, restoring cardiac hemodynamics is the cornerstone for saving patients. Based on oxidative stress theory in acute ALP poisoning, we examined the cardioprotective role of coconut oil and Coenzyme Q10 (COQ10) in ALP poisoning, focusing on their antioxidant capacity. This study was a randomized, controlled, single-blind, phase II clinical trial conducted at Tanta Poison Control Center over 1 year. Eighty-four ALP poisoned patients received supportive treatment and were randomly allocated to three equal groups. Gastric lavage was performed using sodium bicarbonate 8.4% with saline in group I. Alternatively, group II received 50ml coconut oil, and group III initially received 600mg CoQ10 dissolved in 50ml coconut oil; and repeated 12hours later. In addition to patient characteristics, clinical, laboratory, electrocardiography (ECG), and total antioxidant capacity (TAC) data were recorded and repeated 12hours later. Patient outcomes were evaluated. There was no significant difference among groups considering patient characteristics, initial cardiotoxicity severity, vital, laboratory data, ECG changes, and TAC. However, 12hours post-admissions, group III was significantly improved in all clinical, laboratory, and ECG parameters than comparable groups. Significant correlations were observed between elevated TAC in groups II and III with hemodynamic, serum troponin, and ECG variables. Accordingly, the need for intubation, mechanical ventilation, and the total vasopressor dose was significantly decreased in group III compared with other groups. Therefore, coconut oil and COQ10 are promising cardioprotective adjuvant therapy ameliorating the ALP-induced cardiotoxicity.

Effects of lysophospholipids and multi-enzymes on growth performance, antioxidant capacity, intestinal health, and cecal microflora of male cherry valley ducks.

Improvement of nutrient utilization to promote growth performance is always pursued in poultry. In this study, a total of 360 1-d-old male ducklings was randomly assigned to 3 treatments in terms of diet treatment groups. Three treatments were as follows: basal diet (Con group) or basal diet supplemented with 300 mg/kg multi-enzymes (ENZ group) or 500 mg/kg lysophospholipids (LPL group). On day 42, ducks were slaughtered for samplings. The results revealed that supplementary LPL improved the body weight (BW) at day 14 and average daily gain (ADG) during days 1 to 14 and improved the feed conversion rate (FCR) for the overall period (P < 0.05) by improving nutrient utilization of dry matter and ether extract (P < 0.05) compared with the Con group. Dietary ENZ improved the FCR from days 15-42 and 1-42, and nitrogen utilization (P < 0.05) compared with the Con group. Jejunal villus height and villus height/crypt depth ratio were higher (P < 0.05) in the LPL group and tended to be higher (P < 0.1) in the ENZ group compared to the Con group. Supplementation with either LPL or ENZ reduced interleukin-1β concentration in jejunal mucus (P < 0.05). Both LPL and ENZ enhanced serum total superoxide dismutase activity (P < 0.05), whereas only supplementation with LPL elevated total antioxidant capacity (P < 0.05). In terms of cecal microbiota, microbial richness tended to be reduced by LPL, with low observed-OTUs and Chao1 (0.05 < P < 0.1). Supplementation with ENZ led to higher abundances of cellulolytic bacteria such as Fibrobacterota, [Eubacterium]_xylanophilum_group, and Bifidobacterium. Overall, both LPL and ENZ improved FCR, which may be relevant to ameliorative intestinal health, overall antioxidant ability, and cecal microbiome.

Dexamethasone and Citicoline Mitigate Cisplatin-Induced Peripheral Neuropathy: A Novel Experimental Study in Mice.

Given the rising prevalence of cisplatin-induced peripheral neuropathy (CisIPN), investigations to alleviate its adverse effects are required. Oxidative stress and free radical development are essential pathways of CisIPN. Specifically, dexamethasone and citicoline are characterized by anti-inflammatory and antioxidant activities that might reduce CisIPN incidence and severity. The current study assessed the possible impacts of novel interventions, dexamethasone, and, citicoline on CisIPN. Seventy-two male mice were randomly allocated into nine groups (n: 8/each group). Different doses of dexamethasone (7.5, 15, 30 mg/kg, i.p.), citicoline (10, 20, 40 mg/kg, i.p.), and the combination (dexamethasone 7.5 mg/kg + citicoline 10 mg/kg, i.p.) were injected in the first three days and one day before receiving cisplatin (2 mg/kg, i.p.). The tail-flick method was used for assessing nociception. Besides, malondialdehyde (MDA), interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), total antioxidant capacity (TAC), and mice weight differences (ΔW) were measured. Different doses of dexamethasone and citicoline enhanced latency time (p<0.05). Moreover, dexamethasone 15 mg/kg diminished the level of MDA and increased TAC (p<0.05) and in 30 mg/kg, MDA was reduced (p<0.05). Besides, 20 and 40 mg/kg of citicoline reduced MDA and elevated TAC (p<0.05), and 10 mg/kg merely reduced MDA (p<0.05). Dexamethasone in all doses declined IL-1β and TNF-α levels, and citicoline only at 40 mg/kg lessened their levels (p<0.05). Interestingly, ΔW declined more in the dexamethasone and citicoline groups than the cisplatin group (p<0.05). Dexamethasone and citicoline attenuate CisIPN through anti-inflammatory activity, improving the antioxidant capacity, and inhibiting lipid peroxidation.

Soy isoflavones protects against cognitive deficits induced by chronic sleep deprivation via alleviating oxidative stress and suppressing neuroinflammation

Mounting evidence suggests that there is a close association between chronic sleep deprivation (CSD) and cognitive deficits. The animal model of CSD-induced cognitive deficits is commonly used to seek potential treatments. Soy isoflavones (SI) have been reported to possess antioxidant, anti-inflammation, and neuroprotective effects. In the present study, the effects of SI on CSD-induced memory impairment were investigated. The mice were subjected to the sleep interruption apparatus and continuously sleep deprived for 2 weeks, while orally administrated with SI (10, 20, and 40 mg/kg) or Modafinil (MOD,100 mg/kg) during the CSD process. Immediately after the SD protocol, cognitive performance of mice was evaluated by the object location recognition (OLR) test, the novel object recognition (NOR) test, and the Morris water maze (MWM) task, as well as the hippocampus, was extracted for evaluation of oxidative stress parameters and inflammation levels through biochemical parameter assay and western blotting analysis. The results showed that SI administration remarkably improved the cognitive performance of CSD-treated mice in OLR, NOR, and MWM tests. In addition, SI significantly elevated total antioxidant capacity and superoxide dismutase enzyme activities, decreased malondialdehyde level, promoting antioxidant element nuclear erythroid-2-related factor 2, and its downstream targets, including heme oxygenase 1, and quinone oxidoreductase 1 protein expressions. Moreover, SI treatment significantly suppressed nuclear factor kappa B p65, nitric oxide synthase, and cyclooxygenase 2 activation, as well as the pro-inflammatory cytokines (Tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-1β [IL-1β]) release in the hippocampus of CSD-treated mice. In summary, the current study provides an insight into the potential of SI in treatment of cognitive deficits by CSD.

Measurement of oxidative stress and total antioxidant capacity in hyperthyroid patients following treatment with carbimazole and antioxidant

Hyperthyroidism is a common endocrine disorder in which the thyroid produces too many hormones, resulting in the metabolism speed up. The present study was designed to measure oxidative stress and total antioxidant capacity in hyperthyroid patients following treatment with carbimazole and antioxidants supplements. This randomized clinical trial study was conducted to compare Malondialdehyde (MDA) and total antioxidant capacity (TAC) among 25 newly diagnosed hyperthyroid patients (Group A), 25 hyperthyroid patients treated with carbimazole (Group B) and 25 hyperthyroid patients treated with carbimazole and antioxidants supplement (Group C) of both sexes. In this study, the mean serum malondialdehyde (MDA) of the three groups were 4.60 ± 1.08 μmol/L (Group A), 2.79 ± 0.58 μmol/L (Group B), and 1.57 ± 0.29 μmol/L (Group C). We found the mean MDA level was significantly higher in Group A than Group B and Group C. This study found the MDA level was significantly higher in hyperthyroid patients treated with carbimazole alone (Group B, 2.79 ± 0.58 umol/L) than hyperthyroid patients treated with carbimazole and antioxidant combined (Group C, 1.57 ± 0.29 umol/L) among the study groups (p < 0.001). The results showed that the mean serum TAC was significantly lower in newly diagnosed hyperthyroid (Group A, 527.8 ± 78.44 umol/L] patients compared to carbimazole treated alone (Group B, 951.80 ± 99.67 umol/L) and combination with the antithyroid drug (carbimazole) and antioxidant treated (Group C, 1113.56 ± 121.69 umol/L). There was more improvement found in the treatment combined with the antithyroid drug (carbimazole) and antioxidant (Group C).Conventional treatment of hyperthyroid patients significantly reduced oxidative stress and elevated serum TAC but not up to normal level. Therefore, the supplementation of antioxidants could be utilized to improve thyroid function in hyperthyroid patients by boosting antioxidants and restoring oxidant-antioxidant balance. However, further studies are required to determine the optimal dosage, route of administration, and timing of antioxidant therapy needed before this supplementation could be officially recommended as adjuvant therapy.

Geraniol isolated from lemon grass to mitigate doxorubicin-induced cardiotoxicity through Nrf2 and NF-κB signaling

BackgroundGeraniol, a natural monoterpene, is a component of many plant essential oils. It contains many medicinal and pharmacological properties. Doxorubicin is an anticancer drug; however, its clinical usage is limited due to its cumulative and dose-dependent cardiotoxicity. This study investigates geraniol as a protective agent against doxorubicin-induced cardiotoxicity and explores possible underlying mechanisms of action. Methods: Male Sprague-Dawley rats were allocated into five groups. Groups 1 and 2 were administered saline and geraniol 200 mg/kg/day/orally, respectively, for 15 days. Group 3 was administered intraperitoneal doxorubicin (5 mg/kg/IP on the 5th, 10th and 15th days to achieve a cumulative dose of 15 mg/kg) to induce cardiotoxicity. The fourth and fifth groups were treated with either geraniol 100 mg/kg or 200 mg/kg orally and doxorubicin to equal the doxorubicin dose administered to Group 3. Results: Treatment with geraniol significantly ameliorated cardiac damage and restored serum cardiac injury marker levels in doxorubicin treated animals. Geraniol upregulated Nrf2 and HO-1 expression, elevated total antioxidant capacity, decreased the nuclear accumulation of kappa-light-chain enhancer of activated B cells (NF-κB), decreased the phosphorylation and degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), suppressed tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-18 (IL-18) levels, and restored the levels of Bax and caspase-3 and 9 in heart tissue. Conclusion: Geraniol may function as a potential activator of nuclear factor erythroid 2-related factor 2 (Nrf2), which subsequently improves Nrf2-dependent antioxidative signaling, diminishes apoptosis and subdues the inflammatory response. The downstream result is protection of the heart from doxorubicin-induced cardiotoxicity.

Oxidative stress and DNA damage status in couples undergoing in vitro fertilization treatment.

SummaryThis study examined the status of oxidative stress in 599 couples undertaking in vitro fertilization (IVF) treatment and its association with reproductive hormones, smoking, and outcomes. Oxidative stress biomarkers such as malondialdehyde, 8-hydroxy-2-deoxyguanosine, hydrogen peroxide (H2O2), catalase (CAT), and total antioxidant capacity (TAC) were determined in follicular fluid and seminal plasma. Tail moment (TM) was used to evaluate DNA damage in the sperm and granulosa cells. Reproductive hormones in serum and cotinine (COT) in urine, follicular fluid, and seminal plasma samples were determined. Separate multivariate linear regression was used to assess associations between levels of each oxidative stress biomarker and each hormone and smoking parameter (modeled as natural log-transformed). The findings indicate that some oxidative stress and DNA damage biomarkers played a role in disrupting certain reproductive hormones in women and their male partners either by overproducing reactive oxygen species or reducing antioxidant defense capacity. Although women were nonsmokers, COT levels > 50 and 10 µg/L in urine and follicular were observed in 5.7 and 1.7%, respectively. Levels of follicular fluid COT were positively associated with H2O2 and TM. We used log-binomial multivariate regression to estimate relative risks for the association between oxidative stress/DNA damage and IVF binary outcomes (fertilization rate > 50%, biochemical pregnancy, clinical pregnancy, and live birth). An increase in the CAT levels of follicular fluid was associated with a 48 and 41% decrease in the risk of poor fertilization rate (≤50%) and unsuccessful live birth, respectively. After the models were adjusted for hormonal factors, the associations remained the same, except that the elevated TAC in follicular fluid became significantly associated with a decrease of 42% in the risk of poor fertilization rate (≤50%). The higher antioxidant activity (CAT and TAC) in follicular fluid might positively impact specific IVF outcomes.Lay summaryOxidative stress occurs when antioxidant molecules are insufficient in the body to destroy free radicals that can damage the cells, proteins and DNA, causing different health conditions, including infertility. The role of oxidative stress in female infertility has not received as much attention as male infertility, and research is still limited. This study explored whether the overproduction of free radicals can impact the success of in vitro fertilization (IVF) treatment using several biological markers such as hydrogen peroxide, catalase, and total antioxidant capacity. Our findings revealed that the high antioxidant levels in the fluid surrounding the egg were linked with a high fertilization rate. Additionally, oxidative stress status in couples was associated negatively with several reproductive hormones and smoking status. Biomarkers of oxidative stress and DNA damage might have potential applications in evaluating IVF patients’ clinical characteristics such as causes of infertility, hormonal profile, fertilization rate, implantation and live birth.

Decreased Superoxide Dismutase Concentrations (SOD) in Plasma and CSF and Increased Circulating Total Antioxidant Capacity (TAC) Are Associated with Unfavorable Neurological Outcome after Aneurysmal Subarachnoid Hemorrhage.

Background: Subarachnoid hemorrhage (SAH) is a devastating disease with high morbidity and mortality. Hypoxia-induced changes and hemoglobin accumulation within the subarachnoid space are thought to lead to oxidative stress, early brain injury, and delayed vasospasm. This study aimed to evaluate the antioxidant status and its impact on neurological outcome in patients with aneurysmal SAH. Methods: In this prospective observational study, 29 patients with aneurysmal SAH were included (mean age 54.7 ± 12.4). Blood and cerebrospinal fluid (CSF) samples were collected on days (d) 1, 3, and 7. In addition, 29 patients without intracranial hemorrhage served as controls. The antioxidant system was analyzed by glutathione peroxidase (GSH-Px; U/L) and total and free glutathione-sulfhydryl (GSH; mg/L) in the plasma. Superoxide dismutase (SOD, U/mL) and total antioxidant capacity (TAC, µmol/L) were measured in the serum and CSF. Clinical data were compiled on admission (Hunt and Hess grade, Fisher grade, and GCS). Neurological and cognitive outcome (modified Rankin scale (mRS), Glasgow Outcome Scale Extended (GOSE) and Montreal Cognitive Assessment (MoCA)) was assessed after 6 weeks (6 w) and 6 months (6 m). Results: Plasma levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.36 U/L; d3: 1.25 ± 0.33 U/L, p = 0.99; d7: 1.52 ± 0.4 U/L, p = 0.019) and were significantly higher compared to controls (1.11 ± 0.27 U/L) at day 7 (p < 0.001). Concordantly, CSF levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.41 U/L; d3: 1.77 ± 0.73 U/L, p = 0.10; d7: 2.37 ± 1.29 U/L, p < 0.0001) without becoming significantly different compared to controls (1.74 ± 0.8 U/L, p = 0.09). Mean plasma TAC at day 1 (d1: 77.87 ± 49.72 µmol/L) was not statistically different compared to controls (46.74 ± 32.42 µmol/L, p = 0.25). TAC remained unchanged from day 1 to 7 (d3: 92.64 ± 68.58 µmol/L, p = 0.86; d7: 74.07 ± 54.95 µmol/L, p = 0.8) in plasma. TAC in CSF steeply declined from day 1 to 7 in patients with SAH becoming significantly different from controls at days 3 and 7 (d3: 177.3 ± 108.7 µmol/L, p = 0.0046; d7: 85.35 ± 103.9 µmol/L, p < 0.0001). Decreased SOD levels in plasma and CSF are associated with a worse neurological outcome 6 weeks (mRS: CSF p = 0.0001; plasma p = 0.027/GOSE: CSF p = 0.001; plasma p = 0.001) and 6 months (mRS: CSF p = 0.001; plasma p = 0.09/GOSE: CSF p = 0.001; plasma p = 0.001) after SAH. Increased plasma TAC correlated with a worse neurological outcome 6 weeks (mRS: p = 0.001/GOSE p = 0.001) and 6 months (mRS p = 0.001/GOSE p = 0.001) after SAH. Conclusion: In our study, a reduction in the antioxidative enzyme SOD and elevated TAC were associated with a poorer neurological outcome reflected by mRS and GOSE at 6 weeks and 6 months after SAH. A lower initial SOD CSF concentration was associated with the late deterioration of cognitive ability. These findings support the mounting evidence of the role of oxidative stress in early brain injury formation and unfavorable outcome after SAH.

Effects of quercetin supplementation on inflammatory factors and quality of life in post-myocardial infarction patients: A double blind, placebo-controlled, randomized clinical trial.

Myocardial infarction (MI) is one of the leading causes of death in the world. Epidemiological studies have shown that dietary flavonoids are inversely related to cardiovascular morbidity and mortality. The study aimed to determine whether quercetin supplementation can improve inflammatory factors, total antioxidant capacity (TAC) and quality of life (QOL) in patients following MI. This randomized double-blind, placebo-controlled trial was conducted on 88 post-MI patients. Participants were randomly assigned into quercetin (n = 44) and placebo groups (n = 44) receiving 500 mg/day quercetin or placebo tablets for 8 weeks. Quercetin supplementation significantly increased serum TAC compared to placebo (Difference: 0.24 (0.01) mmol/L and 0.00 (0.00) mmol/L respectively; p < .001). TNF-α levels significantly decreased in the quercetin group (p = .009); this was not, however, significant compared to the placebo group. As for QOL dimensions, quercetin significantly lowered the scores of insecurity (Difference: -0.66 (12.5) and 0.00 (5.55) respectively; p < .001). No significant changes in IL-6, hs-CRP, blood pressure and other QOL dimensions were observed between the two groups. Quercetin supplementation (500 mg/day) in post-MI patients for 8 weeks significantly elevated TAC and improved the insecurity dimension of QOL, but failed to show any significant effect on inflammatory factors, blood pressure and other QOL dimensions.

Intradialytic Cardiovascular Exercise Training Alters Redox Status, Reduces Inflammation and Improves Physical Performance in Patients with Chronic Kidney Disease.

Redox status (RS) perturbations and inflammation are fundamental features of chronic kidney disease (CKD) that are substantially exacerbated in end-stage renal disease (ESRD). This study aimed at investigating the efficacy of a 6-month intradialytic exercise training program on RS, inflammation and physical performance in patients with ESRD. Twenty hemodialysis (HD) patients (17 males, three females) were randomly assigned to either an intradialytic training (bedside cycling) group (TR; n = 10) or a control group (CON; n = 10) for 6 months. Anthropometrics [body mass and height, body mass index (BMI), body composition], physical performance (VO2peak), functional capacity [North Staffordshire Royal Infirmary (NSRI) walk test, sit-to-stand test (STS-60)], quality of life (short form-36 (SF-36) as well as RS [thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), reduced (GSH) and oxidized (GSSG) glutathione, GSH/GSSG, total antioxidant capacity (TAC), catalase activity (CAT)] and high-sensitivity C-reactive protein (hs-CRP) were assessed at baseline and after the 6-month intervention. Peak oxygen consumption (VO2peak) increased by 15% only in TR (p < 0.01). Performance in NSRI, STS-60 and SF-36 improved by 4–13% only in TR (p < 0.01). Exercise training reduced TBARS (by 28%), PC (by 31%) and hs-CRP (by 15%), and elevated GSH (by 52%), GSH/GSSG (by 51%), TAC (by 59%) and CAT (by 15%) (p < 0.01). These findings suggest that engagement in chronic intradialytic cardiovascular exercise alters RS, reduces inflammation and improves performance in patients with ESRD.

Altered redox status, DNA damage and modulation of L-tryptophan metabolism contribute to antimicrobial action of curcumin.

Identification and development of newer and better antimicrobials from natural products represent ongoing research efforts by many investigators. Curcumin is a polyphenol commonly found in the plant Curcuma longa (better known as turmeric). It has been reported to possess several bioactivities including antioxidant, anti-cancer, anti-inflammatory, anti-diabetic, anti-fibrotic, and antimicrobial properties. However, little is known about the antimicrobial mode of action of curcumin, thus undermining its prospects as an alternative antimicrobial agent. In this study, we investigated the mechanism of antimicrobial action by curcumin. The mechanism of inhibition was evaluated in representatives of Gram negative (Escherichia coli) and Gram positive (Staphylococcus aureus) bacteria isolates, treated with either curcumin singly or in combination with ascorbic acid (1000 μg/mL). Results showed that curcumin has broad antimicrobial capacity. In addition, curcumin only and/or co-treatment with ascorbic acid caused lipid peroxidation in S. aureus and E. coli, and by extension led to DNA damage, indicative of oxidative stress. It is plausible that the oxidative might be related to the activation of the kynurenine pathway in S. aureus but not in E. coli. Furthermore, curcumin exposure led to elevated total antioxidant capacity (TAC) and level of total thiol, but decreased nitric oxide level in the bacteria isolates. Together, the findings suggest that oxidative stress and DNA damage might be partly responsible for the antimicrobial action of curcumin.

Carob (Ceratonia siliqua L.) fruit hydro-alcoholic extract alleviates reproductive toxicity of lead in male mice: Evidence on sperm parameters, sex hormones, oxidative stress biomarkers and expression of Nrf2 and iNOS.

Carob(Ceratonia siliqua L.)is an evergreen tree with fruits that have potent antioxidant activity. The aim of this study was to investigate alleviative effects of carob fruithydro-alcoholic extract (CFHAE)against reproductive toxicity induced by lead (Pb) in male mice. Forty-two NMRI adult male mice were randomly categorized into 7 groups (N=6). Group I was the control group and received no treatment. Group II was the sham group and received 0.2 ml distilled water per day. Group III (Pb group) received Pb acetate 1000 ppm/kg/day. Groups IV and V received CFHAE 500 and 1000 mg/kg/day, respectively. Groups VI and VII received both Pb 1000 ppm/kg/day and CFHAE at doses of 500 and 1000 mg/kg/day, respectively at the same time. The groups were treated by gavage. After 35 days, sperm parameters (count, motility, morphology, viability, DNA damage, and teratozoospermia index), total antioxidant capacity (TAC), reduced glutathione content (GSH), antioxidant enzymes (SOD, CAT, and GPx) activity, MDA levels, and sex hormones (FSH, LH, and testosterone) concentrations in serum, testicular expression of Nrf2 and iNOS genes and histopathological alterations were evaluated. Our findings revealed that co-administration ofCFHAE with Pb significantly(p<0.05 to p<0.01) improved sperm parameters, elevated sex hormones, TAC, GSH content, and antioxidant enzymes activity of serum, decreased serum MDA levels, and down-regulated testicular expression of Nrf2 and iNOS genes compared with Pb group. Also, CFHAE ameliorated histopathological alterations in testis tissue caused by Pb. CFHAEcan alleviate reproductive toxicity following Pb exposure in male mice.