Reactive Oxygen Metabolites Research Articles

The Mitochondrial Blueprint: Unlocking Secondary Metabolite Production

Mitochondrial metabolism plays a pivotal role in regulating the synthesis of secondary metabolites, which are crucial for the survival and adaptation of organisms. These metabolites are synthesized during specific growth stages or in response to environmental stress, reflecting the organism’s ability to adapt to changing conditions. Mitochondria, while primarily known for their role in energy production, directly regulate secondary metabolite biosynthesis by providing essential precursor molecules, energy, and reducing equivalents necessary for metabolic reactions. Furthermore, they indirectly influence secondary metabolism through intricate signaling pathways, including reactive oxygen species (ROS), metabolites, and redox signaling, which modulate various metabolic processes. This review explores recent advances in understanding the molecular mechanisms governing mitochondrial metabolism and their regulatory roles in secondary metabolite biosynthesis, which highlights the involvement of transcription factors, small RNAs, and post-translational mitochondrial modifications in shaping these processes. By integrating current insights, it aims to inspire future research into mitochondrial regulatory mechanisms in Arabidopsis thaliana, Solanum tuberosum, Nicotiana tabacum, and others that may enhance their secondary metabolite production. A deeper understanding of the roles of mitochondria in secondary metabolism could contribute to the development of new approaches in biotechnology applications.

Rumen-protected methionine supplementation improves lactation performance and alleviates inflammation during a subclinical mastitis challenge in lactating dairy cows

This study aimed to evaluate the effects of rumen-protected Met on lactation performance, inflammation, and immune response, and liver glutathione of lactating dairy cows during a subclinical mastitis challenge (SMC). Thirty-two Holstein cows (145 ± 51 DIM) were enrolled in a randomized complete block design. At -21 d relative to the SMC, cows were assigned to dietary treatments, and data were collected before and during the SMC. Cows were blocked according to parity, DIM, and milk yield and received a basal diet (17.4% CP; Lys 7.01% MP and Met 2.14% MP) plus 100 g/d of ground corn (CON; n = 16) or a basal diet plus 100 g/d of ground corn and rumen-protected Met (SM, Smartamine M at 0.09% of dietary DM; n = 16), fed as a top-dress. At 0 d, the mammary gland's rear right quarter was infused with 100,000 cfu of Streptococcus uberis (O140J). Milk yield was recorded twice daily from 0 until 3 d relative to SMC. Milk samples were collected during each milking from 0 to 3 d relative to SMC, blood samples were collected at 0, 6, 12, 24, 48, and 72 h relative to SMC. The mTOR pathway activation was assessed in immune cells in blood and milk samples by measuring quantity and phosphorylation status of mTOR-related proteins, including AKT, S6RP, and 4EBP1. For the ratio of phosphorylated to total AKT, S6RP, and 4EBP1, blood samples were collected at 0, 12, and 24 h, and milk samples at 24 h relative to SMC. Liver biopsies were performed at -10 d and 24 h relative to SMC for measurement of glutathione. Linear mixed models with repeated measures were used to analyze the results. There was a trend for greater milk yield per milking (+ 0.8 kg) and per day (+1.7 kg) after SMC in SM cows compared with CON. The DMI was not affected by dietary treatments. Reactive oxygen metabolites were lower in SM cows than in CON. Milk somatic cell linear score was not affected by dietary treatments, and a score >4 at 24 h confirmed subclinical mastitis. The SM cows had greater milk fat percentage at 24 and 36 h post SMC, resulting in overall greater milk fat. Milk protein tended to be greater in SM cows than in CON. We observed greater liver glutathione in SM cows than in CON. Among inflammation biomarkers, ceruloplasmin was lower for SM cows compared with CON. In milk, greater phosphorylated (p) AKT:AKT and pS6RP:S6RP ratios were observed in immune cell populations from SM cows compared with CON. Blood neutrophils had a greater p4EBP1:4EBP1 ratio in SM cows compared with CON. Overall, our results show that Met supplementation during an SMC positively affected milk performance, lowered the risk of oxidative stress, and attenuated inflammation partially by increasing liver glutathione and immune cells' protein synthesis via mTOR signaling.

Oxidative Status and Lipid Metabolism Analytes in Dogs with Mast Cell Tumors: A Preliminary Study

Mast cell tumors (MCTs) are common skin neoplasms in dogs. Prognostic indicators include histologic grade, clinical stage, high Ki-67 index, elevated argyrophilic nucleolus organizer regions (AgNOR) index, c-kit mutations, and recurrence after surgery. Blood serum redox status has been shown to correlate with prognostic factors in canine lymphoma and mammary tumors. This study aimed to assess the correlation between established prognostic factors and serum redox status and lipid metabolism analytes in dogs with MCTs. Dogs with cutaneous (n = 33) or subcutaneous (n = 6) MCTs, without comorbidities, were studied. Staging was evaluated based on cytology of regional lymph nodes and ultrasound-guided liver and spleen aspiration cytology. Histologic grading and immunohistochemical staining for Ki-67 and KIT patterns were performed on excised tumor specimens. Dogs were categorized by Patnaik grading (1–3), Kiupel grading (low/high), metastatic status, Ki-67 positive nuclei per cm2 (>23 or ≤23), and KIT pattern (I, II–III). Paraoxonase-1, Butyrylcholinesterase, Cupric Reducing Antioxidant Capacity (CUPRAC), Diacron Reactive Oxygen Metabolites (d-ROMs), and oxy-adsorbent levels were measured before any therapeutic intervention. ANOVA and independent t-tests were used to detect differences in the mean values among groups. Paraoxonase-1 activity was significantly lower in Patnaik grade 3 (p = 0.003) and Kiupel high-grade (p = 0.022) MCTs. No significant differences were found in CUPRAC, d-ROMs, or oxy-adsorbent levels across different prognostic groups. This study found a significant correlation between histologic grading and Paraoxonase-1 activity, suggesting a potential role of Paraoxonase-1 as a prognostic biomarker in canine MCTs.

The impact of cooling and Moringa supplementation on oxidative stress in serum and milk, including milk cytokines, in heat stressed lactating sows and their litters

Abstract Heat stress (HS) poses a significant challenge to the United States swine industry. Sows and their piglets are particularly vulnerable to heat stress, as the peri-parturient phase is characterized by heightened metabolism and increased oxidative stress and inflammation. The study examined the effects of using conductive electronic cooling pads (ECP) and dietary supplementation with 4% Moringa (M) leaf powder on controlling oxidative stress and inflammation caused by heat stress (HS) in sows and their piglets. Forty-eight late gestation sows were assigned to four treatment groups: HS fed corn-soybean meal (HS+CS), ECP fed corn-soybean meal (ECP+CS), HS+M, and ECP+M. Blood was collected from sows on gestation (G) day 112, and lactation (L) day 14 and L20, and from piglets (2 male and 2 female) in each litter on postnatal (PN) day 1 and PN20. Colostrum was collected within 2h of birth of first neonate, and mature milk was collected on L14. Piglet fecal samples were collected on PN14 to measure calprotectin concentration as a marker of intestinal inflammation. Biological antioxidant potential (BAP), derivatives of reactive oxygen metabolites (dROMs) and oxidative stress index (OSi) were measured in blood and milk samples using Free Radical Elective Evaluator. Milk samples pooled by day of lactation and treatment group, were analyzed using cytokine array. Levels of inflammatory cytokines in colostrum were affected by Moringa supplementation and cooling, but not mature milk. Notably, the anti-inflammatory cytokines interleukin (IL)-10 and IL-1ra were 2.14 and 1.57 Log2 higher in colostrum of HS+M compared to other groups. The oxidative stress index of colostrum was higher (P = 0.0002) than mature milk. Level of BAP in sow serum was greater in ECP+CS and HS+M (P = 0.0291) compared to other groups. Moringa had an overall effect of increasing dROMs (P = 0.0035) and levels of OSi were lowest in ECP+CS (P = 0.0296) sow serum. Treatments did not affect piglet serum oxidative index (P > 0.05) or calprotectin levels (P > 0.05). Findings support further studies to investigate the efficacy of using ECP and Moringa supplementation to mitigate inflammation and oxidative stress imposed by heat stress conditions in lactating sows.

Apigeninidin chloride disrupts Toxoplasma gondii Mitochondrial membrane potential and induce reactive oxygen species and metabolites production.

Apigeninidin chloride (APi) is a form of 3-deoxyanthrocyanidins (3-DAs) abundantly produced by the red Sorghum bicolor plant. It has been previously reported to be effective against Toxoplasma gondii (T. gondii) tachyzoites grown in vitro with less cytotoxic effect. However, its possible mechanism(s) of action has not been elucidated. Biochemically, we discovered that APi induced high reactive oxygen species (ROS) and mitochondria superoxide (MitoSOX) productions in tachyzoites, leading to mitochondrial membrane potential (MMP) disruption in vitro. To confirm our biochemical results at the molecular level, we performed a liquid chromatography-mass spectrometry (LC-MS) analysis on APi-treated parasites to assess any metabolite and lipid alterations often associated with high ROS/MitoSOX production in cells. Noteworthy is that we detected several important oxidative stress-induced metabolites such as hexanal, aldehydes, methyl undeo10-enoate, butadiynyl phenyl ketone, 16-hydroxyhexadecanoic acid (16-OH, 16:0), 2-hydroxytricosanoic acid (C23:0; O), 3-oxodecanosanoic acid (C22:1; O), 2-hydroxypropylsterate, and furan fatty acids F6 (19FU-FA). These metabolites are associated with lipid, protein, and nucleic acid disruptions. Using atovaquone (Atov) as a control, we observed that it disrupted intracellular tachyzoites' mitochondrial membrane potential, increased ROS and MitoSOX production, and altered metabolite and lipid production similar to what was observed with our experimental compound APi. Overall, our results indicated that APi targets T. gondii tachyzoite growth through inducing oxidative stress, mitochondrial dysfunction, and eventually parasite death.

Associations between milk infrared-predicted plasma biomarkers of stress resilience and fertility in dairy cattle: insights for enhancing breeding programs and herd management

Fertility is a crucial aspect of dairy herd efficiency and sustainability. Among factors influencing fertility in dairy cattle, metabolic stress and systemic inflammation of animals are of main relevance, especially in the postpartum stage when ovarian activity begins and cows are inseminated. Our study aimed to infer the associations between milk infrared-predicted blood biomarkers of stress resilience and fertility traits, namely the interval from calving to first service (iCF), days open (DO), and the pregnancy rate at first service (PRF) in a multi-breed population of 89,097 dairy cows. The blood metabolites (15 blood biomarkers related to hepatic damage and function, oxidative stress, and inflammation/innate immunity) were predicted using milk Fourier-transform mid-infrared (MIR) spectroscopy. A gradient boosting machine (GBM) approach with leave-one-batch-out cross-validation (R2 range from 0.45 to 0.82) was implemented to an independent calibration database of 1,367 lactating cows reared in 5 herds. Calibration equations were then applied to a population database of 1,799,186 MIR milk spectral data, that were then merged with fertility data collected by the Breeders Federation of Alto Adige (Bolzano province, Italy) generating a final database of 285,145 records. The 2 databases were merged according to the milk test day (and thus the MIR spectrum) closest to the date of insemination. The interval fertility traits were fitted as the hazard of either receiving the first service after calving at time t for iCF or becoming pregnant after calving at time t for DO in a Cox proportional-hazards model. Statistical analyses were performed including in the model the number of lactations, year of calving, and herd as fixed effects. The independent effect of the MIR-based predictions of metabolites was also included with each metabolite evaluated separately and discretized into 7 levels based on percentiles. Pregnancy rate at first service, on the other hand, was analyzed using logistic regression and the same explanatory variables. The metabolites linked to liver function and damage, such as aspartate aminotransferase, total bilirubin, and alkaline phosphatase, had a relevant influence on iCF and DO in terms of the hazard ratio (HR). Relevant results were also obtained for the biomarkers related to oxidative stress and inflammation/innate immunity. Specifically, increasing levels of ceruloplasmin, total reactive oxygen metabolites, and advanced oxidation protein products resulted in a relevant decrease in the HR of cows becoming pregnant. The logistic regression analysis did not reveal any significant effect of the aforementioned biomarkers on PRF, indicating that the effects of the stress response mainly concern the resumption of the ovarian cycle after calving. The results for the associations of the predicted biomarkers of the stress response with iCF and DO were consistent with expected physiological patterns. In conclusion, the predicted biomarkers investigated revealed to be promising novel phenotypes for assessing animal health and welfare, in the view of enhancing fertility in dairy cattle also through selective breeding, thus improving the overall efficiency of dairy herds.

Reduction of Blood Oxidative Stress Following Colorectal Cancer Resection

Background: Colorectal cancer is a major global health burden, with surgical resection being the standard treatment aimed at curative tumor removal. Oxidative stress plays a crucial role in colorectal cancer progression and prognosis. This study hypothesized that physical removal of colorectal cancer, a primary source of oxidative stress, would reduce blood levels of reactive oxygen metabolite derivatives (d-ROMs), a marker of oxidative stress, and biologic antioxidant potential (BAP) levels, a marker of antioxidant potential. Methods: This study included 123 patients who underwent radical resection for colorectal cancer. d-ROM and BAP levels were measured before and one month after surgery. Results: The clinicopathological analysis showed a correlation between preoperative d-ROM levels and tumor size (p < 0.001). This study confirmed a significant reduction in d-ROM levels following tumor resection, indicating reduced systemic oxidative stress. The reduction was significant in stages II and III, but not in stage I. The d-ROM ratio before and after tumor resection was significantly higher in cases with positive lymph node metastasis and larger tumor size. BAP levels showed no significant changes post-surgery. Conclusions: These results suggest that d-ROMs could serve as a valuable biomarker for monitoring tumor burden and surgical efficacy in patients with colorectal cancer.

Serum Derivatives–Reactive Oxygen Metabolite Levels as a Marker of Clinical Conditions in Patients with Bronchial Asthma, COPD, or Asthma–COPD Overlap: A Prospective Study

Background: Oxidative stress plays an important role in the pathophysiology of bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and asthma–COPD overlap (ACO), but its relevance has not been fully elucidated. The aim of this study was to measure the levels of oxidative stress and investigate its clinical significance in patients with BA, COPD, or ACO. Methods: We recruited 214 patients between June 2020 and May 2023 (109 patients with BA, 63 with COPD, and 42 with ACO). To assess clinical conditions, we evaluated patient characteristics, results of respiratory function tests and blood tests, and administered several questionnaires. We evaluated oxidative stress using the test for derivatives–reactive oxygen metabolites (d–ROMs) in serum. Results: The d–ROMs levels were significantly higher in patients with COPD or ACO than in patients with BA. There was no difference in serum d–ROMs levels between the COPD and ACO groups. In BA, d–ROMs levels were positively correlated with interleukin (IL)-6, IL-8, serum amyloid A (SAA), and C-reactive protein (CRP) levels; white blood cell (WBC) and neutrophil counts; and St. George’s Respiratory Questionnaire (SGRQ) scores, and they were negatively correlated with forced expiratory volume in 1 s (%FEV1) and asthma control test (ACT) score. In COPD, d–ROMs levels were positively correlated with IL-6, SAA, and CRP levels; WBC, neutrophil, and eosinophil counts; and COPD assessment test (CAT) and SGRQ scores, and they were negatively correlated with forced vital capacity (%FVC), %FEV1, and %FEV1/FVC scores. In ACO, d–ROMs levels were positively correlated with IL-6, SAA, tumor necrosis factor alpha (TNF-α), and CRP levels; and CAT and SGRQ scores, and they were negatively correlated with %FVC and %FEV1 scores. Conclusions: Serum d–ROMs levels may serve as a marker reflecting clinical conditions such as systemic inflammation, symptom severity, and airflow limitation in patients with BA, COPD, and ACO.

Lower adaptive immunity in invasive Egyptian geese compared to sympatric native waterfowls

Successful invasive species increase their spreading success by trading-off nutritional and metabolic resources allocated to reproduction and range expansion with other costly body functions. One proposed mechanism for the reallocation of resources is a trade-off with the immune function and the regulation of oxidative status. Relying on a panel of blood-based markers of immune function and oxidative status quantified in an invasive species (Egyptian goose) and two native competing species (mallard and mute swan) in Germany, we tested the hypothesis that the invasive species would have (i) lower investment in immune function, (ii) lower levels of oxidative damage, and (iii) no higher antioxidant defences compared to the native species. We found lower levels of adaptive immune markers (lymphocytes and immunoglobulin Y), in the invasive species compared to the two native species. Innate immune profile was generally similar between Egyptian geese and mallards. By contrast, mute swans showed higher levels of heterophils and lysozymes, and lower levels of bacteria killing ability compared to both Egyptian geese and mallards. Mute swans also showed higher levels of haemolysis and haemagglutination, but lower levels of monocytes and haematocrit compared to Egyptian geese. Reactive oxygen metabolites, a marker of oxidative damage, were higher in mallards and lower in Egyptian geese compared to the other waterfowl species, while levels of antioxidants were generally similar among the three species. Our results point to a reduced investment in adaptive immune function in the invasive species as a possible resources-saving immunological strategy due to the loss of co-evolved parasites in the new colonised habitats, as observed in a previous study. A lower investment in immune function may benefit other energy-demanding activities, such as reproduction, dispersal, and territoriality, while maintaining relatively higher innate immunity is beneficial since invasive species mainly encounter novel pathogens. Results pointed out also other important species-specific differences in baseline immune status, supporting previous findings on the relationship between species' body mass and immune profile.

Reproduction results in parallel changes of oxidative stress and immunocompetence in a wild long-living mammal-edible dormouse Glis glis.

Oxidative stress (OS) and impaired immune function (IF) have been proposed as key physiological costs of reproduction. The relationship between OS and IF remains unresolved, particularly in long-living iteroparous species. We studied physiological markers of maintenance (OS, IF markers) in lactating, post-lactating and non-lactating females of edible dormice-a long-living rodent. We predicted the OS balance and IF to be compromised by lactation, especially in older females expected to face stronger trade-offs between life functions. We found that the age predictor (body size) correlated negatively with white blood cell level (WBC), positively with neutrophils to lymphocytes ratio and had no effect on OS markers. Oxidative damage markers (reactive oxygen metabolites (ROMs); but not antioxidant capacity) and body size-adjusted WBC were the lowest in lactating, higher in post-lactating and the highest in non-lactating females. Body size/age did not affect this correlation suggesting a similar age-independent allocation strategy during reproduction in this species. The path analysis testing the causal relationship between ROMs and WBC revealed that IF is more likely to affect OS than vice versa. Our study indicates the trade-off between crucial life functions during reproduction and suggests that immunosuppression reduces the risk of OS; therefore, mitigating oxidative costs of reproduction.

Long-term effects of transition milk feeding on feed intake, growth performance, feeding behavior, and oxidative status of Holstein calves

This study investigated the long-term effects of feeding 5-d transition milk (TRANS) compared with milk replacer (MR) on parameters, including intake, growth, feeding behavior and oxidative stress. Fifty Holstein calves (30 females and 20 males) were fed either 12 L/day TRANS or MR for the first 5 d after an initial colostrum feeding of 3.5 L. Thereafter, all calves were fed with 12 L of MR/d (140 g/L) and were gradually weaned starting in wk 8 until wk 14. Throughout the 14 wk the calves had unrestricted access to concentrate (up to 9.8 kg/calf/day), hay, and water. After weaning all heifers were fed a total mixed ration for young cows. Oxidative status was assessed in blood samples from birth to first insemination. Parameters assessed included the ferric reducing ability of plasma (FRAP) for antioxidant capacity and the concentration of reactive oxygen metabolites by the dROM (detection of reactive oxygen metabolites) assay. In addition, the activity of glutathione peroxidase (GSH-Px), oxidative damage in the form of lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and as advanced oxidation protein products (AOPP) were measured. An oxidative stress index (OSi) was calculated: dROM/FRAP x 100. Total protein (TP) concentration was also quantified via the Bradford assay. The only significant difference in feeding behavior between the 2 treatment groups was a higher concentrate intake by the TRANS calves during the weaning phase. Body weight and ADG did not differ significantly between the TRANS and MR groups. TRANS calves showed a trend for fewer cases of health disorders. Markers of oxidative status, including TBARS, AOPP, GSHPx, FRAP and ROM, showed no treatment effects but varied significantly over time. Of note, the oxidative stress index as ratio between pro- and antioxidants in both groups peaked during weaning and then returned to baseline, suggesting an effective response to this transition phase Overall, the results indicate that feeding TRANS during the first 5 d of life had no long-term effect on the parameters studied as compared with MR feeding under the present rearing conditions. These results provide insight into the changes of oxidative status with age and confirm that the relatively high milk feeding level, slow and late weaning enables calves to adapt well to solely solid feed.

The Impact of Flavonoid Supplementation on Serum Oxidative Stress Levels Measured via D-ROMs Test in the General Population: The PREVES-FLAVON Retrospective Observational Study.

Oxidative stress has emerged as a key contributor to numerous NCDs (non-communicable diseases), including cardiovascular diseases, cancer, and diabetes. This study aims to explore the potential of targeted interventions to mitigate oxidative stress as part of a primary prevention strategy. The study included 32 healthy participants (11 men, 21 women) aged 45-65 who completed both the initial and follow-up assessments of the Healthy Days Initiative, a community-based wellness program organized by the non-profit Associazione O.R.A. ETS. Through blood analysis, vital sign assessment, lifestyle questionnaires, and individualized recommendations, participants received guidance on improving their health and reducing disease risk. The initiative also offered the opportunity for participants to consume a flavonoid supplement containing quercitrin, rutin, and hesperidin, with the goal of reducing oxidative stress. Participants who opted for supplementation were instructed to take 1-2 tablets daily for two weeks. Data collected included demographic information, anthropometric measurements, vital signs, dietary and lifestyle habits, medical history, WHO-5 Well-Being Index scores, and blood parameters. Significant reductions were observed in glucose levels (from 82 to 74.5 mg/dL), reactive oxygen metabolites (d-ROMs) (from 394.5 to 365.5 U.CARR), and systolic blood pressure (from 133 to 122 mmHg) after the two-week flavonoid intervention. Most participants (26/31) reported no side effects, and the majority (30/31) expressed a willingness to continue using a product combination of quercitrin, rutin, and hesperidin or a similar product long-term. While limited in scope and duration, the PREVES-FLAVON study contributes valuable insights to the growing body of evidence suggesting that flavonoid supplementation may play a significant role in reducing risk factors associated with NCDs in primary prevention settings. By targeting novel risk factors such as oxidative stress, this intervention holds promise for mitigating the global burden of NCDs and promoting healthy aging.

Altered oxidant and antioxidant levels are associated with vascular stiffness and diabetic kidney disease in type 1 diabetes after exposure to acute and chronic hyperglycemia

BackgroundHyperglycemia-induced oxidative stress is a well-established pathological mediator of vascular complications in diabetes. We assessed plasma oxidant and antioxidant levels in response to acute and chronic hyperglycemia in relation to vascular stiffness and varying degrees of kidney disease in type 1 diabetes individuals.MethodsThe acute hyperglycemia study included 22 type 1 diabetic individuals with normal albumin excretion rate (AER) and 13 non-diabetic controls. These individuals received an acute glucose challenge during a 120-minute hyperglycemic clamp. The chronic hyperglycemia study included 118 type 1 diabetic individuals with chronically low (n = 60) or high (n = 58) HbA1c concentrations and varying degrees of diabetic kidney disease (DKD) classified as normal, moderate, or severe albuminuria (AER). Levels of malondialdehyde (MDA), reactive oxygen metabolites (ROMs), total antioxidant capacity (TAC), biological antioxidant potential (BAP) and superoxide dismutase (SOD) were measured from plasma or serum samples in the FinnDiane study.ResultsLevels of MDA (p < 0.01) and ROMs (p < 0.01) were elevated in type 1 diabetes individuals compared to non-diabetic controls at baseline. Acute hyperglycemia further increased MDA levels (p < 0.05) and sustained the elevation of ROMs in type 1 diabetes individuals. Acute hyperglycemic challenge impaired TAC in both non-diabetic (p < 0.05) and type 1 diabetes (p < 0.01) individuals compared to baseline whereas BAP was increased (p < 0.05) with no difference observed in non-diabetic controls. There was a positive association between high circulating MDA and AIx (r2 = 0.611, p = 0.05), and between delta ROMs and delta AIx (r2 = 0.955, p = 0.014) in combined analysis of individuals with type 1 diabetes and non-diabetic controls. Type 1 diabetes individuals with varying status of DKD, showed elevated levels of ROMs in those with high HbA1c compared to their counterpart with low HbA1c (p < 0.05). Individuals with severe albuminuria showed elevated ROM levels (p < 0.01) and depressed antioxidant capacity (p < 0.01) compared to those with normal AER of comparable HbA1c concentrations.ConclusionsBiomarkers of oxidative stress are associated with vascular stiffness and DKD following acute and chronic hyperglycemic exposure and may provide added value to HbA1c in understanding disease pathology, predicting risk and assessing the status of secondary complications of type 1 diabetes.

Tele-Pulmonary Rehabilitation and Mediterranean-like Lifestyle, Adjunctively to Continuous Positive Airway Pressure in Obstructive Sleep Apnea Patients: Effects in Fitness and Oxidative Indicators

Obstructive sleep apnea (OSA), often overlooked by clinicians, may lead to negative outcomes if left untreated. In this study, we examined the efficacy and efficiency of a 12-week unsupervised tele-rehabilitation program in OSA patients and focused on the potential changes in their fitness indicators and oxidative status. Forty OSA patients were allocated into two groups: the CPAPgroup (AHI 52.0 ± 31.5 events/h; age, 49.7 ± 9.4 years; BMI, 32.1 ± 7.6 kg/m2; control group) versus the non-CPAPgroup (AHI 38.2 ± 21.5 events/h; age, 49.3 ± 10.7 years; BMI, 32.3 ± 5.1 kg/m2; intervention group; personalized recommendations for nutrition—based on the Mediterranean diet—and exercise programs). Measurements included anthropometric characteristics and body composition through whole-body bioelectrical impedance analysis. In addition, participants underwent blood sampling for reactive oxygen metabolites’ levels (d-ROM), plasma antioxidant capacity (PAT), and Lipoprotein (a) (Lp(a)), as well as a 6 min walk test (6MWT). Statistically significant differences were detected in both groups (CPAPgroup versus non-CPAPgroup) after 12 weeks between Lp(a) (−32.2 ± 25.5%, p = 0.021 versus −17.7 ± 16.3%, p = 0.034) and 6MWT (16.6 ± 9.3%, p &lt; 0.001 versus 7.5 ± 6.6%, p = 0.002). ΔNRO2 (oxygen saturation difference between nadir during sleep and resting awake) was significantly associated with d-ROMs levels (p = 0.045), resting mean arterial pressure (p = 0.024), and chest circumference in maximal inhalation and exhalation (Δchest, p &lt; 0.001). To conclude, lifestyle interventions with unsupervised tele-exercise-rehabilitation pulmonary programs and Mediterranean-like diet may serve as adjunctive-to-CPAP therapeutic elements.

Effects of Melatonin on Exercise-Induced Oxidative Stress in Adults with Obesity Undergoing a Multidisciplinary Body Weight Reduction Program.

Background: Obesity is characterized by increased oxidative stress, which, in a vicious circle, promotes chronic low-grade inflammation. Melatonin, a well-documented antioxidant, might be useful as a supplement to enhance the cardiometabolic benefits of any body weight reduction program (BWRP). Objectives/Methods: The present study aimed to evaluate the post-exercise oxidative stress and inflammation in a group of subjects with obesity treated with melatonin (2 mg/die) or placebo, undergoing a 2-week BWRP, with the administration of a single bout of acute exercise at the start and the end of the protocol (G1-G15). Results: Eighteen adults with obesity were enrolled and distributed to the two arms of the study: the melatonin group (F/M: 7/2; age: 27.8 ± 5.6 years; body mass index [BMI]: 43.0 ± 4.9 kg/m2) and the placebo group (F/M: 6/3; age: 28.8 ± 5.0 years; BMI: 42.8 ± 4.0 kg/m2). BWRP induced a decrease in BMI and waist circumference (WC) in both groups; plasma glucose, blood glycated hemoglobin (HbA1c), and neutrophil to lymphocyte ratio (NLR) were reduced only in the placebo group. Importantly, plasma biological antioxidant potential (BAP) increased throughout BWRP. Paradoxically, melatonin enhanced post-exercise production of plasma derivatives of reactive oxygen metabolites (d-ROMs) and erythrocytic glutathionyl-Hb (HbSSG) (at G1 and G15). Finally, differently from the placebo group, melatonin-treated subjects did not exhibit the BWRP-induced decrease in plasma levels of interleukin-6 (IL-6), before and after exercise, at the end of two weeks (G15). Conclusions: Melatonin is presumably an antioxidant with "conditional" prooxidant actions. The use of melatonin as a supplement in subjects with obesity might be deleterious due to the abolishment of BWRP-induced cardiometabolic benefits.

Understanding the Role of Oxidative Stress in Platelet Alterations and Thrombosis Risk among Frail Older Adults.

Frailty and cardiovascular diseases are increasingly prevalent in aging populations, sharing common pathological mechanisms, such as oxidative stress. The evidence shows that these factors predispose frail individuals to cardiovascular diseases but also increase the risk of thrombosis. Considering this background, this review aims to explore advances regarding the relationship between oxidative stress, platelet alterations, and cardiovascular diseases in frailty, examining the role of reactive oxygen species overproduction in platelet activation and thrombosis. The current evidence shows a bidirectional relationship between frailty and cardiovascular diseases, emphasizing how frailty not only predisposes individuals to cardiovascular diseases but also accelerates disease progression through oxidative damage and increased platelet function. Thus, oxidative stress is the central axis in the increase in platelet activation and secretion and the inadequate response to acetylsalicylic acid observed in frail people by mitochondrial mechanisms. Also, key biomarkers of oxidative stress, such as isoprostanes and derivate reactive oxygen metabolites, can be optimal predictors of cardiovascular risk and potential targets for therapeutic intervention. The potential of antioxidant therapies in mitigating oxidative stress and improving cardiovascular clinical outcomes such as platelet function is promising in frailty, although further research is necessary to establish the efficacy of these therapies. Understanding these mechanisms could prove essential in improving the health and quality of life of an aging population faced with the dual burden of frailty and cardiovascular diseases.

Rumen-protected methionine supplementation during the transition period under artificially induced heat stress: Effects on cow-calf performance

This study aimed to evaluate the effects of rumen-protected Met on lactation performance, inflammation and immune response, and liver glutathione of lactating dairy cows during a subclinical mastitis challenge (SMC). Thirty-two Holstein cows (145 ± 51 DIM) were enrolled in a randomized complete block design. At -21 d relative to the SMC, cows were assigned to dietary treatments, and data were collected before and during the SMC. Cows were blocked according to parity, DIM, and milk yield and received a basal diet (17.4% CP; Lys 7.01% MP and Met 2.14% MP) plus 100 g/d of ground corn (CON; n = 16) or a basal diet plus 100 g/d of ground corn and rumen-protected Met (SM, Smartamine M at 0.09% of dietary DM; n = 16), fed as a top-dress. At 0 d, the mammary gland's rear right quarter was infused with 100,000 cfu of Streptococcus uberis (O140J). Milk yield was recorded twice daily from 0 until 3 d relative to SMC. Milk samples were collected during each milking from 0 to 3 d relative to SMC, blood samples were collected at 0, 6, 12, 24, 48, and 72 h relative to SMC. The mTOR pathway activation was assessed in immune cells in blood and milk samples by measuring quantity and phosphorylation status of mTOR-related proteins, including AKT, S6RP, and 4EBP1. For the ratio of phosphorylated to total AKT, S6RP, and 4EBP1, blood samples were collected at 0, 12, and 24 h, and milk samples at 24 h relative to SMC. Liver biopsies were performed at -10 d and 24 h relative to SMC for measurement of glutathione. Linear mixed models with repeated measures were used to analyze the results. There was a trend for greater milk yield per milking (+ 0.8 kg) and per day (+1.7 kg) after SMC in SM cows compared with CON. The DMI was not affected by dietary treatments. Reactive oxygen metabolites (ROM) were lower in SM cows than in CON. Milk somatic cell linear score was not affected by dietary treatments, and a score >4 at 24 h confirmed subclinical mastitis. The SM cows had greater milk fat percentage at 24 and 36 h post SMC, resulting in overall greater milk fat. Milk protein tended to be greater in SM cows than in CON. We observed greater liver glutathione in SM cows than in CON. Among inflammation biomarkers, ceruloplasmin was lower for SM cows compared with CON. In milk, greater pAKT:AKT and pS6RP:S6RP ratios were observed in immune cell populations from SM cows compared with CON. Blood neutrophils had a greater p4EBP1:4EBP1 ratio in SM cows compared with CON. Overall, our results show that Met supplementation during an SMC positively affected milk performance, lowered the risk of oxidative stress, and attenuated inflammation partially by increasing liver glutathione and immune cells' protein synthesis via mTOR signaling.

From Vineyard to Vision: Efficacy of Maltodextrinated Grape Pomace Extract (MaGPE) Nutraceutical Formulation in Patients with Diabetic Retinopathy.

Despite recent advances, pharmacological treatments of diabetic retinopathy (DR) do not directly address the underlying oxidative stress. This study evaluates the efficacy of a nutraceutical formulation based on maltodextrinated grape pomace extract (MaGPE), an oxidative stress inhibitor, in managing DR. A 6-month, randomized, placebo-controlled clinical trial involving 99 patients with mild to moderate non-proliferative DR was conducted. The MaGPE group showed improvement in best-corrected visual acuity (BCVA) values at T3 (p < 0.001) and T6 (p < 0.01), a reduction in CRT (at T3 and T6, both p < 0.0001) and a stabilization of vascular perfusion percentage, with slight increases at T3 and T6 (+3.0% and +2.7% at T3 and T6, respectively, compared to baseline). Additionally, the levels of reactive oxygen metabolite derivatives (dROMs) decreased from 1100.6 ± 430.1 UCARR at T0 to 974.8 ± 390.2 UCARR at T3 and further to 930.6 ± 310.3 UCARR at T6 (p < 0.05 vs. T0). Similarly, oxidized low-density lipoprotein (oxLDL) levels decreased from 953.9 ± 212.4 µEq/L at T0 to 867.0 ± 209.5 µEq/L at T3 and markedly to 735.0 ± 213.7 µEq/L at T6 (p < 0.0001 vs. T0). These findings suggest that MaGPE supplementation effectively reduces retinal swelling and oxidative stress, contributing to improved visual outcomes in DR patients.

Assessing the Peripheral Levels of the Neurotransmitters Noradrenaline, Dopamine and Serotonin and the Oxidant/Antioxidant Equilibrium in Circus Horses.

Due to the paucity of information on circus management effects on the welfare of horses, this study investigated the plasma concentrations of noradrenaline, dopamine and serotonin, known to be indices of mental status, as well as the reactive oxygen metabolites (d-Roms) and the biological antioxidant potential (BAP), likely to denote the oxidant/antioxidant equilibrium of organisms, in horses managed in different Italian circuses. For the study, 56 circus horses of different breeds and ages were enrolled and divided into six groups according to the horses' management (circus management, groups G1-G5; classic riding management representing the control group, CG). From each horse, blood samples were collected in order to assess the concentration of selected parameters. One-way ANOVA showed no differences (p > 0.05) in serotonin, dopamine, noradrenaline, d-Roms and BAP values between circus and control horses. No differences related to the breed of the horses enrolled in the study were found in the values of all investigated parameters (p > 0.05). Furthermore, neurotransmitters showed overlapping levels between the different age classes of investigated horses (p > 0.05); contrariwise, the age of the horse displayed a significant effect on BAP values, with the oldest horses (16-21 age class) exhibiting lower BAP values compared to 4-5, 6-10 and 11-15 age classes (p < 0.05), whereas the d-Roms showed similar values in horses of different age classes (p > 0.05). The results gathered in the present study suggest that the mental status of horses under circus management was not compromised; however, better attention and care in the management of older horses is advocated, as they showed a lower biological antioxidant potential than younger horses; thus, they could be more susceptible to oxidative stress.

Impact of dietary fat types on expression levels of dopamine and serotonin transporters in the ileum of broiler chickens

Various types of dietary fats undergo distinct fermentation processes by gut microbes, potentially leading to the production of neurotransmitters that can influence the gut. Serotonin and dopamine are recognized neurotransmitters with positive effects on gut function. A broiler chicken trial was conducted to evaluate the influence of dietary fat types on protein expression of 2 neurotransmitter transporters, dopamine (DAT) and serotonin (5-HTT). A total of 560 day-old (Ross 708) male broiler chicks were randomly assigned to 7 dietary treatments. The experimental treatments included a basal diet of corn-soybean meal (SBM), supplemented with 3% of various fats: poultry fat (CON), olive oil (OLIV), fish oil (FISH), canola oil (CANO), lard (LARD), coconut oil (COCO), or flaxseed oil (FLAX). Bodyweight (BW) and feed conversion ratio (FCR) were recorded. Ileal tissues were aseptically collected to determine the expression levels of DAT and 5-HTT through western blot analysis. In addition, plasma samples were analyzed for reactive oxygen metabolites (d-ROM) tests on d 55. Results showed that dietary fat type inclusion did not have any detrimental effect on growth performance parameters. The expression levels of DAT were higher (P < 0.05) in FLAX treatments compared to CON treatments on d 20 and d 55, respectively. Similarly, with 5-HTT levels, FLAX, CANO, and LARD treatments were higher (P < 0.05) than CON treatments on d 20 and d 55. However, higher levels of oxidative stress (d-ROM values) were recorded in COCO (32.75 Carr U), CANO (29 Carr U), and CON treatments (25.5 Carr U) compared to FLAX (18.5 Carr U; P < 0.05) treatment. These findings suggest that incorporating dietary flaxseed oil at a 3% level in the diet has significant potential to elevate the expression levels of intestinal DAT and 5-HTT without inducing oxidative stress.