Plasma Malondialdehyde Levels Research Articles

Phytosterol supplementation enhances the growth performance, feed utilization, antioxidant status and glucose metabolism of juvenile largemouth bass (Micropterus salmoides) fed a high-starch diet

IntroductionPrevious studies found that phytosterols could influence growth performance, feed utilization and lipid metabolism as well as improve the antioxidant capacity of animals.MethodsTo investigate the effects of dietary phytosterol supplementation on juvenile largemouth bass (Micropterus salmoides) fed a high-starch diet, a 56- day feedingtrial was conducted with four dietary feeds for juvenile largemouth bass: extruded floating feed isonitrogenous and isoenergetic diets were formulated to contain 10% and 15% α-starch; on the basis of a 15% α-starch diet, two other diets were formulated with supplementation of 0.1% and 0.5% phytosterol, respectively. After the feeding trials, the survival rate, weight gain and specific growth rate, feed conversion ratio, intraperitoneal fat ratio, feed intake, protein efficiency ratio and activities of three digestive enzymes, as well as the concentrations of nine plasma biochemical indices, hepatic enzyme activities and glycogen contents, were measured and calculated, and the data were statistically analyzed.ResultsThe results of the present study showed that the survival rate, weight gain and specificgrowthrates were significantly greater in plants fed high-starch diets supplemented with phytosterols. As the supplemental phytosterol concentration increased, the feed conversion ratio and intraperitoneal fat ratio significantly decreased; the protease and lipase levels in the pyloric zone markedly increased; the plasma cholesterol, triglyceride, glucose, malondialdehyde, aspartate transaminase and alanin transaminase levels significantly decreased; the glucokinase and pyruvate kinase levelsmarkedly increased; and the hepatic glycogen content significantly decreased.DiscussionIn summary, dietary phytosterol supplementation promoted the growth performance, feed utilization and antioxidant status of juvenile largemouth bass fed a highstarch diet; enhanced glucose utilization and metabolism; and alleviated the negative stimulation of glycemia stress in M. salmoide fed a high-starch diet.

STUDY OF PHYSIOLOGICAL AND BIOCHEMICAL VARIATIONS IN POPULATION GROUPS UNDERGOING ACUTE OR CHRONIC STRESS

Objective: Stress arises from derangements of personal and professional activities. The basic reason is changes in lifestyle and psychosocial adaptations. Life becomes demanding, complicated, mechanical, and devoid of health. In today’s modern world, occupational stress has become the major factor for loss of health and peacefulness of mind. Methods: This is an observational descriptive study which was conducted in a group of 84 people between 25 and 60 years of age to study the association of acute stress on salivary amylase level and effect of chronic stress on lipid profile, glycosylated hemoglobin and certain inflammatory markers in people representing different forms of stress. Three groups of the population were studied. Group 1 (n=20) - Patients undergoing any elective surgery (abdominal/genitourinary) or an invasive diagnostic procedure (upper GI endoscopy, lymph node biopsy) Group 2 (n=32) – High/middle socio-economic male or female working for ≥8 h/day with or without stress. Group 3 (n=32) – Low socioeconomic male or female earning <100 Rs/day with or without stress. Salivary alpha-amylase and chromogranin A (CgA) levels are good markers of stress. Results: There was increased levels of cortisol (p<0.0001), alpha amylase (p<0.01), and decreased levels of CgA (p<0.001) pre-procedure period as a marker of acute stress. In the chronic stress group of low income as well as high-income status, glycosylated hemoglobin, and blood lipid profile in both males and females were significantly deranged. Plasma malondialdehyde (MDA) levels and interleukin (IL)-1 and IL-2 were significantly raised in both groups. Serum ferritin level was low in the low socioeconomic group but normal in the high socioeconomic group. Conclusion: Salivary amylase level was raised in acute stress and there is a direct correlation of chronic stress with high low-density lipoprotein/ high-density lipoprotein ratio, raised glycosylated Hemoglobin, serum MDA, IL-1, 2 levels irrespective of economic group.

Longitudinal Assessment of Oxidative Stress Markers in Women with Preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disorder and a major contributor to maternal and fetal morbidity and mortality. Role of oxidative stress in early pregnancy with the pathophysiology of the disorder is unclear. The current study aims to analyse maternal levels of oxidative stress markers (MDA and protein carbonyl) longitudinally across gestation and placental levels of oxidative stress markers (MDA, protein carbonyl and 8-oxo-2'-deoxyguanosine) in women with PE and compare them with non-PE women. 324 pregnant women (216 non-PE and 108 PE women) were longitudinally followed during pregnancy. Women with preeclampsia were stratified as early onset preeclampsia (EOP) and late onset preeclampsia (LOP) Maternal blood at four time points across gestation (11-14weeks, 18-22weeks, 26-28weeks, and at delivery) and placenta were collected. Maternal and placental levels of oxidative stress markers were assessed using commercially available kits. Maternal plasma MDA and protein carbonyl levels were comparable between the PE and non-PE group at all timepoints across gestation. Maternal plasma MDA were significantly higher levels at 26-28weeks in EOP women when compared to non-PE women (p < 0.05). Placental 8-oxo-dG levels were lower in the EOP group as compared to non-PE (p < 0.05). Elevated plasma MDA levels were positively associated with birth length at 18-22weeks and 26-28weeks in the PE group (p < 0.05 for both). Maternal plasma MDA levels were positively associated with systolic blood pressure at 18-22weeks. Oxidative stress in early pregnancy is not associated with risk of PE.

ML365 ameliorates postoperative cognitive impairment in aged mice by inhibiting NLRP3 inflammasome activation in the hippocampus

The aim of this study was to examine the effects of ML365, a two-pore potassium channel (K2P) inhibitor, on postoperative cognitive impairment (POCD). A mouse model of POCD was constructed by subjecting aged C57BL/6 mice to exploratory laparotomy. Changes in cognitive function were assessed using the Morris water maze test. Western blotting and qPCR were used to detect hippocampal NLRP3, Caspase-1 and IL-1β expression levels on days 3 and 7 post-surgery. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression level was also assessed by western blotting. Pathological changes and nerve damage in the hippocampal CA1 and CA3 regions were detected by H&E staining, while the concentration of malondialdehyde (MDA) in the plasma was measured. We found that pretreatment with ML365 (administered intraperitoneally at a dose of 10 mg/kg) 30 min prior to exploratory laparotomy effectively ameliorated POCD in mice. ML365 pretreatment also reduced NLRP3, Caspase-1, ASC and IL-1β expression levels in the hippocampus, improved POCD-induced pathological changes in the hippocampal CA1 and CA3 areas of aged mice, and decreased levels of plasma MDA and oxidative stress. Together, our findings indicate that ML365 can alleviate POCD in mice by inhibiting NLRP3 inflammasome activation in the hippocampus.

MTHFRC 677T Gene Polymorphism and Homocysteine in North China Patients with Varicocele

To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, homocysteine, and male infertility with varicocele in North China. One Hundred infertile males with varicocele (VC; grade II-III, VC group) and 100 healthy males with normal semen parameters and no varicocele (NC group) were recruited for PCR microarray, blood and semen testing. Compared with the CC genotype in the NC group, the TT genotype in the NC group and the CC genotype in the VC group showed no significant changes in sperm motility (P=0.191; P=0.130), sperm density (P=0.591, P=0.643), plasma homocysteine level (P=0.511; P=0.677), and seminal plasma MDA (P=0.752; P=0.451). In contrast, VC patients with the TT genotype had higher plasma homocysteine level and seminal plasma MDA levels (P &lt;0.001), lower partial pressure of oxygen in seminal pulse (PO2; P &lt;0.001) and poorer sperm quality (P &lt;0.001), as compared with the CC genotype. This suggests that MTHFR C677C&gt;T may not be a risk factor for male Varicocele in North China. However, this may affect the oxidative stress associated with homocysteine expression, which in turn affects semen parameters in VC patients. Larger studies are needed to validate our findings.

Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study.

A particular attribute of the brain lies in the ability to learn, acquire information from the environment, and utilize the learned information. Previous research has noted that various factors (e.g., age, stress, anxiety, pathological issues), including antipsychotic medications, affect the brain and memory. The current study aimed to reveal the effects of chronic metformin treatment on the cognitive performance of rats and on commonly measured markers for oxidative stress. Wistar male rats (n = 40) were randomly divided into four groups: CTR (n = 10)-control group, METF (n = 10)-animals receiving metformin 500 mg/kg, HAL (n = 10)-animals receiving haloperidol 2 mg/kg, and HALMETF (n = 10)-animals receiving haloperidol 2 mg/kg and metformin 500 mg/kg. The medication was administered daily by oral gavage for 40 days. Memory and learning were assessed using the Morris Water Maze (MWM) test. At the end of the MWM, the rodents were decapitated under anesthesia, and the brain and blood samples were assayed by liquid chromatography for markers of oxidative stress (malondialdehyde, MDA, reduced/oxidized glutathione ratio, GSH/GSSG). The quantification of brain-derived neurotrophic factor (BDNF) was performed using the conventional sandwich ELISA technique. In the HALMETF group, metformin attenuated the negative effects of haloperidol. Brain and plasma MDA levels increased in the HAL group. Brain and plasma GSH/GSSG ratios and BDNF levels did not reveal any differences between groups. In conclusion, metformin treatment limits the deleterious cognitive effects of haloperidol. The effect on oxidative stress markers may also point toward an antioxidant-like effect of metformin, but this needs further tests for confirmation.

Oxidative stress and pro-inflammatory cytokines following perchloroethylene exposure in young female dry-cleaning workers.

The involvement of Perchloroethylene (PCE) in the development of autoimmune diseases has been reported. However, few studies investigated immunotoxicity in PCE-exposed workers. To study changes in the oxidative stress and cytokine profile of young female dry-cleaning workers exposed to PCE. Thirty-eight exposed workers and 38 unexposed controls were recruited. All the participants were young nonsmoker females. Individual interviews were conducted by a physician. Blood samples were collected and hematological tests were performed by an automated Coulter Counter. Plasma PCE levels were determined using gas chromatography/flame ionization detection. Plasma total antioxidant capacity (TAC), Catalase (CAT), Superoxide dismutase (SOD), and Malondialdehyde (MDA) levels were measured using the colorimetric method. The levels of plasma cytokines interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by commercially kits. The levels of plasma PCE averaged 561±96 ng/ml in the exposed group compared with 1.3±0.5 ng/ml in the controls. The hematological tests failed to find abnormalities in the exposed workers. Exposed workers presented significantly increased plasma levels of MDA, SOD and CAT. There were no significant differences between the two groups for level of plasma TAC. Significantly increased plasma IL-1β and TNF-α and decreased IL-2 and IL-8 levels were seen in the exposed workers. There were no significant differences between the two groups for IL-4, IL-6, and IFN-γ. PCE exposure resulted in changed cytokine profile in dry-cleaning workers, suggesting the potential immunotoxicity of PCE at low exposure levels.

Hinokitiol attenuates gentamicin-induced nephrotoxicity by reversing oxidative stress and inflammation

IntroductionGentamicin (GEN) is a nephrotoxic aminoglycoside antibiotic, Hinokitiol, also known as (sng yóu chn) in traditional Chinese medicine (TCM), is a natural substance derived from the wood of certain coniferous trees, whereas hinokitiol (HE) has anti-inflammatory and antioxidant effects. This study aims to determine the protective role of HE in GEN-induced kidney injury. MethodsAdult male Wistar rats were separated into three groups: one treated with GEN, one treated with GEN plus pre-treated with HE, and one treated with vehicle. The levels of creatinine, urea, malondialdehyde (MDA), and superoxide dismutase (SOD) in the blood were measured. Histopathological alterations in renal tissues were evaluated, and inflammatory markers (TNF- α, NF-κB) were detected. ResultsGEN-induced nephrotoxicity raised plasma creatinine, urea, and MDA levels while decreasing SOD levels. The combination of HE and GEN considerably reduced these effects. Renal tissues from GEN-treated rats showed lymphoid infiltration and tubular atrophy, whereas these were significantly decreased in the HE pre-treatment group. HE pre-treatment substantially reduced elevated TNF-α and NF-κB in GEN-administered animals. ConclusionThe study shows that HE protects against GEN-induced kidney damage, attributed to decreased oxidative stress and inflammatory pathways. These findings point to the possible therapeutic utility of HE in the treatment of GEN-related nephrotoxicity.

Oxidative Stress Markers During Summer and Rainy Season in Deccani Sheep

The present study was designed to study the effect of two different seasons (summer and rainy) on the activities of some oxidative stress markers (SOD, GSHPx and MDA) in Deccani sheep. The experiment was carried out at the Department of Veterinary Physiology, KNP College of Veterinary Science, and Shirwal. Dist. Satara on eight apparently healthy, non-pregnant, non-lactating Deccani sheep above two years of age maintained under semi-intensive housing conditions at Livestock Farm Complex, KNP College of Veterinary Science, Shirwal, Dist. Satara. The meteorological data recorded during the present study were obtained from the Indian Meteorological Department, Pune. The monthly calculated mean values of THI during the study period revealed significantly (P &lt; 0.01) higher THI during Summer (77.81 ± 0.19) than in the Rainy season (74.92 ± 0.16). In the present study, the mean plasma activity of SOD was significantly (P &lt; 0.01) higher during the summer season (510.93 ± 24.77 U/ ml) than in the rainy season (436.58 ± 26.30 U/ ml). The mean erythrocyte activity of glutathione peroxidase showed significantly (P &lt; 0.05) higher values in the summer season than in the rainy season (102.12 ± 5.03 U/gHb and 85.63 ± 3.89 U/gHb). The mean plasma levels of MDA were significantly (P &lt; 0.01) higher during the summer season (5.29± 0.09 nmol/ml ) than in the rainy season (3.27± 0.09 nmol/ml). The finding indicates that oxidative stress markers like SOD, GSHPx and MDA could be used as a sensitive biomarker of oxidative stress caused due to heat stress in Deccani sheep.

In vitro Effects of Propofol and Bupivacaine on Pregnant Women’s Plasma Cholinesterase Activity and Malondialdehyde Level

Background: Propofol and bupivacaine are commonly used anesthetics for cesarean section (CS), and they might modulate plasma cholinesterase (ChE) activity and oxidative stress during the last stage of pregnancy. This study aimed to assess the in vitro effects of propofol and bupivacaine on plasma ChE activity and malondialdehyde (MDA) levels in pregnant women before undergoing elective CS. Methods: The plasma samples of 20 women set for elective CS were pooled for the in vitro determination of the effects of propofol and bupivacaine separately on plasma ChE activity (10 minutes of incubation with different concentrations at 37ºC) and the MDA level after the in vitro exposure of plasma samples containing different anesthetic concentrations to H2O2 (100 µM, incubated for 1 hour at 37ºC). Results: Bupivacaine at 1.1 and 2.2 µM significantly inhibited plasma ChE in vitro in a concentration-dependent manner by 13% and 20%, respectively. Propofol at 25 and 50 µM did not affect plasma ChE. A unique finding in this study was that both propofol and bupivacaine revealed an antioxidant effect, as both propofol at concentrations of 25, 50, and 100 µM and bupivacaine at 1.1, 2.2, and 4.4 µM reduced the MDA level in a concentration-dependent manner in vitro after the incubation of plasma samples with H2O2 as a source of oxidant. Conclusions: The in vitro findings suggest that bupivacaine exerts anti-ChE activity that should be taken into consideration in CS anesthesia, and both propofol and bupivacaine possess antioxidant properties that need additional clinical studies.

Bonny Light Crude Oil Toxicity: Histopathological and Biochemical Upshots on Cardiac and Hepatocellular Tissues

Aim: Evaluate the acute toxicity effect of bonny light crude oil on histopathological and biochemical disrupting effects on cardiac and hepatocellular tissues. Oil spills, gas flaring, natural seeps, industrial discharge, and the destruction of ecosystems have led to ecological devastation, health problems, and socioeconomic challenges for communities in the Niger Delta; one of the world's largest oil-producing regions. Crude oil spillage has been a persistent and severe environmental concern in the Niger Delta for many years. The spilled oil covers water surfaces, diminishes oxygen levels, and poses significant health risks to aquatic life, birds, loss of biodiversity, and the well-being of the human population that heavily relies on these resources for their sustenance. Study Design: A total of 50 albino rats were randomly divided into three (3) groups; control group, low dose group, and high dose group. The control group consisted of 10 albino rats while the low dose and high dose groups consisted of 20 albino rats each. The control group was fed with normal (uncontaminated) rat feeds and sterile water only (that is, a dosage of 0.00mL/g of rat feed), and the low dose (0.005mL/g) group was fed with 300g of rat feeds mixed with 1.5mL of BLCO while high dose (0.01mL/g) group was fed with 300g of feeds mixed with 3.0mL of BLCO. The treated feeds were administered once every day for 35 days. Methodology: After day 35, the rats were allowed to fast overnight and anesthetized with chloroform (CHCl3). Blood specimens (5 ml) were collected by slitting the neck of the rats into an anticoagulant labeled bottle. The livers and hearts of the experimental rats were harvested and preserved in 10% formalin in different labeled plastic containers prior to tissue processing and histological examinations. Blood specimens were centrifuged at 4500 rpm for 10 minutes to obtain plasma. Plasma levels of ALT, AST, ALP, cTnT, cTnI, MDA, and SOD were estimated. All weights were measured in grams. Results: The result indicated that low and high-dose treated groups showed a significant decrease in body weight. The SOD and MDA indicated significantly lower and higher values respectively in the low and high-dose treated groups when compared to the control rats. However, no significant difference in SOD values was seen between the low and high dose treated groups. The ALT, AST, and ALP values indicated significantly higher values in the low and high-dose treated groups compared to the control group. More so, dose-dependent increases were also observed in AST and ALT. However, ALP indicated no significant difference between the control and the low-dose treated rats. In addition, cTnT and cTnI values indicated significantly higher values in the low and high-dose treated groups compared to the control group. However, cTnT and cTnI indicated no significant difference between the high-dose and the low-dose treated rats. The P value was set to P=.05 Conclusion: Bonny light crude oil in feed at small doses over a period of 35 days induced myocardial and hepatic injuries indicated by increased levels of AST, ALT, ALP, cTn-T, and cTn-I. More so, histopathological changes further showed the disrupting changes in hepatic and cardiac tissues.

Assessment of plasma malondialdehyde levels among free-diver fishermen in southeast Maluku district: exploring influencing factors on oxidative stress.

Indonesia, with its expansive territorial waters, hosts numerous fishing communities residing on various islands. Many of these communities rely on diving activities, predominantly free diving without standardized safety equipment. This practice poses risks, including the potential for hypoxia-induced oxidative stress, which plays a role in disease pathogenesis. This study aimed to investigate the levels of malondialdehyde (MDA) in freediving fishermen and explore potential influencing factors. The research involved 30 freediving fishermen, aged 20-60, who engaged in diving at least twice weekly over the last 3 months. Blood plasma MDA levels were assessed using the Will method. Results revealed a median age of 40.5 years (range: 20-59), a body mass index of 23.1 ± 2.8, and a mean blood pressure of 132/85 mmHg. A significant portion of the subjects exhibited smoking habits (90%) and alcohol consumption (76.7%). The median MDA level among subjects was measured at 0.42 nmol/mL (range: 0.34-0.70). However, no discernible relationship was found between smoking habits, alcohol consumption, and MDA level categories, as determined by the Fisher exact test (p > 0.05). While these findings shed light on the MDA levels in freediving fishermen, further research is warranted to explore additional factors that may influence these levels. This comprehensive understanding is crucial for addressing the health risks associated with free diving practices in this unique population.

Effects of coenzyme Q10 supplementation on oxidative stress biomarkers following reperfusion in STEMI patients undergoing primary percutaneous coronary intervention.

It is well-established that oxidative stress is deeply involved in myocardial ischemia-reperfusion injury. Considering the potent antioxidant properties of coenzyme Q10 (CoQ10), we aimed to assess whether CoQ10 supplementation could exert beneficial effects on plasma levels of oxidative stress biomarkers in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPIC). Seventy patients with the first attack of STEMI, eligible for PPCI were randomly assigned to receive either standard treatments plus CoQ10 (400 mg before PPCI and 200 mg twice daily for three days after PPCI) or standard treatments plus placebo. Plasma levels of oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured at 6, 24, and 72 hours after completion of PPCI. The changes in plasma levels of the studied biomarkers at 6 and 24 hours after PPCI were similar in the both groups (P values>0.05). This is while at 72 hours, the CoQ10- treated group exhibited significantly higher plasma levels of SOD (P value<0.001), CAT (P value=0.001), and TAC (P value<0.001), along with a lower plasma level of MDA (P value=0.002) compared to the placebo-treated group. The plasma activity of GPX showed no significant difference between the groups at all the study time points (P values>0.05). This study showed that CoQ10 has the potential to modulate the balance between antioxidant and oxidant biomarkers after reperfusion therapy. Our results suggest that CoQ10, through its antioxidant capacity, may help reduce the reperfusion injury in ischemic myocardium.

Insights into Dietary Different Co-Forms of Lysine and Glutamate on Growth Performance, Muscle Development, Antioxidation and Related Gene Expressions in Juvenile Grass Carp (Ctenopharyngodon idellus).

The study aimed to compare the effects of crystalline L-lysine and L-glutamate (CAA), Lys-Glu dipeptide (KE) on the growth and muscle development of grass carp (Ctenopharyngodon idellus), and related molecular mechanisms. Five experimental diets (CR, 0.5% CAA, 1.5% CAA, 0.5% KE, 1.5% KE) containing Lys and Glu as free (Lys and Glu, CAA) dipeptide (Lys-Glu, KE) forms were prepared, respectively. A total of 450 juvenile grass carp with an initial weight of 10.69 ± 0.07g were randomly assigned to 15 cages, and 5 treatments with 3 replicates of 30 fish each for 61days of feeding. The results showed that the group of 0.5% KE exhibited the best growth performances according to the indicator's weight gain rate (WGR) and specific growth rate (SGR), although no statistically significant occurred among all groups; diet supplemented with 0.5% CAA significantly elevated the condition factor (CF) and viscerasomatic index (VSI) of juvenile grass carp. Diet supplemented with different Lys and Glu co-forms at different levels promoted the muscle amino acid content compared with those of CR group. Comparing with the CR group and other groups, the hardness of 0.5% CAA group significantly increased, and the springiness of 0.5% KE group excelled. Both the muscle fiber diameter and density of 0.5% KE group showed significant difference with those of the CR group, and a negative correlation between them was also observed. To uncover the related molecular mechanism of the differences caused by the different co-forms of Lys and Glu, the effect of different diets on the expressions of protein absorption, muscle quality, and antioxidation-related genes was analyzed. The results suggested that comparing with those of CR group, the dipeptide KE inhibited the expressions of genes associated with protein metabolism, such as AKT, S6K1, and FoxO1a but promoted PCNA expression, while the free style of CAA would improve the FoxO1a expression. Additionally, the muscle development-related genes (MyoD, MyOG, and Myf5) were significantly boosted in CAA co-form groups, and the expressions of fMYHCs were blocked but fMYHCs30 significantly promoted in 0.5% KE group. Finally, the effect of different co-forms of Lys and Glu on muscle antioxidant was examined. The 0.5% CAA diet was verified to increase GPX1a but obstruct Keap1 and GSTP1 expressions, resulting in enhanced SOD activity and reduced MDA levels in plasma. Collectively, the different co-forms of Lys and Glu influenced the growth of juvenile grass carp, and also the muscle development and quality through their different regulation on the protein metabolism, muscle development- and antioxidative-related genes.

Effect of organic mineral supplementation in reducing oxidative stress in Holstein calves during short-term heat stress and recovery conditions

BackgroundThis study investigated the effects of inorganic and organic minerals on physiological responses, oxidative stress reduction, and rumen microbiota in Holstein bull calves (123.81 ± 9.76 kg; 5 months old) during short-term heat stress (HS) and recovery periods. Eight Holstein calves were randomly assigned to four treatment groups: no mineral supplementation (Con), inorganic minerals (IM), organic minerals (OM), and high-concentration organic minerals (HOM) and two thermal environments (HS and recovery) using 4 × 2 factorial arrangement in a crossover design of four periods of 35 d. Calves were maintained in a temperature-controlled barn. The experimental period consisted of 14 d of HS, 14 d of recovery condititon, and a 7-d washing period.ResultsBody temperature and respiration rate were higher in HS than in the recovery conditions (P < 0.05). Selenium concentration in serum was high in the HOM-supplemented calves in both HS (90.38 μg/dL) and recovery periods (102.00 μg/dL) (P < 0.05). During the HS period, the serum cortisol was 20.26 ng/mL in the HOM group, which was 5.60 ng/mL lower than in the control group (P < 0.05). The total antioxidant status was the highest in the OM group (2.71 mmol Trolox equivalent/L), followed by the HOM group during HS, whereas it was highest in the HOM group (2.58 mmol Trolox equivalent/L) during the recovery period (P < 0.05). Plasma malondialdehyde and HSP70 levels were decreased by HOM supplementation during the HS and recovery periods, whereas SOD and GPX levels were not significantly affected (P > 0.05). The principal coordinate analysis represented that the overall rumen microbiota was not influenced by mineral supplementation; however, temperature-induced microbial structure shifts were indicated (PERMANOVA: P < 0.05). At the phylum level, Firmicutes and Actinobacteria decreased, whereas Fibrobacteres, Spirochaetes, and Tenericutes increased (P < 0.05), under HS conditions. The genus Treponema increased under HS conditions, while Christensenella was higher in recovery conditions (P < 0.05).ConclusionHOM supplementation during HS reduced cortisol concentrations and increased total antioxidant status in Holstein bull calves, suggesting that high organic mineral supplementation may alleviate the adverse effects of HS.

A Single Dose of Microencapsulated Cocoa Supplementation Does Not Speed up Muscle Force Recovery after Eccentric Exercise-Induced Muscle Damage: A Placebo-Controlled, Double-Blind, Crossover Study

Exercise-induced muscle damage is associated with symptoms such as inflammation, delayed-onset muscle soreness, and impaired muscle performance. The intake of cocoa polyphenols has been suggested to improve muscle recovery due to their antioxidant and anti-inflammatory capacity. However, their bioavailability presents a challenge. Therefore, food microencapsulation may be an alternative to protect polyphenols, ensuring their biological effects. This study aimed to investigate the effect of a single dose of microencapsulated cocoa on the changes in muscle damage markers after eccentric exercise. In this randomized, double-blind, crossover study, fourteen healthy volunteers with previous resistance training experience performed 6 × 10 maximal isokinetic eccentric contractions of their elbow flexors using an isokinetic dynamometer after ingesting 25 g of microencapsulated cocoa or placebo. Peak isometric torque was measured using maximal voluntary isometric contractions, and pain was measured using a visual analogic scale both before and 24 h, 48 h, and 72 h after the damage protocol. Plasma glutathione and malondialdehyde levels were measured using high-performance liquid chromatography, and concentrations of myoglobin and C-reactive protein were determined using a fluorescence immunoassay analyzer. Significant decreases were seen in the peak isometric torque and pain measures from pre- to 72 h post-eccentric exercise. A significant main effect for time was found only for plasma myoglobin at 2 h, 48 h, and 72 h, and for C-reactive protein at 2 h, compared to the pre-eccentric exercise values. No significant time-treatment effects were observed (all p &gt; 0.05). This study demonstrated that microencapsulated cocoa cannot improve muscle recovery after eccentric exercise, at least when a single dose is consumed.

Oxidative Stress Mediates Epigenetic Modifications and the Expression of miRNAs and Genes Related to Apoptosis in Diabetic Retinopathy Patients.

Knowledge on the underlying mechanisms and molecular targets for managing the ocular complications of type 2 diabetes mellitus (T2DM) remains incomplete. Diabetic retinopathy (DR) is a major cause of irreversible visual disability worldwide. By using ophthalmological and molecular-genetic approaches, we gathered specific information to build a data network for deciphering the crosslink of oxidative stress (OS) and apoptosis (AP) processes, as well as to identify potential epigenetic modifications related to noncoding RNAs in the eyes of patients with T2DM. A total of 120 participants were recruited, being classified into two groups: individuals with T2MD (T2MDG, n = 67), divided into a group of individuals with (+DR, n = 49) and without (-DR, n = 18) DR, and a control group (CG, n = 53). Analyses of compiled data reflected significantly higher plasma levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and significantly lower total antioxidant capacity (TAC) in the +DR patients compared with the -DR and the CG groups. Furthermore, the plasma caspase-3 (CAS3), highly involved in apoptosis (AP), showed significantly higher values in the +DR group than in the -DR patients. The microRNAs (miR) hsa-miR 10a-5p and hsa-miR 15b-5p, as well as the genes BCL2L2 and TP53 involved in these pathways, were identified in relation to DR clinical changes. Our data suggest an interaction between OS and the above players in DR pathogenesis. Furthermore, potential miRNA-regulated target genes were identified in relation to DR. In this concern, we may raise new diagnostic and therapeutic challenges that hold the potential to significantly improve managing the diabetic eye.

Oxidative Stress Induced by Chemotherapy: Evaluation of Glutathione and Its Related Antioxidant Enzyme Dynamics in Patients with Colorectal Cancer.

One of the mechanisms of chemotherapy is to increase the oxidative stress of cancer cells, leading to their apoptosis. Glutathione (GSH) and its related antioxidant enzymes might be stimulated to cope with increased oxidative stress during chemotherapy. Here, we studied the fluctuation in oxidative stress and GSH-related antioxidant capacities before tumor resection, after tumor resection, and after resection either with or without chemotherapy in patients with colorectal cancer (CRC). This was a cross-sectional and follow-up design. We followed patients before having tumor resection (pre-resection), one month after tumor resection (post-resection), and after the first scheduled chemotherapy (post-chemo). If patients were required to receive chemotherapy after tumor resection, they were assigned to the chemotherapy group. Eligible patients were scheduled to undergo six to twelve cycles of chemotherapy at 2-week intervals and received single, double, or triple chemotherapeutic drugs as required. Those patients who did not require chemotherapy were assigned to the non-chemotherapy group. Indicators of oxidative stress and GSH-related antioxidant capacities were determined at the above three time points. We found in 48 patients of the chemotherapy group and in 43 patients of the non-chemotherapy group different fluctuations in levels of oxidative stress indicators and GSH-related antioxidant capacities starting from pre-resection, post-resection through the post-chemo period. Both groups showed significantly or slightly increased levels of advanced oxidation protein products (AOPP), GSH, and its related enzymes in tumor tissues compared to adjacent normal tissues. Patients in the chemotherapy group had significantly lower plasma levels of GSH and glutathione disulfide (GSSG), but had significantly higher plasma glutathione peroxidase and glutathione reductase activities than patients in the non-chemotherapy group post-chemo. Plasma levels of malondialdehyde and AOPP were positively or negatively associated with GSH and GSSG levels post-chemo after adjustment for age, sex, and histological grading in patients receiving chemotherapy. These significant associations were, however, not seen in patients without chemotherapy. Patients with CRC may require higher GSH demands to cope with a greater oxidative stress resulting from chemotherapy.

Modification of Peripheral Blood Flow and Angiogenesis by CO2 Water-Bath Therapy in Diabetic Skeletal Muscle with or without Ischemia.

Previously, it was shown that both blood flow and angiogenesis in the ischemic hind limb of diabetic rats were increased upon CO2 treatment for 4 weeks. In the present study, we have compared the effects of 6 weeks CO2 therapy in diabetic rats with or without peripheral ischemia. Diabetes was induced in rats by a tail vein injection of streptozotocin (65 mg/kg body weight), whereas peripheral ischemia was produced by occluding the femoral artery at 2 weeks of inducing diabetes. Both diabetic and diabetic-ischemic animals were treated with or without CO2 water-bath at 37 °C for 6 weeks (30 min/day; 5 days/week) starting at 2 weeks, after the induction of ischemia. CO2 treatment did not affect heart rate and R-R interval as well as plasma levels of creatine kinase, glucose, cholesterol, triglycerides and high density lipoproteins. Unlike the levels of plasma Ox-LDL, MDA and TNF-α, the levels of NO in diabetic group were increased by CO2 water-bath treatment. On the other hand, the levels of plasma Ox-LDL and MDA were decreased whereas that of NO was increased without any changes in TNF-α level in diabetic-ischemic animals upon CO2 therapy. Treatment of diabetic animals with CO2 increased peak, mean and minimal blood flow by 20, 49 and 43% whereas these values were increased by 53, 26 and 80% in the diabetic-ischemic group by CO2 therapy, respectively. Blood vessel count in diabetic and diabetic-ischemic skeletal muscles was increased by 73 and 136% by CO2 therapy, respectively. These data indicate that peripheral ischemia augmented the increase in blood flow and development of angiogenesis in diabetic skeletal muscle upon CO2 therapy. It is suggested that greater beneficial effects of CO2 therapy in diabetic-ischemic animals in comparison to diabetic group may be a consequence of difference of changes in the redox-sensitive signal transduction mechanisms.

Mildronate Ameliorates Kidney Function and Reduces Inflammation in SCD Mice

INTRODUCTION:Sickle cell disease (SCD) is a genetic hemoglobin disorder characterized by hemolytic anemia, vaso-occlusive crisis and inflammation that affects organs such as the kidney, liver, brain, spleen, and heart. SCD is driven by a mutation in the β-globin gene that causes sickling of red blood cells (RBCs). More than 50% of SCD patients are affected by chronic kidney diseases (CKD) and other comorbidities. Vasculopathy is caused by hemolysis-related endothelial dysfunction and inflammation, which collectively contribute to the development of renal disease. Mildronate (also known as Meldonium) is an anti-ischemic and cardio protecting medication approved in Eastern Europe. Mildronate facilitates a switch from fatty acid oxidation to less oxygen-intensive glycolysis that allows less oxygen consumption by peripheral tissues and higher oxygenation of heart. We hypothesized that mildronate administration would reduce tissue hypoxia and decrease inflammation in SCD mice. METHODS: The study was approved by the Institutional Animal Care and Use Committee at Howard University (IACUC). We employed the Townes SCD mouse model, which mimics SCD complications. SCD and control mice were injected with mildronate (400 mg/kg in saline) intraperitoneally or saline as vehicle control over the course of ten days. Blood and plasma were collected and used for hematological parameters analysis. Cytokines were measured by Bio-plex suspension array in plasma and real-time RT-PCR or ELISA in organs. Protein expression of HO-1, HIF-1α, NFκB and NRF2 was measured by Western blot. The effect of Mildronateon systemic and renal oxidative stress was measured by malondialdehyde (MDA) using ELISA (Abcam). RESULTS: We observed significant reduction in the cytokine's levels of IFN-γ, IL-1, and TNF-α in plasma of SCD mice after mildronate injection. We also observed reduction in IL-6, IL-10 and IL-17 levels but differences were not statistically significant. There were no significant changes in hematological parameters (Hematocrit, MCV, MCH, CMCH, Erythrocytes, Hemoglobin) after mildronate injection. Also, we did not observe changes in MDA levels in plasma or kidney in SCD mice compared to control mice, both non-injected and mildronate injected. We further evaluated HO-1 and NRF2 protein expression by western blot and observed no significant differences between SCD mice with or without mildronate injection. In H&amp;E staining, cortex glomerular area and medullar congestion area were significantly reduced after mildronate injection. We also observed reduction of proteinuria in SCD mice injected with mildronate. DISCUSSION: Our examination of the effect of mildronate showed decreases inflammation in the mildronate injected SCD mice evidenced by reduced levels of IFN-γ, IL-1, IL-17, IL-6, IL-10, and TNF-α in circulation. There was a slight decrease in the expression levels of Nrf2 and HO-1 after mildronate injection. HO-1 is crucial for the catabolism of hemoglobin and protects against tissue damage in hemolysis. The HO-1 promoter has binding sites for several transcription factors, including phosphorylated Nrf2. Previous studies from our lab showed increased HIF-1α expression in PBMCs obtained from SCD patients. Here we did not detect significant changes in NFκB-p65 or HIF-1α expression levels. While we expected mildronate to decrease the oxidative stress, we did not observe significant reduction in MDA levels in treated mice compared to control mice. CONCLUSION: Mildronate improved kidney function in SCD mice by reducing circulatory and renal inflammation. In future, we plan to assess in more details the mildronate's impact on kidney function and inflammation. ACKNOWLEDGMENTS: This work was supported by NIH grants 1R01HL125005, 5U54MD007597, and 1SC1HL150685.