Plasma Malondialdehyde Levels Research Articles

Biochemical changes in overweight and obese patients after taking 5 mg of Tadalafil for two weeks

Background: obesity enhances a chronic inflammation and oxidative stress and damages the vascular endothelium. Tadalafil restores signaling of NO signaling and may decrease circulating oxidative stress and markers of inflammation, and improves parameters of metabolism through a number of mechanisms. The aim of this study to show what the effects of the administration of tadalafil (TAD) on inflammation, and oxidative stress markers in obese male patients. Methods: 32 male subjects with BMI more than 23 and age range 30-50 years old underwent with TAD 5mg for 14 days .Plasma level of MDA , GsH ,IL-6 and Hs-CRP before the taking of drugs and after 14 days of treatment . Results: Treatment with TAD caused a non-significant reduction in MDA group (0.093±0.027 versus 0.082± 0.032, P- value is 0.196), a non-significant increase in plasma GsH (0.1074±0.007 versus 0.109±0.009 , p-value is 0.538), a non-significant of reduction in plasma level of plasma Hs-CRP and IL-6 (4.377± 0.702 versus 4.272± 0.693, p-value is 0.599) and (24.668± 6.001 versus 23.56± 2.587 ,p-value is 0.401)respectively . Conclusion: We have concluded that TAD therapy has non –significant effect on anti-inflammatory and anti-oxidant activity if used in short term but this effect may be significant if used for long term or use large dose

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.

Acute phase reactions in Daboia siamensis venom and fraction-induced acute kidney injury: the role of oxidative stress and inflammatory pathways in in vivo rabbit and ex vivo rabbit kidney models.

This study examines the direct nephrotoxic effects of Daboia siamensis venom (RVV) and venom fractions in in vivo and isolated perfused kidneys (IPK) to understand the role of inflammation pathways and susceptibility to oxidative stress in venom or fraction-induced acute renal failure. We administered RVV and its venom fractions (PLA2, MP, LAAO, and PDE) to rabbits in vivo and in the IPK model. We measured oxidative stress biomarkers (SOD, CAT, GSH, and MDA) in kidney tissue, as well as inflammatory cytokines (TNF-α, IL-1β, IFN-γ, IL-4, IL-5, and IL-10), MDA and GSH levels in plasma and urine. We also calculated fractional excretion (FE) for pro-/anti-inflammatory cytokines and oxidative stress biomarkers, including the ratios of pro-/anti-inflammatory cytokines in urine after envenomation. In both kidney models, significant increases in MDA, SOD, CAT, and GSH levels were observed in kidney tissues, along with elevated concentrations of MDA and GSH in plasma and urine after injecting RVV and venom fractions. Moreover, RVV injections led to progressive increases in FEMDA and decreases in FEGSH. The concentrations of IL-4, IL-5, IL-10, IFN-γ, and TNF-α in plasma increased in vivo, as well as in the urine of the IPK model, but not for IL-1β in both plasma and urine after RVV administrations. Urinary fractional excretion of TNF-α, IL-1β, IFN-γ, IL-4, IL-5, and IL-10 tended to decrease in vivo but showed elevated levels in the IPK model. A single RVV injection in vivo disrupted the balance of urinary cytokines, significantly reducing either the TNF-α/IL-10 ratio or the IFN-γ/IL-10 ratio. RVV induces renal tubular toxicity by increasing oxidative stress production and elevating inflammatory cytokines in urine. During the acute phase of acute kidney injury, the balance of urine cytokines shifts toward anti-inflammatory dominance within the first two hours post-RVV and venom fractions.

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.

Can curcumin supplementation break the vicious cycle of inflammation, oxidative stress, and uremia in patients undergoing peritoneal dialysis?

Background & AimsTurmeric (a source of curcumin) is an excellent food to modulate oxidative stress, inflammation, and gut dysbiosis in patients with chronic kidney disease (CKD). However, no studies report the benefits of curcumin in patients undergoing peritoneal dialysis (PD). This study aims to evaluate the effects of curcuminoid supplementation on oxidative stress, inflammatory markers, and uremic toxins originating from gut microbiota in patients with CKD undergoing PD. MethodsThis longitudinal, randomized, single-blind, placebo-controlled trial evaluated 48 patients who were randomized into two groups: Curcumin (three capsules of 500mg of Curcuma longa extract, with 98.42% total curcuminoids) or placebo (three capsules of 500mg of starch) for twelve weeks. In the peripheral blood mononuclear cells (PBMCs), the transcriptional expression levels of Nrf2, HOX-1 and NF-κB were evaluated by quantitative real-time PCR. Oxidative stress was evaluated by malondialdehyde (MDA) and total Thiol (T-SH). TNF-α and IL-6 plasma levels were measured by ELISA. P-cresyl sulphate plasma level, a uremic toxin, was evaluated by high-performance liquid chromatography (HPLC) with fluorescent detection. ResultsTwenty-four patients finished the study: 10 in the curcumin group (57.5 ± 11.6 years) and 14 in the placebo group (56.5 ± 10.0 years). The plasma levels of MDA were reduced after 12 weeks in the curcumin group (p = 0.01), while the placebo group remained unchanged. However, regarding the difference between the groups at the endpoint, no change was observed in MDA. Still, there was a trend to reduce the p-CS plasma levels in the curcumin group compared to the placebo group (p = 0.07). Likewise, the concentrations of protein thiols, mRNA expression of Nrf2, HOX-1, NF-κB, and cytokines plasma levels did not show significant changes. ConclusionCurcuminoid supplementation for twelve weeks attenuates lipid peroxidation and might reduce uremic toxin in patients with CKD undergoing PD. This study was registered on Clinicaltrials.gov as NCT 04413266

Determination of Plasma Malondialdehyde Values as a Laboratory Index of Lipid Peroxidation Reaction in Multiple Sclerosis Patients and Its Comparison With Normal People

Background: Lipid peroxidation reaction and plasma malondialdehyde (MDA) production are important prognoses in the formation and development of neurodegenerative diseases. The link between lipid peroxidation reaction and plasma MDA in multiple sclerosis (MS) patients is poorly understood. In this study, the plasma MDA values of people with MS and normal people were measured. Methods: In this study, 70 patients with MS and 70 thermally healthy individuals were selected. Their blood samples were poured into the buffer, and the plasma was separated. Then, plasma MDA values were measured through the thiobarbituric acid (TBA) method. Results: The results showed that the values of plasma MDA in two groups of patients with MS and healthy people are 1.49±0.46 and 0.58±0.15 μmol/L, respectively. Conclusion: The findings of this research revealed that the levels of plasma MDA in MS patients are higher than those in healthy people. Therefore, these patients exhibited elevated oxidative stress.

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.

Integrating serum pharmacochemistry and network pharmacology to explore the molecular mechanisms of Acanthopanax senticosus (Rupr. & Maxim.) Harms on attenuating doxorubicin-induced myocardial injury

Ethnopharmacological relevanceAcanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. or Siberian ginseng, has a rich history of use as an adaptogen, a substance believed to increase the body's resistance to stress, fatigue, and infectious diseases. As a traditional Chinese medicine, AS is popular for its cardioprotective effects which can protect the cardiovascular system from hazardous conditions. Doxorubicin (DOX), on the other hand, is a first-line chemotherapeutic agent against a variety of cancers, including breast cancer, lung cancer, gastric cancer, and leukemia, etc. Despite its effectiveness, the clinical use of DOX is limited by its side effects, the most serious of which is cardiotoxicity. Considering AS could be applied as an adjuvant to anticancer agents, the combination of AS and DOX might exert synergistic effects on certain malignancies with mitigated cardiotoxicity. Given this, it is necessary and meaningful to confirm whether AS would neutralize the DOX-induced cardiotoxicity and its underlying molecular mechanisms. Aim of the studyThis paper aims to validate the cardioprotective effects of AS against DOX-induced myocardial injury (MI) while deciphering the molecular mechanisms underlying such effects. Materials and methodsFirstly, the cardioprotective effects of AS against DOX-induced MI were confirmed both in vitro and in vivo. Secondly, serum pharmacochemistry and network pharmacology were orchestrated to explore the in vivo active compounds of AS and predict their ways of functioning in the treatment of DOX-induced MI. Finally, the predicted mechanisms were validated by Western blot analysis during in vivo experiments. ResultsThe results demonstrated that AS possessed excellent antioxidative ability, and could alleviate the apoptosis of H9C2 cells and the damage to mitochondria induced by DOX. In vivo experiments indicated that AS could restore the conduction abnormalities and ameliorate histopathological changes according to the electrocardiogram and cardiac morphology. Meanwhile, it markedly downregulated the inflammatory factors (TNF-α, IL-6, and IL-1β), decreased plasma ALT, AST, LDH, CK, CK-MB, and MDA levels, as well as increased SOD and GSH levels compared to the model group, which collectively substantiate the effectiveness of AS. Afterward, 14 compounds were identified from different batches of AS-dosed serum and selected for mechanism prediction through HPLC-HRMS analysis and network pharmacology. Consequently, the MAPKs and caspase cascade were confirmed as primary targets among which the interplay between the JNK/Caspase 3 feedback loop and the phosphorylation of ERK1/2 were highlighted. ConclusionsIn conclusion, the integrated approach employed in this paper illuminated the molecular mechanism of AS against DOX-induced MI, whilst providing a valuable strategy to elucidate the therapeutic effects of complicated TCM systems more reliably and efficiently.

Endoplasmic Reticulum Stress Promotes the Expression of TNF-α in THP-1 Cells by Mechanisms Involving ROS/CHOP/HIF-1α and MAPK/NF-κB Pathways.

Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free fatty acids. It is debated whether the endoplasmic reticulum (ER) stress in monocytic cells can contribute to amplify metabolic inflammation; if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 cells and primary human monocytes by treatments with lipopolysaccharide (LPS), palmitic acid (PA), or oleic acid (OA), in the presence or absence of the ER stressor thapsigargin (TG). Gene expression of tumor necrosis factor (TNF)-α and markers of ER/oxidative stress were determined by qRT-PCR, TNF-α protein by ELISA, reactive oxygen species (ROS) by DCFH-DA assay, hypoxia-inducible factor 1-alpha (HIF-1α), p38, extracellular signal-regulated kinase (ERK)-1,2, and nuclear factor kappa B (NF-κB) phosphorylation by immunoblotting, and insulin sensitivity by glucose-uptake assay. Regarding clinical analyses, adipose TNF-α was assessed using qRT-PCR/IHC and plasma TNF-α, high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and oxidized low-density lipoprotein (OX-LDL) via ELISA. We found that the cooperative interaction between metabolic and ER stresses promoted TNF-α, ROS, CCAAT-enhancer-binding protein homologous protein (CHOP), activating transcription factor 6 (ATF6), superoxide dismutase 2 (SOD2), and nuclear factor erythroid 2-related factor 2 (NRF2) expression (p ≤ 0.0183),. However, glucose uptake was not impaired. TNF-α amplification was dependent on HIF-1α stabilization and p38 MAPK/p65 NF-κB phosphorylation, while the MAPK/NF-κB pathway inhibitors and antioxidants/ROS scavengers such as curcumin, allopurinol, and apocynin attenuated the TNF-α production (p ≤ 0.05). Individuals with obesity displayed increased adipose TNF-α gene/protein expression as well as elevated plasma levels of TNF-α, CRP, MDA, and OX-LDL (p ≤ 0.05). Our findings support a metabolic-ER stress cooperativity model, favoring inflammation by triggering TNF-α production via the ROS/CHOP/HIF-1α and MAPK/NF-κB dependent mechanisms. This study also highlights the therapeutic potential of antioxidants in inflammatory conditions involving metabolic/ER stresses.

The Association Between the Levels of Oxidative Stress Indicators (MDA, SOD, and GSH) in Seminal Plasma and the Risk of Idiopathic Oligo-asthenotera-tozoospermia: Does Cu or Se Level Alter the Association?

Epidemiological studies on the associations between the levels of oxidative stress (OS) indicators (MDA, SOD, and GSH) in seminal plasma and the risk of idiopathic oligo-asthenotera-tozoospermia (OAT) are still inconsistent. Additionally, whether the associations can be altered by the status of essential trace elements is still unknown. To investigate the relationship between MDA, SOD, and GSH levels in seminal plasma and the risk of idiopathic OAT, and further to examine whether levels of iron (Fe), copper (Cu), and selenium (Se) in seminal plasma can alter the associations. A total of 148 subjects (75 idiopathic OAT cases and 73 controls) were included in this study. Seminal plasma samples from all the participants were measured for levels of MDA, SOD, GSH, Fe, Cu, and Se. Unconditional logistic regression models were used to examine the associations between three oxidative stress indicators and the risk of idiopathic OAT. Bayesian kernel machine regression was performed to determine the joint effects of levels of three OS indicators on the risk of idiopathic OAT. Subgroup analyses were performed to explore whether the above associations can be different when Fe, Cu, and Se were in different levels. The level of MDA in seminal plasma was positively associated with the risk of idiopathic OAT, with adjusted odds ratio (OR) and 95% confidence interval (CI) of 2.38 (1.17, 4.83), and SOD and GSH levels were not associated with the risk of idiopathic OAT. In BKMR analyses, we found a significant positive association between the mixture of MDA, SOD, and GSH levels and the risk of idiopathic OAT at concentrations below the 65th percentile, while a negative association at concentrations above it. In subgroup analysis, a positive association was observed between MDA levels in seminal plasma and the risk of idiopathic OAT in the high-Cu group (adjusted OR = 3.66, 95%CI = 1.16, 11.57), while no significant association was found in the low-Cu group (adjusted OR = 1.43, 95%CI = 0.44, 4.58). Additionally, a negative association was found between GSH levels in seminal plasma and the risk of idiopathic OAT in the high-Se group (adjusted OR = 0.34, 95%CI = 0.11, 0.99), while no significant association was observed in the low-Se group (adjusted OR = 1.96, 95%CI = 0.46, 8.27). The levels of MDA, SOD, and GSH in seminal plasma were associated with the risk of idiopathic OAT, and the levels of Cu and Se in seminal plasma may alter the associations.

Baseline and recurrent exposure to the standard dose of artemisinin-based combination therapies (ACTs) induces oxidative stress and liver damage in mice (BALB/c)

BackgroundIn malaria-endemic countries, repeated intake of artemisinin-based combination therapies (ACTs) is rampant and driven by drug resistance, improper usage, and easy accessibility. Stress effects and potential liver toxicity due to the frequent therapeutic use of ACTs have not been extensively studied. Here, we investigated the effects of repeated treatment with standard doses of the commonly used ACTs artemether/lumefantrine (A/L) and artesunate-amodiaquine (A/A) on oxidative stress and liver function markers in male mice (BALB/c).MethodsForty Five mice were divided into three groups: control, A/L, and A/A. The drugs were administered three days in a row per week, and the regimen was repeated every two weeks for a total of six cycles. The levels of oxidative stress and liver function markers were measured in both plasma and liver tissue after initial (baseline) and repeated exposures for the second, third, and sixth cycles.ResultsExposure to A/L or A/A caused a significant (p < 0.001) increase in plasma malondialdehyde (MDA) levels after the first and repeated exposure periods. However, Hepatic MDA levels increased significantly (p < 0.01) only after the sixth exposure to A/A. Following either single or repeated exposure to A/L or A/A, plasma and liver glutathione peroxidase (GPx) and catalase (CAT) activities, plasma aspartate and alanine transaminase, alkaline phosphatase activity, and bilirubin levels increased, whereas total plasma protein levels decreased significantly (p < 0.001). Varying degrees of hepatocyte degeneration and blood vessel congestion were observed in liver tissues after a single or repeated treatment period.ConclusionIrrespective of single or repeated exposure to therapeutic doses of A/L or A/A, plasma oxidative stress and liver damage were observed. However, long-term repeated A/A exposure can led to hepatic stress. Compensatory processes involving GPx and CAT activities may help reduce the observed stress.

Effects of Lactobacillus rhamnosus Supplementation on Growth Performance, Immune Function, and Antioxidant Capacity of Newborn Foals.

This study aimed to explore the effects of Lactobacillus rhamnosus GG (LGG) supplementation on the growth performance, immune function, and antioxidant capacity of foals. Fifteen newborn foals with similar birth weight (51.67 ± 6.07 kg) and good health were randomly assigned to three groups: control group and test groups I and II, which were supplemented with 5.0 × 109 CFU/day and 1.0 × 1010 CFU/day LGG, respectively, for 150 days. LGG intake increased the daily body height (P < .01) and weight (P < .01) gain of foals aged 120 to 150 days. The foals' IgA (P < .05) and IgG (P < .01) plasma levels increased at 30 and 150 days, respectively, and IL-6 plasma level increased at 90 days (P < .01). Plasma total antioxidant capacity level was significantly higher in test group I than in the control and test group II at 30 days (P < .01), whereas glutathione peroxidase level was significantly higher in test group II than in the control and test group I at 30 days (P < .01). Both test groups had significantly higher superoxide dismutase level than the control group (P < .01) and significantly decreased malondialdehyde plasma level at 90 and 150 days (P < .05). Overall, our findings indicate that dietary supplementation of LGG can improve the growth performance, immune function, and antioxidant capacity of newborn foals.

The correlation between plasma malondialdehyde levels and pain in adolescent females diagnosed with primary dysmenorrhea

Background: Endometrial inflammation factors play a crucial role in the common pathophysiology of primary dysmenorrhea. Malondialdehyde (MDA), a byproduct of inflammatory processes, might be correlated with primary dysmenorrhea in adolescents. Objective: To assess plasma MDA levels in patients with primary dysmenorrhea. Methods: This cross-sectional study involved the collection of blood samples from 23 teenage females with primary dysmenorrhea and 23 age-matched individuals without this condition. Plasma MDA levels were quantified through spectrophotometry. The independent t-test was employed to ascertain the disparity in plasma MDA levels between the two groups, while the Pearson correlation test was utilized to analyze the relationship between pain severity and oxidative stress levels. Results: Plasma MDA levels were significantly higher in females with primary dysmenorrhea than in the control group (0.631 ± 0.105 and 0.395 ± 0.076, respectively). A significant difference in oxidative stress levels was observed between the case and control groups (p&lt;0.001). Furthermore, a robust positive correlation was observed between plasma MDA levels and pain severity in adolescent females with dysmenorrhea (r2 = 0.564, p&lt;0.001). Conclusion: The plasma MDA is increased in adolescent females with primary dysmenorrhea.