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Studying acute changes in vascular endothelial cells in humans is challenging. We studied ten African American women and used the J-wire technique to isolate vein endothelial cells before and after a four-hour lipid and heparin infusion. Dynamic changes in lipid-induced oxidative stress and inflammatory markers were measured with fluorescence-activated cell sorting. We used the surface markers CD31 and CD144 to identify human endothelial cells. Peripheral blood mononuclear cells isolated from blood were used as a negative control. The participants received galantamine (16 mg/day) for 3 months. We previously demonstrated that galantamine treatment effectively suppresses lipid-induced oxidative stress and inflammation. In this study, we infused lipids to evaluate its potential to increase the activation of endothelial cells, as assessed by the levels of CD54+ endothelial cells and expression of Growth arrest-specific 6 compared to the baseline sample. Further, we aimed to investigate whether lipid infusion led to increased expression of the oxidative stress markers IsoLGs and nitrotyrosine in endothelial cells. This approach will expedite the in vivo identification of novel pathways linked with endothelial cell dysfunction induced by oxidative stress and inflammatory cytokines. This study describes an innovative method to harvest and study human endothelial cells and demonstrates the dynamic changes in oxidative stress and inflammatory markers release induced by lipid infusion., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Polystichum braunii (Spenn.) Fée is a traditional remedy for rheumatoid arthritis, a chronic inflammatory disorder of polygenetic origin. The current project was intended to demonstrate the role of inflammatory and oxidative stress biomarkers in the anti-arthritic activity of the P. braunii extracts. Methanolic and aqueous extracts of the plant roots were prepared by triple maceration. The phytochemical evaluation of the plant extracts was carried out by high-performance liquid chromatography (HPLC). The plant extracts at 150, 300, and 600 mg/kg/day and piroxicam (10 mg/kg/day) were orally administered to Wistar rats for 21 days that were previously immunized with Complete Freund's adjuvant (150 µl on right hind paw) except normal and arthritic control rats. Both plant extracts mitigated the paw oedema, restored the immune organ and body weights, and ameliorated the level of blood parameters such as haemoglobin, red blood cells, platelets, white blood cells, alkaline phosphatase (ALP), C-reactive proteins, and rheumatoid factor. The evaluation of gene expression using quantitative-real-time polymerase chain reaction (qRT-PCR) revealed the substantial downregulation of tumor necrosis factor (TNF)-α, Interleukin (IL)-6, IL-1β, cyclo-oxygenase (COX)-2, nuclear factor (NF)-κB, and upregulation of IL-4, IL-10 and I-κB in polyarthritic rats treated with the plant extracts. Methanolic plant extract exhibited the maximum effect on upregulation of IL-4 (79 ± 3%), IL-10 (62.66 ± 4.93%), and I-κB (73.66 ± 3.05%) at 600 mg/kg/day. Treatment with the plant extracts also reduced the level of prostaglandin E2 and TNF-α in the serum of arthritic rats' dose dependently. It was also found that the plant extracts and piroxicam increased (p < 0.05) the activities of superoxide dismutase and catalase in the liver tissue while reduced the level of malondialdehyde in arthritic rats. Histological examination of ankle joints revealed that the plant extracts decreased the pannus formation, inflammation, and synovial hyperplasia in arthritic animals. HPLC analysis depicted that the plant extracts had contained kaempferol, quercetin, gallic acid, and other phenolic acids. It can be elucidated from the results that the extracts of P. braunii roots exhibited anti-arthritic activity in Wistar rats through modulation of inflammatory cytokines and boosting the antioxidant defense mechanism.

Vitis vinifera (grapes) is used as a fruit worldwide and known for its pharmacological properties. The present paper assesses the chemopreventive potential of Vitis vinifera against 12-O-tetradecanoyl-13-phorbol acetate (TPA)-mediated tumor promotion in 7,12-dimethyl-benz[a]anthracene (DMBA) initiated mice skin. Skin tumor initiation was achieved by a single topical application of DMBA (40 microg/animal/0.20 ml acetone) to mice. Two weeks after the initiation, promoting agent, TPA (5.0 microg/animal/0.2 ml acetone) was applied two times a week for 20 weeks. Pretreatment of Vitis vinifera 1h prior to each application of TPA resulted in protection against cutaneous tumorigenesis in dose-dependent manner. This inhibition was evident when tumor data was considered as the percentage of mice with tumor and the number of tumors per mouse. We have shown that typical application of Vitis vinifera prior to that of TPA resulted in significant inhibition against TPA-caused induction of epidermal ODC activity (P<0.001) and DNA synthesis. Application of Vitis vinifera at a dose level of 5.0 mg and 10.0 mg kg(-1) body weight in acetone prior to that of TPA treatment resulted in partial significant inhibition of oxidative stress in dose-dependent manner. The concomitant increase in the microsomal lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.001). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes were recovered to the partial significant level. Hence, it can be suggested that Vitis vinifera can be used as a chemopreventive agent against oxidative stress and carcinogenesis.

Hypertension is the primary modifiable risk factor for cardiovascular, renal, and cerebrovascular diseases and is considered the main contributing factor to morbidity and mortality worldwide. Approximately 50% of hypertensive and 25% of normotensive people exhibit salt sensitivity of blood pressure, which is an independent risk factor for cardiovascular disease. Human and animal studies demonstrate that the immune system plays an important role in the etiology and pathogenesis of salt sensitivity of blood pressure, kidney damage, and vascular diseases. Antigen-presenting and adaptive immune cells are implicated in salt-sensitive hypertension and salt-induced renal and vascular injury. Elevated sodium activates antigen-presenting cells to release proinflammatory cytokines including IL (interleukin) 6, tumor necrosis factor-α, IL-1β, and accumulate isolevuglandin-protein adducts. In turn, these activate T cells release prohypertensive cytokines including IL-17A. Moreover, high-salt intake is associated with gut dysbiosis, leading to inflammation, oxidative stress, and blood pressure elevation but the mechanistic contribution to salt-sensitivity of blood pressure is not clearly understood. Here, we discuss recent advances in research investigating the cause, potential biomarkers, and therapeutic targets for salt-sensitive hypertension as they pertain to the gut microbiome, immunity, and inflammation. [ABSTRACT FROM AUTHOR]

Obesity affects over 40% of the adult population and is a major risk factor for morbidity and mortality due to cardiovascular disease. Black women have one of the highest prevalences of obesity, insulin resistance, hypertension, and cardiovascular events in the US. We previously found that free radical-mediated lipid peroxidation contributes to IL-6 production in dendritic cells leading to inflammation and hypertension. Thus, we hypothesized that F2-isoprostanes (F2-IsoPs), products and biomarkers of endogenous lipid peroxidation, contribute to increased inflammation and IL-6 production among obese Black women. We studied a total of 88 obese Black women of age 42.0 ± 9.8 years, weight 102 ± 16 kg, and body mass index (BMI) 37.68 ± 5.08. Systolic and diastolic blood pressure were 124 ± 14/76.2 ± 9.9 mmHg, heart rate was 68.31 ± 10.26 beats/min, and fasting insulin was 15.0 ± 8.7 uU/mL. Plasma F2-IsoPs were measured using gas chromatography/negative ion chemical ionization mass spectrometry (GC/NICI-MS). Plasma cytokines, including IL-6, IL-8, IL-10, IL-1β, TNF-a, and C-reactive proteins were measured using multiplex Luminex technology. Anthropometric measurements were performed using dual-energy X-ray absorptiometry. Using Pearson's correlation analysis, we found that BMI was positively correlated with plasma F2-IsoPs, while inversely correlated with insulin sensitivity in obese Black women. Further, F2-IsoPs were positively correlated with inflammatory marker IL-6 levels while negatively correlated with anti-inflammatory marker IL-10. In addition, we found that plasma F2-IsoPs levels were significantly associated with reduced insulin sensitivity. These results suggest that F2-IsoPs may be associated with obesity-induced cardiovascular risk in Black women by increasing the production of inflammatory cytokine IL-6 and decreasing the production of anti-inflammatory IL-10. [ABSTRACT FROM AUTHOR]

A high caloric food causes deposition of fats that may progress to obesity. Obesity is a risk factor for various metabolic and cardiovascular diseases, including but limited to diabetes mellitus. This study is aimed at determining the ameliorating effect of Malva Neglecta wallr aqueous-methanolic extract (MNME) on obesity and diabetes in Wistar rats. The MNME was chemically characterized by high-performance liquid chromatography (HPLC). The plant extract was evaluated by in vitro α-amylase inhibition and DPPH scavenging activities. Obesity was induced by administering high sugar and fat diet (HSFD) to rats for six weeks, followed by intraperitoneal injection of alloxan monohydrate (150 mg/kg) to induce diabetes. Oral treatments with MNME 250, 500, and 750 mg/kg/day were given to diabetic obese rats for 14 days. The HPLC analysis showed the presence of phenolic acids and flavonoids. The plant extract showed significant antioxidant (P < 0.001) and alpha-amylase (P < 0.0001) inhibition activities. The administration of MNME displayed a considerable decrease in fasting blood glucose, body weight, liver function tests, urea, cholesterol, leptin, and insulin levels in diabetic obese rats as compared to the disease control group and maximum effect were observed at 750 mg/kg/day of MNME. The MNME significantly increased (P < 0.05 − 0.001) the levels of GSH, SOD, and CAT in the liver, kidney, and pancreas while notably (P < 0.05 − 0.001) reduced the malondialdehyde level in kidney and pancreas of diabetic obese rats in contrast to disease control rats. This experimental study concludes that the MNME had exhibited antiobesity and antidiabetic activities through reduction of oxidative stress, leptin, α-amylase activity, and insulin resistance due to the presence of phenolic acid and flavonoid compounds. [ABSTRACT FROM AUTHOR]

Objectives: Tramadol, an atypical opioid, is clinically efficacious in treating moderate to severe pain. The aim of current study was to find out the toxicological effects of tramadol exposure to pregnant rats and fetuses during the late phase of pregnancy. Methods: Wistar pregnant rats were exposed to 1.25, 2.5, or 5 mg/kg/day tramadol from 14th to 20th day of pregnancy. The same therapy was given to nonpregnant rats for 7 days. The body weight, oral glucose and lipid tolerance tests, and effect on complete blood parameters in both pregnant and nonpregnant rats were determined. On 20th day, maternal placentas were excised and weighed while fetuses were observed for any deformity and growth retardation. Oxidative stress biomarkers were estimated in the liver and kidney tissue homogenates of the pregnant and nonpregnant rats while the whole fetus homogenate was processed for the same. Moreover, histopathology of the liver and kidney of pregnant and nonpregnant rats were carried out. Results: Tramadol administration did not significantly alter the area under curve of the blood glucose and triglyceride levels in both the pregnant and nonpregnant rats. It reduced the live fetuses, placental weights, fetal length, and fetal weights. Tramadol treated pregnant rats showed significantly (p <.05) reduced red blood cells, hematocrit, hemoglobin, and platelets with reference to control group. Similarly, structural abnormalities and malfunctioning of the liver and kidney of pregnant rats were instituted; however, it did not affect the structural integrity of nonpregnant rats. A substantial (p <.001–.0001) altered glutathione and malondialdehyde levels in the fetuses, pregnant, and nonpregnant animals (tissue homogenates) at all dosage levels were indicative of tramadol induced oxidative stress. Furthermore, tramadol exposure resulted in more significant (p <.01–.001) alteration of lipid profile in the pregnant than the nonpregnant animals. Conclusion: Acquired results suggested the maternotoxic and fetotoxic effects of tramadol exposure during the late gestation period. [ABSTRACT FROM AUTHOR]

The study was planned to evaluate toxicity of M. oleifera leaf methanol extract in Wistar rats, cytotoxic potential and chemically characterize it. Acute toxicity study revealed no mortality at 2,000 mg/kg dose. In subchronic toxicity, 150, 300, and 600 mg/kg extract were administered in both sexes for 90 days. A decrease in body weight, cholesterol, and low‐density lipoproteins, as well as an increase in the platelet count were observed. The histology of heart, lung, and kidney was normal. The oxidative stress biomarkers were normal in the liver tissue. In vitro cytotoxicity assay revealed that IC50 of the plant extract was more than 1,000 µg/ml. FTIR explored various functional groups and HPLC analysis indicated the presence of kaempferol and quercetin in the plant extract. These results showed that the plant extract might be safe up to 2,000 mg/kg single dose. The long term use of the plant extract was mostly devoid of major system toxicities. Practical applications: M. oleifera is a multipurpose tree. It is a cruciferous plant that has nutritional as well as medicinal properties. It is exhibited a multitude of nutraceutical or pharmacological properties such as anti‐inflammatory, lipid‐lowering, anticancer, hypoglycemic, and antihypertensive activities. It is widely used by local inhabitants for their health, food, agriculture, and cosmetic purposes. Among other plant parts, its leaves are mostly used as a functional food because of abundant proteins, β‐carotene, polyphenol, vitamin C, and vitamin E. The current study was designed to validate its safety in acute and long term use. The data of this study suggested that the plant can be safely used as a nutraceutical as well as a nutritional food. [ABSTRACT FROM AUTHOR]

Background: Mortality rate is increasing due to cardiovascular problems throughout the world. These cardiac problems are directly associated with dyslipidemia. Aim: The aim of this study was to evaluate the antihyperlipidemic effect of aqueous extract and methanol extract of Trachyspermum ammi at 1 g/kg, 3 g/kg and 5 g/kg dose levels in rats. Materials and Methods: For this purpose, 45 male albino rats were used and randomly divided into nine equal groups (n = 5). The lipid levels were increased after 24 h of single intraperitoneal injection of Triton X-100 (100 mg/kg) in rats. Aqueous and methanol extracts equivalent to 1 g/kg, 3 g/kg and 5 g/kg were administered orally to the rats for 21 days. Atorvastatin (10 mg/kg) was used as standard drug. Blood samples were collected at 0, 2nd, 9th, 16th and 23rd day by a direct cardiac puncture in VacuetteR heparin tubes. Serum was separated and then analyzed for lipid profile, liver function test (LFT) and renal function test (RFT) using standard diagnostic kits. Results: Results showed that extracts at 3 g/kg and 5 g/kg decreased the levels of total cholesterol, triglyceride and low-density lipoprotein and increased high-density lipoprotein concentration in serum. T. ammi also decreased LFT and RFT parameters at the end of the study. Conclusion: T. ammi possessed antioxidant and antihyperlipidemic activities along with hepato-and nephro-protective effects. [ABSTRACT FROM AUTHOR]

In our article entitled "Moringa rivae leaf extracts attenuate Complete Freund's adjuvant-induced arthritis in Wistar rats via modulation of inflammatory and oxidative stress biomarkers", we described the anti-arthritic effects of the plant leaves from Pakistan that we referred to as Moringa rivae (Saleem et al. 2019). Unfortunately, the identity of the plant material was incorrect. In fact, the plant leaves under study were later identified as belonging to wild type Moringa oleifera Lam. rather than Moringa rivae Chiov. [ABSTRACT FROM AUTHOR]

The redox-sensitive Sp family transcription factor has been linked to the regulation of angiotensin II type 1 receptor ( AT1R). However, the exact mechanism of AT1R regulation in renal cells is poorly understood. We tested the specificity of reactive oxygen species ( ROS), superoxide vs. hydrogen peroxide (H2O2), and the specific role of Sp3 transcription factor, if any, in the regulation of AT1R in human kidney cells ( HK2 cells). Superoxide dismutase ( SOD) inhibitor diethyldithiocarbamate ( DETC), but not H2O2 treatment, increased fluorescence levels of superoxide probe dihydroethidium ( DHE). H2O2, but not DETC, treatment increased the fluorescence of the H2O2-sensitive probe dichloro-dihydro-fluorescein ( DCFH). These data suggest that SOD inhibition by DETC increases the superoxide but not H2O2 and exogenously added H2O2 is not converted to superoxide in renal cells. Furthermore, DETC, but not H2O2, treatment increased nuclear accumulation of Sp3, which was attenuated with the superoxide dismutase ( SOD)-mimetic tempol. DETC treatment also increased AT1R mRNA and protein levels that were attenuated with tempol, whereas H2O2 did not have any effects on AT1R mRNA. Moreover, Sp3 overexpression increased, while Sp3 depletion by si RNA decreased, protein levels of AT1R. In addition, Sp3 si RNA in the presence of DETC decreased AT1R protein expression. Furthermore, DETC treatment increased the levels of cell surface AT1R as measured by biotinylation and immunofluorescence studies. Angiotensin II increased PKC activity in vehicle-treated cells that further increased in DETC-treated cells, which was attenuated by AT1R blocker candesartan and SOD-mimetic tempol. Taken together, our results suggest that superoxide, but not H2O2, via Sp3 up-regulates AT1R expression and function in the renal cells. [ABSTRACT FROM AUTHOR]

Significance: Salt sensitivity of blood pressure (SSBP) is an independent risk factor for mortality and morbidity due to cardiovascular disease, and disproportionately affects blacks and women. Several mechanisms have been proposed, including exaggerated activation of sodium transporters in the kidney leading to salt retention and water. Recent Advances: Recent studies have found that in addition to the renal epithelium, myeloid immune cells can sense sodium via the epithelial Na+ channel (ENaC), which leads to activation of the nicotinamide adenine dinucleotide phosphate oxidase enzyme complex, increased fatty acid oxidation, and production of isolevuglandins (IsoLGs). IsoLGs are immunogenic and contribute to salt-induced hypertension. In addition, aldosterone-mediated activation of ENaC has been attributed to the increased SSBP in women. The goal of this review is to highlight mechanisms contributing to SSBP in blacks and women, including, but not limited to increased activation of ENaC, fatty acid oxidation, and inflammation. Critical Issues: A critical barrier to progress in management of SSBP is that its diagnosis is not feasible in the clinic and is limited to expensive and laborious research protocols, which makes it difficult to investigate. Yet without understanding the underlying mechanisms, this important risk factor remains without treatment. Future Directions: Further studies are needed to understand the mechanisms that contribute to differential blood pressure responses to dietary salt and find feasible diagnostic tools. This is extremely important and may go a long way in mitigating the racial and sex disparities in cardiovascular outcomes. Antioxid. Redox Signal. 35, 1477–1493. [ABSTRACT FROM AUTHOR]