Peculiarities of the influence of antihypertensive therapy on endothelial function, oxidative stress and immune activation in obese patients

This article aims to improve combined antihypertensive therapy on the basis of studying the antioxidant properties of bisoprolol and indapamid, their impact on endothelial dysfunction (ED) and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity. A combination of a β-blocker (BAB) with a diuretic (D) (bisoprolol 2.5, 5, 10 mg and indapamid 1.5–2.5 mg/day) was prescribed to 102 patients with essential hypertension of 1–3 grades, 30 to 65 years old (mean age – 54.54 ± 0.91 years), who previously had not been receiving regular antihypertensive therapy. The daily dose of bisoprolol was administered by continuous slow titration, starting with low doses of 1.25 mg/day. Of the patients 82 were women and 20 men, the duration of disease averaged 9.0 ± 0.71 years. The control group included 16 healthy subjects matched for age and sex. The level of stable terminal metabolites of nitric oxide NO (nitrite NO2– and nitrate NO3–), the concentration of S-nitrosothiol and NO-synthases (NOS), SOD, and catalase activity was determined biochemically. The contents of serum 8-iso-PgF2α (8-isoprostane), TNF-alpha and its type I soluble receptor (sTNF-αRI) were determined in all subjects using the “8-isoprostane ELISA” (Usbiological,USA), “ProCon TNFα” (ProteinContour,Russian Federation) and “sTNF-RI EASIA” (BioSource Europe SA,Belgium) ELISA kits, respectively. During the course of combined antihypertensive therapy we observed a significant decrease of S-nitrosothiols levels, i-NOS activity, reduction of TNF-α type I of its soluble receptor (sTNF-αRI), and oxidative stress marker – 8-iso-PgF2α in the examined patients. Nitrites and nitrates serum levels, activity of e-NOS, superoxide dismutase and catalase, by contrast, were increased in patients with hypertension and concomitant obesity. These changes may reflect the fact that against the background of the therapy there was a reduction in tension of oxidative stress, which leads to an improvement in endothelial function. Significant reduction ratio of TNF-α/sTNF-αRI shows suppression of autoimmune and apoptotic activity in patients under treatment. Thus, the improvement of endothelial function, a significant decrease in autoimmune activation due to lower tension of oxidative stress in the examined patients optimizes use of a combination of bisoprolol and indapamid for differentiated therapy in hypertensive patients with obesity.

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Beneficial effects of combined therapy with lacidipine and candesartan in obese hypertensive patients

Romanian Journal of Internal Medicine ◽

10.2478/rjim-2018-0018 ◽

2018 ◽

Vol 56 (4) ◽

pp. 257-264

Author(s):

Tatiana Ashcheulova ◽

Nina Gerasimchuk ◽

Olga Kovalyova ◽

Oleksii Honchar

Keyword(s):

Oxidative Stress ◽

Endothelial Function ◽

Antihypertensive Therapy ◽

Inflammatory Cytokines ◽

Overweight And Obesity ◽

Oxidative Stress Marker ◽

Hypertensive Patients ◽

Tnf Α ◽

And Oxidative Stress ◽

Pro Inflammatory Cytokines

Abstract Introduction. Obesity is becoming one of the leading risk factors of coronary heart disease, hypertension, cerebrovascular disease. Despite the presence of a large number of antihypertensive agents and scientific substantiation of antihypertensive treatment principles it would be wrong to assume that the problem is completely solved. Development of endothelial dysfunction is one of the key pathogenic mechanisms in hypertension. This process is proven to have contributed by immune inflammation activation which is mediated by pro-inflammatory cytokines and oxidative stress. Aims. To investigate the additional benefits of the combined antihypertensive therapy with lacidipine and candesartan on the basis of studying their antioxidant properties, impact on endothelial function and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity. Methods. A combination of a calcium channel blocker and angiotensin receptor blocker (lacidipine 2 mg, 4 mg, and candesartan 4mg, 8mg, 16mg) was prescribed to 30 patients with essential hypertension of grades 1-3, 30 to 65 years old (mean age - 54.7 ± 5.8 years), who previously have not been receiving regular antihypertensive therapy. Results. During the course of combined antihypertensive therapy with lacidipine and candesartan, a significant reduction in i-NOS activity, TNF-α to its type I soluble receptor ratio (TNF- α/sTNF-αRI), and oxidative stress marker - 8-iso-PgF2α has been observed. Activity of e-NOS, levels of SOD and catalase, in contrast, have increased by the end of observation period. Conclusion. The improvement of endothelial function due to lower level of oxidative stress and a significant decrease of immune activation has been observed in hypertensive patients with overweight and obesity under the influence of combined antihypertensive therapy with lacidipine and candesartan.

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Oxidative Stress Status in Patients with Choledocholithiasis: Before and After Endoscopic Sphincterotomy and Biliary Clearance

Revista de Chimie ◽

10.37358/rc.18.8.6493 ◽

2018 ◽

Vol 69 (8) ◽

pp. 2172-2176

Author(s):

Catalin Victor Sfarti ◽

Alin Ciobica ◽

Carol Stanciu ◽

Gheorghe G. Balan ◽

Irina Garleanu ◽

...

Keyword(s):

Oxidative Stress ◽

Endoscopic Sphincterotomy ◽

Specific Activity ◽

Oxidative Stress Marker ◽

Control Group ◽

Oxidative Stress Parameter ◽

Extrahepatic Cholestasis ◽

Biliary Clearance ◽

Oxidative Stress Status ◽

Before And After

Choledocholithiasis may cause biliary obstruction which leads to hepatocellular injury. Oxidative stress has been proposed as a possible mechanism involved in this disorder. This study evaluates the oxidative stress burden in patients with choledocholithiasis and secondary cholestasis, before and after endoscopic sphincterotomy. Experimental part: Patients diagnosed with choledocholithiasis and secondary extrahepatic cholestasis were included in the study between January 1st 2016 and October 31st 2016. In all patients oxidative stress markers were collected within 2 hours before and 48 hours after therapeutic ERCP. Selected markers were superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA). The results were compared to those from a group of 40 healthy subjects. Significantly lower concentrations of SOD (p = 0.03) and GPX (p [ 0.0001) activities, associated with an increased level of MDA level (p [ 0.0001) were shown in patients before biliary clearance compared with the healthy control group. After ERCP the only oxidative stress parameter which showed improvement was the SOD specific activity (p = 0.037). This study shows that extrahepatic cholestasis secondary to choledocholithiasis is associated with increased oxidative stress status. After biliary clearance one oxidative stress marker was significantly improved (SOD), suggesting a possible antioxidant effect of such procedure.

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MicroRNA-513b-5p targets COL1A1 and COL1A2 associated with the formation and rupture of intracranial aneurysm

Scientific Reports ◽

10.1038/s41598-021-94116-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zheng Zheng ◽

Yan Chen ◽

Yinzhou Wang ◽

Yongkun Li ◽

Qiong Cheng

Keyword(s):

Cell Death ◽

Intracranial Aneurysm ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Control Group ◽

Type I ◽

Mrna Levels ◽

Reporter Assay ◽

Over Expression ◽

Tnf Α

AbstractCollagen-type I alpha 1 chain (COL1A1) and COL1A2 are abnormally expressed in intracranial aneurysm (IA), but their mechanism of action remains unclear. This study was performed to investigate the mechanism of COL1A1 and COL1A2 affecting the occurrence and rupture of IA. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-miR-513b-5p, COL1A1, COL1A2, TNF-α, IL-6, MMP2, MMP3, MMP9 and TIMP4 in patients with ruptured IA (RA) (n = 100), patients with un-ruptured IA (UA) (n = 100), and controls (n = 100). Then, human vascular smooth muscle cells (HASMCs) were cultured, and dual luciferase reporter assay was performed to analyse the targeting relationship between miR-513b-5p and COL1A1 or COL1A2. The effects of the miR-513b-5p mimic and inhibitor on the proliferation, apoptosis, and death of HASMC and the RIP1-RIP3-MLKL and matrix metalloproteinase pathways were also explored. The effect of silencing and over-expression of COL1A1 and COL1A2 on the role of miR-513b-5p were also evaluated. Finally, the effects of TNF-α on miR-513b-5p targeting COL1A1 and COL1A2 were tested. Compared with those in the control group, the serum mRNA levels of miR-513b-5p, IL-6 and TIMP4 were significantly decreased in the RA and UA groups, but COL1A1, COL1A2, TNF-α, IL-1β, MMP2, MMP3 and MMP9 were significantly increased (p < 0.05). Compared with those in the UA group, the expression of COL1A1, COL1A2, TNF-α, IL-1β and MMP9 was significantly up-regulated in the RA group (p < 0.05). Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis. Over-expression of COL1A1 or COL1A2, rather than silencing COL1A1/2, could improve the inhibitory effect of miR-513b-5p on cell activity by regulating the RIP1-RIP3-MLKL and MMP pathways. Furthermore, over-expression of miR-513b-5p and/or silencing COL1A1/2 inhibited the TNF-α-induced cell proliferation and enhanced the TNF-α-induced cell death and apoptosis. The mechanism may be related to the inhibition of collagen I and TIMP4 expression and promotion of the expression of RIP1, p-RIP1, p-RIP3, p-MLKL, MMP2 and MMP9. MiR-513b-5p targeted the inhibition of COL1A1/2 expression and affected HASMC viability and extracellular mechanism remodelling by regulating the RIP1-RIP3-MLKL and MMP pathways. This process might be involved in the formation and rupture of IA.

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Antioxidant activity of Lactobacillus plantarum NJAU-01 in an animal model of aging

BMC Microbiology ◽

10.1186/s12866-021-02248-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qingfeng Ge ◽

Bo Yang ◽

Rui Liu ◽

Donglei Jiang ◽

Hai Yu ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Capacity ◽

Lactobacillus Plantarum ◽

Meat Product ◽

The Other ◽

Oxidative Stress Marker ◽

Control Group ◽

Intragastric Administration ◽

Aging Effects ◽

Sterile Saline

Abstract Background Excessive reactive oxygen species (ROS) can cause serious damage to the human body and may cause various chronic diseases. Studies have found that lactic acid bacteria (LAB) have antioxidant and anti-aging effects, and are important resources for the development of microbial antioxidants. This paper was to explore the potential role of an antioxidant strain, Lactobacillus plantarum NJAU-01 screened from traditional dry-cured meat product Jinhua Ham in regulating D-galactose-induced subacute senescence of mice. A total of 48 specific pathogen free Kun Ming mice (SPF KM mice) were randomly allocated into 6 groups: control group with sterile saline injection, aging group with subcutaneously injection of D-galactose, treatments groups with injection of D-galactose and intragastric administration of 107, 108, and 109 CFU/mL L. plantarum NJAU-01, and positive control group with injection of D-galactose and intragastric administration of 1 mg/mL Vitamin C. Results The results showed that the treatment group of L. plantarum NJAU-01 at 109 CFU/mL showed higher total antioxidant capacity (T-AOC) and the antioxidant enzymatic activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) than those of the other groups in serum, heart and liver. In contrast, the content of the oxidative stress marker malondialdehyde (MDA) showed lower levels than the other groups (P < 0.05). The antioxidant capacity was improved with the supplement of the increasing concentration of L. plantarum NJAU-01. Conclusions Thus, this study demonstrates that L. plantarum NJAU-01 can alleviate oxidative stress by increasing the activities of enzymes involved in oxidation resistance and decreasing level of lipid oxidation in mice.

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Neurological Alterations and Testicular Damages in Aging Induced by D-Galactose and Neuro and Testicular Protective Effects of Combinations of Chitosan Nanoparticles, Resveratrol and Quercetin in Male Mice

Coatings ◽

10.3390/coatings11040435 ◽

2021 ◽

Vol 11 (4) ◽

pp. 435

Author(s):

Reham Z. Hamza ◽

Mohammad S. Al-Harbi ◽

Munirah A. Al-Hazaa

Keyword(s):

Oxidative Stress ◽

Chitosan Nanoparticles ◽

Oxidative Stress Marker ◽

Control Group ◽

Antioxidant Enzyme Activities ◽

Enzymatic Antioxidants ◽

Protective Effects ◽

Biochemical Alterations ◽

Wide Range ◽

Neurological Alterations

Aging is a neurological disease that is afforded by incidence of oxidative stress. Chitosan has received global interests due to its wide medical uses. Quercetin (Q) is a bioflavonoid and widely distributed in vegetables and fruits. Resveratrol is considered as a potent antioxidant and is a component of a wide range of foods. The using of either chitosan nanopartciles (CH-NPs), querectin (Q), and resveratrol (RV) to reduce the oxidative stress and biochemical alterations on brain and testicular tissues induced by D-galactose (DG) (100 mg/Kg) were the aim of the present study. This study investigated the probable protective effects of CH-NPs in two doses (140,280 mg/Kg), Q (20 mg/Kg) and RV (20 mg/Kg), against DG induced aging and neurological alterations. Brain antioxidant capacity as malonaldehyde (MDA), catalase (CAT), and glutathione reductase (GRx), as well as histopathological damages of the brain and testicular tissues were measured. The DG treated group had significantly elevated the oxidative stress markers by 96% and 91.4% in brain and testicular tissues respectively and lower significantly the antioxidant enzyme activities of both brain and testicular tissues than those of the control group by 86.95%, 69.27%, 83.07%, and 69.43%. Groups of DG that treated with a combination of CH-NPs in two doses, Q and RV, the levels of oxidative stress marker declined significantly by 68.70%, 76.64% in brain tissues and by 74.07% and 76.61% in testicular tissues, and the enzymatic antioxidants increased significantly by 75.55%, 79.24%, 62.32%, and 61.97% as compared to the DG group. The present results indicate that CH-NPs, Q, and RV have protective effects against DG-induced brain and testis tissue damage at the biochemical and histopathological levels. Mechanisms of this protective effect of used compounds against neurological and testicular toxicity may be due to the enhanced brain and testis antioxidant capacities.

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Oxydative stress markers and cytokine levels in rosuvastatin-medicated hypercholesterolemia patients

Turkish Journal of Biochemistry ◽

10.1515/tjb-2018-0267 ◽

2018 ◽

Vol 44 (4) ◽

pp. 530-538

Author(s):

Aysun Çetin ◽

İhsan Çetin ◽

Semih Yılmaz ◽

Ahmet Şen ◽

Göktuğ Savaş ◽

...

Keyword(s):

Oxidative Stress ◽

Interleukin 1 ◽

Paraoxonase 1 ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Phenotypic Effect ◽

Necrosis Factor Alpha ◽

Stress Markers ◽

Tnf Α ◽

Before And After

Abstract Background Limited research is available concerning the relationship between oxidative stress and inflammation parameters, and simultaneously the effects of rosuvastatin on these markers in patients with hypercholesterolemia. We aimed to investigate the connection between cytokines and oxidative stress markers in patients with hypercholesterolemia before and after rosuvastatin treatment. Methods The study consisted of 30 hypercholesterolemic patients diagnosed with routine laboratory tests and 30 healthy participants. The lipid parameters, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), paraoxonase-1 (PON1) and malondialdehyde (MDA) levels in controls and patients with hypercholesterolemia before and after 12-week treatment with rosuvastatin (10 mg/kg/day), were analyzed by means of enzyme-linked immunosorbent assay. Results It was found that a 12-week cure with rosuvastatin resulted in substantial reductions in IL-1β, IL-6 and TNF-α and MDA levels as in rising activities of PON1 in patients with hypercholesterolemia. Before treatment, the PON1 levels were significantly negatively correlated with TNF-α and IL-6 in control group, while it was positively correlated with TNF-α in patients. Conclusion Our outcomes provide evidence of protected effect of rosuvastatin for inflammation and oxidative damage. It will be of great interest to determine whether the correlation between PON1 and cytokines has any phenotypic effect on PON1.

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Endothelial Function and Arterial Stiffness Should Be Measured to Comprehensively Assess Obstructive Sleep Apnea in Clinical Practice

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.716916 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jinmei Luo ◽

Xiaona Wang ◽

Zijian Guo ◽

Yi Xiao ◽

Wenhao Cao ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Arterial Stiffness ◽

Endothelial Function ◽

Augmentation Index ◽

Reactive Hyperemia ◽

Control Group ◽

Apnea Hypopnea Index ◽

Obstructive Sleep ◽

Tnf Α

Objective: An effective clinical tool to assess endothelial function and arterial stiffness in patients with obstructive sleep apnea (OSA) is lacking. This study evaluated the clinical significance of subclinical markers for OSA management in males without serious complications.Patients/Methods: Males without serious complications were consecutively recruited. Clinical data, biomarker tests, reactive hyperemia index (RHI), and augmentation index at 75 beats/min (AIx75) measured by peripheral arterial tonometry were collected. An apnea hypopnea index (AHI) cutoff of ≥15 events/h divided the patients into two groups.Results: Of the 75 subjects, 42 had an AHI ≥15 events/h. Patients with an AHI ≥15 events/h had higher high-sensitivity C-reactive protein, tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor, and AIx75 values than the control group but no statistical difference in RHI was observed. After controlling for confounders, TNF-α was negatively correlated with the average oxygen saturation (r = −0.258, P = 0.043). RHI was correlated with the rapid eye movement (REM) stage percentage (r = 0.306, P = 0.016) but not with AHI (P > 0.05). AIx75 was positively correlated with the arousal index (r = 0.289, P = 0.023) but not with AHI (r = 0.248, P = 0.052).Conclusions: In males with OSA without severe complications, TNF-α and AIx75 are independently related to OSA. The role of RHI in OSA management requires further elucidation. These markers combined can comprehensively evaluate OSA patients to provide more evidence for the primary prevention of coronary heart disease and treatment response assessment.

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Dapagliflozin protects H9c2 cells against injury induced by lipopolysaccharide via suppression of CX3CL1/CX3CR1 axis and NF-κB activity

Current Molecular Pharmacology ◽

10.2174/1874467214666211008142347 ◽

2021 ◽

Vol 14 ◽

Author(s):

Yousef Faridvand ◽

Maryam Nemati ◽

Elham Zamani-Gharehchamani ◽

Hamid Reza Nejabati ◽

Arezoo Rezaie Nezhad Zamani ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Sglt2 Inhibitor ◽

Binding Activity ◽

Control Group ◽

H9c2 Cell ◽

H9c2 Cells ◽

Dna Binding Activity ◽

Inflammatory Conditions ◽

Tnf Α

Background: Dapagliflozin, a selective Sodium-glucose cotransporter-2 (SGLT2) inhibitor, has been shown to play a key role in the control and management of the metabolic and cardiac disease. Objective: The current study aims to address the effects of dapagliflozin on the expression of fractalkine (FKN), known as CX3CL1, and its receptors CX3CR1, Nuclear factor-kappa B(NF-κB) p65 activity, Reactive oxygen species (ROS), and inflammation in LPS-treated H9c2 cell line. Methods: H9c2 cells were cultured with lipopolysaccharide (LPS) to establish a model of LPS-induced damage and then subsequently were treated with dapagliflozin for 72 h. Our work included measurement of cell viability (MTT), Malondialdehyde (MDA), intracellular ROS, tumor necrosis factor-α (TNF-α), NF-κB activity, and expression CX3CL1/CX3CR1. Results: The results showed that LPS-induced reduction of cell viability was successfully rescued by dapagliflozin treatment. The cellular levels of MDA, ROS, and TNF-α, as an indication of cellular oxidative stress and inflammation, were significantly elevated in H9c2 cells compared to the control group. Furthermore, dapagliflozin ameliorated inflammation and oxidative stress through the modulation of the levels of MDA, TNF-α, and ROS. Correspondingly, dapagliflozin reduced the expression of CX3CL1/CX3CR1, NF-κB p65 DNA binding activity and it also attenuated nuclear acetylated NF-κB p65 in LPS-induced injury in H9c2 cells compared to untreated cells. Conclusion: These findings shed light on the novel pharmacological potential of dapagliflozin in the alleviation of LPS-induced CX3CL1/CX3CR1-mediated injury in inflammatory conditions such as sepsis-induced cardiomyopathy.

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Abstract 1476: Angiotensin II Induced Hypertrophic Response And Oxidative Stress Is Attenuated In Mice Lacking The Gene For Tnf-α

Circulation ◽

10.1161/circ.116.suppl_16.ii_304-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Srinivas Sriramula ◽

Nithya Mariappan ◽

Elizabeth McILwain ◽

Joseph Francis

Keyword(s):

Oxidative Stress ◽

Angiotensin Ii ◽

Cardiac Hypertrophy ◽

Collagen Type ◽

Resonance Spectroscopy ◽

Type I ◽

Ang Ii ◽

Hypertrophic Response ◽

Tnf Α ◽

And Oxidative Stress

Tumor necrosis factor-alpha (TNF-α) and angiotensin II (Ang II) play an important role in the pathophysiology of cardiovascular disease in part by inducing the cardiac hypertrophic response and oxidative stress. Recently we demonstrated that angiotensin induced hypertensive response is attenuated in mice lacking the gene for TNF-α. In this study, we examined whether Ang II induced cardiac hypertrophy and increased oxidative stress is mediated through TNF-α. Methods and results: Male TNF-α (−/−) and age matched control (WT) mice were subcutaneously implanted with osmotic minipumps containing Ang II (1 μg/kg/min) or saline for 14 days. Human recombinant TNF-α was injected in one group of TNF-α (−/−) mice (10 μg/kg/day) for 14 days. In WT+Ang mice, a temporal increase in blood pressure was observed during the study as measured by radio telemetry transmitters. At the end of the study, echocardiography revealed an increase in thickness and dimensions of left ventricle (LV) and decreased fractional shortening (%FS) in WT+Ang mice. Real time RT-PCR showed that Ang II- infusion resulted in an increase in heart/bodyweight ratio and of cardiac hypertrophy markers ANP and BNP, and profibrotic genes Collagen Type I, Collagen Type II, and TGF-β in WT mice. Electron Spin resonance spectroscopy revealed an increase in total ROS, superoxide and peroxynitrite in the WT+ANG mice when compared to control WT mice. However, these changes were all attenuated in TNF-α (−/−)+Ang mice. Ang II infusion also increased significantly the mRNA expression of gp91Phox, NOX-1, NOX-4 and AT1R in the LV of WT mice, but not in TNF-α (−/−) mice. Interestingly, injection of TNF-α in the TNF-α (−/−) mice, treated with Ang II resulted in increased cardiac hypertrophy and oxidative stress. Conclusions: Findings from the present study suggest that TNF-α plays an important role in the development of cardiac hypertrophy and oxidative stress in Ang II-induced hypertension.

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Comparative Transcriptome Analysis Reveals the Protective Mechanism of Glycyrrhinic Acid for Deoxynivalenol-Induced Inflammation and Apoptosis in IPEC-J2 Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5974157 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Xiaoxiang Xu ◽

Guorong Yan ◽

Juan Chang ◽

Ping Wang ◽

Qingqiang Yin ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Transcriptome Analysis ◽

Animal Feed ◽

Control Group ◽

Protective Mechanism ◽

Dependent Manner ◽

Gene Expressions ◽

Lactate Dehydrogenase Release ◽

Tnf Α

Deoxynivalenol (DON) is the most common mycotoxin that frequently contaminates human food and animal feed, resulting in intestinal diseases and systemic immunosuppression. Glycyrrhinic acid (GA) exhibits various pharmacological activities. To investigate the protective mechanism of GA for DON-induced inflammation and apoptosis in IPEC-J2 cells, RNA-seq analysis was used in the current study. The IPEC-J2 cells were treated with the control group (CON), 0.5 μg/mL DON, 400 μg/mL GA, and 400 μg/mL GA+0.5 μg/mL DON (GAD) for 6 h. Results showed that 0.5 μg/mL DON exposure for 6 h could induce oxidative stress, inflammation, and apoptosis in IPEC-J2 cells. GA addition could specifically promote the proliferation of DON-induced IPEC-J2 cells in a dose- and time-dependent manner. In addition, GA addition significantly increased Bcl-2 gene expression ( P < 0.05 ) and superoxide dismutase and catalase activities ( P < 0.01 ) and decreased lactate dehydrogenase release, the contents of malonaldehyde, IL-8, and NF-κB ( P < 0.05 ), the relative mRNA abundances of IL-6, IL-8, TNF-α, COX-2, NF-κB, Bax, and caspase 3 ( P < 0.01 ), and the protein expressions of Bax and TNF-α. Moreover, a total of 1576, 289, 1398, and 154 differentially expressed genes were identified in CON vs. DON, CON vs. GA, CON vs. GAD, and DON vs. GAD, respectively. Transcriptome analysis revealed that MAPK, TNF, and NF-κB signaling pathways and some chemokines played significant roles in the regulation of inflammation and apoptosis induced by DON. GA may alleviate DON cytotoxicity via the TNF signaling pathway by downregulating IL-15, CCL5, and other gene expressions. These results indicated that GA could alleviate DON-induced oxidative stress, inflammation, and apoptosis via the TNF signaling pathway in IPEC-J2 cells.

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