Role Of Tumor Necrosis Factor-alpha Research Articles

The Role of Tumor Necrosis Factor (TNF) Alpha with Visual Field Defects in Primary Open Angle Glaucoma (POAG)

Introduction & ObjectivesGlaucoma is a group of progressive optic neuropathy disease characterized by degeneration ofretinal ganglion cells. This causes changes in the optic nerve and loss of visual field. Several studieshave revealed that there is a role for TNF Alpha in glaucoma cases. To determine the role TumorNecrosis Factor (TNF) Alpha Levels between visual field defects in Primary Open-angle Glaucomapatients.
 MethodsThis study is Observational Analytical with cross sectional data collection method. Examination ofthe field of view using the Humphrey visual field perimetry.
 ResultsThe sample of this research was 30 people with 16 (53.3%) male and 14 people (46.7%) female.Using the Spearman correlation test, it showed that there was no significant correlation betweenTNF alpha and field of view (p = 0.119).
 ConclusionTNF Alpha level was not significantly related to visual field defects.

Structural and Biochemical Effects of Plumbagin on Sofosbuvir-induced Renal Cortical Injury in Rats: Role of Tumor Necrosis Factor-Alpha, Interleukin-6, JAK2/STAT3, and Nuclear Factor Kappa B-induced Inflammation

Abstract Introduction: Hepatitis caused by virus C results in serious health complications. Sofosbuvir is effective for treating hepatitis C but, with side effects especially on kidneys. Plumbagin is a natural plant with a powerful anti-inflammatory effect. Aim: The assessment of plumbagin effect on the renal cortical damage in rats induced by sofosbuvir, by assessing tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), JAK2/STAT3 and nuclear factor kappa B (NF-κB). Materials and Methods: Forty adult rats (250–300 g) were divided into: group 1 (control); Group 2 received sofosbuvir 36 mg/kg; Group 3 received sofosbuvir and low dose of plumbagin (5 mg/kg); Group 4 received sofosbuvir and mid-dose of plumbagin (10 mg/kg); Group 5 received sofosbuvir and high dose of plumbagin (20 mg/kg); and Group 6 (sofosbuvir recovery). Drugs were taken once daily orally for 8 weeks. Blood samples were collected for the assessment of renal functions and serum TNF-α and IL-6. Renal specimens were processed for both measuring tissue JAK2/STAT3 levels and for histological and immunohistochemical studies. Results: Group 2 showed a significant rise of blood urea and serum creatinine, serum TNF-α and IL-6, tissue JAK2/STAT3, hematoxylin and eosin significant histopathological changes, significant increase of collagen area density at Masson’s trichrome and significant rise of NF-κB-positive cells. Plumbagin treated groups showed dose-dependent amelioration of the preceding results. The recovery group showed partial recovery. Conclusion: Plumbagin has an ameliorating dose-dependent effect against sofosbuvir-induced renal cortical damage in rats rather than those left to recover alone through its antiinflammatory action. Hence, plumbagin could be promising for the treatment of different inflammatory diseases.

Unraveling the Role of Tumor Necrosis Factor-Alpha in Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

Diabetic peripheral neuropathy (DPN) is a prevalent and debilitating complication of diabetes mellitus, leading to sensory abnormalities, decreased balance, and increased risk of foot problems. Although tumor necrosis factor-alpha (TNF-α) has emerged as a potential factor in the pathogenesis of DPN, its role remains contested. This study intends to thoroughly analyze the association between TNF-α and DPN by combining data from various global studies. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and included 23 articles investigating TNF-α levels in DPN patients for systematic review and 11 articles for meta-analysis. Data were extracted, and heterogeneity was examined. A random-effect model was chosen due to high heterogeneity. The major outcome measure across studies was serum TNF-α levels. The meta-analysis found a significant mean difference of 15.2464 (95% confidence interval = 4.4963; 25.9965) under the random-effect model due to the substantial heterogeneity (I2 = 98.1%) among included studies. The meta-analysis indicates a consistent elevation in TNF-α levels in individuals with DPN compared to those without neuropathy. This underlines the potential of TNF-α as a biomarker and contributor to diabetic neuropathy. Despite heterogeneity, the study's extensive scope and systematic approach enhance the trustworthiness and generalizability of the findings.

Plasma tumour necrosis factor-alpha-related proteins in prognosis of heart failure with pulmonary hypertension.

Patients with heart failure (HF) exhibit poor prognosis, which is further deteriorated by pulmonary hypertension (PH), with negative impact on morbidity and mortality. As PH due to left HF (LHF-PH) is among the most common causes of PH, there is an urge according to the 2021 European Society of Cardiology HF guidelines to find new biomarkers that aid in prognostication of this patient cohort. Given the role of tumour necrosis factor-alpha (TNF-α) in HF progression, we aimed to investigate the prognostic value of plasma proteins related to TNF-α in patients with LHF-PH, in relation to haemodynamic changes following heart transplantation (HT). Twenty TNF-α-related plasma proteins were analysed using proximity extension assay in healthy controls (n=20) and patients with LHF-PH (n=67), before and 1year after HT (n=19). Plasma levels were compared between the groups, and the prognostic values were determined using Kaplan-Meier and Cox regression analyses. Plasma levels of lymphotoxin-beta receptor (LTBR), TNF receptor superfamily member 6B (TNFRSF6B), and TNF-related apoptosis-inducing ligand receptors 1 and 2 (TRAIL-R1 and TRAIL-R2, respectively) were higher in LHF-PH pre-HT vs. controls (P<0.0001), as well as higher in pre-HT vs. post-HT (P<0.001). The elevated pre-HT levels of LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 decreased towards the levels of healthy controls after HT. Higher preoperative levels of LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 in LHF-PH were associated with worse survival rates (P<0.002). In multivariate Cox regression models, each adjusted for age and sex, LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 predicted mortality (P<0.002) [hazard ratio (95% confidence interval): 1.12 (1.04-1.19), 1.01 (1.004-1.02), 1.28 (1.14-1.42), and 1.03 (1.02-1.04), respectively]. Elevated pre-HT plasma levels of the TNF-α-related proteins LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 in LHF-PH decreased 1year after HT, displaying a normalization pattern towards the levels of the healthy controls. These proteins were also prognostic, where higher levels were associated with worse survival rates in LHF-PH, providing new insight in their potential role as prognostic biomarkers. Larger studies are warranted to validate our findings and to investigate their possible pathobiological mechanisms in LHF-PH.

Role of tumor necrosis factor-alpha -238 G>A promoter region polymorphism on recurrent miscarriage: An association study and meta-analysis.

Recurrent miscarriage (RM) is defined as the loss of two or more consecutive pregnancies. A functional SNP, -238G>A in the promoter region of TNF-α, affects the gene transcription activity with implications on human pregnancy. Previous limited studies, linking the TNF-α -238 G>A to the risk of recurrent miscarriage have been inconclusive. The PCR-RLFP technique was used to evaluate this polymorphism in 199 RM cases and 215 control women from Amritsar, Punjab. For a meta-analysis, a total of 13 eligible studies (including the present study) comprising 2947 cases and 2933 controls were included. To evaluate the association among different genetic models, odds ratio with a 95% confidence interval (CI) and chi-square were used. Genotype and allelic frequency did not differ significantly between both groups (p=.07 and p=.24, respectively). In the present meta-analysis, a significant association was found with the recessive model (OR-1.78 CI:1.24-2.55, p=.002). Although, TNF-α -238 G>A polymorphism did not provide any risk in the case-control study but provided risk towards the development of RM with the recessive genetic model in the pooled analysis.

Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders.

Tumor necrosis factor-alpha (TNF-α) is a pleiotropic immune cytokine that belongs to the TNF superfamily of receptor ligands. The cytokine exists as either a transmembrane or a soluble molecule, and targets two distinct receptors, TNF-α receptor 1 (TNFR1) and TNF-α receptor 2 (TNFR2), which activate different signaling cascades and downstream genes. TNF-α cellular responses depend on its molecular form, targeted receptor, and concentration levels. TNF-α plays a multifaceted role in normal physiology that is highly relevant to human health and disease. In the central nervous system (CNS), this cytokine regulates homeostatic functions, such as neurogenesis, myelination, blood-brain barrier permeability and synaptic plasticity. However, it can also potentiate neuronal excitotoxicity and CNS inflammation. The pleiotropism of TNF-α and its various roles in the CNS, whether homeostatic or deleterious, only emphasizes the functional complexity of this cytokine. Anti-TNF-α therapy has demonstrated effectiveness in treating various autoimmune inflammatory diseases and has emerged as a significant treatment option for CNS autoimmune diseases. Nevertheless, it is crucial to recognize that the effects of this therapeutic target are diverse and complex. Contrary to initial expectations, anti-TNF-α therapy has been found to have detrimental effects in multiple sclerosis. This article focuses on describing the various roles, both physiological and pathological, of TNF-α in the CNS. Additionally, it discusses the specific disease processes that are dependent or regulated by TNF-α and the rationale of its use as a therapeutic target.

Prospective Roles of Tumor Necrosis Factor-Alpha (TNF-α) in COVID-19: Prognosis, Therapeutic and Management

The coronavirus disease 2019 (COVID-19) became a worldwide concern at the beginning of 2020 and has affected millions. Several previous studies revealed the impact of the imbalanced innate immune response on the progression of COVID-19 and its disease outcomes. High levels of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins are produced readily by innate immune cells to fight Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infections. Nonetheless, cytokine-mediated inflammatory events are also linked to detrimental lung injury and respiratory failure, which can result in deaths among COVID-19 patients. TNF-α is amongst the early cytokines produced to mediate proinflammatory responses and enhance immune cell infiltration in response to SARS-CoV-2 infections. In COVID-19, TNF-α-mediated inflammation can cause detrimental tissue damage and gradually promotes lung fibrosis, which later results in pneumonia, pulmonary edema, and acute respiratory distress syndrome. This review, therefore, aims to deliberate the immunomodulatory roles of TNF-α in promoting inflammation and its relation with COVID-19 morbidity and mortality. In addition, this review also proposes the potential of TNF-α as a biomarker for the prognosis of severe COVID-19 and its related complications and as a molecular target for anti-TNF-α therapy.

Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.

The Role of TNF-α and Total IgE in Pathogenicity of Iraqi Fuel Stations Workers with Allergic Rhinitis

Allergic Rhinitis (AR) is a chronic immune system inflammation that occurs when the body overreacts to antigens in the environment (triggers) and produces a variety of symptoms in the nasal mucosa and paranasal sinuses due to the release of many interleukins and cytokines. We investigated the influence of the allergen on serum levels of TNF-α and Total IgE in patients with AR and their function in initiating allergic rhinitis in Iraqi petrol station workers in Baghdad. One hundred individuals with allergic rhinitis and thirty healthy workers between the ages of 20 and 59 were examined. For immunological testing, sandwich ELISA was used to evaluate serum levels of TNF-α and Total IgE. A complete blood cell count (CBC) was used for hematological testing. Findings showed a positive connection between TNF-α and Total IgE, with a correlation of (r=0.32). The TNF-α binary logistic regression analysis (BLR) was conducted to be highly significant (B = 0.02, OR = 1.02, p =0.065), viewing that an increase of one unit in TNF-α increases the odds of belonging to the AR group. TNF-α had the highest area under the curve (AUC) compared to other markers, with a value of (AUC = 0.995), indicating that it is an excellent predictor and strong marker for AR, with a sensitivity and specificity of 94% and 100%, respectively. After our research, we reached the significance of the study from the clarity of the role of tumor necrosis factor-alpha in the disease and its development and the coincidence of its increase with immunoglobulin E and considering. It is also a diagnostic marker of the disease.

The role of tumor necrosis factor-alpha (TNF-α) inhibitor in steven johnson syndrome/toxic epidermal necrolysis (SJS/TEN) management: a systematic review

Background. Steven Johnson Syndrome and Toxic Epidermal Necrolysis are dermatologic emergencies with high mortality rates characterized by extensive skin involvement. TNF-α has a role in inducing the production of granulysin that enhances keratinocyte cell death. Thus, the use of TNF-α inhibitors such as etanercept and infliximab is promising to halt the disease progression. This systematic review aims to evaluate the efficacy of TNF-α inhibitor in SJS/TEN management. Method. A systematic review using an online database was conducted based on PRISMA guidelines. Inclusion criteria were studied about the role of TNF-α inhibitor in SJS/TEN management. The exclusion criteria were a letter to the editor, commentary report, review, meta-analysis, study not used humans as a study subject, not available in full text and not in English or Bahasa Indonesia. Result. Fourteen studies are included in this systematic review consisting of ten case reports, three cohort retrospective studies, and one randomized controlled trial. TNF-α inhibitors such as etanercept and infliximab are beneficial for SJS/TEN management because they accelerate skin healing time and re-epithelization, reduce in-hospital duration and mortality rate, and minimal complications and side effects. TNF-α inhibitors should be given quickly after the disease onset, and combination with other immunosuppressive agents should be avoided to prevent the excessive immunosuppressive effect. Conclusion. TNF-α inhibitors such as etanercept and infliximab promise therapy to halt SJS/TEN progression.

The Role of Tumor Necrosis Factor-alpha (TNF-α) in the Pathogenesis of Oral Diseases

The Role of Tumor Necrosis Factor-alpha (TNF-α) in the Pathogenesis of Oral Diseases

P-EP018. A systematic review on the role of tumor necrosis factor-alpha in post-traumatic epilepsy

Introduction. Post-traumatic epilepsy (PTE) is one of the detrimental outcomes of traumatic brain injury (TBI), resulting in unprovoked recurrent seizures which impacts heavily on the quantity of life. However, the pathological relationship between PTE and TBI remains unclear, and commonly prescribed anti-epileptic drugs (AED) are ineffective against PTE. Fortunately, emerging research implicates neuroinflammation particularly the tumor necrosis factor-alpha (TNF-α) as the key mediator for PTE development. Thus, this systematic review aims to examine the currently available literature regarding the role of TNF-α in PTE pathology and consecutively, evaluate TNF-α as a possible target for PTE treatment. Methods. A comprehensive literature search was conducted on four databases including PubMed, CINAHL, Embase, and Scopus. Articles were screened according to the inclusion and exclusion criteria as per the PRISMA guidelines. Articles with relevance in investigating TNF-α expression in PTE were considered in this review. Qualitative analysis on the selected animal studies were performed using SYRCLE tool. Results. Critical evaluation of four articles; one in-vitro study, two in-vivo studies and one computational study, that met the inclusion criteria suggests a proportional relationship between TNF-α expression and seizure susceptibility post injury, and that neutralization or suppression of TNF-α release results in reduced susceptibility to seizures after TBI. Conclusion. In conclusion, this review elucidates the importance of TNF-α expression in epileptogenesis post-injury and urges future research to focus more on clinical studies involving TNF-α which may provide a clearer insight to PTE prevention and therefore improving the lives of PTE patients.

Role of Tumor Necrosis Factor-Alpha in Schizophrenia and Cognitive Impairment

Background: Neuroinflammation and excitotoxicity play a key role as triggers and support for neurodegenerative processes, increase levels of TNF-α have been found in schizophrenic patients. Improved inflammatory processes have been demonstrated in acute and chronic schizophrenia. In schizophrenia is characterized by a collection of core symptoms that trigger individuals experiencing several cognitive disorders.&#x0D; Objective: To investigate the relationship of serum TNF-α levels to impaired cognitive function in schizophrenic patients in Medan, Indonesia.&#x0D; Method: This research is cross sectional analytical correlative study involving 40 male schizophrenic patients at Prof. Dr. M. Ildrem Mental Hospital through July to September 2019 that fulfilled our inclusion and exclusion criteria. Serum TNF-α levels were analyzed using Quantikine HS Human TNF-α Assay with a minimum detection limit of 0.1062 pg/ml while in the other hand, cognitive function test was carried out by using the Mini Mental State Examination.&#x0D; Results: Serum TNF-α levels with a mean of 25.1216 with a standard deviation of 1.7629. There is a positive correlation with moderate correlation (r = 0.4 - &lt;0.6) on cognitive function with the strength of correlation r = 0.434&#x0D; Conclusion: We found that there is a link between serum TNF-α level and cognitive function as assessed with the Mini-Mental State Examination (MMSE).

TNFα enhances trovafloxacin-induced in vitro hepatotoxicity by inhibiting protective autophagy

Trovafloxacin (TVX) is associated with idiosyncratic drug-induced liver injury (iDILI) and inflammation-mediated hepatotoxicity. However, the inflammatory stress-regulated mechanisms in iDILI remain unclear. Herein, we elucidated the novel role of tumor-necrosis factor alpha (TNFα), an inflammatory stress factor, in TVX-induced in vitro hepatotoxicity and synergistic toxicity. TVX specifically induced synergistic toxicity in HepG2 cells with TNFα, which inhibits autophagy. TVX-treated HepG2 cells induced protective autophagy by inhibiting the expression of mTOR signaling proteins, while ATG5 knockdown in HepG2 cells, responsible for the impairment of autophagy, enhanced TVX-induced toxicity due to the increase in cytochrome C release and JNK pathway activation. Interestingly, the expression of mTOR signal proteins, which were suppressed by TVX, disrupted the negative feedback of the PI3K/AKT pathway and TNFα rebounded p70S6K phosphorylation. Co-treatment with TVX and TNFα inhibited protective autophagy by maintaining p70S6K activity, which enhanced TVX-induced cytotoxicity. Phosphorylation of p70S6K was inhibited by siRNA knockdown and rapamycin to restore TNFα-inhibited autophagy, which prevented the synergistic effect on TVX-induced cytotoxicity. These results indicate that TVX activates protective autophagy in HepG2 cells exposed to toxicity and an imbalance in negative feedback regulation of autophagy by TNFα synergistically enhanced the toxicity. The finding from this study may contribute to a better understanding of the mechanisms underlying iDILI associated with inflammatory stress.

An Overview of The Role of Tumor Necrosis Factor-Alpha in Epileptogenesis and Its Terapeutic Implications.

The complex association between neuroinflammation and seizures has been widely investigated in recent years. As mediators of inflammatory response, cytokines like tumor necrosis factor-α (TNF-α) are potential therapeutic targets for epileptic disorders. TNF-α is a pleiotropic cytokine with a controversial role in epileptogenesis, seemingly capable to both favor the genesis of seizures and elicit neuromodulatory responses. Anti-TNF agents are a group of monoclonal antibodies engineered to inhibit the response to this cytokine for antinflammatory purposes. The clinical experience of the use of these drugs in neurological conditions like multiple sclerosis showed controversial results. Evidence in favor of the employment of anti-TNF agents for the treatment of epilepsy are still limited to certain forms of disorders, notably Rasmussen encephalitis, and in carefully selected patients.

The Role of Tumor Necrosis Factor-alpha as a Marker of Inflammation and a Predictor of in-hospital Complications in Patients with Acute Coronary Syndrome

The Role of Tumor Necrosis Factor-alpha as a Marker of Inflammation and a Predictor of in-hospital Complications in Patients with Acute Coronary Syndrome

The dual role of tumor necrosis factor-alpha (TNF-α) in breast cancer: molecular insights and therapeutic approaches.

Breast cancer is the most prevalent cancer among women worldwide and the fifth cause of death among all cancer patients. Breast cancer development is driven by genetic and epigenetic alterations, with the tumor microenvironment (TME) playing an essential role in disease progression and evolution through mechanisms like inflammation promotion. TNF-α is one of the essential pro-inflammatory cytokines found in the TME of breast cancer patients, being secreted both by stromal cells, mainly by tumor-associated macrophages, and by the cancer cells themselves. In this review, we explore the biological and clinical impact of TNF-α in all stages of breast cancer development. First of all, we explore the correlation between TNF-α expression levels at the tumor site or in plasma/serum of breast cancer patients and their respective clinical status and outcome. Secondly, we emphasize the role of TNF-α signaling in both estrogen-positive and -negative breast cancer cells. Thirdly, we underline TNF-α involvement in epithelial-to-mesenchymal transition (EMT) and metastasis of breast cancer cells, and we point out the contribution of TNF-α to the development of acquired drug resistance. Collectively, these data reveal a pro-tumorigenic role of TNF-α during breast cancer progression and metastasis. We systemize the knowledge regarding TNF-α-related therapies in breast cancer, and we explain how TNF-α may act as both a target and a drug in different breast cancer therapeutic approaches. By corroborating the known molecular effects of TNF-α signaling in breast cancer cells with the results from several preclinical and clinical trials, including TNF-α-related clinical observations, we conclude that the potential of TNF-α in breast cancer therapy promises to be of great interest.

Clinical and epidemiological features of urinary tract infection in children of Primorsky Krai

Summary:The review covers the findings of the epidemiological trial on urinary tract infections (UTI) incidence, acute and chronic pyelonephritis in children of Primorsky territory. The significant impact of environmental climatic and heliogeophysical risk factors on pyelonephritis morbidity in children was detected. The most significant factors of UTI development in Primorsky territory were defined. Clinical and laboratory features of this pathology in children at the present day are represented. The ideas of pathogenesis of bacterial inflammation in urinary tract have been broaden. The role of tumor necrosis factor-alpha and its type 2 soluble receptor in persistence and in progression of the inflammation process, which can lead to non-reversible sclerotic changes in kidney tissue, was determined. The role of nitrogen oxide in pathogenetic mechanisms of renal hypertension in children was determined. The complex rehabilitation of patients with local mineral water was considered. The obtained data can be used in further researches, in the work of children›s medical institutions of cities and regions of Primorsky territory.

Extracellular Vesicles Secreted in Response to Cytokine Exposure Increase Mitochondrial Oxygen Consumption in Recipient Cells.

Extracellular vesicles (EVs) are small, membrane-bound nanoparticles released from most, if not all cells, and can carry functionally active cargo (proteins, nucleic acids) which can be taken up by neighboring cells and mediate physiologically relevant effects. In this capacity, EVs are being regarded as novel cell-to-cell communicators, which may play important roles in the progression of neurodegenerative diseases, like Alzheimer’s disease (AD). Aside from the canonical physical hallmarks of this disease [amyloid β (Aβ) plaques, neurofibrillary tangles, and widespread cell death], AD is characterized by chronic neuroinflammation and mitochondrial dysfunction. In the current study, we sought to better understand the role of tumor necrosis factor-alpha (TNF-α), known to be involved in inflammation, in mediating alterations in mitochondrial function and EV secretion. Using an immortalized hippocampal cell line, we observed significant reductions in several parameters of mitochondrial oxygen consumption after a 24-h exposure period to TNF-α. In addition, after TNF-α exposure we also observed significant upregulation of two microRNAs (miRNAs; miR-34a and miR-146a) associated with mitochondrial dysfunction in secreted EVs. Despite this, when naïve cells are exposed to EVs isolated from TNF-α treated cells, mitochondrial respiration, proton leak, and reactive oxygen species (ROS) production are all significantly increased. Collectively these data indicate that a potent proinflammatory cytokine, TNF-α, induces significant mitochondrial dysfunction in a neuronal cell type, in part via the secretion of EVs, which significantly alter mitochondrial activity in recipient cells.

Antioxidant and anti-inflammatory activities of alpha lipoic acid protect against indomethacin-induced gastric ulcer in rats

Little is known about the role of tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1), and inducible nitric oxide synthase (iNOS) in the gastric ulcer and the effect of alpha lipoic acid (ALA) in their modulation. Hence, this experimental study was designed to assess the possible protective effect of ALA against indomethacin (IND)-induced gastric ulcer in rats, as well as to determine the possible underlying mechanisms with a special focus on TNF-α, PAI-1, and iNOS. Adult male rats (n = 28) were divided into four equal groups: the control group received distilled water, the vehicle group received 0.5% carboxymethylcellulose, the ulcer group received a single oral dose of IND (50 mg/kg) and the ALA-treated group received ALA (100 mg/kg) orally for 3 days before ulcer induction. Four hours after IND administration, all rats were sacrificed. The ulcer index, and gastric tissue homogenate contents of total antioxidant capacity (TAC), malondialdehyde (MDA), TNF-α, and PAI-1 were evaluated. Immunohistochemical evaluation of iNOS protein expression and histopathological examination of gastric tissue were investigated. The results revealed that ALA pretreatment significantly decreased the ulcer index, the gastric levels of MDA, TNF-α, PAI-1, and iNOS protein expression while increased the gastric levels of TAC as well as improved the histopathological appearance of gastric tissues. In conclusion, ALA ameliorated the IND-induced gastric ulceration. This could be attributed to its antioxidant and anti-inflammatory activities via suppression of TNF-α-induced elevation of both PAI-1 level and iNOS expression in the gastric tissue.