Alantolactone triggers oxeiptosis in human ovarian cancer cells via Nrf2 signaling pathway.

Introduction: A growing body of evidence indicated that Alantolactone (ALT) promotes Reactive Oxygen Species (ROS) generation exclusively in cancer cells. Therefore, the aim of this study was to investigate the effect of ALT on the molecular mechanism of oxeiptosis, as a novel cell death pathway due to the high levels of intracellular ROS in ovarian cancer. Methods: MTT assay was used to evaluate the effect of ALT on SKOV3 cell viability. mRNA and protein expression levels of Nrf2 (nuclear factor erythroid 2-related factor 2), KEAP1 (Kelch-like ECH-associated protein 1), PGAM5 (phosphoglycerate mutase family member 5), AIFM1 (Mitochondrial Apoptosis-Inducing Factor), Glutathione synthetase (GSS) and glutathione peroxidase (GPX) were analyzed by real time PCR and western blotting methods respectively. Results: Our findings showed that ALT inhibits the proliferation of skov3 cells in a time and dose dependent manner and IC50 was 32 µM at 24h.A significant down-regulation of Nrf2, GSH and GPX mRNA levels was seen in skov3 cells incubated with 32 and 64 µM of ALT in comparison with control group, while, mRNA expression levels of PGAM5 and KEAP1 were increased.Western blot analysis showed that ALT significantly decreases protein levels of Nrf2 and increases PGAM5 and KEAP1.ALT dephosphorylated PS116-AIFM1 and total AIFM1 protein level was elevated. Conclusion: Our results provided evidence that ALT could be a potential option for ovarian cancer treatment by ROS-mediated oxeiptosis.

Investigating the Relationship between the Levels of IL18, RANKL Gene Expression, MicroRNA-146a and Inflammatory Factors with the Severity of COVID-19.

COVID-19 can induce lung inflammation, and inflammatory factors play an essential role in its pathogenesis. This inflammation can be controlled to a great extent by microRNAs(miRs). This study evaluated miR-146a-5p expression levels in the serum of patients with COVID-19 and their association with the expression of interleukin (IL)-18 and receptor activator of nuclear factor kappa-Β ligand (RANKL) genes, and lung damage. patients with COVID-19 were divided into two groups: mild and severe phases. The severe phase is defined as having a positive polymerase chain reaction (PCR) for SARS-CoV2, and acute pulmonary symptoms. The subjects' demographic, clinical, and paraclinical characteristics were collected according to a pre-prepared checklist. Total RNA was isolated from all samples using the Trizol kit to assess gene expression. The extracted product was then evaluated for the expression of miR-146a and the target genes (i.e., IL-18 and RANKL) using real-time PCR. The miR-146a gene's mean expression in mild and severe patients was 0.73 and 1.89, respectively, and this difference was statistically significant between the two groups. Also, the mean Expression of the IL-18 gene, 1.37±0.38 in the mild and 2.83±0.58 in the severe groups of the disease, demonstrated a significant difference between the two groups. In contrast, the expression levels of the RANKL gene did not show a significant difference between the two groups. Therefore, it may be hypothesized that altered levels of miR-146a may contribute to the severe COVID-19 that is more commonly observed in smokers, but further research is required.

The role of exosomes in the molecular mechanisms of metastasis: Focusing on EMT and cancer stem cells.

Exosomes are cell-derived small membrane-encapsulated vesicles that transfer biomolecules to surrounding cells. Exosomes play fundamental roles in cell-cell communications. They can also aggravate cancer progression and metastasis. Metastasis is a complicated and multi-serial process that is regulated by various mechanisms. Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are important participants in cancer metastasis. Recent studies demonstrate that exosomes are associated with metastasis by modulating the EMT and the function of CSCs. Accumulating evidence shows that exosomes are implicated in regulating tumor cell metastasis by modulating signaling pathways involved in EMT and CSCs. This review aims to discuss the effect of exosomes on signaling pathways associated with EMT and CSCs, as well as possible therapeutic strategies of exosomes in cancer metastasis.

Combination effects of capecitabine, irinotecan and 17-AAG on colorectal cancer cell line (HT-29).

Objevtive: Evasion of apoptosis is a major feature of cancer cells, therefore designing treatment strategies to target apoptotic pathways seems effective. In this study, we investigate the effect of 17-AAG (17-allylaminogeldanamycin) alone and in double and triple combination with capecitabine (Cap) and irinotecan (IR) on HT-29 colon cancer cell line apoptosis. Methods: Capase-3, 8, 9, p53 and NF-κB genes expression were analyzed by Real-time PCR. DNA laddering assay was performed to confirm Real-time PCR results. Results: Our results showed that all single treatment groups elevated expression of caspase-3, 8, and 9 significantly and IR/Cap was the only double combination group that could upregulate caspase-8 and -9. NF-κB was down-regulated in single treatment and IR/Cap double combination group, significantly. 17-AAG mono-treatment and IR/Cap and Cap/17-AAG double combination group significantly upregulated p53 gene expression. Conclusion: Our findings showed proapoptotic effects of 17-AAG alone and in combination with Cap and IR. These findings propose 17-AAG in combination with routine chemotherapy, as a new protocol for colorectal cancer combination therapy.

Effects of anti-TNF biologic drugs on uveitis severity in Behçet patients: systematic review and Meta-analysis.

AIM: To investigate effects of anti-TNF biologic drugs on uveitis severity (comparing visual acuity logMAR levels) in Behçet patients. METHODS: Three databases PubMed, Scopus, and the Web of Science were searched for qualified papers focusing on the anti-TNF-α factors treatment in Behçet's disease (BD)-associated uveitis. Studies that were designed pre and post anti-TNF drug treatment, were selected. After determining the search strategy for this study, the relevant data were extracted. RESULTS: The initial search was performed in the target databases and a total of about 1458 articles were found. Fifteen articles were selected for systematic review and only 12 of them had inclusion criteria for Meta-analysis (with visual acuity data). The mean dose of prednisolone before and after biological treatments was reported in 5 studies (28.56 and 7.56 mg/kg, respectively). Also, the preliminary results indicate a significant reduction in visual acuity logMAR levels (MD=-1.5 IU/L, 95%CI: -2.1, -0.01). CONCLUSION: Biological drugs significantly reduce the dose of prednisolone and affect visual acuity values.

Alantolactone and ZnO nanoparticles induce apoptosis activity of cisplatin in an ovarian cancer cell line (SKOV3).

Background and purpose: Ovarian cancer is one of the leading causes of cancer mortality in women. Despite the increase in cases of this cancer, the current therapeutic strategy is not effective. This study aimed to investigate the effect of cisplatin (Cis) with alantolactone (ALT) and ZnO nanoparticles (ZnONPs) in inducing apoptosis in SKOV3 ovarian cancer cells line. Experimental approach: To evaluate the viability of SKOV3 cells and determine the IC50 of Cis, ALT, and ZnONPs, MTT assay was used. Real-time PCR and western blotting were used to evaluate the expression levels of genes (XIAP, cyclin D1, Bcl-2, Bax, and MDM2) and proteins (XIAP, cyclin D1, Bcl-2, Bax), respectively. Also, cellular ROS levels were assessed by fluorimetry. Findings / Results: Our results showed that ALT and ZnONPs significantly increased the response to Cis in SKOV3 cells compared to the control and this response is remarkably increased in the triple combination (ALT-Cis-ZnONPs). The expression of XIAP, cyclin D1, and Bcl-2 genes and proteins in the groups treated with ALT, Cis, and ZnONPs as a single agent, double and triple combination were significantly reduced compared to the control, while Bax was generally shown an increase. Also, the level of intracellular ROS is higher in the treatment groups than in the control group and the highest increase was observed in the triple combination. Conclusion and implications: Taken together, our data demonstrated the potential therapeutic approach of using ALT and ZnONPs that may enhance the apoptotic effects of Cis on the SKOV3 cells.

Significance of Cardiac Troponins as an Identification Tool in COVID-19 Patients Using Biosensors: An Update.

Coronavirus disease 2019 (COVID-19) has rapidly developed as a global health emergency. Respiratory diseases are significant causes of morbidity and mortality in these patients with a spectrum of different diseases, from asymptomatic subclinical infection to the progression of severe pneumonia and subsequent acute respiratory distress syndrome. Individuals with cardiovascular disease are more likely to become infected with SARS-CoV-2 and develop severe symptoms. Hence, patients with underlying cardiovascular disease mortality rate are over three times. Furthermore, note that patients with a history of cardiovascular disease are more likely to have higher cardiac biomarkers, especially cardiac troponins, than infected patients, especially those with severe disease, making these patients more susceptible to cardiac damage caused by SARS-2-CoV. Biomarkers are important in decision-making to facilitate the efficient allocation of resources. Viral replication in the heart muscle can lead to a cascade of inflammatory processes that lead to fibrosis and, ultimately, cardiac necrosis. Elevated troponin may indicate damage to the heart muscle and may predict death. After the first Chinese analysis, increased cardiac troponin value was observed in a significant proportion of patients, suggesting that myocardial damage is a possible pathogenic mechanism leading to severe disease and death. However, the prognostic performance of troponin and whether its value is affected by different comorbidities present in COVID-19 patients are not known. This review aimed to assess the diagnostic value of troponin to offer insight into pathophysiological mechanisms and reported new assessment methods, including new biosensors for troponin in patients with COVID-19.

Evaluating the effect of Alantolactone on the expression of N-cadherin and Vimentin genes effective in epithelial-mesenchymal transition (EMT) in breast cancer cell line (MDA-MB-231).

OBJECTIVE: Breast cancer is the second leading cause of death and the most common cancer among women. 10 to 20 percent of breast cancer samples have a negative triple phenotype that is more metastatic and more difficult to diagnose. Tumor invasion to other tissues and the formation of a secondary tumor depend on the epithelial to mesenchymal transition process, and the STAT3 pathway, which is associated with tumor proliferation and invasion and is the target gene for the drug, alantolactone. In this study, the EMT process is evaluated in negative triple-breasted cancer cells treated with alantolactone. METHODS: We used MDA-MB-231 cell line for assessing the survival rate of triple negative breast cancer cells and MTT test for determining alantolactone dose. We used three doses of 0.01 0.1, and 1 µM of alantolactone for evaluating the cell behavior in cancer invasion pathway. Real-time PCR was used to evaluate the expression of Vimentin, and N-cadherin genes. All of the tests were repeated thrice and the data were analyzed using Prism version 7.0. RESULTS: The expression of Vimentin and N-cadherin decreased significantly at 1 µM alantolactone compared to the control group, p < 0.05. CONCLUSION: Alantolactone affects the expression of Vimentin and N-cadherin through STAT3 signaling pathway and suppresses EMT process, metastasis and cancer invasion. This component may be used for treatment of patients with breast cancer.

Combination Therapy of Stem Cell-derived Exosomes and Biomaterials in the Wound Healing.

Wound healing is a serious obstacle due to the complexity of evaluation and management. While novel approaches to promoting chronic wound healing are of critical interest at the moment, several studies have demonstrated that combination therapy is critical for the treatment of a variety of diseases, particularly chronic wounds. Among the various approaches that have been proposed for wound care, regenerative medicine-based methods have garnered the most attention. As is well known, regenerative medicine's three primary tools are gene/cell therapy, biomaterials, and tissue engineering. Multifunctional biomaterials composed of synthetic and natural components are highly advantageous for exosome carriers, which utilizing them is an exciting wound healing method. Recently, stem cell-secreted exosomes and certain biomaterials have been identified as critical components of the wound healing process, and their combination therapy appears to produce significant results. This paper presents a review of literature and perspectives on the use of stem cell-derived exosomes and biomaterials in wound healing, particularly chronic wounds, and discusses the possibility of future clinical applications.

Revealed pathophysiological mechanisms of crosslinking interaction of affected vital organs in COVID-19.

SARS-CoV-2 is one of the main serious challenges of human societies, which emerged in December 2019 from China and quickly extends to all parts of the world. The virus was previously believed to only affect the lungs and respiratory system, but subsequent research has revealed that it affects a variety of organs. For this reason, this disease is known as a multiorgan disease. Current article aimed to highlight latest information and updates about molecular studies regarding pathogenesis of SARS-CoV-2 in kidney, liver, and cardiovascular and respiratory systems, as well as the mechanisms of interaction of these organs with each other to cause clinical manifestations in patients.

Crosslink between p53 and metastasis: focus on epithelial-mesenchymal transition, cancer stem cell, angiogenesis, autophagy, and anoikis.

INTRODUCTION: P53, as a tumor suppressor gene, is believed to be one of the most mutated genes in cancer cells. The mutant forms of this protein often play a tumorigenic role in cancer cells. Recent evidence shows that p53 plays a critical role in the migration, metastasis, and invasion of cancer cells. The present article aims to investigate the molecular mechanism that induces metastasis in cancer cells generated by the mutant P53, and to highlight the compounds targeting mutant-p53 together with their clinical applications. METHODS: A detailed literature search was conducted to find information about the role of the mutant-p53 in the processes involved in metastasis in various databases. RESULTS: A growing body of evidence suggests that Mutant-p53 enhances tumor metastasis affecting the Epithelial-mesenchymal transition (EMT) process, cancer stem cells, angiogenesis, autophagy, anoikis, and any other mechanisms regarding metastasis. CONCLUSIONS: Taken together, targeting mutant-p53 by altering the processes involved in metastasis could be a potential therapeutic strategy in the treatment of metastatic cancer.

The emerging role of miR-200 family in metastasis: focus on EMT, CSCs, angiogenesis, and anoikis.

INTRODUCTION: Cancer is the second major threat to human society and one of the main challenges facing healthcare systems. One of the main problems of cancer care is the metastases of cancer cells that cause 90% of deaths due to cancer. Multiple molecular mechanisms are involved in cancer cell metastasis. Therefore, a better understanding of these molecular mechanisms is necessary for designing restrictive strategies against cancer cell metastasis. Accumulating data suggests that MicroRNAs (miRNAs) are involved in metastasis and invasion of human tumors through regulating multiple genes expression levels that are involved in molecular mechanisms of metastasis. The goal of this review is to present the molecular pathways by which the miR 200 family manifests its effects on EMT, cancer stem cells, angiogenesis, anoikis, and the effects of tumor cell metastases. METHODS: A detailed literature search was conducted to find information about the role of the miR-200 family in the processes involved in metastasis in various databases. RESULTS: Numerous lines of evidence revealed an association between the mir-200 family and metastasis of human tumors by impressing processes such as cancer stem cells, EMT, angiogenesis, and anoikis. CONCLUSIONS: Understanding the molecular mechanisms associated with metastasis in which the miR-200 family is involved can be effective in treating metastatic cancers.

Critical roles of TLRs on the polarization of mesenchymal stem cells for cell therapy of viral infections: a notice for COVID-19 treatment.

Mesenchymal stem cells (MSCs), as one of the leading cell-based therapy, have provided a strong link between clinical investigation and basic research. MSCs have been successfully employed in treating graft versus host disease (GvHD), autoimmune disease, and several other diseases, particularly with high immune activity. Recently, MSCs have attracted attention to treating untreatable viral infections such as severe coronavirus disease 2019 (COVID-19). Given that the Toll-like receptors (TLRs) are directly able to detect internal and external hazard signals, and their stimulation has an intense effect on the ability to grow, differentiate, migrate, and maintain MSCs, it seems stimulation of these receptors can have a direct impact on the interaction of MSCs and immune cells, altering the ability to modify immune system responses. Hence, this mini-review focused on TLRs' critical roles in the polarization of MSCs for developing MSC-based therapy in viral infections. Consequently, according to the literature review, a polarization process, mediated by TLRs concerning anti-inflammatory and proinflammatory phenotype, may be considered for MSC-therapy against viral infections.

A comprehensive review of anticancer mechanisms of action of Alantolactone.

Cancer is considered as the main challenge of human communities, and it annually imposes a significant economic burden on society. Natural products have been used for treatment of many diseases including inflammation, infections, neurological disorders, atherosclerosis, asthma and cancer for many years. Sesquiterpene lactones (STLs) refers to a group of natural products with different biological activities. A type of STL that has recently attracted much attention is Alantolactone (ALT). In recent years, many studies have investigated the molecular mechanism of this compound affecting cancer cells and results suggest that this compound exerts its anticancer effects by providing free radicals and inhibiting some of the signaling pathways that are effective in progression of cancer cells. The present study is aimed to introduce the latest molecular mechanisms of ALT proposed by researchers in recent years.

Ameliorative effects of tropisetron on liver injury in streptozotocin-induced diabetic rats.

This study aimed to evaluate the effect of tropisetron on liver injury induced by diabetes. Thirty-five male Wistar rats were assigned to five groups (n = 7): control (C), tropisetron (T), diabetic (D), diabetic + tropisetron (D + T) and diabetic + glibenclamide (D + G). Diabetic rats were treated with tropisetron (3 mg/kg body weight/day) or glibenclamide (1 mg/kg/day) for two weeks. Liver from diabetic rats exhibited a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), cholesterol (Chol), triglycerides (TG), low-density lipoprotein (LDL), and atherogenic index, and a significant decrease in liver glycogen, serum albumin and high-density lipoprotein. Treatment with tropisetron significantly abrogated diabetes-induced perturbation in these parameters. These effects were equipotent with glibenclamide, suggesting that tropisetron treatment is associated with a hepatoprotective effect against diabetic injury. Therefore, the results of this study manifested the significance of using tropisetron as a promising remedial agent to improve diabetic complications.

Exercise and insulin-like growth factor 1 supplementation improve angiogenesis and angiogenic cytokines in a rat model of diabetes-induced neuropathy.

NEW FINDINGS: What is the central question of this study? Do changes in levels of angiogenesis-related mediators [vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1) and nuclear factor-κB (NF-κB)] in the sciatic nerve mediate diabetic neuropathy in the streptozotocin-induced type 1 diabetic male rat? Can exercise and insulin-like growth factor 1 (IGF-I) treatment improve the diabetes-related decrease in angiogenesis in sciatic nerve in these animals? What is the main finding and its importance? Levels of VEGF-A, TSP-1 and NF-κB change in the sciatic nerve of diabetic rats and might mediate diabetic neuropathy. Treatment with IGF-I and exercise could increase angiogenesis in the diabetic rats by increasing VEGF-A and decreasing TSP-1 and NF-κB expression in the sciatic nerve. ABSTRACT: Diabetic neuropathy is a severe complication of diabetes that affects 40-50% of diabetic people in the world. The aim of this study was to characterize alterations in angiogenesis and related molecular mediators in the sciatic nerve in diabetic conditions alone or in diabetes in combination with exercise and/or administration of insulin-like growth factor 1 (IGF-I). Forty male Wistar rats were assigned into one of five groups, namely control, diabetes, diabetes + exercise, diabetes + IGF-I and diabetes + exercise + IGF-I. Type 1 diabetes was induced by i.p. injection of streptozotocin (60 mg kg-1 ). After 30 days of treatment with exercise or IGF-I alone or in combination, diabetic neuropathy was evaluated with a hotplate, glycated haemoglobin was measured, angiogenesis was determined by immunostaining for PECAM-1/CD31, and expressions of vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1) and nuclear factor-κB (NF-κB) were determined by enzyme-linked immunosorbent assay.After 4 weeks, the diabetes group showed a significant decrease in capillary density and VEGF-A levels, but a significant increase in glycated haemoglobin in blood, TSP-1 and NF-κB levels in the sciatic nerve compared with the control group, and these effects were ameliorated by exercise and IGF-I. However, simultaneous treatment of diabetic rats with IGF-I and exercise did not have any synergistic effects. These findings indicate that diabetes-induced neuropathy may be associated, in part, with decreased angiogenesis mediated by overproduction of TSP-1 and NF-κB, in addition to reduced production of VEGF-A. The findings also showed that exercise and IGF-I can reduce neuropathy, followed by increased angiogenesis, by changes in TSP-1, NF-κB and VEGF-A production levels.

Bidirectional and Opposite Effects of Naïve Mesenchymal Stem Cells on Tumor Growth and Progression.

Cancer has long been considered as a heterogeneous population of uncontrolled proliferation of different transformed cell types. The recent findings concerning tumorigeneses have highlighted the fact that tumors can progress through tight relationships among tumor cells, cellular, and non-cellular components which are present within tumor tissues. In recent years, studies have shown that mesenchymal stem cells (MSCs) are essential components of non-tumor cells within the tumor tissues that can strongly affect tumor development. Several forms of MSCs have been identified within tumor stroma. Naïve (innate) mesenchymal stem cells (N-MSCs) derived from different sources are mostly recruited into the tumor stroma. N-MSCs exert dual and divergent effects on tumor growth through different conditions and factors such as toll-like receptor priming (TLR-priming), which is the primary underlying causes of opposite effects. Moreover, MSCs also have the contrary effects by various molecular mechanisms relying on direct cellto- cell connections and indirect communications through the autocrine, paracrine routes, and tumor microenvironment (TME). Overall, cell-based therapies will hold great promise to provide novel anticancer treatments. However, the application of intact MSCs in cancer treatment can theoretically cause adverse clinical outcomes. It is essential that to extensively analysis the effective factors and conditions in which underlying mechanisms are adopted by MSCs when encounter with cancer. The aim is to review the cellular and molecular mechanisms underlying the dual effects of MSCs followed by the importance of polarization of MSCs through priming of TLRs.

Application of nanomaterials in three-dimensional stem cell culture.

Petri dish cultured cells have for long provided scientists an aperture to understanding cell's behavior both in normal and disease states as well as in vitro and in vivo. But recent advances have brought to light how the architecture and composite nature of the immediate environment within which the cell is proliferated can profoundly influence its phenotypic features and functions, thus making obvious, limitations of the conventional two-dimensional cell culture despite it cost effectiveness. Fortunately, the transition to three-dimensional (3D) cell culture has occurred concurrently with expanded knowledge of nanoscience and materials, thereby lending significant impetus for innovative research. This review is focused on the application of nanoparticles in 3D stem cell breeding, recent trends and developments in medical sciences for improved drug delivery, and treatment approaches to some human diseases. We also reviewed prevailing challenges and concerns of nanotoxicity as it continues to impede and delay clinical applications as well the ongoing concerted and multidisciplinary efforts to overcome them.

The human amniotic fluid mesenchymal stem cells therapy on, SKOV3, ovarian cancer cell line.

PURPOSE: One of the most common malignancies peculiar to female health with few symptoms, low response to therapy, difficult diagnosis, frequent relapse, and high mortality, is ovarian cancer. Thus, our experiment, using Human amniotic fluid mesenchymal stem cells (hAFMSCs) as a therapeutic tool, aims to find an efficient treatment approach for patients suffering from SKOV3 ovarian cancer. MATERIAL & METHODS: In this study, we obtained 5 ml amniotic fluid from 16-20 week pregnant women who underwent amniocentesis for routine prenatal diagnosis by karyotyping in Al-Zahra Hospital of Tabriz University of Medical Sciences, Iran. Using trans wells in 24 wells plate, hAFMSCs were isolated from all samples, co-cultured with SKOV3 ovarian cancer cell line, and characterized via flow cytometry and RT-PCR. Human skin fibroblast cells (HSFCs) were isolated and used as a negative control. SKOV3 and HSFCs' viability after 5 days was evaluated by MTT assay. Cell cycle and apoptotic genes were analyzed by real-time PCR. RESULTS: We successfully isolated and characterized hAFMSCs through it positivity for CD44 and CD90 specific mesenchymal stem cell markers and negativity for CD31 and CD45. Oct4 and NANOG were evaluated by RT-PCR as pluripotency markers, and visualized on 2% gel electrophoresis. We established hAFMS cell lines after 5 days of co-culturing the SKOV3 cells, viability was decreased; however, HSFCs did not show toxicity by MTT assay. The genes indicated upregulation and high expression by a real-time PCR. CONCLUSIONS: Our findings showed that hAFMSCs have natural tumor tropism, and can release soluble factors in a cell culture, which cause an efficient anticancer effect. Thus, we can use hAFMSCs for complete anticancer therapy on SKOV3 cell line at cell culture condition and possibly in vivo in the near future.

The protective impact of betaine on the tissue structure and renal function in isoproterenol-induced myocardial infarction in rat.

BACKGROUND: Myocardial infarction is one of the most common life threatening diseases that may lead to renal disorders via oxidative stress and inflammation. Betaine is a safe and well-tolerated compound exhibiting beneficial antioxidant and anti-inflammatory properties. Previous studies have demonstrated protective effects of betaine against myocardial infarction and renal injury. This study aimed to investigate the protective effect of betaine on tissue structure and renal function after isoprenaline-induced myocardial infarction in rats. METHODS: Fifty Wistar strain male albino rats, weighing 200 ± 10, were selected for the study. The animals were housed individually under standard environmental conditions (Light-dark cycle, temperature and constant humidity) for 1 week. After acclimatization, they were randomly divided into five groups. G1, G2, and G3 groups received betaine at doses of 50, 150, and 250 mg/kg body weight/day via gavage for a period of 60 days. After 60 days, isoprenaline is injected subcutaneously (200 mg/kg body weight). In the isoprenaline group (G4), the rats were injected with isoprenaline (200 mg/kg body weight) and the control group (G5) received a standard diet (Without isoprenaline). Then, isoproterenol solution was used for induction of myocardial infarction. At the end, the expression of nitric oxide synthase (iNOS) protein was detected using immunohistochemical analysis and kidney tissues were assessed via histopathological analysis. In addition, serum level of TNF-α and creatinine level were measured via ELISA test and colorimetric methods, respectively. RESULTS: The results of our study indicate that isoproterenol-induced renal histopathological injury without changing creatinine level. Betaine has protective effects against renal injuries induced by isoprenaline and the expression of nitric oxide synthase (nNOS) protein showed no significant difference in all groups. Further, betaine reduced TNF-α level significantly. CONCLUSION: According to our results, betaine has protective effects on isoprenaline-induced renal failure via a decrease in TNF-α level and nitric oxide synthase.