Unraveling the Impact of miRNA-17 in Glial Tumors and Cerebral Metastases: A Step Towards Enhanced Diagnosis and Prognosis.

BACKGROUND/AIM: MicroRNAs (miRNAs) have been identified as key regulators in various cancer types, including brain tumors. This study aimed to investigate the differential expression of miRNA-17 in glial tumors, cerebral metastases, and normal glial tissues. MATERIALS AND METHODS: A total of 42 patients were included in this cross-sectional study. Tissue samples were obtained from patients with glial tumors or cerebral metastases and from normal glial tissues. miRNA-17 expression levels were computed by using real-time polymerase chain reaction. Receiver operating characteristics analysis was used to determine the predictive potential of miRNA-17. RESULTS: In this study, we demonstrated a statistically significant difference in miRNA-17 expression levels between glial tumors and the control group (p=0.001), with higher miRNA-17 expression observed in glial tumors. Similarly, there was statistically higher miRNA-17 expression in metastatic cases compared with the control group (p=0.007). CONCLUSION: These findings suggest miRNA-17 might be a potential biomarker for differentiating glial tumors and cerebral metastases from normal glial tissue, although further research is necessary to validate these findings and investigate the potential role of miRNA-17 in the pathogenesis of these brain tumors.

Expression of miRNA-451 and miRNA-885 in Meningiomas.

BACKGROUND/AIM: Meningiomas are one of the most common intracranial tumors, accounting for 30% of the tumors of the central nervous system. MicroRNAs (miRNAs) are noncoding RNAs containing approximately 18-22 nucleotides that regulate gene expression by interfering with transcription or inhibiting translation. Recent studies have reported that miRNAs could provide information about the molecular pathogenesis of several types of tumors. This study aimed to examine the expression levels of miRNA-885 and -451 and to determine their potential roles as biomarkers in meningioma. MATERIALS AND METHODS: In total, 29 patients with meningioma (9 males and 20 females) were included in this study. The expression levels of miRNA were determined using real-time polymerase chain reaction. In addition, receiver operating characteristic curve analysis was used to analyze the predictive potential of miRNAs. RESULTS: Our results indicated a significant increase in miRNA-451 expression levels (p=0.003); however, there was no significant change in miRNA-885 expression levels (p=0.139) in patients with meningioma compared with the control group. Moreover, miRNA-885 and miRNA-451 expression levels did not differ significantly based on the histopathological grade of meningioma. CONCLUSION: miRNA-451 may be a novel potential marker for the diagnosis and prognosis, and a target for meningioma treatment.

Serum miRNA-582-5p and miRNA-363 as Potential Non-Invasive Biomarkers for Glioblastoma Multiforme.

AIM: To determine expression levels of miRNA-582-5p and miRNA-363 in serum of patients with Glioblastoma Multiforme and assess their biomarker potential. MATERIAL AND METHODS: The study population consisted of 71 subjects including 35 patients and 36 healthy controls. Realtime polymerase chain reaction was used to determine serum expression levels of miRNA-582-5p and miRNA-363 in patients and control individuals. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic potential of miRNA-582-5p and miRNA-363. Serum caspase-9 level was measured using enzyme-linked immunosorbent assay. RESULTS: Normalized expression levels of miRNA-582-5p and miRNA-363 were calculated using the 2-ΔΔCt method. We found that miRNA-582-5p and miRNA-363 were significantly upregulated in patients compared with healthy controls. High levels of miRNA- 582-5p (Fold change 2.86, p < 0.0001) and miRNA-363 (Fold change 3.51, p < 0.0001) were significantly associated with Glioblastoma Multiforme. Additionally, ROC analyses demonstrated that levels of miRNA-582-5p [area under the curve (AUC)=0.938, p=0.0001] and miRNA-363 [AUC=0.951, p=0.0001] were significantly different between the groups. In contrast, there was no correlation between levels of serum caspase-9 and those of miRNA-582-5p (p=0.144) or miRNA-363 (p=0.050). CONCLUSION: High serum levels of miRNA-582-5p and miRNA-363 are associated with Glioblastoma Multiforme, and are potential biomarkers.

Determination of IDH1, IDH2, MGMT, TERT and ATRX Gene Mutations in Glial Tumors.

BACKGROUND/AIM: The most frequent and dangerous kind of primary brain tumor is glioblastoma multiforme (GBM). The survival rates associated with GBM are very short and molecular markers for predicting survival are needed. The aim of our study was to evaluate isocitrate dehydrogenase 1 and 2 (IDH1, IDH2), telomerase reverse transcriptase (TERT), O-6- methylguanine-DNA methyltransferase (MGMT) and alpha-thalassemia/mental retardation, X-linked (ATRX) genes with next-generation sequencing (NGS) to find potential pathological mutations and their effect on survival. MATERIALS AND METHODS: Thirty patients who had undergone craniotomy and were diagnosed with high-grade glioma were evaluated for this study. Peripheral blood samples were obtained from all participants. IDH1, IDH2, TERT, MGMT and ATRX genes were evaluated with next-generation sequencing from the samples. Survival analysis evaluated the effects of all these mutations on survival. RESULTS: The median age of the patients was 58.5 (range=11- 74) years, and 56.7% (n=17) were under 60 years of age. According to sex, male patients comprised 66.7%. Targeted NGS detected 21 chromosomal aberrations. When more than three chromosomal anomalies were accepted as a reference, anomaly in three or fewer chromosomes negatively affected overall survival (hazard ratio=2.83). CONCLUSION: Targeted NGS generates therapeutically meaningful information, providing better prognostic information than conventional histology. Our study shows that NGS provides important information on survival by helping to detect chromosomal changes that can be detected in routine blood samples. It is clear that incorporating molecular diagnostics into our standard-of-care routine will help us better understand our patients' outcomes.

Investigation of Circulating miRNA-133, miRNA-26, and miRNA-378 as Candidate Biomarkers for Left Ventricular Hypertrophy.

BACKGROUND/AIM: Left ventricular hypertrophy (LVH) involves increased muscular mass of the left ventricle due to increased cardiomyocyte size and is caused by cardiomyopathies. Several microRNAs (miRNAs) have been implicated in processes that contribute to heart disease. This study aimed to examine miRNA-133, miRNA-26 and miRNA-378 as candidate biomarkers to define prognosis in patients with LVH. PATIENTS AND METHODS: The study group consisted of 70 patients who were diagnosed with LVH and 16 unaffected individuals who served as the control group. Real-time polymerase chain reaction (RT-PCR) was used to analyze serum miRNA-133, miRNA-26, and miRNA-378 expression levels in LVH patients and the control group. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic capability of miRNA-378. RESULTS: When crossing threshold (CT) values were compared between patient and control samples, we found that there were no statistically significant differences in miRNA-133 and miRNA-26 CT values, while the miRNA-378 expression was significantly increased in LVH patients. ROC analysis demonstrated that the expression levels of miRNA-378 (AUC=0.484, p=0.0013) were significantly different between groups. CONCLUSION: We observed a statistically significant relationship between miRNA-378 expression levels and LVH, suggesting that circulating miRNA-378 may be used as a novel biomarker to distinguish patients who have LVH from those who do not.

Investigation of the Effects of MicroRNA-221 Expression Levels in Glioblastoma Multiforme Tumors.

BACKGROUND/AIM: The aim of our study was to examine miRNA-221 as a candidate biomarker to define prognosis and/or classification for glial tumors. MATERIALS AND METHODS: This study included 39 patients who underwent glial tumor surgery and 40 healthy individuals as the control group. miRNA expression levels were determined by real-time polymerase chain reaction (RT-PCR). Receiver operating characteristic curve analysis was used for analyzing the predictive ability of miRNA-221. RESULTS: The levels of miRNA-221 expression were determined by comparing the ΔCT values of miRNAs and the internal control. When the expression levels of miRNA-221 were compared according to the ΔCT method, miRNA-221 was found to be significantly increased in the patient group compared to the control group (p<0.0001). CONCLUSION: Increased expression levels of miRNA-221 could be a biomarker for glial tumors.

Investigation of Caspase 9 Gene Polymorphism in Patients With Non-small Cell Lung Cancer.

BACKGROUND/AIM: Non-small cell lung cancer (NSCLC) is one of the most common forms of lung cancer and the leading cause of cancer-related deaths in the world. Caspase 9 (CASP9) plays a central role in the intrinsic apoptotic pathway. The aim of the study was to investigate the role of caspase 9 gene polymorphism in patients with non-small cell lung cancer. MATERIALS AND METHODS: The study included 96 NSCLC cases and 67 controls. CASP9 Ex5+32 G>A polymorphism was investigated by real-time polymerase chain reaction. RESULTS: There was a significant difference between the groups in the frequency of CASP9 genotypes (p=0.008). The number of the carriers of the ancestral GG genotype, was significantly higher in the NSCLC group than in the control (p=0.009). The heterozygote GA genotype and mutant A allele frequency were significantly higher in the control group compared to the NSCLC group (p=0.005, p=0.009, respectively). Serum CASP9 levels were significantly lower in the patients group than in the control group (p<0.0001). CONCLUSION: CASP9 Ex5+32 GG genotype was a risk factor whereas the variant A allele could be a risk-reducing factor for NSCLC.

Characteristics of Coronary Artery Disease Patients Who Have a Polymorphism in the Cholesterol Ester Transfer Protein (CETP) Gene.

BACKGROUND/AIM: Cholesterol ester transfer protein (CETP) is responsible for the transformation of high density lipoprotein (HDL) to low density lipoprotein (LDL) and is a risk factor for atherosclerosis. Our study investigated the association of the rs5883 CETP gene polymorphism with HDL and LDL levels, in 45 coronary artery disease patients and 45 control patients. MATERIALS AND METHODS: CETP gene polymorphism was detected using Real Time-Polymerase Chain Reaction (RT-PCR). Lipoprotein levels were measured using Quantimetrix system. RESULTS: There were lack of associaition regarding CETP polymorphism in atherosclerosis and HDL and LDL levels (p>0.05) BMI was higher among coronary artery disease patients (CADP) compared to the control group (28.97±6.38, 26.52±4.39 respectively, p<0.03). Frequency of CADP (82.6 %, n=19) who were taking treatment was higher (17.4 %, n=4) (p<0.00). The frequencies of hypertension and type-2 diabetes were higher among CADP (p<0.00). Families of CADP have more CADP (p<0.02). Small HDL particle levels were higher in the control group (p<0.00). CONCLUSION: In Turkey, BMI, and frequencies of hypertension and type-2 diabetes were higher among CADP than among healthy controls. Furthermore, the genotypes of the rs5883 CETP gene polymorphism did not differ between CADP and healthy controls.

The Evaluation of Glutathione Reductase and Malondialdehyde Levels in Patients With Lumbar Disc Degeneration Disease.

BACKGROUND/AIM: Increased oxidative stress plays a crucial role in pathogenesis of various diseases. The present study aims to investigate glutathione reductase (GR) and malondialdehyde (MDA) enzymes as markers of oxidative stress mechanisms in lumbar disc degeneration disease (LDDD). PATIENTS AND METHODS: The study group consisted of 39 patients diagnosed with LDD and 37 healthy individuals in the control group. The enzyme-linked immunosorbent assay (ELISA) method was used to determine serum GR and MDA levels in the two study groups. RESULTS: Serum GR levels were significantly lower (p=0.008), while MDA levels were significantly higher in the patient group compared to the controls (p=0.025). CONCLUSION: Oxidative stress mechanisms play a crucial role in disc degeneration and GR deficiency could be an eligible risk factor for LDDD.

Association of rs2228570 Polymorphism of Vitamin D Receptor Gene with Lumbar Degenerative Disc Disease.

AIM: To investigate the association between the vitamin D receptor (VDR) gene rs2228570 FokI polymorphism and the development of lumbar degenerative disc disease (LDDD) in the Turkish population. MATERIAL AND METHODS: This was a prospective case-control study that included 45 patients with LDDD and 49 healthy individuals (control group). The clinical investigations of the LDDD patients consisted of neurological examinations, lumbar magnetic resonance imaging studies, visual analog scale (VAS) scores, and Oswestry Disability Index scores. The VDR gene rs2228570 FokI polymorphism was analyzed via a real-time polymerase chain reaction. RESULTS: Individuals with the VDR GG genotype had a significantly increased risk of LDDD, while those with the AG genotype had a significantly decreased risk. In addition, the A allele may have a protective effect against LDDD in the Turkish population. Moreover, the VAS pain results showed that the GG genotype had a significantly higher score than the others. CONCLUSION: VDR rs2228570 AG genotype is at a decreased risk and the GG genotype is at an increased risk of LDDD in the Turkish population. Since genetic polymorphisms often show ethnic differences, further functional studies are needed to evaluate the genotype and phenotype correlations in large cohorts of various ethnicities.

The Relationship Between Sepsis-induced Immunosuppression and Serum Toll-like Receptor 9 Level.

BACKGROUND/AIM: Our aim was to determine serum TLR-9 levels in sepsis and evaluate the relationship between sepsis and serum TLR-9 levels. MATERIALS AND METHODS: The study group consisted of 80 consecutive patients with sepsis and 100 healthy individuals. The demographic characteristics, co-morbidities and hemodynamic data of all patients were recorded. RESULTS: TLR-9 serum levels in sepsis were statistically significantly lower compared to the control group. It was also seen that when the lactate level was >5 mmol/l in patients in the sepsis group, the serum TLR-9 levels were substantially higher. CONCLUSION: There is a relationship between sepsis-induced immunosuppression and serum TLR-9 levels. The host immunity system can be activated by means of TLR-9-related systems, while hyperlactatemia may play a stimulating role in the re-activation of the immune system.

Circulating microRNAs as Novel Biomarkers for Atherosclerosis.

BACKGROUND/AIM: In this study, we determined the expression of selected circulating microRNAs (miRNA) and their potential roles as biomarkers in patients with atherosclerosis and a control group. MATERIALS AND METHODS: In order to obtain insight into miRNA expression levels in atherosclerosis, we analyzed miRNA expression levels by real-time polymerase chain reaction (RT-PCR) in case (n=89) and healthy control (n=93) groups. Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of miRNAs. RESULTS: miRNA221 and miRNA221 expression levels were significantly lower in patients than controls (p=0.011 and p=0.004, respectively). Receiver operator curve analysis demonstrated that expression levels of miRNA221 [area under curve (AUC)=0.623, p=0.0086) and miRNA222 (AUC=0.654, p=0.0006) were significantly different between groups. There were positive correlations between miRNA122a and triglyceride (p=0.046) and very-low-density lipoprotein (p=0.029) levels. CONCLUSION: miRNA221 and miRNA222 could be convenient biomarkers for diagnosis of atherosclerosis.

Objective measures of sleep in fibromyalgia syndrome: Relationship to clinical, psychiatric, and immunological variables.

We aimed to investigate the changes in the objective and subjective sleep variables during painful episodes of fibromyalgia and post-episode period, and to evaluate the impact of the sleep variables on the current clinical, psychological, and immunologic parameters. Thirty-one consecutive patients who were referred to the Erenköy Physical Therapy and Rehabilitation Polyclinic with a diagnosis of fibromyalgia were evaluated before and in the sixth week of the acute pain treatment. The sleep variables were measured by polysomnography, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale. The clinical and psychiatric assessment of patients was performed by using Fibromyalgia Impact Questionnaire; Patient Health Questionnaire-Somatic, Anxiety, and Depressive Symptoms; and Visual Analog Scale. Serum pro-inflammatory molecules were measured to evaluate the immunological status. The pain treatment significantly affected subjective sleep variables, psychiatric variables, clinical variables, and IL-6 levels. The subjective sleep parameters, clinical and psychiatric variables, and IL-6 levels were improved with pain treatment in fibromyalgia. The objective sleep variables, IL-1 and TNF-alpha levels were not significantly improved with the pain treatment, and they were not related to clinical presentation of patients with fibromyalgia. Subjective variability of sleep contributes to the clinical presentation, suggesting that the objective structure is trait-specific with IL-1 and TNF-alpha.

Tumor Necrosis Factor-Alpha (TNF-α-308 G>A) Polymorphism in High-grade Gliomas.

BACKGROUND/AIM: High-grade gliomas (HGG) consist of anaplastic oligoastrocytomas, anaplastic oligodendrogliomas, anaplastic astrocytomas and glioblastoma multiforme. The present study aimed to evaluate TNF-α -308 G>A polymorphism in a Turkish population. PATIENTS AND METHODS: This was a prospective case-control study that included 45 patients with HGG and 49 healthy individuals. All patients were operated for intracranial tumors and the pathology results consist of high grade (Grade3 and 4) glial tumors. RESULTS: No significant differences were found between the HGG and control groups in terms of the median age (p=0.898). There were no significant differences with regard to gender (p=0.577). The TNF genotype frequency comparison between patients and controls was not statistically significant (p=0.598). CONCLUSION: TNF genotype frequency comparison between the patients and controls was not statistically significant in the Turkish population tested. However, further studies are needed to evaluate the genotype and phenotype correlations in large cohorts of various ethnicities.

SCARB1 Gene Polymorphisms and HDL Subfractions in Coronary Artery Disease.

BACKGROUND/AIM: Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Polymorphisms in the SCARB1 gene are known to be related to plasma lipids. PATIENTS AND METHODS: Real time-polymerase chain reaction (RT-PCR) was used for identification of SCARB1 polymorphisms and the Lipoprint Quantimetrix System was employed in identification of HDL subfractions. RESULTS: According to allelic distribution, in both groups SCARB1 AA genotype led to a two-fold decrease in the risk of developing cardiovascular disease (p=0.04), while the GA genotype increased the risk two-fold (p=0.03). According to the HDL subfraction analysis results, the AA genotype had higher levels of big-sized HDL subfraction (p=0.02). CONCLUSION: The SCARB1AA genotype decreased cardiovascular risk and carrying GA genotype and G allele increased the risk of CAD. AA genotype carriers had higher levels of big-sized HDL subfraction.

Role of Caspase-9 Gene Ex5+32 G>A (rs1052576) Variant in Susceptibility to Primary Brain Tumors.

BACKGROUND/AIM: This study is the first to evaluate the relationship of caspase-9 (CASP-9) gene polymorphism with the risk for primary brain tumor development. MATERIALS AND METHODS: The study group included 43 glioma and 27 meningioma patients and 76 healthy individuals. CASP-9 gene Ex5+32 G>A (rs1052576) polymorphism was analyzed by real-time polymerase chain reaction (RT-PCR). RESULTS: Individuals with the CASP-9 GG genotype had significantly decreased risk of developing a glioma brain tumor (p=0.024). Additionally, the GA genotype was significantly lower in patients with glioma than the control group (p=0.019). A significantly decreased risk of developing glioma was found in the A allele carrier group (p=0.024). However, there was no statistically significant relationship between CASP-9 polymorphism and brain meningioma (p=0.493). CONCLUSION: CASP-9 (rs1052576) mutant A allele seems to be a protective factor for glioma brain tumor. Future studies with a larger sample size will clarify the possible roles of CASP-9 gene in the etiology and progression of primary brain tumors.

Effects of Caspase 9 Gene Polymorphism in Patients with Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most common solid tumors and the second leading cause of the death due to malignancy in men. Caspase 9 (CASP9) is a member of the intrinsic pathway and plays a central role in the apoptosis. PATIENTS AND METHODS: Genotyping of the CASP9 (rs1052576) polymorphism were performed using real-time polymerase chain reaction for blood samples of prostate cancer patients (n=69) and controls (n=76). RESULTS: There were no significant differences between the groups in the frequency of CASP9 genotypes (χ2=1.363; p=0.506). Patients with CASP9 (rs1052576) CT genotype were 12.8 fold higher in pathological stage of pT2a compared to any other stages of cancer (OR=0.078, 95% CI= 0.009-0.062; p=0.004). Also TT genotype carriers were 11.3 times lower in pathological stage of pT2a (OR=11.33, 95% CI=2.39-53.748; p=0.000). C allele carriers were 11.36 fold higher in pathological stage of pT2a compared to any other stages of cancer (OR=0.088, 95% CI=0.019-0.418; p=0.002). CONCLUSION: CASP9 (rs1052576) C allele was decreasing the risk for pathological stage of patients with prostate cancer and also CT genotype had positive impact on pathological stage of patients with prostate cancer. CASP9 (rs1052576) TT genotype was seemed to be associated with higher risk of pathological stage. Those results implicated that CASP9 variations could be associated with severity of prostate cancer.

Analysis of Toll-like Receptor 9 Gene Polymorphisms in Sepsis.

AIM: To analyze the effect of TLR-9 (-1486 T>C) and TLR-9 (C>T) gene polymorphisms both at TLR-9 levels and together with their sepsis parameters. In this regard, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used in order to detect TLR-9 gene polymorphisms, whereas the ELISA technique was used to analyze TLR-9 serum levels in 80 sepsis patients and 100 healthy individuals. MATERIALS AND METHODS: The study group consisted of 80 patients with a diagnosis of sepsis and 100 healthy individuals. TLR-9 C>T polymorphism was identified by PCR-RFLP. RESULTS: There was no substantial difference observed between sepsis and control groups in terms of TLR-9 (-1486 T>C) and TLR-9 (C>T) genotype and allele distribution. When serum TLR-9 levels were compared to TLR-9 (-1486 T>C) and TLR-9 (C>T) genotype and allele distribution, there was a statistically substantial decrease in TLR-9 serum levels of both TLR-9 (-1486 T>C) TT and TLR-9 (C>T) TT individuals in the sepsis group (p=0.011 and p=0.036, respectively). CONCLUSION: There is no relation between sepsis and both TLR-9 (C>T) and TLR-9(-1486 T>C) polymorphisms; however, there is a relation between sepsis and decreased serum TLR-9 levels of both TLR-9 (-1486 T>C) TT and TLR-9 (C>T) TT polymorphisms due to sepsis-associated immunosuppression.

RRM1, RRM2 and ERCC2 Gene Polymorphisms in Coronary Artery Disease.

BACKGROUND/AIM: Coronary artery disease (CAD) is a chronic inflammatory disease seen as formation of atherosclerotic plaques (atheroma) in coronary arteries. Recent published papers show that DNA damage and repair mechanisms play a crucial role on the development and severity of atheromas. In this study, we investigated nucleotide excision repair (NER) pathway-related gene polymorphisms in atherosclerosis. XPD, encoded by ERCC2 gene, is an ATP-depended helicase enzyme involved in the NER pathway. Ribonucleotide reductase (RR) is a tetra meric enzyme, synthesizing deoxyribonucleotides from ribonucleotides for DNA synthesis. RR is encoded by the RRM1 and RRM2 genes, which are two subunits of RR enzyme. MATERIALS AND METHODS: DNA samples isolated from peripheral blood were genotyped with real-time polymerase chain reaction (RT-PCR) for RRM1 (rs12806698), RRM2(rs6859180) and ERCC2 (rs13181) genes. RESULTS: The frequency of the RRM1 AC heterozygote genotype was found to be significantly lower (odds ratio (OR)=0.369, 95% confidence interval (CI)=0.179-0.760; p=0.006), whereas the CC homozygote genotype was found to be significantly higher in patients compared to controls (OR=7.636, 95% CI=2.747-21.229; p=0.000). In addition, the RRM1 A allele was higher in control group (p=0.000, OR=0.131 95%CI=0.047-0.364). For the ERCC2 gene, GG genotype was significantly higher in control group (p=0.017, OR=0.387, 95%CI=0.175-0.152) and TT genotype (p=0.021) was higher in CAD group. TT genotype had a ~3-fold increased risk (OR=3.615, 95%CI=1.148-11.380) for CAD. Carrying T allele appears to be a risk factor for CAD (p=0.017, OR=2.586, 95%CI=1.173-5.699), while the G allele might be a risk-reducing factor (p=0.021, OR=0.277, 95%CI=0.088-0.871) for CAD. CONCLUSION: RRM1 and ERCC gene polymorphisms, having homozygous mutant genotype, might be a risk factor for CAD. RRM1 and ERCC wild type alleles are risk-reducing factor for CAD. Also, carrying RRM1 A allele might have a protective effect for smokers.

Ticagrelor Attenuates Apoptosis of Lung and Myocardial Cells Induced by Abdominal Aorta Ischemia/Reperfusion.

AIM: This study aimed to analyze the effect of ticagrelor pretreatment on the prevention of lung and heart injury induced by abdominal aorta ischemia and reperfusion (I/R) and also to determine the effective dose. MATERIALS AND METHODS: Thirty-five male Sprague-Dawley rats weighing 350-400 g were randomized into five groups. The animals received ticagrelor at doses of 7.5 mg/kg, 15 mg/kg and 25 mg/kg or normal saline 0.1 ml/kg orally via gastric gavage before the ischemic period. In the control and study groups, I/R injury was induced by clamping the aorta infrarenally for 2 hs, followed by 4 h of reperfusion. After sacrifice, hearts and lungs of the animals were extracted for both histopathological and biochemical analysis. RESULTS: There was a significant difference between the animals that received 7.5 mg/kg and 25 mg/kg and 15 mg/kg and 25 mg/kg dose of ticagrelor regarding tissue malondealdehyde (MDA), and glutathione reductase levels in both lung and heart Ticagrelor treatment at 25 mg/kg led to significant cardiac remodeling activity and normal lung architecture against I/R induced injury. The number of TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells in alveolar epithelium and myocytes were increased in the sections from saline (I/R) group rats, and decreased following 25 mg/kg ticagrelor treatment. CONCLUSION: Ticagrelor dose-dependently inhibits platelet aggregation, increases cyclooxygenase-2 and also inhibits cellular uptake of adenosine all resulting in attenuation of I/R injury. Ticagrelor at 25 mg/kg was determined as the dose effective against I/R-induced injury in lung and heart in Sprague-Dawley rats in the present study.