Raziye Akcılar

Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats

AIMS Acute myocardial infarction is a serious acute cardiac disorder and heart disease is still a major public health problem in adults. We investigated the effects of embelin (EMB) and carnosic acid (CA) in animals with isoproterenol (ISO)-induced myocardial injury. MAIN METHODS Adult male Wistar-Albino rats were divided into four groups: control, ISO, ISO with EMB, and ISO with CA. Before myocardial injury was induced, drugs were administered by oral gavage. Myocardial injury was induced by subcutaneous injection of ISO hydrochloride for 2 consecutive days. Serum cardiac troponin I (cTnI), ischemia modified albumin (IMA), heart fatty acid binding protein (HFABP) levels and paraoxonase-1 (PON-1) activity, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), tumor necrosis factor-α (TNF-α) levels, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of nuclear factor-kappa B (NF-κB), P38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2) were analyzed. In addition, cardiac tissues were evaluated histopathologically and immunohistochemically. KEY FINDINGS All tested compounds reduced myocardial damage, apoptosis, cTnI, IMA, HFABP, TOS, and TNF-α levels, NF-κB, p38 MAPK, and phosphorylated c-Jun N-terminal protein kinase (pJNK 1/2) expressions. All tested compounds increased SOD activity, GSH-Px activity, TAS levels, TT levels, phosphorylated extracellular signal-regulated kinase (pERK 1/2), and Nrf2 expressions. SIGNIFICANCE Our results suggest that EMB and CA pretreatment could reduce myocardial injury via antiinflammatory, antioxidant, and antiapoptotic effects.

Antiadhesive and anti-inflammatory effects of pirfenidone in postoperative intra-abdominal adhesion in an experimental rat model

BACKGROUND Pirfenidone (PF) is a potent antifibrotic and anti-inflammatory agent. We investigated the protective effect of PF against postoperative intra-abdominal adhesions. MATERIAL AND METHODS Thirty male Sprague-Dawley rats were divided into three groups (n = 10 in each group). In group 1 (control), adhesion induction was performed by cecal abrasion, and no treatment was administered. In group 2 (vehicle), for 2 wk after adhesion induction, 0.4%-carboxymethylcellulose was administered by gavage. In group 3 (PF treatment), for 2 wk after adhesion induction, 500-mg/kg/d PF was administered by gavage. On the 15th postoperative day, the animals were killed, and cecal and peritoneal tissues were excised. The adhesions were graded macroscopically. The protein concentrations and mRNA expression levels of the following genes were measured in the tissues: matrix metallopeptidase-9 (MMP-9); tissue inhibitor of metalloproteinase-1 (TIMP-1); tumor necrosis factor-alpha (TNF-α); and transforming growth factor-beta 1 (TGF-β1). The tissue samples were also evaluated histopathologically. RESULTS Macroscopic and histopathologic evaluation showed that PF-reduced adhesion and inflammation (P < 0.001, P = 0.004, respectively). Pretreatment with PF-reduced TIMP-1, TNF-α, and TGF-β1 protein concentrations (P < 0.001, P < 0.001, and P < 0.001, respectively) and mRNA expression levels (P = 0.030, P = 0.005, and P = 0.016, respectively) and increased MMP-9 protein concentrations (P < 0.001) and mRNA expression (P = 0.021). CONCLUSIONS The findings of this study suggest that PF can be used as a protective agent to prevent the development of peritoneal adhesions and inflammation during the postoperative period.

The effects of apelin treatment on a rat model of type 2 diabetes

PURPOSE Apelin is an adipokine that plays a role in the regulation of many biological functions in mammals including the neuroendocrine, cardiovascular, immune systems, glucose homeostasis and obesity. It can act via autocrine, paracrine, endocrine, and exocrine signaling. We aimed to identify the role of apelin pathophysiology of diabetes. MATERIAL/METHODS 37 male Wistar Albino rats aged 8-10 weeks were divided in four experimental groups as: control group (C) control+apelin group (C+A), diabetic group (D) diabetic+apelin group (D+A). Apelin and apelin receptor mRNA gene expressions in heart and aorta tissue were determined by real-time polymerase chain reaction. The plasma levels of insulin and plasma apelin were determined by ELISA. RESULTS Plasma levels of insulin, glucose, blood pressure levels were significantly lower in D+A group. There was no statistically significant difference for level of apelin between diabetic groups. On the other hand, differences for apelin and APJ mRNA expression in heart and vascular tissue were found significant between groups. CONCLUSIONS Apelin can be used as a therapeutic agent in the treatment of type II diabetes in the future.

Insulin-like growth factor I (Igf-1) gene polymorphism in patients with non-metastatic breast cancer

We aimed to assess the association between IGF-I gene (CA repeats) polymorphism in breast cancer patients and their clinicopathological features, as well as disease recurrence and survival. Seventy-six non-metastatic breast cancer patients were enrolled in the present study. The IGF-I (CA) repeats were studied with polymerase chain reaction by using proper primers belonging to these gene areas from DNA samples. Results show that the non 19- non 19 homozygote were more common in patients without lymph node involvement (p=0.04), with low histological grade (p=0.04), with positive hormone receptor status (p=0.01), and in patients without recurrence (p=0.06). These results suggest that the non 19-non 19 carriers have some favorable prognostic factors, and IGF-I gene polymorphism (CA repeats) may affect disease recurrence and overall survival.

Micro RNA-320 as a novel potential biomarker in renal ischemia reperfusion

Abstract Aim: MicroRNAs (miR) are important diagnostic and treatment targets due to their different tissue expressions and their central position in the regulation of gene expressions. miR studies might pioneer emerging of new diagnostic tools and treatment goals in kidney diseases. Captopril (CAP) and telmisartan (TEL) were shown to be effective in ischemia reperfusion (IR) injury. There is not any study about the effect of TEL and CAP over miR-21-320-146a. Our aim was to study the effects of CAP and TEL over miR on renal IR model. Methods: We used 12–16 weeks-old Wistar-Albino rats that weigh 300–350 g. Rats (n, 6) were randomized into four groups (Control, IR, IR + CAP, IR + TEL). Urea, creatinine, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), super oxide dismutase (SOD), and miRs were analyzed. Results: Urea, creatinine, TOS, OSI levels of IR + CAP, and IR + TEL groups were lower comparing to IR group. TAS and SOD levels were higher in IR group than IR + TEL group. miR-21-320-146a showed increase in renal IR injury. miR-320, 146a showed significant decrease in IR + CAP and IR + TEL groups comparing to IR group. We showed histopathological recovery and decreased apoptosis in IR + CAP and IR + T groups than IR group. Conclusion: We, for the first time in the literature, showed that miR-320 is increased in IR injury. miR-320 might be a novel diagnosis and treatment target in renal ischemic reperfusion injury. Also, for the first time, we showed that CAP and TEL cause functional and histopathological recovery and lower miR-146a and miR-320.

Effects of captopril, telmisartan and bardoxolone methyl (CDDO-Me) in ischemia-reperfusion-induced acute kidney injury in rats: an experimental comparative study.

Renal ischemia‐reperfusion (IR) injury is one of the most common causes of acute kidney injury. This study investigated the effects of captopril (CAP), telmisartan (TEL) and bardoxolone methyl (BM) in animals with renal IR injury. Adult male Wistar–Albino rats were divided into six groups: control, vehicle, IR, IR with CAP, IR with TEL and IR with BM. Before IR was induced, drugs were administered by oral gavage. After a 60‐min ischemia and a 120‐min reperfusion period, bilateral nephrectomies were performed. Serum urea, creatinine, neutrophil gelatinase‐associated lipocalin (NGAL) levels, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), asymmetric dimethylarginine (ADMA) levels, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH‐Px) activity were measured. Tissue mRNA expression levels of peroxisome proliferator‐activated receptor‐ɣ (PPAR‐ɣ), nuclear factor erythroid 2‐related factor 2 (Nrf2) and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) were analyzed. In addition, renal tissues were evaluated histopathologically and immunohistochemically. All tested drugs reduced renal damage, apoptosis, urea, creatinine, NGAL, TOS, nitric oxide (NO) and ADMA levels, NF‐κB, inducible nitric oxide synthase (iNOS) and endothelin‐1 (ET‐1) expressions (P < 0.001). All tested drugs increased SOD activity, GSH‐Px activity, TAS levels, TT levels, endothelial nitric oxide synthase (eNOS) expression, dimethylarginine dimethylaminohydrolases (DDAHs) expression, Nrf2 expression and PPAR‐ɣ expression (P < 0.001, P < 0.003). These results suggest that CAP, TEL and BM pretreatment could reduce renal IR injury via anti‐inflammatory, antioxidant and anti‐apoptotic effects.

Chitotriosidase as a novel biomarker of early atherosclerosis in hemodialysis patients

Introduction: Increasing evidence suggests that inflammation and increased macrophage activity have a central role in pathogenesis of atherosclerosis. It is shown that chitotriosidase (CHIT‐1) is a marker of macrophage activity in atherosclerotic plaque, and is found associated with severity of atherosclerotic lesion. There is no data about CHIT‐1 activity of hemodialysis patients in the literature. Thus, we hypothesized that in hemodialysis patients, CHIT‐1 levels might be a novel biomarker in early atherosclerosis. Methods: Forty‐five hemodialysis patients were included in the study (age: 61.93 ± 13.34). Intima media thickness (IMT) was evaluated with high‐resolution B‐mode ultrasonography. Biomarker levels were measured in serum of patients. Findings: We found positive correlation among IMT, age (R: 0.426, P: 0.004) and, CHIT‐1 value (R: 0.462, P: 0.001) in spearman correlation analysis. When age, CRP, creatinine, P, Alb, CHIT‐1 were chosen as measures that can effect IMT in multiple regression model, IMT level was related with CHIT‐1 (Beta: 0,396, P: 0.012) and age (Beta: 0,313 P: 0,048) independently. Discussion: In conclusion, this is the first report showing that serum CHIT‐1 level was related independently with carotid IMT in hemodialysis patients. This biomarker might have an unknown role in the development of atherosclerosis during uremia.

Medico-legal Approach to Poisoning Cases in the First Decade of Life

Objective: Organ transplantation is one of the clinical scenarios involving ischemia and reperfusion process. Ischemia/reperfusion is the pivotal mechanism of organ injury during transplantation. Thus, ischemia/reperfusion (I/R) injury is a biphasic phenomenon that can damage the graft by inflammatory responses. The hypothalamic-pituitary-adrenal (HPA) axis is the main hormonal system that is activated under the influence of stress. Normal HPA axis activity leading to the release of glucocorticoids is essential for homeostasis and survival during stress. Cortisol, a key controller of stress response, is released by the HPA axis. The disrupted release of cortisol in response to inflammation has been shown in animal models. Nesfatin-1 is a peptide involved in the regulation of homeostasis and has anti-inflammatory as well as anti-ischemic properties. Therefore, we aimed to identify the effect of chronic peripheral nesfatin-1 application on the plasma level of cortisol in a rat model of intestinal I/R-based stress. Materials and Methods: Two-month-old 28 Wistar Albino male rats that weighed an average of 200–250 g were used and were randomly divided into the following four experimental groups (n=7): laparotomy, I/R, nesfatin-1+laparotomy, nesfatin-1+I/R. Blood samples were collected in tubes with EDTA. Plasma cortisol levels were analyzed by rat enzyme-linked immunosorbent assay (ELISA) kits. Results: Statistically significant decrease was found in the plasma level of cortisol in nesfatin-1+I/R group compared with I/R group (p=0.026) Conclusion: Nesfatin-1 application can inhibit anti-inflammatory responses under the early phase of intestinal I/R and support immune reactions by reducing plasma cortisol level. This effect of nesfatin-1 may also increase the rejection of grafts during transplantation period.

Apelinin Kardiyovasküler Fonksiyonlar Üzerine Etkileri

Apelin reseptorunun endojen bir ligandi olan apelin, adipoz doku, mide, kalp, akcigerler, testis, ovaryum, meme bezleri, beyin, karaciger, iskelet kasi ve bobrek dahil cesitli dokularda eksprese edilmektedir. Apelin, N terminal bolgede signal bir peptid olan 77 aminoasitten olusan bir pre-proprotein olarak sekrete edilir. Endoplazmik retikulumda translokasyon ve sinyal peptidin parcalanmasindan sonra 55 aminoasitten olusan proproteine donusur. Apelin 36, apelin 17 ve apelin 13 gibi bircok aktif fragmanlari bilinmektedir. Etki ve fonksiyonlari hala tam olarak anlasilmamasina ragmen apelin sinyali hipertansiyon, kalp yetersizligi, kardiyovaskuler hastaliklar, tip 2 diyabet, obesite gibi hastaliklarin fizyopatolojisinde onemli bir role sahip olabilir. Apelinin gelecekte koruyucu ve tedavi edici bir ajan olarak kullanilabilecek olmasi hem insan sagligi icin hem de ekonomik anlamda onemli katkilar saglayacaktir. Anahtar Kelimeler: Apelin, apelin reseptor (APJ), kardiyovaskuler hastaliklar