Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy

<p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-1 (IGF-1), transforming growth factor β (TGFβ) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy.</p> <p>Methods</p> <p>Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFβ and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs.</p> <p>Results</p> <p>Ischemic cardiomyopathy was characterized by moderate left ventricular systolic dysfunction and eccentric hypertrophy, with increased expressions of IGF-1, IGF-1R and cyclins B, D1, D3 and E. Tachycardiomyopathy was characterized by severe left ventricular systolic dysfunction and dilation with no identifiable hypertrophic response. In the latter model, only IGF-1 was overexpressed while IGF-1R, cyclins B, D1, D3 and E stayed unchanged as compared to controls. The expressions of TGFβ, cyclins A and D2 were comparable in the 3 groups. The expression of IGF-1R was correlated with the thickness of the interventricular septum, in systole and diastole, and to cyclins B, D1, D3 and E expression.</p> <p>Conclusion</p> <p>These results agree with the notion that IGF-1/IGF-1R and cyclins are involved in the hypertrophic response observed in cardiomyopathies.</p

Cardioprotective effects of Fenugreek (Trigonella foenum-graceum) seed extract in streptozotocin induced diabetic rats

Introduction: Inadequate control of diabetes mellitus (DM) leads to considerable cardiovascular implications like diabetic cardiomyopathy (DCM). Cardiomyocyte apoptosis is one of the main mechanisms of DCM pathogenesis associated with hyperglycemia, oxidative stress, inflammation, hyperlipidemia and several other factors. Trigonella foenum-graecum (Fenugreek) has been long used as a traditional medicine and has many therapeutic effects, including anti-diabetic, anti-hyperlipidemia, anti-inflammatory and anti-oxidant properties. The current study aimed to investigate cardioprotective effects of fenugreek seed on diabetic rats. Methods: Diabetes was induced in forty-two male rats by injection of streptozotocin (STZ) (60 mg/ kg). Diabetic animals were treated with three different doses of fenugreek seed extract (50, 100 and 200 mg/kg) or metformin (300 mg/kg) for six weeks by gavage. Nondiabetic rats served as controls. Glucose, cholesterol, and triglycerides levels were measured in the blood samples, and oxidative stress markers as well as gene expression of ICAM1, Bax and Bcl2 were assessed in the cardiac tissues of the experimental groups. Results: Diabetic rats exhibited increased serum glucose, cholesterol and triglycerides levels, elevated markers of oxidative stress thiobarbituric acid–reacting substances (TBARS) levels , total thiol groups (SH), catalase (CAT) and superoxide dismutase (SOD) activity, and enhanced apoptosis cell death (ratio of Bax/Bcl2). Fenugreek seed extract considerably improved metabolism abnormalities, attenuated oxidative stress and diminished apoptosis index. Conclusion: Our study suggests that fenugreek seed may protect the cardiac structure in STZ-induced diabetic rats by attenuating oxidative stress and apoptosis

The protective effect of medicinal herbs extracts including Cynara scolymus L., Cichorium intybus L. Taraxacum officinal L. and Berberis vulgaris L. in single and in combination form in CCl4 induced rat liver toxicity

Background: Several herbal remedies are used in traditional medicine for treatment of liver disorders, but their efficacy, safety, and dosage have not been investigated so far. Objective: The present study was aimed to evaluate the liver protective effects of medicinal herbs extracts such as Cynara scolymus leave (artichok), Cichorium intybus roots (chichory), Taraxacum officinale root (dandelium), Berberis vulgaris (barberry) root and stems extract in single and in combination form against carbon tetrachloride (CCl4) induced liver toxicity. Methods: Total 70 wistar male rat, aged 5 months were divided in 7 groups of 10 rats each. One group kept as normal and out of six CCl4 intoxicated groups one served as control, one received mixture of four extract and four groups received artichok, chichory, dandelium, and barberry in the dosage of 150, 300, 300 and 250 mg/kg/day respectively. The plant extracts were injected intra peritoneal simultaneously with intoxication for three days. Three days after intoxication and extract treatments the serum liver enzymes levels such as ALT, AST and ALP as well as serum gluthathion and catalase were determined. Results: In group receiving mixture of 4 herbal extract the blood level of ALT, AST and ALP were reduced significantly as compared to control group. In all the groups receiving herbal extracts the serum glutathione and catalase levels did not differ as compared to control groups. Conclusion: In the present study administration of chichory, artichoke, dandelium and barberry in combination form prevent liver intoxication withought influence on serum antioxidant properties

The effects of vitamin D on cardiovascular damage induced by lipopolysaccharides in rats

Introduction: Inflammation and oxidative stress are contributed to cardiovascular diseases. Vitamin D (Vit D) has antioxidant and anti-inflammatory properties. In the current research, the effect of Vit D on cardiac fibrosis and inflammation, and oxidative stress indicators in cardiovascular tissues was studied in lipopolysaccharides(LPS) injected rats. Methods: Rats were distributed into 5 groups and were treated for 2 weeks. Control: received vehicle(saline supplemented with tween-80) instead of Vit D and saline instead of LPS, LPS: treated by 1 mg/kg of LPS and was given vehicle instead of Vit D, LPS-Vit D groups: received 3 doses of Vit D (100, 1000, and 10000 IU/kg) of Vit D in addition to LPS. Vit D was dissolved in saline supplemented with tween-80 (final concentration 0.1%) and LPS was dissolved in saline. The white blood cell (WBC) was counted. Oxidative stress markers were determined in serum, aorta, and heart. Cardiac tissue fibrosis was also estimated using Masson’s trichrome staining method. Results: WBC and malondialdehyde (MDA) were higher in the LPS group than the control group, whereas the thiol content, superoxide dismutase (SOD), and catalase (CAT) were lower in the LPS group than the control group (P<0.01 and P<0.001). Administration of Vit D decreased WBC (P<0.001) and MDA (P<0.05 and P<0.001) while enhanced thiol (dose 10000 IU/Kg) (P<0.001), SOD (dose 10000 IU/kg) (P<0.001), and CAT (P<0.05 and P<0.001) compared to the LPS group. All doses of Vit D also decreased cardiac fibrosis compared to the LPS group (P<0.001). Conclusion: Vit D protected the cardiovascular against the detrimental effect of LPS. This cardiovascular protection can be attributed to the antioxidant and anti-inflammatory properties of Vit D

Ventricular-arterial uncoupling in heart failure with preserved ejection fraction after myocardial infarction in dogs - invasive versus echocardiographic evaluation

Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Activin signaling as an emerging target for therapeutic interventions

After the initial discovery of activins as important regulators of reproduction, novel and diverse roles have been unraveled for them. Activins are expressed in various tissues and have a broad range of activities including the regulation of gonadal function, hormonal homeostasis, growth and differentiation of musculoskeletal tissues, regulation of growth and metastasis of cancer cells, proliferation and differentiation of embryonic stem cells, and even higher brain functions. Activins signal through a combination of type I and II transmembrane serine/threonine kinase receptors. Activin receptors are shared by multiple transforming growth factor-β (TGF-β) ligands such as myostatin, growth and differentiation factor-11 and nodal. Thus, although the activity of each ligand is distinct, they are also redundant, both physiologically and pathologically in vivo. Activin receptors activated by ligands phosphorylate the receptor-regulated Smads for TGF-β, Smad2 and 3. The Smad proteins then undergo multimerization with the co-mediator Smad4, and translocate into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. Signaling through receptors and Smads is controlled by multiple mechanisms including phosphorylation and other posttranslational modifications such as sumoylation, which affect potein localization, stability and transcriptional activity. Non-Smad signaling also plays an important role in activin signaling. Extracellularly, follistatin and related proteins bind to activins and related TGF-β ligands, and control the signaling and availability of ligands

Extract from Teucrium polium L. Protects Rat Heart against Oxidative Stress Induced by Ischemic–reperfusion Injury

Background: The deleterious effect of oxidative stress on myocardial ischemia–reperfusion (I/R) has already been shown in previous studies. Since Teucrium polium has anti-oxidative and cardio-protective properties, the aim of this study was to investigate the effects of this plant on I/R injuries in the isolated rat heart. Materials and Methods: The myocardial I/R injury of rat was created by Langendorff retrograde perfusion technology. The heart was preperfused with Krebs–Henseleit (K-H) solution containing T. polium extract for 20 min before 20 min global ischemia, and then the reperfusion with K-H bicarbonate buffer was conducted for 40 min. The left ventricular developed pressure and the maximum up/down rate of the left ventricular pressure (±dp/dtmax) were recorded by physiological recorder as the myocardial function. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the effluent were measured to determine the myocardial injury degree. Thiobarbituric acid reactive substances (TBARS), total thiol groups (−SH), superoxide anion dismutase (SOD), and catalase (CAT) in myocardial tissue were detected to determine the oxidative stress degree. Results: The results showed that the pretreatment with T. polium significantly enhanced cardiac parameters and the coronary artery flow, decreased the LDH, CK activities, and TBARS level, whereas it increased − SH groups, SOD and CAT activities. Conclusions: Our findings indicated that T. polium could provide protection for heart against the I/R injury which may be related to the improvement of myocardial oxidative stress states

Cardioprotective effects of Achillea wilhelmsii on the isolated rat heart in ischemia–reperfusion

Context: There are some reports about protective effects of Achillea on the heart. Objective: We investigated the effect of Achillea wilhelmsii extract on cardiac function during ischemia–reperfusion (I/R) injury in the isolated rat heart. Materials and methods: 60 male Wistar rats were randomly divided into 6 groups; 1: Control group, 2: Control-ischemia (CI) 3: vitamin C (10 mg/kg), 4–6: Extract groups (E 100, E 200 and E 400 mg/kg). The animals received normal saline, vitamin C or A. wilhelmsii extract orally for 4 weeks. At the end of the treatment, the hearts were subjected to in vitro I/R Injury (20 min of global ischemia, followed by 40 min of reperfusion, Langendorff's mode). Heart rate (HR) and left ventricular pressure (LVP) were measured using a pressure transducer connected to a data acquisition system. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the effluent were measured to determine the myocardial injury degree. The malondialdehyde (MDA), total thiol groups (-SH), superoxide anion dismutase (SOD) and catalase (CAT) in myocardial tissue were detected to determine the oxidative stress degree. Results: Pretreatment with Achillea wilhlemsii significantly decreased the LDH, CK activities, and MDA level, while it increased the LVDP, ±dp/dtmax, rate-pressure product (RPP), SH groups, SOD and CAT activities, and also the coronary artery flow. Discussion and conclusion: Our findings indicated that Achillea wilhelmsii could provide protection for heart against the I/R injury which may be related to the improvement of myocardial oxidative stress states