Heart Tissue Levels Research Articles

CircHIPK3 exacerbates sepsis-induced acute kidney injury and cardiopulmonary function by regulating microRNA-106a-5p/ROCK2 axis

ObjectiveThis work was implemented to define the regulatory mechanism of the circularHIPK3 (circHIPK3)/microRNA-106a-5p (miR-106a-5p)/rho-associated kinases 2 (ROCK2) axis in sepsis-induced acute kidney injury (AKI) and cardiopulmonary function. MethodsSepsis mouse models were established by cecal ligation and puncture (CLP). circHIPK3, miR-106a-5p and ROCK2 expression levels in kidney, heart and lung tissues were assessed. The cardiac function, lung wet/dry weight ratio, and Evans blue dye leakage were assessed. Serum markers of myocardial injury, serum markers of kidney injury, as well as serum inflammatory cytokines were assessed. The histopathological changes of heart, lung, and kidney tissues were observed. Moreover, correlations of miR-106a-5p, ROCK2, and circHIPK3 were verified. ResultsIn CLP mice after down-regulating circHIPK3 or up-regulating miR-106a-5p, there were increased LVEF and LVFS and decreased LVESD and LVEDD, serum cTnI and CK-MB levels, lung wet/dry weight ratio, Evans blue dye leakage, serum creatinine, BUN and NGAL levels, serum IL-6, TNF and MCP-1 levels, and reduced heart, lung and liver injury in CLP mice. circHIPK3 bound to miR-106a-5p, and miR-106a-5p downregulated ROCK2 expression. miR-106a-5p inhibition or ROCK2 overexpression reversed the delaying effects of circHIPK3 interference. ConclusioncircHIPK3 aggravates sepsis-induced AKI and cardiopulmonary function via sponging miR-106a-5p and promoting ROCK2 expression.

Olea europaea L. leaf extract mitigates oxidative and histological damage in rat heart tissue exposed to combined noise and toluene: An experimental study

In many occupational settings, workers are frequently exposed to toluene and noise. However, the individual and combined effects of these exposures on the cardiovascular system have not been fully elucidated. Therefore, this study aimed to investigate the impact of simultaneous exposure to toluene and noise on the rat heart, while also evaluating the potential preventive effect of olive leaf extract (OLE). Forty-eight male Wistar rats were randomly assigned to eight groups (n = 6/group): control group (C), control group that received OLE (C + OLE), group exposed to noise (N), group exposed to noise and receiving OLE (N + OLE), group exposed to toluene (T), group exposed to toluene and receiving OLE (T + OLE), group co-exposed to noise and toluene (NT), and group co-exposed to noise and toluene and receiving OLE (NT + OLE). The rats in this study were subjected to simultaneous exposure to toluene and noise for a duration of six weeks, within a custom-built plexiglass chamber. Toluene was administered at a concentration of 300 ppm, while the noise level was set to 85 dB(A). The exposure chamber was equipped with a generation system, an exposure system, and a monitoring system, ensuring precise and accurate exposure conditions. After the six-week period, heart and blood samples were collected from the rats for subsequent analysis. Plasma levels of cholesterol (CHOL), triglycerides (TG), lactate dehydrogenase (LDH), and creatine kinase (CK) were measured, and histopathological investigation was conducted using HE staining. Additionally, superoxide dismutase (SOD) and catalase (CAT) activities, as well as malondialdehyde (MDA) levels in heart tissue were measured. Our results showed that simultaneous exposure to noise and toluene altered CHOL, TG, LDH, and CK levels, and also caused an increase in lipid peroxidation levels and superoxide dismutase activity, along with a decrease in catalase activity in the heart. A significant alteration in the myocardium was also observed. However, treatment with OLE was found to modulate these oxidative and histological changes, ultimately correcting the deleterious effects induced by the combined exposure to noise and toluene. Therefore, our study suggests that OLE could be a potential preventive measure for individuals exposed to toluene and noise in industrial settings.

Semaglutide ameliorates obesity-induced cardiac inflammation and oxidative stress mediated via reduction of neutrophil Cxcl2, S100a8, and S100a9 expression.

Obesity, which is driven by inflammation and oxidative stress, is a risk factor for cardiovascular disease. Semaglutide, a glucagon-like peptide-1 receptor agonist, is an antidiabetic drug with major effects on weight loss. In this study, single-cell transcriptomics was used to examine non-cardiomyocytes to uncover the mechanism of obesity-induced myocardial damage and the cardioprotective impact of semaglutide. We constructed obese mouse models and measured Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Reactive Oxygen Species (ROS), and Malonic dialdehyde (MDA) levels in serum and heart tissue to determine the levels of inflammation and oxidative stress in obesity and the effect of semaglutide on these levels. Then, utilizing single-cell transcriptomes to screen for key cell populations and differentially expressed genes (DEGs), we assessed the effects of obesity and semaglutide on non-cardiac cells. Finally, a DEG localization analysis was performed to explore DEGs as well as cell types associated with inflammation and oxidative stress. Semaglutide reduced increased TNF-α, IL-6, ROS, and MDA levels in serum and cardiac tissues in obese mouse. Several genes are closely associated with inflammation and oxidative stress. Chemokine (C-X-C motif) ligand 2 (Cxcl2), S100 calcium binding protein A8 (S100a8), and S100 calcium binding protein A9 (S100a9), which were elevated in obesity but decreased following semaglutide treatment, were also expressed particularly in neutrophils. Finally, by decreasing neutrophil Cxcl2, S100a8, and S100a9 expressions, semaglutide may help to reduce cardiac inflammation and oxidative stress. Semaglutide significantly reduced body weight in obese mice as well as exerted anti-inflammatory and antioxidant effects possibly by inhibiting the expression of S100a8, S100a9, and Cxcl2 in neutrophils. These discoveries are expected to reveal new molecular mechanisms underlying obesity-related heart damage and semaglutide's cardioprotective properties.

Inhibition of OAT1/3 and CMPF uptake attenuates myocardial ischemia-induced chronic heart failure via decreasing fatty acid oxidation and the therapeutic effects of ruscogenin

Chronic heart failure (CHF) as a long-term disease is highly prevalent in elder people worldwide. Early diagnosis and treatments are crucial for preventing the development of CHF. Herein, we aimed to identify novel diagnostic biomarker, therapeutic target and drug for CHF. Untargeted metabolomic analysis has been used to characterize the different metabolomic profile between CHF patients and healthy people. Meanwhile, the targeted metabolomic study demonstrated the elevation of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) in the serum of CHF patients and coronary artery ligation-induced CHF mice. Subsequently, we firstly observed that elevation of CMPF impaired cardiac function and aggravated myocardial injury by enhancing fatty acid oxidation (FAO). Interestingly, inhibition of responsible transporters organic anion transporter 1/3 (OAT1/3) has been found to decrease the CMPF level, and suppress FAO-related key protein expressions including peroxisome proliferator-activated receptor alpha, peroxisome proliferative activated receptor-α, carnitine palmitoyl transferase 1, and malonyl CoA decarboxylase in coronary artery ligation-induced CHF mice. Meanwhile, the inhibitor of OAT1/3 presented an excellent improvement in cardiac function and histological injury. Based on the above findings, molecular docking was adopted to screen the potential therapeutic drug targeting OAT1/3, and ruscogenin (RUS) exhibited a great binding affinity with OAT1 and OAT3. Next, it was verified that RUS could remarkedly decrease the expression of OAT1/3 and CMPF levels in heart tissue of CHF mice, as well as suppress the expression of FAO-related proteins. What's more, RUS can effectively improve cardiac function, myocardial fibrosis and morphological damage. Collectively, this study provided a potential metabolic marker CMPF and novel target OAT1/3 for CHF, which were demonstrated to be involved in FAO. And RUS was identified as a potential anti-FAO drug for CHF by regulating OAT1/3.

Evaluating the inhibitory effect of resveratrol on the multiplication of several Babesia species and Theileria equi on in vitro cultures, and Babesia microti in mice.

Introduction: Histone post-translational modification is one of the most studied factors influencing epigenetic regulation of protozoan parasite gene expression, which is mediated by histone deacetylases (KDACs) and acetyltransferases (KATs). Objective and methods: The present study investigated the role of resveratrol (RVT) as an activator of histone deacetylases in the control of various pathogenic Babesia sp. and Theileria equi in vitro, as well as B. microti infected mice in vivo using fluorescence assay. Its role in mitigating the side effects associated with the widely used antibabesial drugs diminazene aceturate (DA) and azithromycin (AZM) has also been investigated. Results: The in vitro growth of B. bovis, B. bigemina, B. divergens, B. caballi and Theileria equi (T. equi) was significantly inhibited (P < 0.05) by RVT treatments. The estimated IC50 values revealed that RVT has the greatest inhibitory effects on B. bovis growth in vitro, with an IC50 value of 29.51 ± 2.46µM. Reverse transcription PCR assay showed that such inhibitory activity might be attributed to resveratrol's stimulatory effect on B. bovis KDAC3 (BbKADC3) as well as its inhibitory effect on BbKATS. RVT causes a significant decrease (P < 0.05) in cardiac troponin T (cTnT) levels in heart tissue of B. microti- infected mice, thereby indicating that RVT may play a part in reducing the cardiotoxic effects of AZM. Resveratrol showed an additive effect with imidocarb dipropionate in vivo. Treatment of B. microti-infected mice with a combined 5mg/kg RVT and 8.5mg/kg ID resulted in an 81.55% inhibition at day 10 postinoculation (peak of parasitemia). Conclusion: Our data show that RVT is a promising antibabesial pharmacological candidate with therapeutic activities that could overcome the side effects of the currently used anti-Babesia medications.

The serum soluble scavenger with 5 domains levels: A novel biomarker for individuals with heart failure.

Background: We aimed to explore the relationship between the serum Soluble Scavenger with 5 Domains (SSC5D) levels and heart failure (HF). Methods and Results: We retrospectively enrolled 276 patients diagnosed with HF or normal during hospitalization in Shanghai General Hospital between September 2020 and December 2021. Previously published RNA sequencing data were re-analyzed to confirm the expression profile of SSC5D in failing and non-failing human and mouse heart tissues. Quantitative real-time polymerase chain reaction assay was used to quantify Ssc5d mRNA levels in murine heart tissue after myocardial infarction and transverse aortic constriction surgery. To understand the HF-induced secreted proteins profile, 1,755 secreted proteins were investigated using human dilated cardiomyopathy RNA-seq data, and the results indicated that SSC5D levels were significantly elevated in failing hearts compared to the non-failing. Using single-cell RNA sequencing data, we demonstrated that Ssc5d is predominantly expressed in cardiac fibroblasts. In a murine model of myocardial infarction or transverse aortic constriction, Ssc5d mRNA levels were markedly increased compared with those in the sham group. Similarly, serum SSC5D levels were considerably elevated in the HF group compared with the control group [15,789.35 (10,745.32-23,110.65) pg/mL, 95% CI (16,263.01-19,655.43) vs. 8,938.72 (6,154.97-12,778.81) pg/mL, 95% CI (9,337.50-11,142.93); p < 0.0001]. Moreover, serum SSC5D levels were positively correlated with N-terminal pro-B-type natriuretic peptide (R = 0.4, p = 7.9e-12) and inversely correlated with left ventricular ejection fraction (R = -0.46, p = 9.8e-16). Conclusion: We concluded that SSC5D was a specific response to HF. Serum SSC5D may function as a novel biomarker and therapeutic target for patients with HF.

Fullerene C60 Attenuates Heart Tissue Inflammation by Modulating COX-2 and TNF-Alpha Signaling Pathways in DMBA Induced Breast Cancer in Rats.

The present study aimed to investigate the therapeutic effect of fullerene C60 nanoparticle against heart tissue damage caused by 7,12-dimethylbenz [a] anthracene (DMBA) in female rats. Female Wistar albino rats, 8weeks old (n = 60) weighing around (150 ± 10g) were used for the study. These rats were divided into 4 groups and each group included 15 rats. Groups: (i) Control Group: Fed with standard diet; (ii) C60 Group: C60 (1.7mg/kg bw, oral gavage); (iii) DMBA Group: DMBA (45mg/kg bw, oral gavage); (iv) C60 and DMBA Group: C60 (1.7mg/kg bw, oral gavage) and DMBA (45mg/kg bw, oral gavage) group. Malondialdehyde (MDA) analysis, catalase activity (CAT), and glutathione (GSH) in heart tissue were determined by spectrophotometer. In addition, heart tissue DNA damage was investigated. Caspase-3, p53, HO-1, COX-2, and TNF-α protein expression levels in heart tissue were determined by western blotting. As a result, Caspase-3, p53, HO-1 protein expression, GSHlevels and CAT activity increased, COX-2, TNF-α protein expression, and MDA levels were significantly decreased in the C60 + DMBAgroup compared to the DMBAgroup. Therefore, the fullerene C60 nanoparticle may be a promising and effective therapy for the treatment of heart diseases associated with inflammation.

Ethyl Acetate Fraction of Moringa oleifera Leaves Mollified Toxicological Activities Actuated by Bitis arietans (Puff adder) Venom

Bitis arietans (Puff adder) venom possess numerous biological active toxins exhibiting toxicological actions after envenoming. Moringa oleifera crude extract has been documented to extenuate toxicities induced by B. arietans venom. This study reported the efficacy of n-hexane, ethyl acetate and ethanol solvent fractions obtained from crude extract of M. oleifera against the lethal dose toxicity, biological activities and oxidative stress induced by B. arietans venom to ascertain the best fraction with active antivenom phytochemicals. Forty-five male rats were randomly selected into nine groups (n=5) for the anti-oxidative stress study. Groups 1 served as control; group 2 to 9 were envenomed by a single intraperitoneal injection of 1.5 mg/kg (LD50) of the venom. Group 2 was not treated post envenomation while groups 3 was treated with polyvalent antivenom. Group 4, 6 and 8 were treated with 300 mg/kg while group 5, 7 and 9 were treated with 600 mg/kg of n-hexane, ethyl acetate and ethanol solvent fractions of M. oleifera respectively. High dose of M. oleifera ethyl acetate solvent fraction best neutralized the lethal dose toxicity and strongly inhibited the heamorrhagic and anticoagulant activities of B. arietans venom. The venom induced oxidative stress with significant (P&lt;0.05) enhancement of Superoxide Dismutase, Catalase and Malondialdehyde levels in serum and heart tissues of untreated envenomed rats. However, ethyl acetate solvent fraction was most effective in normalizing the antioxidant enzyme activities of envenomed treated rats. Results showed that ethyl acetate fraction of M. oleifera possesses active antivenom phytochemicals against B. arietans venom induced toxicities.

Effects of Semaglutide on Cardiac Protein Expression and Cardiac Function of Obese Mice.

Using proteomics to study the effect of semaglutide on cardiac protein expression in obese mice. Assessment of the effect of semaglutide on cardiac function in obese mice. The mice were randomly divided into three groups: the control group (WC), the high-fat group (WF), and the high-fat diet with semaglutide intervention group (WS). Serum samples were collected, and lipids, blood glucose, inflammatory and oxidative stress markers, and cardiac ultrasound, were examined. The cardiac weight of each group of mice was measured, and pathological alterations were examined. Inflammation and oxidative stress levels in heart tissue were evaluated. The labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform was used to find differentially expressed proteins (DEPs) and screen for related pathways and key proteins in a proteomics study. Semaglutide greatly alleviated obesity-induced lipid metabolism abnormalities, improved cardiac ventricular wall thickening, and significantly reduced myocardial collagen content in obese mice. Semaglutide significantly reduces obesity-induced inflammation and oxidative stress. There were 64 DEPs in the WF/WC group, with 39 upregulated proteins and 25 downregulated proteins. The WS/WC group, on the other hand, had 83 DEPs, including 57 upregulated and 26 downregulated proteins. Following functional analysis, DEPs were shown to be largely associated with lipid metabolism and peroxisomes. Apolipoprotein A-II, catalase, diazepam-binding inhibitor, paraoxonase-1, and hydroxysteroid 17-dehydrogenase-4 were all upregulated in the WF group but significantly downregulated in the WS group. A high-fat diet increases the expression of lipid synthesis and transport proteins while increasing inflammation and oxidative stress damage. Semaglutide decreases lipid synthesis alleviates inflammation and oxidative stress and prevents lipid peroxidation and cardiac impairment.

Discovery of 5-(3,4-dihydroxybenzylidene)-1,3-dimethylpyrimidine- 2,4,6(1H,3H,5H)-trione as a novel and effective cardioprotective agent via dual anti-inflammatory and anti-oxidative activities

Myocardial ischemia/reperfusion (MI/R) injury is still the huge unmet medical need without effective therapy in clinic. It is critical to develop pharmacological intervention to scavenge ROS and inhibit NLRP3 activation to have a double benefit against MI/R injury. Cinnamamide derivatives have been demonstrated to possess anti-oxidative and anti-inflammatory activities. Previously, we have reported that a cinnamamide derivative 2 exerts excellent cardioprotective effect via mediation of intracellular oxidative stress via Nrf2 up-regulation against MI/R. In the present study, seventeen compounds have been optimized using cinnamamide-barbiturate hybrid 2 as the lead compound and their cardioprotective activities against MI/R were further determined in vitro and in vivo. Among them, compound 7 showed the most potent cardioprotective effect and low cytotoxicity. While cardiomyocytes were invased by hydrogen peroxide, compound 7 exhibited more excellent cardioprotective effect than that of luteolin and metoprolol, the positive control employed in the present study, as demonstrated by dramatically elevated cell survival rate and decreased LDH leakage rate. Moreover, compound 7 markedly inhibited cardiac expressions of inflammasome activation and pro-inflammatory cytokines release (i.e. NLRP3, IL-1β, IL-18), simultaneouly increasing endogenous antioxidative proteins (i.e. Nrf2, HO-1 and SOD) in vitro. In the rat MI/R model, compound 7 pretreatment profoundly reduced cardiac infarct size in MI/R rats and reversed abnormal changes in myocardial enzymes and lipid peroxidation levels in heart tissues. Mechanistically, compound 7 revealed significant cardioprotective effects by inhibiting NLRP3 and its downstream inflammatory chemokine IL-1β, as well as up-regulating Nrf2 in vivo. Furthermore, at the active site of the co-crystal of NLRP3 and Nrf2, compound 7 exhibited higher binding force in the molecular docking study, which was consistent with the in vitro results. Therefore, compound 7 is expected to be a potential cardioprotective agent possessing dual anti-inflammatory and anti-oxidative activities. Our work provides an important therapeutic strategy for the treatment of ischemic-reperfused heart disease.

Hydrogen sulfide protects against ischemic heart failure by inhibiting RIP1/RIP3/MLKL-mediated necroptosis

The aim of the present study was to explore whether hydrogen sulfide (H2S) protects against ischemic heart failure (HF) by inhibiting the necroptosis pathway. Mice were randomized into Sham, myocardial infarction (MI), MI + propargylglycine (PAG) and MI + sodium hydrosulfide (NaHS) group, respectively. The MI model was induced by ligating the left anterior descending coronary artery. PAG was intraperitoneally administered at a dose of 50 mg/kg/day for 4 weeks, and NaHS at a dose of 4 mg/kg/day for the same period. At 4 weeks after MI, the following were observed: A significant decrease in the cardiac function, as evidenced by a decline in ejection fraction (EF) and fractional shortening (FS); an increase in plasma myocardial injury markers, such as creatine kinase-MB (CK-MB) and cardiac troponin I (cTNI); an increase in myocardial collagen content in the heart tissues; and a decrease of H2S level in plasma and heart tissues. Furthermore, the expression levels of necroptosis-related markers such as receptor interacting protein kinase 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein (MLKL) were upregulated after MI. NaHS treatment increased H2S levels in plasma and heart tissues, preserving the cardiac function by increasing EF and FS, decreasing plasma CK-MB and cTNI and reducing collagen content. Additionally, NaHS treatment significantly downregulated the RIP1/RIP3/MLKL pathway. While, PAG treatment aggravated cardiac function by activated the RIP1/RIP3/MLKL pathway. Overall, the present study concluded that H2S protected against ischemic HF by inhibiting RIP1/RIP3/MLKL-mediated necroptosis which could be a potential target treatment for ischemic HF.

Modulatory Effects of Swimming Training on Hypoxia-Induced Factors in Heart Tissue of Rats Exposed to Chronic Stress

Background: Monitoring cardiac, metabolic, neurological, and aging responses to stressors is critical. This study aimed to investigate the effect of swimming training on HIF-1α and vascular endothelial growth factor (VEGF) levels in heart tissue of rats exposed to chronic stress. Methods: To this end, 30 male Wistar rats (age: 10 - 12 weeks, weight: 220 ± 20 g) were randomly divided into five equal groups of six rats as follows: (1) Con (no treatment for 10 weeks); (2) CS + ST (4 weeks of stress, 4 weeks of swimming); (3) ST (4 weeks of swimming); (4) CS (4 weeks of stress); (5) CS-time (4 weeks of stress, 6 weeks of no treatment). Anxiety-like behaviors were measured by an open field test. Heart tissue was immunohistochemically assessed for HIF-1α expression using a polyclonal antibody. Vascular endothelial growth factor protein levels were also determined using western blot analysis. To analyze the data, Kolmogorov-Smirnov, One-way ANOVA, and Tukey’s post hoc tests were used, and P ≤ 0.05 was considered statistically significant. Results: The results showed that chronic mild stress (CMS) significantly decreased the HIF-1α expression in heart tissue in CS and CS-time groups (P &lt; 0.05). Furthermore, the result revealed that swimming training significantly increased the level of HIF-1α expression in heart tissue in ST and CS + ST groups (P &lt; 0.05). Although swimming training increased HIF-1α levels in the CS + ST group after a period of four weeks of CMS, these increases were smaller than those observed in ST and control groups (P &lt; 0.05). The results from the One-way ANOVA test also demonstrated that the CMS significantly downregulated the VEGF expression in heart tissue in CS and CS-time groups, whereas swimming training significantly increased its level in ST and CS + ST groups (P &lt; 0.05). Although swimming training increased VEGF levels in the CS + ST group after a period of four weeks of CMS, these increases were smaller than those detected in ST and control groups. Conclusions: Although chronic mild stress had the potential to reduce hypoxia-induced factors in heart tissue, swimming training modified these factors.

BRD4 inhibition by JQ1 protects against LPS-induced cardiac dysfunction by inhibiting activation of NLRP3 inflammasomes

JQ1, a BRD4 inhibitor, first identified its therapeutic role in cancer, has gradually demonstrated a protective effect on the heart in recent years; however, it is unclear whether JQ1 also plays a role in LPS-induced cardiac dysfunction. A total of forty eight mice were randomly divided into control, LPS(7.5mg/kg), and LPS + JQ1 (50mg/kg). JQ1 was preprotected for 1h, and LPS was stimulated for 12h, mouse survival and cardiac function were observed, and histopathological, serum myocardial injury markers, and inflammatory indicators, and oxidative stress levels in heart tissue were examined. The experiment found that the cardiac BRD4 levels were upregulated and the heart severe damage in the LPS group compared with the control group. While compared with the LPS group, JQ1 preprotected increased survival rate and cardiac function, reducated cardiomypathological injury and CD45 infiltration, and reduced the release of LDH, CK-MB, IL-1, IL-18, reduced MDA generation, and increased SOD viability. In addition, JQ1 preprotected also upregulated SIRT1, and inhibited the expression of NLRP3, caspase-1p20, and GSDMD. Meanwhile, similar results were obtained in LPS-treated H9C2 cells, and further intervention with the SIRT1 inhibitor EX527 partially blocked the JQ1-mediated down regulation of NLRP3, caspase-1p20, and GSDMD. We propose that JQ1 may improve LPS-induced cardiac dysfunction by inhibiting SIRT1-dependent activation of NLRP3 inflammasomes, which may be a promising strategy for treating sepsis cardiomyopathy.

Oxidative stress in dogs during mid-gestation abortion: Fetal and maternal antioxidant alterations with clinical and hematological features

The present study aimed to evaluate the GSH and MDA levels in dog’s serum and vital organs of aborted fetuses, after application of two abortifacient. Animals of group I (n = 6) were treated twice with subcutaneous injection of 10 mg/kg aglepristone and group II (n = 3) received prostaglandin F2α at a dose of 125 μg/kg every 12 hours until abortion process completed. Hematologic examinations and sedimentation rates were performed of bitches. The duration between first occurrence of vaginal discharge to first expulsion of fetuses ranged between 14-29 hours (mean: 22.6±5.5 h) and 24-33 hours in group I and II, respectively. Both treatments significantly increased the serum MDA levels (P&lt;0.01); however aglepristone increased the MDA levels throughout the study, prostaglandin enhanced plasma MDA levels only on day 1. GSH levels were significantly lower in aglepristone-treated bitches than prostaglandin-treated animals (P&lt;0.05). The treatments resulted similar MDA levels in liver and heart tissues (P&gt;0.05). GSH levels in kidney, muscle and heart tissues did not differ between groups (P&gt;0.05), aglepristone resulted reduced GSH levels in liver tissue (P&lt;0.05). High MDA levels could be evaluated as a useful marker for fetal suffering in pregnancy controls. The MDA and GSH levels, measured in vital organs of fetuses, could suggest possible toxic effects of abortifacients in newborns, as both medical agents are being used in parturition induction.

Geraniol enhances peroxiredoxin‐1, and prevents isoproterenol‐induced oxidative stress and inflammation associated with myocardial infarction in experimental animal models

This study has explored the fact that geraniol prevents isoproterenol(ISO)-induced oxidative stress and inflammation-mediated myocardial infarction (MI) through enhanced expression of peroxiredoxin-1 (Prdx-1) in experimental animal models. The experimental strategies of MI were stimulated through the subcutaneous direction of ISO (85 mg/kg body weight) for 14 days. ISO-directed models showed elevated heart rate levelsand cardiac markers (serum creatine kinase [CK], serum CK-myocardial band, serum C-reactive proteins, and plasma homocysteine); increased cardiac-troponins-T, and troponin-I levels in both serum and myocardium. Moreover, we perceived that a higher level of lipid peroxidation molecules (thiobarbituric acid reactive substances and lipid hydroperoxides) reduced the antioxidant enzyme levels in plasma and heart tissue of ISO-directed rats. However, geraniol treatment prevents ISO-directed enhancement of the heart rate, cardiac and lipid peroxidative genes; reverted the blood pressure, and antioxidant status in ISO-directedrats. Furthermore, gene expression results revealed that geraniol treatment inhibited the mitogen-activatedproteinkinase (MAPK) proteins, inflammatory responder (tumor necrosis factor-α,interleukin6, nuclear factor-κB), and cardiac fibrotic proteins (matrix metalloproteinase-2[MMP-2], MMP-9) in ISO directed rats. Prdx-1 is an antioxidant response element, and it can regulate all the antioxidant proteins and it scavenges harmful radicals. Therefore, enhanced Prdx-1 expression is considered to have a pivotal role in preventing cardiac infarction. In this study, an elevated expression of Prdx1 was noticed in geraniol treated with ISO-directed rats. Hence, we concluded that geraniol is considered a potential phytodrug, and it prevents ISO-directed MAPKs, inflammation, and cardiac markers by enhancing the expression of Prdx1.

Ultrasound-targeted microbubble destruction (UTMD)-mediated miR-150-5p attenuates oxygen and glucose deprivation-induced cardiomyocyte injury by inhibiting TTC5 expression

Cardiomyocyte injury is a typical feature in cardiovascular diseases. Changes in cardiomyocytes strongly affect the progression of cardiovascular diseases. This work aimed to investigate the biological function and potential mechanism of action of miR-150-5p in cardiomyocytes. A myocardial ischemia (MI) injury rat model was constructed to detect miR-150-5p and tetratricopeptide repeat domain 5 (TTC5) expression during heart ischemia injury. Primary cardiomyocytes were isolated for in vitro study. CCK-8 assays were used to detect cardiomyocyte viability. Western blots were used to detect TTC5 and P53 expression. qPCR was utilized to measure RNA expression of miR-150-5p and TTC5. The TUNEL assay was used to determine cell apoptosis. ELISA was used to determine cytokine (TNF-α, IL-1β, IL-6, and IL-8) levels in heart tissues and cell culture supernatants. A dual-luciferase reporter assay was carried out to verify the binding ability between miR-150-5p and TTC5. Oxygen-glucose deprivation (OGD) treatment significantly inhibited cell viability. Ultrasound-targeted microbubble destruction (UTMD)-mediated uptake of miR-150-5p inverted these results. Additionally, UTMD-mediated uptake of miR-150-5p retarded the effects of OGD treatment on cell apoptosis. Besides, UTMD-mediated uptake of miR-150-5p counteracted the effects of OGD treatment on the inflammatory response by regulating cytokine (TNF-α, IL-1β, IL-6, and IL-8) levels. For the mechanism of the protective effect on the heart, we predicted and confirmed that miR-150-5p bound to TTC5 and inhibited TTC5 expression. UTMD-mediated uptake of miR-150-5p attenuated OGD-induced primary cardiomyocyte injury by inhibiting TTC5 expression. This discovery contributes toward further understanding the progression of primary cardiomyocyte injury.

Effects of vitamin D treatment on the heart tissue and adropin levels in thyrotoxicosis rats

Background/Aim: Thyrotoxicosis is a hypermetabolic disease, common in people with iodine deficiency. Cardiac pathologies can be seen in untreated cases. Vitamin D is a supportive therapy for thyrotoxicosis and its deficiency also plays an important role in pathologies including cardiac diseases. Adropin is a peptide hormone regulating the energy homeostasis, and its levels in blood change in cardiac pathologies. Our purpose is to reveal the effects of vitamin D treatment on the heart tissue of rats with thyrotoxicosis and on the adropin levels. Methods: Our study was designed as 25 days. 28 Sprague-Dawley female rats were divided into 4 groups; Control (3ml of distilled water), Thyrotoxicosis (100μg/day L-thyroxine) Treatment (100μg/day L-thyroxine+200IU /day Vit. D), Vit D (200IU/day Vit. D). Firstly, heart tissues were stained with Masson trichrome method. The preparations were examined under the microscope and evaluated semi-quantitatively. After that, serum adropin levels were measured with ELISA method. Malondialdehyde level of heart tissue was evaluated by spectrophotometry. Heart tissue was evaluated in aspects of fibrosis, congestion, edema and impairment of tissue integrity. Results: All of the evaluation parameters of the heart tissue were found highly significantly increased in thyrotoxicosis group, in contrast to the control and vitamin D group. Despite a decrease in the treatment group, there was no significant difference in the thyrotoxicosis group (P<0.001). Serum adropin levels of all groups were found to be decreased in contrast to the thyrotoxicosis group. Similarly, tissue MDA levels were significantly higher in the thyrotoxicosis group compared to the other groups. Conclusion: Consequently, heart tissue damage and differences in adropin levels were found in rats with thyrotoxicosis. It was observed that supportive vitamin D treatment helps to regulate these effects.

Exercise and Urtica Dioica extract ameliorate mitochondrial function and the expression of cardiac muscle Nuclear Respiratory Factor 2 and Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha in STZ-induced diabetic rats

IntroductionDiabetes mellitus can affect and disrupt the levels of PGC1α and NRF2 proteins in the mitochondrial biogenesis pathway. Considering the anti-diabetic properties of Urtica Dioica extract and exercise, this study aimed to investigate the beneficial effects of Urtica Dioica extract and endurance activity on PGC1α and NRF2 protein levels in the streptozotocin-induced diabetic rat heart tissue. Materials and methods58 male Wistar rats were divided into five groups (N = 12) including: healthy control (HC), diabetes control (DC), diabetes Urtica Dioica (D-UD), diabetes exercise training (DT), and diabetes exercise training Urtica Dioica (DT-UD). Diabetes was induced intraperitoneally by STZ (45 mg/kg) injection. Two weeks after the induction of diabetes, the rats were stimulated to carry out the exercise (moderate intensity/5day/week) and the gavage of UD extract (50 mg/kg/day) was administered to the rats for six weeks.In this study, the western blotting method was used to measure the levels of PGC1α and NRF2 proteins. Moreover, cardiography was used to evaluate the functional parameters of the heart (ejection fraction & fractional shortening). Finally, the bioluminescence and ELISA methods were used to determine the content of adenosine triphosphate and citrate synthase. ResultsThe cardiac function parameters, the mitochondrial ATP and the CS content in DC group mice were impaired in comparison with the other study groups and showed a decreasing trend (P < 0.001). The treatment with EX + UD extract was able to minimize the rate of these disorders and acted as a protector of mitochondrial function. There were significant differences in the expression levels of NRF2 (F = 17.7, P = 0.001) and PGC-1α (F = 43.7, P = 0.001) mitochondrial proteins among the different groups. The levels of these proteins were significantly reduced in the DC group in comparison with the HC group (P < 0.001). The treatment with EX or UD extract increased the expression of PGC-1α and NRF2 proteins in the heart muscle of animals in the DT and D-UD groups in comparison with the DC group (P < 0.05). Moreover, the expression of these proteins was more pronounced in the DT-UD group. There was not a significant difference between the DT-UD group and the HC group regarding the expression of these proteins (P > 0.05). ConclusionsThe results of this study showed that treatment with EX and UD extract could treat the disorders which were caused by diabetes in the parameters of cardiac function. Moreover, it was able to improve the expression of the levels of proteins which were involved in mitochondrial biogenesis and its function. Finally, this kind of treatment could attract more attention to the roles of EX and UD extract in the prevention of cardiovascular complications in future studies.

Effects of prenatal testosterone on cumulative markers of oxidative damage to organs of young adult zebra finches (Taeniopygia guttata).

We tested the hypothesis that exposure of avian embryos to androgens in ovo entails long-term costs in the form of oxidative damage to vital cells and organs in adulthood. We injected zebra finch eggs with testosterone (T), monitored postnatal growth, and analyzed markers of oxidative damage in heart and liver in mature birds. We measured 8-oxo-2'-deoxyguanosine and isoprostanes, markers of oxidative damage to DNA and membrane lipids, respectively. T treatment (1) reduced growth rates of female but not male nestlings vs. controls; (2) resulted in less accumulation of 8-oxo-dG, but not IsoPs, in liver tissue of 60-day-old females, but not males; and (3) a trend toward elevated 8-oxo-dG levels in heart tissue of males and females at 60 and 180days old combined. These results generally support the testosterone oxidative damage hypothesis, in that embryonic exposure to higher T resulted in damage to DNA of heart tissue in both sexes. They also suggest that sex-specific effects of androgens on early growth rates may carry over as differences in some forms of oxidative damage in adults. This supports a basic tenet of evolutionary aging theory that developmental influences early in life can be linked to costs later on.

Wogonin Ameliorated Obesity-Induced Lipid Metabolism Disorders and Cardiac Injury via Suppressing Pyroptosis and Deactivating IL-17 Signaling Pathway.

Obesity leads to structural and functional changes in the heart and has become a global burden of disease. Wogonin is a natural flavonoid which possesses cardioprotective, neuroprotective, and anti-cancer properties. However, the effects of wogonin on obesity-induced cardiac injury remain unclear. In this study, the high-fat diet (HFD)-induced obese mice model was successfully established. Moreover, HFD induced a fat mass and cardiac injury in mice. More importantly, wogonin treatment reduced fat mass and improved cardiac function of HFD mice. Consistently, wogonin ameliorated myocardial lipid metabolism in HFD-induced obese mice by reducing triglyceride (TC), total cholesterol (TG), and non-esterified fatty acid (NEFA) levels in serum, as well as the TG and free fatty acids (FFA) levels in heart tissues. Interestingly, wogonin treatment alleviated myocardial pyroptosis in HFD-induced obese mice. Through bioinformatic analysis, the IL-17 signaling pathway was predicted to be modulated by wogonin. Results showed that wogonin deactivated the IL-17 signaling pathway in HFD mice. These findings suggested that wogonin ameliorated obesity-induced disorders of lipid metabolism and cardiac injury via suppressing pyroptosis and deactivating the IL-17 signaling pathway, which provided a novel therapeutic strategy for HFD-induced cardiac injury.