Rat Heart Tissue Research Articles

Exploring the impacts of Pycnogenol on pentraxin-3 levels in the heart tissue of rats administered with gentamicin

Aims: The present study explored if pentraxin-3 (PTX-3) levels, which would be boosted due to cardiac damage by gentamicin, can be regressed thanks to Pycnogenol, which was also previously shown to have desirable impacts on cardiovascular diseases.
 Methods: In the study, we recruited 28 8-10-week-old male Sprague-Dawley rats into four groups: control, gentamicin, gentamycin+Pycnogenol, and Pycnogenol. We stained the tissue samples with hematoxylin-eosin and Masson’s trichome dye for histopathological analysis. Then, malondialdehyde (MDA) levels were measured using the spectrophotometric technique. In addition, we measured PTX-3 levels in the heart tissues by an immunohistochemical method.
 Results: We discovered the heart tissue samples of the rats in the control and Pycnogenol groups were histologically normal. As well as mononuclear cell increase and degeneration of cardiac muscle cells, we observed mild congestion in the gentamicin group compared to the control group. Despite more significant damage to the heart tissue in the gentamicin+Pycnogenol group compared to the control group, we found that the histopathological damage regressed in this group compared to the gentamicin group. While PTX-3 immunoreactivity was similar between the control and Pycnogenol groups, it was significantly elevated in the gentamicin group compared to the control group (p < 0.001). Moreover, the gentamicin+Pycnogenol group had decreased PTX-3 immunoreactivity than the gentamicin group. While MDA values followed a similar pattern between the control and Pycnogenol groups, these values were found to be significantly increased in the gentamicin group compared to the control group (p < 0.001). These values, however, were decreased in the gentamicin+Pycnogenol group compared to the gentamicin group.
 Conclusion: In a nutshell, the present study was able to demonstrate that gentamicin may lead to cardiac damage by boosting PTX-3 levels and that the damage can be regressed thanks to the Pycnogenol treatment.

The effect of eight weeks of high-intensity interval training with L-cysteine consumption on interleukin-13 and oxidative stress of heart tissue in young rats with type 2 diabetes

Background and aims: The purpose of this study was to investigate the effect of 8-weeks of high-intensity interval exercise with L-cysteine (LC) consumption on interleukin (IL)-13 and hydrogen peroxide of the heart tissue in young rats with type 2 diabetes (T2D). Methods: The statistical population of the present study consisted of young (4-month) rats with T2D. Ten rats were selected as a healthy group. Forty rats became diabetic. Diabetic rats were randomly divided into diabetes control, diabetics with exercise, diabetics with supplements, and diabetics with exercise and supplements. High-intensity interval exercises were performed 3 days a week for 8 weeks, and 500 μmol of LC were injected daily. Results: The healthy control group had lower IL-13 than the control group (P=0.001). There was no significant difference in IL-13 between other groups. Based on the results, the diabetes control group had a higher H2 O2 value than the healthy control group (P=0.001). A significant difference was found between the exercise group+LC consumption compared to the diabetes control group, and the H2 O2 levels in this group were less than the diabetic control group (P=0.001). The exercise (P=0.015) and LC (P=0.001) groups had a lower H2 O2 value than the diabetes control group. Eventually, the interval exercise group+LC was also lower than the periodic exercise group (P=0.02). Conclusion: High-intensity interval training, along with the use of LC, reduced hydrogen peroxide in the heart tissue, while it had no significant impact on IL-13.

Ameliorative Effect of Ginger on Blood Glucose Levels and Cardiac TCA Cycle Enzymes Activity in STZ Induced Diabetic Rat

This study aimed to investigate the effects of ginger administration on altered blood glucose levels, cytosolic and mitochondrial enzymes (TCA cycle enzymes) activity in streptozotocin-induced diabetes rats. The study divided Wistar strain rats into five groups: normal control, ginger treated, diabetic control, diabetic plus ginger treated, and diabetic plus glibenclamide treated groups. The diabetic group had significantly elevated blood glucose levels, which were significantly lowered by ginger administration. The cytosolic enzyme G6PDH activity was significantly (P<0.001) decreased along with a significant increase in the LDH activity in diabetic rats heart tissue. The activities of SDH, MDH, GDH in the heart tissue of diabetic rats were significantly decreased, but the daily oral treatment of ginger to diabetic rats for thirty days reversed the above changes in a significant (P<0.001) manner. The study demonstrated that an ethanolic extract of ginger could lower blood glucose levels, improve enzyme activities and body weight in diabetic rats. This suggests that ginger extracts could be used as a cardio-protective supplement to reverse diabetic-induced complications.

Efficacy of antibiotic combinations in an experimental sepsis model with Pseudomonas aeruginosa.

This study aimed to compare the efficacy of fosfomycin, colistin, tobramycin and their dual combinations in an experimental sepsis model. After sepsis was established with a Pseudomonas aeruginosa isolate (P1), antibiotic-administered rats were divided into six groups: Fosfomycin, tobramycin, colistin and their dual combinations were administered by the intravenous or intraperitoneal route to the groups. The brain, heart, lung, liver, spleen and kidney tissues of rats were cultured to investigate bacterial translocation caused by P1. Given the antibiotics and their combinations, bacterial colony counts in liver tissues were decreased in colistin alone and colistin plus tobramycin groups compared with control group, but there were no significant differences. In addition, a non-statistical decrease was found in the spleen tissues of rats in the colistin plus tobramycin group. There was a > 2 log10 CFU/ml decrease in the number of bacterial colonies in the kidney tissues of the rats in the fosfomycin group alone, but the decrease was not statistically significant. However, there was an increase in the number of bacterial colonies in the spleen and kidney samples in the group treated with colistin as monotherapy compared to the control group. The number of bacterial colonies in the spleen samples in fosfomycin plus tobramycin groups increased compared to the control group. Bacterial colony numbers in all tissue samples in the fosfomycin plus colistin group were found to be close to those in the control group. Colistin plus tobramycin combinations are effective against P. aeruginosa in experimental sepsis, and clinical success may be achieved. New in vivo studies demonstrating the ability of P. aeruginosa to biofilm formation in tissues other than the lung are warranted in future.

Allogeneic mitochondrial transplantation ameliorates cardiac dysfunction due to doxorubicin: An in vivo study

Damage to the mitochondria may lead to serious conditions that are difficult to treat. Doxorubicin is one of the most widely used chemotherapeutic drugs for the treatment of malignancies in children and adults, and reportedly causes damage to the mitochondria. Unfortunately, the dangerous cardiac side effects of doxorubicin appear when the patient is in the midst of a vigorous fight against the disease, either by taking doxorubicin alone or in combination with other drugs. This study aimed to determine whether exogenous healthy and functional mitochondria are internalized by cells, can it help the survival of these cells, and can reduce cardiotoxicity. For this purpose, isolated, pure, and functional exogenous mitochondria were injected into the tail vein of a rat model of doxorubicin-induced cardiotoxicity. After that, the heart function of the rats and their antioxidant status, inflammatory markers, and histopathological examination were investigated. Our findings show that intravenous mitochondrial transplantation provided efficient mitochondrial uptake and reduced cardiotoxicity by reducing ROS production, lipid peroxidation, and inflammation. In addition, the levels of ATP and antioxidant enzymes increased after mitochondrial transplantation; therefore all of these complex processes resulted in the reduction of apoptosis and necrosis in rat heart tissue. These promising results open the way to more effective cancer treatment without the side effects of related drugs. Transplanting exogenous mitochondria probably enhances the cell's mitochondrial network, potentially treating mitochondria-related disorders such as cardiovascular and neurodegenerative diseases, although the exact relationship between mitochondrial damage and these conditions remains unclear.

The Effect of High-intensity Interval Training and Moderate-intensity Continuous Training on Oxidative Stress Markers in Left Ventricular Tissue of Male Rats

Objectives: The present study aimed to assess and compare the effects of high-intensity interval training and moderate-intensity continuous training on oxidative stress-related markers in the left ventricular tissue of the heart muscle in healthy male rats. Methods: Fifteen male Wistar rats, aged 50-70 days, were randomly divided into 3 groups: Control group (CON), high-intensity interval training (HIIT), and moderate-intensity continuous training (MICT). After determining the maximum speed of VO2 max, the training program of HIIT (six 2-min periods with 85%-90% VO2 max and five 2-min with 50%-60% VO2 max intensity) and MICT (same distance of running as HIIT with 70% VO2 max intensity) groups were performed for 8 weeks, 5 days per week. Forty-eight hours after the last intervention session, the animals were anesthetized, and their heart tissue was removed and stored at -80° C. Then, the expression rates of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), AMP-activated protein kinase (AMPK), and superoxide dismutase (SOD) genes were measured by real-time PCR, and the concentration of malondialdehyde (MDA) in left ventricular tissue of heart was measured by colorimetry method. One-way analysis of variance and Tukey post hoc test were used for data analysis at the significance level of P<0.05. Results: There were significant differences between the groups’ expression rates of AMPK, PGC-1α, and SOD (P<0.05). The expression rates of AMPK and PGC-1α were higher in the MICT group than in the CON group (P<0.05). No significant difference was observed between HIIT and MICT groups regarding AMPK and PGC-1α (P>0.05). SOD expression was significantly higher in the HIIT group than CON and MICT groups (P<0.05). SOD expression was also higher in the MICT group compared to the CON group (P<0.05). MDA concentration was not significantly different between the studied groups (P>0.05). Discussion: HIIT and MICT induce positive adaptations in the expression of AMPK, PGC-1α, and SOD in the heart tissue of healthy male rats. However, HIIT stimulates SOD gene expression more than MICT.

The Effect of Eight Weeks of High-Intensity Interval Training with L-Cysteine Consumption on CRP and TNF-α in Heart Tissue of Young Rats with Type 2 Diabetes

Background: This study aimed to investigate the effect of 8-weeks of high-intensity interval training (HIIT) with L-cysteine consumption on tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) of heart tissue in young rats with type 2 diabetes. Methods: The statistical population of the present study consisted of young (4 months) rats with type 2 diabetes. Ten rats were selected as a healthy group, and 40 rats became diabetic. Diabetic rats were randomly divided into four groups: diabetes control, diabetics with training, diabetics with supplements, and diabetics with training+supplement. Moreover, high-intensity interval exercises were performed 3 days a week for 8 weeks, and 500 micromoles of L-cysteine were administered daily. Results: The training+supplement group had significantly higher TNF-α levels compared to the diabetic control group (P=0.002). The diabetic control group (P=0.001) and training group (P=0.001) had higher TNF-α levels compared to the healthy control. The supplement group had significantly less TNF-α compared to the diabetic control group (P=0.003), while the supplement group (P=0.019) and the training+supplement group (P=0.013) had lower TNF-α levels compared to the training group. Moreover, the training+supplement group had lower CRP levels compared to the diabetic control group (P=0.001), while the diabetic control (P=0.001), exercise (P=0.002), and supplement group (P=0.031) had higher CRP levels compared to the healthy control. Moreover, the training group (P=0.038) and the supplement group (P=0.002) had lower CRP compared to the diabetic control group. Furthermore, the training+supplement group had a lower CRP level compared to the training group (P=0.03). Conclusion: HIIT along with the L-cysteine consumption reduced TNF-α and CRP in the heart tissue of diabetic rats.

Evaluation of Antioxidant Activity of Secang Wood (Caesalpinia Sappan L) Water Extract in Wistar Rats

Secang (Caesalpinia sappan L.) has a good effect on the health of the human body traditionally. It is a plant that has antioxidant activity because containing phenol and flavonoid compounds. The focus of this study was to evaluate the antioxidant activity of Secang wood water extract in vitro and in vivo. The Ferric Reducing Antioxidant Power method is used to examine antioxidant activity in vitro, while Wistar rats are used to test it in vivo. Test animals are given orally 50 mg/kgBW of the Secang wood water extract. Malondialdehyde levels and Superoxide Dismutase activity in rat heart and liver tissue with maximum physical activity were measured after the five-day intervention. In vitro, tests revealed that Secang wood water extract, which contained 393.7374 mg AAE/g of the sample, had the highest antioxidant capacity. In vivo, a test revealed that consumption of Secang wood water extract significantly (p < 0.05) boosted Superoxide Dismutase activity and lowered Malondialdehyde levels in the Wistar rats compared to the control.

The effect of high-intensity interval training and quercetin nanoliposome consumption on angiogenesis indexes in the heart tissue of myocardial infarction rats

Background: Myocardial infarction is the death of the heart muscle tissue that causes tissue damage and inflammation. Quercetin consumption and interval training can probably prevent the progression of this condition in the active parts of the myocardium by activating angiogenesis pathways and stimulating hypoxia factor-1a (HIF-1a) at the onset of infarction. Objectives: This study investigates the effect of high-intensity interval training and quercetin nanoliposome consumption on angiogenesis indexes in the heart tissue of myocardial infarction rats. Methods: In this experimental study, 30 male rats weighing 250 ± 20 g were randomly divided into five groups including: 1) myocardial infarction + training, 2) myocardial infarction + supplement, 3) myocardial infarction + training + supplement, 4) healthy control, and 5) myocardial infarction. Myocardial infarction was induced by subcutaneous injection of soprenaline hydrochloride at a dose of 80 mg / kg. Groups 2 and 3 received quercetin daily at a dose of 0.25 mg / kg body weight by gavage. Groups 1 and 3 performed 5 sessions of training protocol per week for 8 weeks. The Smirnov-Kolmogorov, one-way analysis of variance and Tukey’s post hoc test were used to analyze the data and the alpha level less than 0.05 was considered as a significant level. Results: Interval training and quercetin supplementation had a significant effect on increasing VEGF and HIF-1a gene expression (P=0.0009). Conclusion: The combined effect of interval training and quercetin consumption may prevent the progression of myocardial infarction by activating angiogenesis factors VEGF and HIF-1a in the early stages, and may play an effective role in preventing this disease.

Effect and mechanism of Qing Gan Zi Shen decoction on heart damage induced by obesity and hypertension

Ethnopharmacological relevanceQing Gan Zi Shen Decoction (QGZS) is a traditional Chinese formula. It has been extensively used for decades in the treatment of hypertension combined with metabolic diseases, but its cardioprotective effects and underlying mechanisms are poorly understood. Aim of the studyTo explore the cardioprotective effects and potential mechanisms of QGZS in an animal model of obese hypertension. Materials and methodsIn this study, spontaneously hypertensive rats (SHRs) were utilized as an animal model to examine the effects of a high-fat diet and two concentrations of QGZS. Echocardiography, hematoxylin eosin (H&E) staining, and wheat germ agglutinin (WGA) staining were employed to assess the cardiac structure and function of the SHRs throughout a 16-week therapy period. Furthermore, Western blotting (WB) and immunofluorescence (IF) were employed to identify the levels of Nrf2 expression in the mitochondria, cytoplasm, and nucleus of the myocardium. Additionally, transmission electron microscopy and enzyme-linked immunosorbent assay (ELISA) were utilized to measure mitochondrial morphology and pro-inflammatory cytokine levels, respectively. Furthermore, Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) techniques were employed to quantify the levels of marker proteins associated with myocardial fibrosis, cardiac inflammation, oxidative stress, and mitochondrial dysfunction. ResultsQGZS inhibited weight gain and depressed systolic and mean arterial pressures in high-fat-fed SHRs. Echocardiographic results demonstrated that QGZS prevented the increase in left ventricular mass, restricted the growth of left ventricular diameter, and improved ejection fraction (EF), fractional shortening (FS), and the ratio of early diastolic peak velocity of transmitral flow (E) to late diastolic peak velocity (A) in high-fat-fed SHRs. This suggested that QGZS prevented ventricular remodeling and protected cardiac systolic and diastolic functions. H&E and WGA staining showed that QGZS improved cardiomyocyte disorders and restricted cardiomyocyte hypertrophy. The underlying mechanisms, QGZS attenuated the oxidative stress state, including reducing the generation of reactive oxygen species (ROS) in the myocardium, revitalizing the antioxidant enzyme system, and protecting mitochondrial function. Moreover, QGZS alleviated the pro-inflammatory state in high-fat-fed SHRs. What's more, QGZS significantly increased the expression level of Nrf2 in nuclei and mitochondria in rat heart tissues, exerting a proximate Nrf2 agonist effect. ConclusionsQGZS exerted cardioprotective effects, in part due to its increasing expression of Nrf2 protein in the heart, which promoted Nrf2 nuclear expression.

Palm Olein Oil Effect on the Heart Tissue of Male Rats

Background: Palm olein oil is one of the most widely used oils, so the available reports show that its consumption has different health effects, some of them are beneficial and some are harmful. Objectives: This study aimed to investigate the effect of heated and unheated date olein in different doses on the hearts of male rats. Methods: In this study, 40 male rats were divided into 5 groups: Sham group with a regular diet, palm oil group with 10% (W/W) palm oil diet, palm oil group with 20% (W/W) palm oil diet, ghee oil group 7.5% (W/W) and heated palm oil group with 20% (W/W) palm oil diet. Palm olein oil was added to rat foods in experimental groups for 60 days. 24 hours later, the rats were dissected, then the heart tissue of the rats was sampled and tissue sections were prepared and analyzed with an optical microscope. Results: The results of this study indicated that fresh unheated palm oil does not have any harmful effects on the heart tissue, but the consumption of heated palm oil causes to damage the heart tissue. Conclusions: The results showed the negative effects are correlated to the dose and the heating. The heart tissues which treated with higher doses and heated palm olein oil had more side effects.

Participation of ASK-1 in the cardiomyocyte-protective role of mechanical ventilation in a rat model of myocardial infarction.

Non-invasive positive-pressure ventilation (NIPPV) has been demonstrated to exhibit a cardioprotective function in a rat model of myocardial infarction (MI). However, the mechanism underlying NIPPV-mediated MI progression requires further investigation. We aimed to investigate the effectiveness and corresponding mechanism of NIPPV in an acute MI-induced heart failure (HF) rat model. Thirty each of healthy wild type (WT) and apoptosis signal-regulating kinase 1 (ASK-1)-deficient rats were enrolled in this study. MI models were established via anterior descending branch ligation of the left coronary artery. The corresponding data indicated that NIPPV treatment reduced the heart infarct area, myocardial fibrosis degree, and cardiac function loss in MI rats, and ameliorated apoptosis and reactive oxygen species (ROS) levels in the heart tissue. Furthermore, the expression level of ASK-1 level, a key modulator of the ROS-induced extrinsic apoptosis pathway, was upregulated in the heart tissues of MI rats, but decreased after NIPPV treatment. Meanwhile, the downstream cleavage of caspase-3, caspase-9, and PARP, alongside p38 phosphorylation and FasL expression, exhibited a similar trend to that of ASK-1 expression. The involvement of ASK-1 in NIPPV-treated MI in ASK-1-deficient rats was examined. Although MI modeling indicated that cardiac function loss was alleviated in ASK-1-deficient rats, NIPPV treatment did not confer any clear efficiency in cardiac improvement in ASK-1-knockdown rats with MI modeling. Nonetheless, NIPPV inhibited ROS-induced extrinsic apoptosis in the heart tissues of rats with MI by regulating ASK-1 expression, and subsequently ameliorated cardiac function loss and MI-dependent pathogenic changes in the heart tissue.

Etoricoxib nanostructured lipid carriers attenuate inflammation by modulating Cyclooxygenase-2 signaling and activation of nuclear factor-κB-p65 pathways in radiation-induced acute cardiotoxicity in rats

The current investigation aimed to explore the potential of etoricoxib nanostructured lipid carriers (ET-NLCs) as an anti-inflammatory drug in radiation-exposed rats, with a focus on assessing its efficacy in reducing inflammation while minimizing cardiac toxicity compared to conventional etoricoxib (ET) treatment. The ET-NLCs were prepared by the low-temperature melt emulsification solidification technique. Various techniques were employed to characterize the NLCs. Rats were exposed to gamma-irradiation (6 Gy) to induce cardiac inflammation and injury, followed by oral administration of ET or ET-NLCs (10 mg/kg b.w.) for 14 consecutive days. Results demonstrated a significant increase in the levels of malondialdehyde (MDA), cyclooxygenase-2 (COX-2), nuclear factor kappa-B p65 (NF-κB-p65), and poly ADP-ribose polymerase (PARP-1) in the heart tissues of gamma-irradiated rats compared to the control group. This increase was accompanied by a reduction in the activity of antioxidant enzymes. However, treatment with ET and ET-NLCs exhibited a positive impact on these levels. Interestingly, the efficacy of ET-NLCs in mitigating radiation-induced inflammation in heart tissue was found to be superior to that of ET. In conclusion, the study suggests that the utilization of NLCs as a drug delivery system for ET may not only enhance its therapeutic efficacy but also help reduce the cardiovascular risks associated with ET, specifically focused on individuals who had been exposed to gamma radiation. These findings open new avenues for further research in the development of effective and safer therapeutic strategies for managing inflammatory diseases and their impact on cardiovascular health.

Antioxidant Activity and Protective Effects of an Oxovanadium (IV) Complex on Heart and Aorta Injury of STZ-Diabetic Rats.

Diabetic people have a much higher rate of cardiovascular disease than healthy people. Therefore, heart and aortic tissues are target tissues in diabetic research. In recent years, the synthesis of new vanadium complexes and investigation of their antidiabetic/lowering effect on the blood glucose levels and antioxidant properties are increasing day by day. Our study aimed to examine the effects of synthesized oxovanadium (IV) complex of 2-[(2,4-dihydroxybenzylidene]hydrazine-1-[(N-(2-hydroxybenzylidene)](S-methyl)carbothioamide [VOL] on diabetic heart and aortic tissues, as well as in vitro lactate dehydrogenase (LDH) and myeloperoxidase (MPO) inhibition, antioxidant properties, and reducing power. Electrochemical characterization of the VOL was carried out by using Cyclic Voltammetry (CV) and Linear Sweep Voltammetry (LSV) methods. In addition, in silico drug-likeness and ADME prediction were also investigated. For in vivo study, male Swiss albino rats were randomly selected and separated into four groups which are control, control + VOL, diabetic and diabetic + VOL. After the experimental procedure, biochemical parameters were investigated in homogenates of heart and aorta tissues. The results showed that VOL has a protective effect on heart and aortic tissue against oxidative stress. According to electrochemical experiments, one reversible oxidative couple and one irreversible reductive response were observed for the complex. In addition, in vitro LDH and MPO inhibition of VOL was examined. It was found that VOL had a protective effect on heart and aortic tissues of diabetic rats, and caused the inhibition of LDH and MPO in in vitro studies. On the other hand, evaluating the synthesized VOL according to in silico drug-likeness and absorption, distribution, metabolism, and excretion (ADME) prediction, it was found that VOL has drug-like properties and exhibited high gastrointestinal absorption. The VOL had a therapeutic impact on the heart and aortic tissues of diabetic rats, according to the findings.

Effect of the nitric oxide synthesis inhibitor L-NAME on the isolated rat heart after hypokinesia

The effects of a non-selective nitric oxide synthase inhibitor L-NAME on the functional parameters of the isolated rat heart after a 30-day period of hypokinesia were studied. Electron paramagnetic resonance spectroscopy was employed in the analysis of a role for L-NAME in the intensity of nitric oxide production in rat heart tissues. The intensity of nitric oxide synthesis was assessed by the intensity of the signal belonging to the (DETC)2-Fe2+-NO complex. It was found that L-NAME decreased nitric oxide production on average by 69%. The Langendorff isolated perfused heart was used to evaluate cardiac activity, and the following parameters were measured: pressure generated by the left ventricle, heart rate, and coronary flow. Addition of the nitric oxide synthesis inhibitor L-NAME induced an increase in inotropic function and normalization of heart rate.

MiR-34a/SIRT1/HIF-1α axis is involved in cardiac angiogenesis of type 2 diabetic rats: The protective effect of sodium butyrate combined with treadmill exercise.

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders worldwide. Recent research has indicated that sodium butyrate (NaB) affects glucose metabolism and exercise has an anti-hyperglycemic effect in diabetes. This study aimed to evaluate the effects of NaB and treadmill exercise on heart angiogenesis through the miR-34a/SIRT1/FOXO1-HIF-1α pathway. Diabetic animals received NaB (400 mg/kg daily, orally) and treadmill exercise for 6 weeks. The effect of NaB and treadmill exercise, alone or combined, on miR-34a expression, SIRT1, FOXO1, HIF-1α levels, and angiogenesis in diabetic heart tissue was measured. Diabetes caused increased miR-34a (p < 0.01) and FOXO1 (p < 0.001) expression levels. Also, SIRT1 (p < 0.001) and HIF-1α (not significant) expression levels were reduced in diabetic rats. NaB and treadmill exercise decreased miR-34a (respectively p < 0.05 and not significant) and FOXO1 (both p < 0.001) expression levels and improved SIRT1 (both not significant) and HIF-1α (respectively p < 0.01 and p < 0.001) levels. Also, NaB combined with treadmill exercise decreased miR-34a (p < 0.001) and FOXO1 (p < 0.001) expression levels, and elevated SIRT1 (p < 0.05) and HIF-1α (p < 0.001) levels in comparison with the diabetic group. NaB and treadmill exercises modulate the expression of miR-34a and the levels of SIRT1, FOXO1, and HIF-1α proteins, thus increasing angiogenesis in the heart tissue of diabetic rats. It can be concluded that NaB and treadmill exercise, alone or combined, may be useful in the treatment of diabetes through the miR-34a/SIRT1/FOXO1-HIF-1α pathway.

Resveratrol prevents Ang II-induced cardiac hypertrophy by inhibition of NF-κB signaling

BackgroundPathological cardiac hypertrophy is a hallmark of various cardiovascular diseases (CVD) including chronic heart failure (HF) and an important target for the treatment of these diseases. Aberrant activation of Angiotensin II (Ang II)/AT1R signaling pathway is one of the main triggers of cardiac hypertrophy, which further gives rise to excessive inflammation that is mediated by the key transcription factor NF-κB. Resveratrol (REV) is a natural polyphenol with multiple anti-inflammatory and anti-oxidative effects, however the ability of REV in preventing Ang II-induced cardiac hypertrophy in combination with NF-κB signaling activation remains unclear. MethodsMurine models of cardiac hypertrophy was conducted via implantation of Ang II osmotic pumps. Primary neonatal rat cardiomyocyte and heart tissues were examined to determine the effect and underlying mechanism of REV in preventing Ang II-induced cardiac hypertrophy. ResultsAdministrations of REV significantly prevented Ang II-induced cardiac hypertrophy, as well as robustly attenuated Ang II-induced cardiac fibrosis, and cardiac dysfunction. Furthermore, REV not only directly prevented Ang II/AT1R signal transductions, but also prevented Ang II-induced expressions of pro-inflammatory cytokines and activation of NF-κB signaling pathway. ConclusionsOur study provides important new mechanistic insight into the cardioprotective effects of REV in preventing Ang II-induced cardiac hypertrophy via inhibiting adverse NF-κB signaling activation. Our findings further suggest the therapeutic potential of REV as a promising drug for the treatment of cardiac hypertrophy and heart failure.

Cardiomodulatory and Antioxidative Potentials of Almond-Citrus Peel Fortified Shortbread in High Fat Diet/L-NAME-Induced Hyperlipidemic-Hypertensive Rats.

In folk medicine, the almond nut (Terminalia catappa) and orange peel (Citrus sinensis) are cost-effective sources of nutraceutical utilized in the treatment of degenerative diseases. Hyperlipidemia and hypertension are two pathological conditions implicated in cardiovascular disorders. This study sought to evaluate the cardiomodulatory effect of almond-citrus peel fortified shortbread in hyperlipidemic-hypertensive rats induced by high fat diet and Nω-nitro-l-arginine methyl ester. The experimental animals were divided into eight groups. The experimental rats were fed with shortbread supplemented with almond and citrus peel at varying inclusions of 0.2% citrus, 50% almond, and almond (50%)- citrus (0.2%) for 21 days. The mean arterial blood pressure (MABP), systolic blood pressure (SBP), and lipid profile of the experimental rats were measured. Thereafter, the activities of angiotensin-1-converting enzyme (ACE), arginase, malondialdehyde (MDA), phosphodiesterase-5, nitric oxide (NO), and antioxidant indices were evaluated. The result showed significant elevation in SBP, MABP, blood cholesterol, triglyceride, ACE, arginase, activities, and MDA levels in the heart tissue of the untreated rats. In contrast, the antioxidant status and NO level were significantly decreased in the untreated groups. Remarkably, the treatment with almond-citrus peel fortified shortbread and the individual effect of almond (50%) and citrus peel (0.2%) all reversed these trends in the hyperlipidemic-hypertensive rats. Intriguingly, the blend of almond (50%)-citrus peel (0.2%) fortified shortbread showed the best antioxidative and cardioprotective effect. The results suggest that almond and citrus peel offer potentials as therapeutic agent in the prevention and management of hyperlipidemia and hypertension.

Eleutheroside E from pre-treatment of Acanthopanax senticosus (Rupr.etMaxim.) Harms ameliorates high-altitude-induced heart injury by regulating NLRP3 inflammasome-mediated pyroptosis via NLRP3/caspase-1 pathway.

Eleutheroside E, a major natural bioactive compound in Acanthopanax senticosus (Rupr.etMaxim.) Harms, possesses anti-oxidative, anti-fatigue, anti-inflammatory, anti-bacterial and immunoregulatory effects. High-altitude hypobaric hypoxia affects blood flow and oxygen utilisation, resulting in severe heart injury that cannot be reversed, thereby eventually causing or exacerbating high-altitude heart disease and heart failure. The purpose of this study was to determine the cardioprotective effects of eleutheroside E against high-altitude-induced heart injury (HAHI), and to study the mechanisms by which this happens. A hypobaric hypoxia chamber was used in the study to simulate hypobaric hypoxia at the high altitude of 6000m. 42 male rats were randomly assigned to 6 equal groups and pre-treated with saline, eleutheroside E 100mg/kg, eleutheroside E 50mg/kg, or nigericin 4mg/kg. Eleutheroside E exhibited significant dose-dependent effects on a rat model of HAHI by suppressing inflammation and pyroptosis. Eleutheroside E downregulated the expressions of brain natriuretic peptide (BNP), creatine kinase isoenzymes (CK-MB) and lactic dehydrogenase (LDH). Moreover, The ECG also showed eleutheroside E improved the changes in QT interval, corrected QT interval, QRS interval and heart rate. Eleutheroside E remarkably suppressed the expressions of NLRP3/caspase-1-related proteins and pro-inflammatory factors in heart tissue of the model rats. Nigericin, known as an agonist of NLRP3 inflammasome-mediated pyroptosis, reversed the effects of eleutheroside E. Eleutheroside E prevented HAHI and inhibited inflammation and pyroptosis via the NLRP3/caspase-1 signalling pathway. Taken together, eleutheroside E is a prospective, effective, safe and inexpensive agent that can be used to treat HAHI.

GC-MS-based profiling and ameliorative potential of Carissa opaca Stapf ex Haines fruit against cardiac and testicular toxicity: An In vivo study

Fruit of Carissa opaca Stapf ex Haines (C. opaca) is a feed additive and is commonly used against cardiac dysfunction, fever, asthma, diarrhea, gastrointestinal ailments, and skin diseases. In this study, we aimed to evaluate the metabolic profile and antioxidant potential of C. opaca fruit against carbon tetrachloride (CCl4)-induced cardiotoxicity and testicular toxicity in rats. Gas Chromatoghraphy-Mass Spectrometry (GC-MS) analysis of C. opaca fruit for the identification of potential metabolic profile, followed by methanolic extract of C. opaca and its derived fractions including n-hexane, ethyl acetate, chloroform, butanol, and aqueous were used to assess the antioxidant potential of fruits. Ten groups of rats received different treatments and got evaluated for cardiac and testicular antioxidant enzymes, histological architecture, and serum hormonal levels. GC-MS analysis of methanolic extract of C. opaca fruit showed the presence of some bioactive metabolites like cyclodecane, diethyl 2,6-pyridine dicarboxylate, tetrahydro-geraniol, S-[2-[N, N-Dimethylamino]ethyl]morpoline, 2,3-Methylenedioxyphenol, alpha-d-Glucopyranoside, 5,10-Diethoxy-2,3,7,8-tetrahydro-1H, 6H-dipyrrolo [1,2-a; 1′,2′-d] pyrazine and 1,3-Benzothiazol-2(3H)-one,3-(3,3-dimethyl-1-oxobutyl) that corresponds the medicinal properties of C. opaca fruit. Prepared fractions of C. opaca fruits mitigated the toxicity induced by CCl4 in the heart and testicular tissues of rats. Oxidative stress was caused by the inhibition of activities of glutathione and other antioxidant enzymes of the body, while on the other hand elevating the levels of nitrite and hydrogen peroxide. Treatment with C. opaca fruit extract normalized the levels of enzymes, reproductive hormones, and free radicals thus restoring the histopathological and enzymatic biomarkers towards the normal group. The study supports the indigenous use of fruits as an alternative medicine against cardiac dysfunction by providing scientific evidence of protection against CCl4-induced injuries, and it also concludes the antioxidant defensive role in testicular tissues.