scholarly journals Cucumis melo Enhances Enalapril Mediated Cardioprotection in Rats with Isoprenaline Induced Myocardial Injury

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 557
Author(s):  
Syed Mohammed Basheeruddin Asdaq ◽  
Saidareddy Venna ◽  
Yahya Mohzari ◽  
Ahmed Alrashed ◽  
Hamdan Najib Alajami ◽  
...  
Keyword(s):  
Cucumis Melo ◽  
Combined Therapy ◽  
Myocardial Damage ◽  
Thiobarbituric Acid ◽  
Heart Tissue ◽  
Acute Injury ◽  
Tissue Homogenate ◽  
High Dose ◽  
Chronic Therapy ◽  
End Of Treatment

This study sought to investigate the cardioprotective potency and interaction of muskmelon (Cucumis melo) with enalapril (ENA) against myocardial damage caused by acute and chronic isoprenaline (ISO) treatments in rats. In the acute model, 150 mg/kg (s.c) of ISO was administered for two consecutive days at the end of pretreatment with either ENA, muskmelon, or both in their respective groups. ISO was introduced into the chronic therapy of ENA/muskmelon/ENA + muskmelon groups during the last 10 days at 3 mg/kg. Muskmelon was tested at three doses (100, 200, and 500 mg/kg, p.o., 30 days), and one normal dose of ENA (10 mg/kg) was used. Blood samples were taken at the end of treatment, and the animals were sacrificed. Biochemical markers such as LDH and CK-MB, as well as antioxidant (superoxide dismutase (SOD) and catalases) and thiobarbituric acid reactive species (TBARS) were measured in both serum and heart tissue homogenate (HTH). To confirm the biochemical findings, histological slides of heart tissue were prepared. ISO administration induced an elevation in the amount of TBARS, which was increased in all groups in which it was administered. Prior treatment with muskmelon and ENA in animals resulted in a rise in biomarker activity in homogenated heart tissue and a decrease in serum. In terms of alleviating the abnormal conditions caused by ISO, the group given a high dose of muskmelon and combined therapy had the best outcomes. The activities of SOD and catalase were substantially higher in the treated classes. Histological findings showing the cytoprotective actions of the high dose of muskmelon and ENA have confirmed the biochemical outcomes of both models. It is therefore concluded that the high dose of muskmelon (500 mg/kg) has a promising cardioprotective potential that is improved more efficiently in the acute injury model in the presence of ENA.

scholarly journals Cytoprotective Potential of Aged Garlic Extract (AGE) and Its Active Constituent, S-allyl-l-cysteine, in Presence of Carvedilol during Isoproterenol-Induced Myocardial Disturbance and Metabolic Derangements in Rats

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3203
Author(s):  
Syed Mohammed Basheeruddin Asdaq ◽  
Obulesu Challa ◽  
Abdulhakeem S. Alamri ◽  
Walaa F. Alsanie ◽  
Majid Alhomrani ◽  
...  
Keyword(s):  
Myocardial Dysfunction ◽  
Combined Therapy ◽  
Myocardial Damage ◽  
Thiobarbituric Acid ◽  
Significant Rise ◽  
Garlic Extract ◽  
High Dose ◽  
Aged Garlic Extract ◽  
Active Constituent ◽  
Aged Garlic

This study was conducted to determine the potential interaction of aged garlic extract (AGE) with carvedilol (CAR), as well as to investigate the role of S-allyl-l-cysteine (SAC), an active constituent of AGE, in rats with isoproterenol (ISO)-induced myocardial dysfunction. At the end of three weeks of treatment with AGE (2 and 5 mL/kg) or SAC (13.1 and 32.76 mg/kg), either alone or along with CAR (10 mg/kg) in the respective groups of animals, ISO was administered subcutaneously to induce myocardial damage. Myocardial infarction (MI) diagnostic predictor enzymes, lactate dehydrogenase (LDH) and creatinine kinase (CK-MB), were measured in both serum and heart tissue homogenates (HTH). Superoxide dismutase (SOD), catalase, and thiobarbituric acid reactive species (TBARS) were estimated in HTH. When compared with other groups, the combined therapy of high doses of AGE and SAC given alone or together with CAR caused a significant decrease in serum LDH and CK-MB activities. Further, significant rise in the LDH and CK-MB activities in HTH was noticed in the combined groups of AGE and SAC with CAR. It was also observed that both doses of AGE and SAC significantly increased endogenous antioxidants in HTH. Furthermore, histopathological observations corroborated the biochemical findings. The cytoprotective potential of SAC and AGE were dose-dependent, and SAC was more potent than AGE. The protection offered by aged garlic may be attributed to SAC. Overall, the results indicated that a high dose of AGE and its constituent SAC, when combined with carvedilol, has a synergistic effect in preventing morphological and physiological changes in the myocardium during ISO-induced myocardial damage.

scholarly journals Short Communication: Augmentation of cardioprotective effect of captopril by Costus speciosus against isoproterenol induced myocardial toxicity in rats

2017 ◽  
Vol 9 (3) ◽  
pp. 295-299
Author(s):  
ABDULRAHMAN A.I. AL-YAHYA ◽  
MOHAMMED ASAD ◽  
ABDULMONIEM SADABY ◽  
KHALID ELFAKKI IBRAHIM
Keyword(s):  
Short Communication ◽  
Methanolic Extract ◽  
Myocardial Damage ◽  
Heart Tissue ◽  
Cardioprotective Effect ◽  
Pharmacodynamic Interaction ◽  
Costus Speciosus ◽  
End Of Treatment ◽  
Extent Of Damage ◽  
Dose Dependent

Al-Yahya AAI, Asad M, Sadaby A, Ibrahim KE. 2017. Short Communication: Augmentation of cardioprotective effect of captopril by Costus speciosus against isoproterenol induced myocardial toxicity in rats. Nusantara Bioscience 9: 295-299. This study determined the pharmacodynamic interaction of captopril, a known cardioprotective effect with methanolic extract of Costus speciosus rhizomes (Costaceae) that is known for its powerful antioxidant action during isoproterenol induced cardiac toxicity in rats. A methanolic extract of the rhizomes was prepared by maceration. Rats were administered the methanolic extract at two different doses of 200 mg/k or 400 mg/kg orally and captopril was administered orally at a dose of 30 mg/kg. All the drugs alone or in combination were once daily for two weeks. At the end of treatment period, two doses of isoproterenol (150 mg/kg, s.c) were administered to rats at 24 hr interval. Blood was withdrawn to estimate creatinine kinase-MB (CK-MB) activities. The heart tissue was subjected to histological examinations to determine the extent of damage. Isoproterenol induced severe damage to the myocardium that was indicated through an elevation in serum CK-MB activity and the same was confirmed by histological examinations. Costus speciosus at both the tested doses attenuated the damage produced by isoproterenol. Both the doses caused a decrease in the biomarker activity as well as reduced the myocardial damage as observed in histological examination. A similar effect was observed with captopril. The co-administration of captopril with either dose of Costus speciosus demonstrated excellent cardioprotection suggesting that combination of this herb with captopril augments its cardioprotective action. It was concluded that Costus speciosus shows dose-dependent cardioprotection and augments the cardioprotective effect of captopril during isoproterenol induced cardiotoxicity in rats.

Molecular mechanism of TLR4 mediated T cell immune effect in transfusion-induced acute lung injury based on Slit2/Robo4 signaling pathway

2020 ◽  
Vol 13 ◽  
Author(s):  
Kun Xiao ◽  
Fei Zhao ◽  
WenJie Xie ◽  
Jian Ding ◽  
XiaoAn Gong ◽  
...  
Keyword(s):  
T Cell ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Lung Tissue ◽  
Acute Injury ◽  
Tissue Homogenate ◽  
Control Group ◽  
Pathological Features ◽  
Mhc I ◽  
Immune Effect

Objective: To explore and investigate the molecular mechanism of TLR4 mediated T cell immune effect in transfusion-induced acute injury based on SLIT2/ROBO4 signaling pathway. Methods: Sixty C57/BL6 male mice (Wild type, WT) aged 8 to 10 weeks were randomly divided into 5 groups: 1) normal type WT, 2) LPS control group of WT type lipopolysaccharide, 3) WT type TRALI group (LPS + MHC-I mAb), 4) (TLR4 antibody) lipopolysaccharide LPS control group, 5) (TLR4 antibody) TRALI group (LPS + MHC-I mAb). Mice were dosed with LPS (0.1 mg / kg), and MHC-I mAb (2 mg / kg) was injected into the tail vein 24 hours later for modeling. After 2 hours, mice were sacrificed and experimental samples were collected. HE staining was performed to detect pathological features. The myeloperoxidase (MPO) activity and the level of IL-2, IL-6, TNF, IFN-γ, IL-17A as well as IL-10 were measured in the lung tissue homogenate supernatant. Blood, spleen single cell suspension and bronchoalveolar lavage fluid (BALF) were collected to detect the ratio of Treg and Th17 cells by flow cytometry, respectively. RT-PCR and WB indicated the mRNA or protein expression of CDH5 (Cadherin-5), SLIT2 and ROBO4 in mouse lung tissue and pulmonary vascular tissue respectively. Results: TLR4 mAb treatment decreases the pathological features of LPS induced ALI model in vivo. And so does the MPO activity as well as the level of proinflammatory factors in the lung tissue. TLR4 exerts its function through the changes of Treg/Th17 ratio via SLIT2/ROBO4 signaling pathway and downregulating CDH5 and SETSIP in ALI model. Conclusion: TLR4 mediates immune response in LPS induced ALI model through SLIT2/ROBO4 signaling pathway.

Renoprotective effects of a novel Nox1/4 inhibitor in a mouse model of Type 2 diabetes

2012 ◽  
Vol 124 (3) ◽  
pp. 191-202 ◽  
Author(s):  
Mona Sedeek ◽  
Alex Gutsol ◽  
Augusto C. Montezano ◽  
Dylan Burger ◽  
Aurelie Nguyen Dinh Cat ◽  
...  
Keyword(s):  
Body Weight ◽  
Low Dose ◽  
Transforming Growth Factor ◽  
Disease Process ◽  
Thiobarbituric Acid ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
High Dose ◽  
Diabetic Mice ◽  
Mitogen Activated Protein

Nox (NADPH oxidase)-derived ROS (reactive oxygen species) have been implicated in the development of diabetic nephropathy. Of the Nox isoforms in the kidney, Nox4 is important because of its renal abundance. In the present study, we tested the hypothesis that GKT136901, a Nox1/4 inhibitor, prevents the development of nephropathy in db/db (diabetic) mice. Six groups of male mice (8-week-old) were studied: (i) untreated control db/m, (ii) low-dose GKT136901-treated db/m (30 mg/kg of body weight per day), (iii) high-dose GKT136901-treated db/m (90 mg/kg of body weight per day), (iv) untreated db/db; (v) low dose GKT136901-treated db/db; and (vi) high-dose GKT136901-treated db/db. GKT136901, in chow, was administered for 16 weeks. db/db mice developed diabetes and nephropathy as evidenced by hyperglycaemia, albuminuria and renal injury (mesangial expansion, tubular dystrophy and glomerulosclerosis). GKT136901 treatment had no effect on plasma glucose or BP (blood pressure) in any of the groups. Plasma and urine TBARSs (thiobarbituric acid-reacting substances) levels, markers of systemic and renal oxidative stress, respectively, were increased in diabetic mice. Renal mRNA expression of Nox4, but not of Nox2, increased, Nox1 was barely detectable in db/db. Expression of the antioxidant enzyme SOD-1 (superoxide dismutase 1) decreased in db/db mice. Renal content of fibronectin, pro-collagen, TGFβ (transforming growth factor β) and VCAM-1 (vascular cell adhesion molecule 1) and phosphorylation of ERK1/2 (extracellular-signal-regulated kinase 1/2) were augmented in db/db kidneys, with no change in p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase). Treatment reduced albuminuria, TBARS and renal ERK1/2 phosphorylation and preserved renal structure in diabetic mice. Our findings suggest a renoprotective effect of the Nox1/4 inhibitor, possibly through reduced oxidative damage and decreased ERK1/2 activation. These phenomena occur independently of improved glucose control, suggesting GKT136901-sensitive targets are involved in complications of diabetes rather than in the disease process.

Abstract 229: Determination of Phase-specific Biomarkers of Viral Myocarditis Induced by Theiler’s virus Using Multivariate Analyses of Viral Genome, Troponin, Transcriptome and Echocardiography Data

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Eiichiro Kawai ◽  
Seiichi Omura ◽  
Fumitaka Sato ◽  
Nicholas E Martinez ◽  
Viromi Fernando ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Replication ◽  
Microarray Data ◽  
Viral Genome ◽  
Troponin I ◽  
Multivariate Analyses ◽  
Viral Myocarditis ◽  
Myocardial Damage ◽  
Heart Tissue ◽  
Viral Rna

Viral myocarditis has been proposed to be initiated by viral replication in the heart (acute phase), followed by immune-mediated damage (subacute phase), where each phase requires anti-viral and immunomodulatory treatments, respectively. There are no specific biomarkers to distinguish acute from subacute phases of myocarditis while serum troponin, echocardiography, and myocardial biopsy data have been used for diagnosis clinically. To determine the phase-specific biomarkers, we used a mouse model for myocarditis induced by Theiler’s murine encephalomyelitis virus (TMEV), which belongs to the genus Cardiovirus, the family Picornaviridae. We conducted multivariate analyses of viral genome, serum cardiac troponin I, echocardiography, histology, and transcriptome using microarray data of the heart tissue harvested on 4 (acute) and 7 (subacute) days post infection (dpi). The level of viral RNA semi-quantified by RT-PCR was 10-fold higher on 4 dpi (ΔCt = 2.5×10-2 ± 4.9×10-3) than 7 dpi (ΔCt = 2.6×10-3 ± 3.0×10-4) (P < 0.05). Serum troponin was undetectable in 4 of 10 mice on 4 dpi and only in 1 of 10 mice on 7 dpi; the serum troponin levels (ng/ml) on 4 dpi (42.9 ± 15.6) were significantly lower than 7 dpi (249.9 ± 62.8) (P < 0.05). The levels of viral RNA and troponin were strongly correlated on 4 dpi (r = 0.79, P < 0.05), but not 7 dpi (P = 0.12), suggesting that viral replication could be a major cause of myocardial damage only on 4 dpi. We found multiple high intensity cardiac lesions using echocardiography with histological myocarditis on 7 dpi, but not 4 dpi. Transcriptome analyses of microarray data showed upregulation of genes associated with innate immune responses in samples from 4 and 7 dpi, compared with controls. Samples from 7 dpi showed upregulation of genes associated with T, B, and antigen presenting cells and downregulation of cardiac myosin-related genes (Myl4, Myl7, and Mybphl), compared with 4 dpi, suggesting that acquired immune responses contribute to cardiomyocyte damage on 7 dpi. In summary, the chronological order of emergence of biomarker candidates was 1) viral genome and innate immunity, 2) troponin, and 3) acquired immunity and echo and histological changes.

scholarly journals Salidroside pretreatment protects against myocardial injury induced by heat stroke in mice

2019 ◽  
Vol 47 (10) ◽  
pp. 5229-5238
Author(s):  
Guo-dong Chen ◽  
Heng Fan ◽  
Jian-Hua Zhu
Keyword(s):  
Oxidative Stress ◽  
Myocardial Injury ◽  
Troponin I ◽  
Heat Stroke ◽  
Cardiac Injury ◽  
Myocardial Damage ◽  
Thiobarbituric Acid ◽  
Protective Effects ◽  
Creatine Kinase Mb ◽  
Factor Α

Objective To explore the protective effects and mechanisms of salidroside on myocardial injury induced by heat stroke (HS) in mice. Methods We pretreated mice with salidroside for 1 week and then established an HS model by exposure to 41.2°C for 1 hour. We then examined the effects of salidroside on survival. We also assessed the severity of cardiac injury by pathology, and analyzed changes in levels of myocardial injury markers, inflammatory cytokines, and oxidative stress. Results Salidroside pretreatment significantly reduced HS-induced mortality and improved thermoregulatory function. Salidroside also provided significant protection against HS-induced myocardial damage, and decreased the expression levels of cardiac troponin I, creatine kinase-MB, and lactate dehydrogenase. Moreover, salidroside attenuated HS-induced changes in the inflammation markers tumor necrosis factor-α, interleukin (IL)-6, and IL-10, and down-regulated the oxidative stress response indicated by thiobarbituric acid reactant substances, malondialdehyde, reduced glutathione, and superoxide dismutase. Conclusions Salidroside pretreatment protected against HS-induced myocardial damage, potentially via a mechanism involving anti-inflammatory and anti-oxidative effects.

scholarly journals Continuous Infusion of Flumazenil in the Management of Benzodiazepines Detoxification

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna Benini ◽  
Rossella Gottardo ◽  
Cristiano Chiamulera ◽  
Anna Bertoldi ◽  
Lorenzo Zamboni ◽  
...  
Keyword(s):  
Plasma Level ◽  
Hospital Admission ◽  
Continuous Infusion ◽  
Clinical Setting ◽  
Withdrawal Syndrome ◽  
Withdrawal Symptoms ◽  
High Dose ◽  
End Of Treatment ◽  
Before And After ◽  
Treatment Changes

An effective approach in the treatment of benzodiazepine (BZD) overdosing and detoxification is flumazenil (FLU). Studies in chronic users who discontinued BZD in a clinical setting suggested that multiple slow bolus infusions of FLU reduce BZD withdrawal symptoms. The aim of this study was to confirm FLU efficacy for reducing BZD withdrawal syndrome by means of continuous elastomeric infusion, correlated to drugs plasma level and patients' compliance.Methods: Seven-day FLU 1 mg/day subcutaneously injected through an elastomeric pump and BZDs lormetazepam, clonazepam, and lorazepam were assessed by HPLC-MS/MS in serum of patients before and after 4 and 7 days of FLU continuous infusion treatment. Changes in withdrawal severity were assessed by using the BZD Withdrawal Scale (BWS).Results: Fourteen patients (mean age ± SD 42.5 ± 8.0 years, 5 male and 9 female), admitted to the hospital for high-dose BZD detoxification, were enrolled in the study. Serum FLU concentrations significantly decreased from 0.54 ± 0.33 ng/ml (mean ± SD) after 4 days of treatment to 0.1 ± 0.2 ng/ml at the end of infusion. Lormetazepam concentrations were 502.5 ± 610.0 ng/ml at hospital admission, 26.2 ± 26.8 ng/ml after 4 days, and 0 at the end of treatment. BWS values decreased during FLU treatment temporal period. FLU was well-tolerated by patients.Conclusions: Elastomeric FLU infusion for BZD detoxification is a feasible administration device to maintain adequate, constant, and tolerated FLU concentrations for reducing BZD withdrawal symptoms.

scholarly journals Out-patient high-dose-rate endobronchial brachytherapy for palliation of lung cancer: an observational study

2016 ◽  
Vol 67 (3) ◽  
Author(s):  
A. Scarda ◽  
M. Confalonieri ◽  
C. Baghiris ◽  
S. Binato ◽  
R. Mazzarotto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Observational Study ◽  
Dose Rate ◽  
Malignant Tumour ◽  
High Dose Rate ◽  
Advanced Lung Cancer ◽  
High Dose ◽  
End Of Treatment ◽  
Co Morbidity ◽  
Central Airway

Background and Aim. Out-patient high-dose-rate endobronchial brachytherapy (HDREB) is a possible option in the palliation of symptoms in patients with advanced lung cancer, but literature data is limited and the technique is still under development in Italy. Our aim was to evaluate safety and effectiveness of out-patient HDREB for palliation of malignant endobronchial tumours in the context of a multidisciplinary approach. Methods. Out-patient HDREB sessions were scheduled at weekly intervals (500-1000 cGy per session) with prior Diodi-laser resection in some cases. Response was assessed bronchoscopically, clinically and functionally at the end of treatment and one month after the last HDREB session. Inclusion criteria was: histological evidence of malignant tumour not susceptible to surgical treatment for extension or co-morbidity. Results. 150 outpatient HDREB sessions were carried out on consecutive 35 patients (mean age 69 yrs, M/F 29/6) with symptoms due to central airway obstruction. A shortterm endoscopic response was observed in 15/28 patients. After delivering 2000 cGy dyspnoea decreased significantly. After one month cough decreased and haemoptysis disappeared. Palliation was obtained in all patients except one during. Lung function tests did not significantly improve after HDREB. No fatal complication occurred. A temporary radiation bronchitis was observed in six patients. Conclusions. This non-comparative, prospective observational study showed a palliative response of HDREB in most of patients with advanced endoluminal lung cancer. The safety of the procedure was good and the rate of non-fatal serious complications was very low.

Arbutin prevents alterations in mitochondrial and lysosomal enzymes in isoproterenol-induced myocardial infarction: An in vivo study

2020 ◽  
Vol 40 (1) ◽  
pp. 100-112
Author(s):  
S Sivasangari ◽  
L Asaikumar ◽  
L Vennila
Keyword(s):  
Myocardial Infarction ◽  
Lysosomal Enzymes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Heart Tissue ◽  
Lipoprotein Cholesterol ◽  
Tissue Homogenate ◽  
Mitochondrial Enzymes ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

The present study demonstrated the protective effects of arbutin (ARB) on hyperlipidemia, mitochondrial, and lysosomal membrane damage and on the DNA damage in rats with isoproterenol (ISO)-induced myocardial infarction (MI). Rats were pretreated with ARB (25 and 50 mg/kg body weight (bw)) for 21 days. After pretreatment with ARB, MI was induced by subcutaneous injection of ISO (60 mg/kg bw) for two consecutive days at an interval of 24 h. The levels of TC, TG, and FFA were increased and decreased the level of PL in the heart tissue of ISO-induced MI rats. Very-low-density lipoprotein cholesterol and low-density lipoprotein cholesterol were increased while high-density lipoprotein cholesterol was decreased in the plasma of ISO-administered rats. A heart mitochondrial fraction of the ISO rats showed a significant decrease in the activities of mitochondrial enzymes isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase. The activities of lysosomal enzymes (β-glucosidase, β-glucuronidase, α-galactosidase, β-galactosidase, cathepsin-B, and cathepsin-D) were increased significantly in the heart tissue homogenate of disease control rats. In ISO-induced MI, rat’s significant increase in the percentage of tail DNA and tail length, and a decrease in the level of head DNA were also observed. ARB administration to MI rats brought all these parameters to near normality, showing the protective effect of ARB against MI in rats. The results of this study demonstrated that the 50 mg/kg bw of ARB shows higher protection than 25 mg/kg bw against ISO-induced damage.

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