scholarly journals Therapeutic activity of sarpogrelate, and dopamine D2 receptor agonists on cardiovascular and renal systems in alloxan-induced diabetic rats

2020 ◽  
Author(s):  
Mohamed Fouad ◽  
Hekma A. Abd El Latif ◽  
May Galal ◽  
Mohammed El Yamani ◽  
Sherifa Hassaneen ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Myocardial Injury ◽  
Troponin I ◽  
Staining Method ◽  
Diabetic Rats ◽  
Tetrazolium Chloride ◽  
Blood Concentrations ◽  
Dopamine D2 ◽  
Long Term Treatment ◽  
Kidney Hypertrophy

Abstract Background: The investigation aims to represent the activity of sarpogrelate, a particular 5-HT (2A) receptor blocker, in reducing myocardial injury prompted by extended haul utilization of D2 agonist drugs in diabetic rats. Dopamine D2 agonists are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia. An affiliation showed between the enlistment of myocardial injury ailment and long term treatment with dopamine D2 agonist drugs identified with the partial initiation of 5-HT 2a receptors. Methods: Both bromocriptine and cabergoline were managed independently and combined with sarpogelate for about a month to diabetic nephropathy rats. Both tail-cuff blood pressure and BGL were recorded weekly. For all animals, kidney hypertrophy index, serum creatinine, blood urea nitrogen, alanine transaminase, and aspartate transaminase levels were measured after one month of treatment. The severity of the cardiac injury was assessed by the estimation of LDH-1, cardiac troponin I, and TNFα. Triphenyl tetrazolium chloride staining method used to determine experimental myocardial infarction (MI) size. Results: Bromocriptine and cabergoline created a significant reduction in BGL, BP, and kidney hypertrophy index in diabetic nephropathy rats. Administration of bromocriptine, cabergoline, alone, or in combination with sarbogrelate fundamentally diminished blood concentrations of ALP, AST, urea, and creatinine. Bromocriptine and cabergoline alone showed noteworthy ascending of LDH-1, Troponin I, and TNFα1 levels in the serum (p<0.05). Paradoxically, utilizing bromocriptine and cabergoline with sarpogrelate treatment altogether diminished the degree of the myocardial biomarkers in the serum. A mix of bromocriptine or cabergoline with sarpogrelate diminished the level of the myocardial infarct size in the heart assessed utilizing the TTC staining method. Conclusions: The examination exhibited that both bromocriptine and cabergoline could be utilized safely in blend with sarpogrelate for a long duration of treatment for diseases like hypertension and diabetes.

scholarly journals Therapeutic activity of sarpogrelate and dopamine D2 receptor agonists on cardiovascular and renal systems in rats with alloxan-induced diabetes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mohammed Ahmed Fouad Shalaby ◽  
Hekma A. Abd El Latif ◽  
Mohamed El Yamani ◽  
May Ahmed Galal ◽  
Sherifa Kamal ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Myocardial Injury ◽  
Troponin I ◽  
Staining Method ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Blood Concentrations ◽  
Receptor Agonists ◽  
Long Term Treatment ◽  
Kidney Hypertrophy

Abstract Background Dopamine D2 receptor agonists, bromocriptine and cabergoline, are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia. An affiliation was found between the initiation of myocardial injury ailment and long term treatment with dopamine D2 agonist drugs identified with the partial activation of 5-hydroxytryptamine receptor 2 A (5-HT2A). The investigation aimed to examine the activity of sarpogrelate (a 5-HT2A receptor blocker) in reducing myocardial injury prompted by extended haul utilisation of D2 receptor agonists in rats with alloxan-induced diabetes. Methods Both bromocriptine and cabergoline were managed independently and combined with sarpogrelate for about a month in diabetic nephropathy rats. Both tail-cuff blood pressure and the BGL were recorded weekly. For all animals, the kidney hypertrophy index, serum creatinine, blood urea nitrogen, alanine transaminase, and aspartate transaminase levels were measured after one month of treatment. The severity of the cardiac injury was assessed by the estimation of lactate dehydrogenase-1 (LDH-1), cardiac troponin I, and tumor necrosis factor alpha 1 (TNF1). The triphenyltetrazolium chloride (TTC) staining method was used to determine the experimental myocardial infarction (MI) size. Results Bromocriptine and cabergoline created a significant reduction in BGL, BP, and kidney hypertrophy index in diabetic nephropathy rats. Administration of bromocriptine and cabergoline, alone, or in combination with sarpogrelate fundamentally diminished the blood concentrations of alkaline phosphatase (ALP), Aspartate aminotransferase (AST), urea, and creatinine. Bromocriptine and cabergoline alone showed a noteworthy increase in the LDH-1, Troponin I, and TNF1 levels in the serum (p < 0.05). Paradoxically, utilising bromocriptine or cabergoline with sarpogrelate treatment altogether decreased the levels of the myocardial biomarkers in the serum. A mix of bromocriptine or cabergoline with sarpogrelate diminished the level of the myocardial infarct size in the heart assessed through the TTC staining method. Conclusions The examination demonstrated that the combined use of sarpogrelate with bromocriptine or cabergoline decreased the potential adverse effects of these two drugs on the myocardial tissues.

scholarly journals Therapeutic activity of sarpogrelate, and dopamine D2 receptor agonists on cardiovascular and renal systems in alloxan-induced diabetic rats

2020 ◽  
Author(s):  
Mohamed Fouad ◽  
Hekma A. Abd El Latif ◽  
May Galal ◽  
Mohammed El Yamani ◽  
Sherifa Hassaneen ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Myocardial Injury ◽  
Troponin I ◽  
Dopamine D2 Receptor ◽  
Myocardial Infarct ◽  
D2 Receptor ◽  
Myocardial Infarct Size ◽  
Duration Of Treatment ◽  
Blood Concentrations ◽  
Dopamine D2

Abstract Background Dopamine D2 agonists are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia. An affiliation showed between the enlistment of myocardial injury ailment and long haul treatment with dopamine D2 agonist drugs identified with the partial initiation of 5-HT 2a receptors.Methods The investigation aims to represent the activity of sarpogrelate, a particular 5-HT (2A) receptor blocker, in diminishing myocardial injury prompted by extended haul utilization of D2 agonist drugs in diabetic rodents. Both bromocriptine and cabergoline managed independently and combined with sarpogelate for about a month to diabetic nephropathy rats.Results Bromocriptine and cabergoline created a significant reduction in BGL, BP, and kidney hypertrophy index in diabetic nephropathy rats. Administration of bromocriptine, cabergoline, alone, or in combination with sarbogrelate fundamentally diminished blood concentrations of ALP, AST, urea, and creatinine. Bromocriptine and cabergoline alone showed noteworthy ascending of LDH-1, Troponin I, and TNFα1 levels in the serum (p < 0.05). Paradoxically, utilizing bromocriptine and cabergoline with sarpogrelate treatment altogether diminished the degree of the myocardial biomarkers in the serum. A mix of bromocriptine or cabergoline with sarpogrelate diminished the level of the myocardial infarct size in the heart assessed utilizing the TTC staining method.Conclusions The examination exhibited that both bromocriptine and cabergoline could be utilized securely in blend with sarpogrelate for a long duration of treatment for diseases like hypertension and diabetes.

scholarly journals Cardiac, Energy and Hormonal Blood Markers, and Lactatemia in Cows with Displaced Abomasum

2020 ◽  
Vol 48 ◽  
Author(s):  
Ana Clara Sarzedas Ribeiro ◽  
Gliére Silmara Leite Soares ◽  
Luiz Teles Coutinho ◽  
Jobson Filipe De Paula Cajueiro ◽  
Rodolfo José Cavalcanti Souto ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Insulin Sensitivity ◽  
Myocardial Injury ◽  
Troponin I ◽  
Cardiac Biomarkers ◽  
Lower Sensitivity ◽  
Blood Concentrations ◽  
Peripheral Tissues ◽  
Creatine Kinase Mb ◽  
Cardiac Energy

Background: Displaced abomasum (DA) is a common and economically important disorder that affects dairy cattle. Nutritional factors and adaptive responses that occur in the peripartum play a central role in the pathogenesis. The measurement of blood metabolites represents a useful tool for monitoring and prognostic determination in affected animals. Therefore, the objective was to evaluate cardiac, energy and hormonal blood markers, lactatemia, and insulin sensitivity in cows diagnosed with right displaced abomasum (RDA) and left displaced abomasum (LDA), comparing them with each other.Materials, Methods & Results: Nineteen cases of abomasum displacement in cows were studied, including 9 cases of RDA and 10 cases of LDA. The diagnosis was established by means of physical examination and measurement of the concentration of chlorides in the ruminal fluid (> 30mEq/L). After diagnosis, clinical-surgical therapeutic management was instituted. At the time of diagnosis (M1) and at the resolution of the case (M2), blood samples were collected to assess the variables: non-esterified fatty acids (NEFA), beta hydroxybutyrate (βHB), L-lactate, creatine kinase (CK), creatine kinase MB (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), glucose, insulin, and cortisol. In addition, insulin sensitivity was estimated using the Revised Quantitative Insulin Sensitivity Check Index (RQUICKI) and RQUICKI-βHB. The means of the variables were compared, separating the effects of groups (RDA and LDA) and moments (M1 and M2), at the level of 5% probability. The concentrations of NEFA, CK-MB, L-lactate, glucose, insulin, and cortisol were higher at M1 and the RQUICKI and RQUICKI-βHB indices were lower at this moment. L-lactate, CK, and CK-MB were higher in the RDA group, while cTnI, βHB, and LDH did not present a group or moment effect. Cardiac markers correlated with the energy profile metabolites, L-lactate, and cortisol.Discussion: The high concentrations of NEFA at M1 reflected the condition of negative energy balance. βHB concentrations were stable, that may be related to the number of days postpartum in which the animals were diagnosed. The hyperglycemic condition and the increase in serum cortisol concentrations found at M1 can be induced by the condition of metabolic stress resulting from the disease. Hyperinsulinemia were recorded in the present study could be an important factor related to the pathogenesis of DA, since there seems to be a correlation between hyperinsulinemia and decreased abomasal emptying rate. The RQUICKI and RQUICKI-βHB indices was significantly lower at M1, which may indicate lower sensitivity of peripheral tissues to insulin at this time. Changes in serum activity of LDH and CK may result from tissue damage due to organ displacement, in addition to damage associated with surgery and the administration of injectable drugs, mainly intramuscularly. The elevation in plasma L-lactate at M1 and in the RDA group may be associated with abomasal hypoperfusion. The high positive correlations found between L-lactate and the variables glucose, insulin, and cortisol reinforcing the association between the concentration of L-lactate and the moment of greatest stress. The increase in cardiac biomarkers may be related to the occurrence of ischemia/reperfusion injury in the abomasum, which involves oxidative stress and the production of inflammatory mediators. The hyperglycemic condition and the higher concentrations of NEFA can also contribute to the occurrence of myocardial injury. The correlations found between cardiac biomarkers and plasma L-lactate, strengthen the idea that there is a relationship between L-lactate and myocardial injury. In this sense, the measurement of blood concentrations of cTnI, CK-MB, and L-lactate could contribute as severity markers and prognosis indicators in cattle with DA. 

scholarly journals Effects of Low-Dose and Early versus Late Perindopril Treatment on the Progression of Severe Diabetic Nephropathy in (mREN-2)27 Rats

2002 ◽  
Vol 13 (3) ◽  
pp. 684-692
Author(s):  
Sally A. Mifsud ◽  
Sandford L. Skinner ◽  
Mark E. Cooper ◽  
Darren J. Kelly ◽  
Jennifer L. Wilkinson-Berka
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Early Treatment ◽  
Enzyme Inhibitor ◽  
Late Onset ◽  
Diabetic Rats ◽  
Moderate Increase ◽  
Citrate Buffer ◽  
Late Intervention ◽  
Kidney Hypertrophy

ABSTRACT. It was previously reported that transgenic (mRen-2)27 rats with streptozotocin-induced diabetes mellitus progressively develop advanced nephropathy in 12 wk. These lesions are largely prevented when the angiotensin-converting enzyme inhibitor perindopril is administered from the time of induction of diabetes mellitus. This study aimed to determine the lowest dose of early perindopril treatment required for substantial improvement of renal function and structure and to investigate whether late intervention prevents or reverses the progression of established renal lesions. At 6 wk of age, female heterozygous Ren-2 rats were randomized to receive either streptozotocin (diabetic) or citrate buffer (control). Rats were gavaged, beginning early after the induction of diabetes mellitus or the administration of control vehicle, with 0, 0.02, 0.2, or 2 mg/kg per d perindopril for 12 wk. A separate group of diabetic Ren-2 rats received late treatment with 2 mg/kg per d perindopril throughout week 8 to week 12, when rats were hypertensive and albuminuric and exhibited increased kidney weight and glomerulosclerotic index (GSI). Among diabetic rats, early 0.02 mg/kg per d perindopril treatment reduced systolic BP, GSI, and renal collagen staining but had no effect on albuminuria or kidney hypertrophy. Early 0.2 or 2 mg/kg per d perindopril treatment further reduced systolic BP, GSI, and renal collagen staining and decreased albuminuria and kidney hypertrophy. Late intervention was as antihypertensive and antialbuminuric as early 0.2 or 2 mg/kg per d perindopril treatment but did not prevent a moderate increase in GSI. In conclusion, early treatment with 0.2 mg/kg per d perindopril was the lowest dosage to largely prevent severe diabetic nephropathy in transgenic Ren-2 rats. Late-onset perindopril treatment of diabetic rats with established nephropathy was as efficacious as early treatment with respect to various renal parameters, such as albuminuria, but was associated with moderate progression of glomerulosclerosis.

scholarly journals Reducing NADPH Synthesis Counteracts Diabetic Nephropathy through Restoration of AMPK Activity in Type 1 Diabetic Rats

Cell Reports ◽  
2020 ◽  
Vol 32 (13) ◽  
pp. 108207
Author(s):  
Xiao Wei ◽  
Zongshi Lu ◽  
Li Li ◽  
Hexuan Zhang ◽  
Fang Sun ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Diabetic Rats ◽  
Ampk Activity

scholarly journals Misclassification of Myocardial Injury by a High-Sensitivity Cardiac Troponin I Assay

2021 ◽  
Author(s):  
Peter A. Kavsak ◽  
Shawn Mondoux ◽  
Andrew Worster ◽  
Janet Martin ◽  
Vikas Tandon ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
High Sensitivity ◽  
Cardiac Troponin I

scholarly journals The role of neurohormonal blockers in the primary prevention of acute-, early-, and late-onset anthracycline-induced cardiotoxicity

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Ahmed Ayuna ◽  
Nik Abidin
Keyword(s):  
Primary Prevention ◽  
Myocardial Injury ◽  
Troponin I ◽  
Late Onset ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Main Body ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

Abstract Background Anthracycline-induced cardiotoxicity has been classified based on its onset into acute, early, and late. It may have a significant burden on the quality and quantity of life of those exposed to this class of medication. Currently, there are several ongoing debates on the role of different measures in the primary prevention of cardiotoxicity in cancer survivors. Our article aims to focus on the role of neurohormonal blockers in the primary prevention of anthracycline-induced cardiotoxicity, whether it is acute, early, or late onset. Main body of the abstract PubMed and Google Scholar database were searched for the relevant articles; we reviewed and appraised 15 RCTs, and we found that angiotensin-converting enzyme inhibitors (ACEI) and B-blockers were the most commonly used agents. Angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRAs) were used in a few other trials. The follow-up period was on the range of 1–156 weeks (mode 26 weeks). Left ventricular ejection fraction (LVEF), left ventricular diameters, and diastolic function were assessed by either echocardiogram or occasionally by cardiac magnetic resonance imaging (MRI). The occurrence of myocardial injury was assessed by troponin I. It was obvious that neurohormonal blockers reduced the occurrence of LVEF and myocardial injury in 14/15 RCTs. Short conclusion Beta-blockers, especially carvedilol and ACEI, especially enalapril, should be considered for the primary prevention of acute- and early-onset cardiotoxicity. ARB and MRA are suitable alternatives when patients are intolerant to ACE-I and B-blockers. We recommend further studies to explore and establish the role of neurohormonal blockers in the primary prevention of the acute-, early-, and late-onset cardiotoxicity.

scholarly journals Longitudinal obesity exposure over two decades is associated with subclinical myocardial injury: the Nord-Trondelag Health Study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.N Lyngbakken ◽  
H Rosjo ◽  
K Hveem ◽  
T Omland
Keyword(s):  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
Linear Increase ◽  
Normal Weight ◽  
Public Institution ◽  
Health Study ◽  
Funding Source ◽  
Study Visit ◽  
Increased Risk

Abstract Background Obesity is associated with subclinical myocardial injury as quantified by concentrations of cardiac troponin, but whether excess weight history is associated with increased cardiac troponin I (cTnI) remains unclear. We aimed to explore the association of obesity with cTnI using different indices of cumulative obesity exposure. Methods We analyzed cTnI with a high-sensitivity assay in 14,157 participants with follow-up over two decades in the prospective observational Nord-Trøndelag Health (HUNT) Study at study visit 4 (2017–2019). All subjects were free from known cardiovascular disease at baseline, and we excluded subjects with BMI &lt;18.5 kg/m2. BMI was assessed at study visit 2 (1995–1997), 3 (2006–2008) and 4, and we categorized participants as normal weight (BMI &lt;25), overweight (BMI ≥25 to &lt;30) and obesity (BMI ≥30). At each study visit, BMI was designated a score of 0 (normal weight), 1 (overweight) or 2 (obesity), totaling a score from 0 to 6. Cumulative obesity exposure was calculated as average BMI above 25 kg/m2 between visits multiplied by the time between visits (excess BMI years, kg/m2 × years). Results Median age at visit 4 was 64.1 (range 40.9 to 101.5) years and 60% were women. Concentrations of cTnI were detectable in 77.2% of study participants, and were median 2.2 (1.3 to 3.9) ng/L. There was a linear increase in cTnI with increasing BMI score (p for trend &lt;0.001) and increasing BMI score was associated with increased risk of high cTnI (p for trend &lt;0.001; Table 1). For every 100 excess BMI years, there was a 15.6 (95% CI, 13.0 to 18.2) % increase in cTnI at study visit 4 (Figure 1). Conclusion Cumulative obesity exposure is associated with a linear increase in cTnI, a highly sensitive index of subclinical myocardial injury, reflecting the detrimental effect of long standing obesity on cardiovascular health. Figure 1. BMI years and cTnI Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): South-Eastern Norway Regional Health Authority

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