Adenine-Induced Chronic Renal Failure in Rats: A Model of Chronic Renocardiac Syndrome with Left Ventricular Diastolic Dysfunction but Preserved Ejection Fraction. | LitMetric
Background/aims: Cardiovascular disease is the major cause of death in patients with chronic kidney disease (CKD). Rats with adenine-induced chronic renal failure (ACRF) develop severe renal insufficiency and metabolic abnormalities that closely resemble those in patients with uremia. The aim of the present study was to determine left ventricular (LV) morphology and function in rats with ACRF.
Methods: Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without adenine (controls, C). After 9-13 weeks animals were anesthetized with isoflurane and cardiac function was assessed both by echocardiography and by LV catheterization.
Results: Rats with ACRF showed increases in serum creatinine (323±107 vs. 33±5 µM, P< 0.05), mean arterial pressure (115±6 vs. 106±7 mmHg, P< 0.05) and LV weight (3.4±0.3 vs. 2.5±0.2 mg/kg, P< 0.05) vs. controls. Rats with ACRF had reduced early diastolic tissue Doppler velocities in the LV, enlarged left atrial diameter (4.8±0.8 vs. 3.5±0.4 mm, P< 0.05) and elevated LV end-diastolic pressure (15±5 vs. 8±1 mmHg, P< 0.01). Cardiac output was increased in ACRF rats (211±66 vs. 149±24 ml/min, P< 0.05) and systolic function preserved. In the LV of ACRF rats there were statistically significant (P< 0.05) increases in cardiomyocyte diameter, proliferation and apoptosis, while there was no difference between groups in fibrosis.
Conclusion: Rats with ACRF develop LV hypertrophy and diastolic dysfunction while systolic performance was preserved. There was an increased hypertrophy and apoptosis of cardiomyocytes in the LV of ACRF rats. The cardiac abnormalities in ACRF rats resemble those in patients with CKD in which heart failure with preserved ejection fraction is common. Hence, this experimental model is well suited for studying pathophysiological mechanisms in chronic renocardiac syndromes.
Aims: Acute myocardial infarction causes lethal cardiomyocyte injury during ischaemia and reperfusion (I/R). Histones have been described as important Danger Associated Molecular Proteins (DAMPs) in sepsis. The objective of this study was to establish whether extracellular histone release contributes to myocardial infarction.
ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 2601, Australia.
Extracellular histones in neutrophil extracellular traps (NETs) or in chromatin from injured tissues are highly pathological, particularly when liberated by DNases. We report the development of small polyanions (SPAs) (~0.9-1.
A high-throughput screening aimed at finding new inhibitors for the KAT6A enzyme led to the identification of CTX-0124143, an aryl acylsulfonohydrazide with an inhibitory concentration (IC) of 1.0 μM.
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A notable outcome of this research was the discovery of WM-1119, a highly potent KAT6A inhibitor with IC of 6.3 nM, which binds to the Ac-CoA site and demonstrates a 56% oral bioavailability in
Department of Pharmacology, EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia.
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Purpose: This work describes the first live imaging and radiation delivery performed on a prototype 1.0 T inline MRI-Linac system in a rat brain tumor model, which was conducted on 29 January 2019.
