Solasonine ameliorates cerebral ischemia-reperfusion injury via suppressing TLR4/MyD88/NF-κB pathway and activating AMPK/Nrf2/HO-1 pathway
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Cited by 2 publications
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Protective effect of canagliflozin on post-resuscitation myocardial function in a rat model of cardiac arrest
Background Currently, most patients with cardiac arrest (CA) show reversible myocardial dysfunction, hemodynamic instability, systemic inflammation and other pathophysiological state in early stage of resuscitation, some patients may eventually progress to multiple organ failure. There is evidence that heart failure is the terminal stage in the development of various cardiovascular diseases. Although the cardio-protective effect of canagliflozin (CANA) has been confirmed in large clinical studies and recommended in domestic and international heart failure-related guidelines, the effectiveness of CANA after resuscitation remains unclear. In this study, we constructed a modified CA/CPR rat model to investigate whether CANA administered on post-resuscitation improves myocardial function. Methods Twenty-fourth healthy male Sprague–Dawley rats were randomized into four groups: (1) Sham + placebo group, (2) Sham + CANA group, (3) CPR + placebo group, and (4) CPR + CANA group. Ventricular fibrillation was induced by transcutaneous electrical stimulation on epicardium. After 6 min untreated ventricular fibrillation, chest compressions was initiated. The rats were received an injection of placebo or canagliflozin (3 ug/kg) randomly 15 min after restore of spontaneous circulation (ROSC). Electrocardiogram (ECG) and blood pressure were continuously detected in each group throughout the experiment. The rats were killed 6 h after ROSC to collected the arterial serum and myocardial tissue. Myocardial injury was estimated with concentrations of inflammatory factors, oxidative stress indexes and, apoptosis index, myocardial injury markers, echocardiography and myocardial pathological slices. Results After resuscitation, mean arterial pressure (MAP) were significantly increased after cardiopulmonary resuscitation in CANA group rats when compared with placebo group. Heart rate, body lactate returned and left ventricular ejection fraction (LVEF) to normal levels in a shorter time and the myocardial injury was obviously attenuated in CPR + CANA group. Inflammatory factors (IL-6, TNF-α) and oxidative stress indexes (MAD, SOD, CAT) were dramatically decreased with the administration of CANA. The expression of apoptosis index (BAX, caspase-3) were higher in CPR + placebo group and the expression of anti-apoptosis index (Bcl-2) was lower (P < 0.05). Conclusions The administration of CANA effectively reduces myocardial ischaemia/reperfusion (I/R) injury after cardiac arrest and cardiopulmonary resuscitation (CPR), and the underlying mechanism may be related to anti-inflammation, oxidative stress and apoptosis.
Protective effect of canagliflozin on post-resuscitation myocardial function in a rat model of cardiac arrest
Background Currently, most patients with cardiac arrest (CA) show reversible myocardial dysfunction, hemodynamic instability, systemic inflammation and other pathophysiological state in early stage of resuscitation, some patients may eventually progress to multiple organ failure. There is evidence that heart failure is the terminal stage in the development of various cardiovascular diseases. Although the cardio-protective effect of canagliflozin (CANA) has been confirmed in large clinical studies and recommended in domestic and international heart failure-related guidelines, the effectiveness of CANA after resuscitation remains unclear. In this study, we constructed a modified CA/CPR rat model to investigate whether CANA administered on post-resuscitation improves myocardial function. Methods Twenty-fourth healthy male Sprague–Dawley rats were randomized into four groups: (1) Sham + placebo group, (2) Sham + CANA group, (3) CPR + placebo group, and (4) CPR + CANA group. Ventricular fibrillation was induced by transcutaneous electrical stimulation on epicardium. After 6 min untreated ventricular fibrillation, chest compressions was initiated. The rats were received an injection of placebo or canagliflozin (3 ug/kg) randomly 15 min after restore of spontaneous circulation (ROSC). Electrocardiogram (ECG) and blood pressure were continuously detected in each group throughout the experiment. The rats were killed 6 h after ROSC to collected the arterial serum and myocardial tissue. Myocardial injury was estimated with concentrations of inflammatory factors, oxidative stress indexes and, apoptosis index, myocardial injury markers, echocardiography and myocardial pathological slices. Results After resuscitation, mean arterial pressure (MAP) were significantly increased after cardiopulmonary resuscitation in CANA group rats when compared with placebo group. Heart rate, body lactate returned and left ventricular ejection fraction (LVEF) to normal levels in a shorter time and the myocardial injury was obviously attenuated in CPR + CANA group. Inflammatory factors (IL-6, TNF-α) and oxidative stress indexes (MAD, SOD, CAT) were dramatically decreased with the administration of CANA. The expression of apoptosis index (BAX, caspase-3) were higher in CPR + placebo group and the expression of anti-apoptosis index (Bcl-2) was lower (P < 0.05). Conclusions The administration of CANA effectively reduces myocardial ischaemia/reperfusion (I/R) injury after cardiac arrest and cardiopulmonary resuscitation (CPR), and the underlying mechanism may be related to anti-inflammation, oxidative stress and apoptosis.
Mechanisms of mitophagy and oxidative stress in cerebral ischemia–reperfusion, vascular dementia, and Alzheimer’s disease
Neurological diseases have consistently represented a significant challenge in both clinical treatment and scientific research. As research has progressed, the significance of mitochondria in the pathogenesis and progression of neurological diseases has become increasingly prominent. Mitochondria serve not only as a source of energy, but also as regulators of cellular growth and death. Both oxidative stress and mitophagy are intimately associated with mitochondria, and there is mounting evidence that mitophagy and oxidative stress exert a pivotal regulatory influence on the pathogenesis of neurological diseases. In recent years, there has been a notable rise in the prevalence of cerebral ischemia/reperfusion injury (CI/RI), vascular dementia (VaD), and Alzheimer’s disease (AD), which collectively represent a significant public health concern. Reduced levels of mitophagy have been observed in CI/RI, VaD and AD. The improvement of associated pathology has been demonstrated through the increase of mitophagy levels. CI/RI results in cerebral tissue ischemia and hypoxia, which causes oxidative stress, disruption of the blood–brain barrier (BBB) and damage to the cerebral vasculature. The BBB disruption and cerebral vascular injury may induce or exacerbate VaD to some extent. In addition, inadequate cerebral perfusion due to vascular injury or altered function may exacerbate the accumulation of amyloid β (Aβ) thereby contributing to or exacerbating AD pathology. Intravenous tissue plasminogen activator (tPA; alteplase) and endovascular thrombectomy are effective treatments for stroke. However, there is a narrow window of opportunity for the administration of tPA and thrombectomy, which results in a markedly elevated incidence of disability among patients with CI/RI. It is regrettable that there are currently no there are still no specific drugs for VaD and AD. Despite the availability of the U.S. Food and Drug Administration (FDA)-approved clinical first-line drugs for AD, including memantine, donepezil hydrochloride, and galantamine, these agents do not fundamentally block the pathological process of AD. In this paper, we undertake a review of the mechanisms of mitophagy and oxidative stress in neurological disorders, a summary of the clinical trials conducted in recent years, and a proposal for a new strategy for targeted treatment of neurological disorders based on both mitophagy and oxidative stress.
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