Interrupted ER homeostasis contributes to the etiology of obesity cardiomyopathy although it remains elusive how ER stress evokes cardiac anomalies in obesity. Our study evaluated the impact of ER stress inhibition on cardiac anomalies in obesity. Lean and ob/ob obese mice received chemical ER chaperone tauroursodeoxycholic acid (TUDCA, 50 mg/kg/d, p.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
December 2023
Binge drinking exerts cardiac toxicity through various mechanisms, including oxidative stress and inflammation. NLRP3 inflammasomes possess both pro- and anti-inflammatory properties, although the role of NLRP3 in ethanol-induced cardiotoxicity remains unknown. This study is designed to examine the role of NLRP3 inflammasome in acute ethanol cardiotoxicity and the underlying mechanisms of action.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
February 2024
Advanced aging evokes unfavorable changes in the heart including cardiac remodeling and contractile dysfunction although the underlying mechanism remains elusive. This study was conducted to evaluate the role of endothelin-1 (ET-1) in the pathogenesis of cardiac aging and mechanism involved. Echocardiographic and cardiomyocyte mechanical properties were determined in young (5-6 mo) and aged (26-28 mo) wild-type (WT) and cardiomyocyte-specific ET receptor knockout (ETKO) mice.
View Article and Find Full Text PDFInhibiting aldose reductase (ALR2, AR) as well as maintaining a concomitant antioxidant (AO) activity via dual-acting agents may be a rational approach to prevent cellular glucotoxicity and at least delay the progression of diabetes mellitus (DM). This study was aimed at evaluating the dual-acting AR inhibitor (ARI) cemtirestat (CMTI) on tissue oxidative stress (OS) and carbonyl stress (CS) biomarkers in rats exposed to fructose alone (F) or fructose plus streptozotocin (D; type-2 diabetic). D and F rats were either untreated or treated daily with low- or high-dose CMTI, ARI drug epalrestat (EPA) or antioxidant stobadine (STB) for 14 weeks.
View Article and Find Full Text PDFFructose, endogenously produced as a consequence of activation of the polyol pathway under hyperglycemic conditions, contribute to formation of advanced glycoxidation end products (AGEs) and carbonyl stress. Oxidative stress is increased in diabetes (DM) due to AGEs formation and the utilization of NADPH by aldo-keto reductase, AKR1B1(AR), the first enzyme in polyol pathway. Since inhibition of AR is an attractive approach for the management of diabetic eye diseases, we aimed to compare the effects of a novel AR inhibitor (ARI)/antioxidant (AO) compound cemtirestat on eye tissues with the effects of ARI drug epalrestat and AO agent stobadine in rat model for glycotoxicity.
View Article and Find Full Text PDFIntroduction: Except for methylprednisolone, there is no current low-cost and low-side-effect drug/barrier method to prevent epidural fibrosis after spine surgery. However, the use of methylprednisolone has led to substantial controversy because of its serious side effects on wound healing. This study aimed to evaluate the effects of enalapril and oxytocin on preventing the development of epidural fibrosis in a rat laminectomy model.
View Article and Find Full Text PDFObjectives: Cerebral stroke is a serious clinical condition in which oxidative stress, inflammation, necrosis, apoptosis, and autophagy play important roles in its pathogenesis. This study investigated the neuroprotective and healing effects of calcium dobesilate (CD) on cerebral hypoxia/reperfusion injury in rats.
Methods: Forty Wistar albino male rats, each weighing 300-350 g, were separated into the Control group (no surgery and no pharmacological agent was administered); Sham-A group (only surgery was performed); DBL-A group (surgery was performed and CD 100 mg/kg/day was administered intraperitoneally for 3 days); Sham-C group (only surgery was performed); and DBL-C group (surgery was performed and 100 mg/kg/day CD was administered intraperitoneally for 10 days).
Biochim Biophys Acta Gen Subj
December 2022
Background: Binge drinking leads to compromised mitochondrial integrity and contractile function in the heart although little effective remedy is readily available. Given the possible derangement of autophagy in ethanol-induced cardiac anomalies, this study was designed to examine involvement of Beclin1 in acute ethanol-induced cardiac contractile dysfunction, in any, and the impact of Beclin1 haploinsufficiency on ethanol cardiotoxicity with a focus on autophagy-related ferroptosis.
Methods: WT and Beclin1 haploinsufficiency (BECN) mice were challenged with ethanol for one week (2 g/kg, i.
Introduction: Proinflammatory cytokines released from nerve endings and surrounding injured tissue after nerve damage can prolong the inflammation process, delay nerve healing or result in poor quality nerve healing. In this case, due to the loss of function in the muscles innervated by the damaged nerve, the patient may have neurological and functional difficulties which may reduce the patient's quality of life and create an economic burden. Although the attempts of many pharmacological agents to heal crush injury of peripheral nerves have been recorded in literature, a drug that can provide adequate recovery of the crushed nerve and can be applied in daily life has not been defined as yet.
View Article and Find Full Text PDFMitochondrial Ca overload contributes to obesity cardiomyopathy, yet mechanisms that directly regulate it remain elusive. The authors investigated the role of Parkin on obesity-induced cardiac remodeling and dysfunction in human hearts and a mouse model of 24-week high-fat diet (HFD) feeding. Parkin knockout aggravated HFD-induced cardiac remodeling and dysfunction, mitochondrial Ca overload, and apoptosis without affecting global metabolism, blood pressure, and aortic stiffness.
View Article and Find Full Text PDFMesenchymal stem cells (MSCs)-based therapy has displayed some promises in ischemia heart diseases although its efficacy may be affected by changes in surrounding environments. This study evaluated the role of autophagy insufficiency using Beclin1 haploinsufficiency (BECN) on intra-myocardial MSC transplantation-evoked effect against myocardial infarction. Donor MSCs from C57BL/6 mice were labelled with cell-tracker CM Dil and were delivered into LV free wall adjacent to infarct region in wild-type (WT) and BECN recipient mice following ligation of left main coronary artery (MI-MSCs).
View Article and Find Full Text PDFAldose reductase (AR) catalyzes the conversion of glucose to sorbitol in a NADPH-dependent reaction, thereby increasing the production of reactive oxygen species (ROS). Since AR activation is linked to redox dysregulation and cell damage in neurodegenerative diseases, AR inhibitors (ARIs) constitute promising therapeutic tools for the treatment of these disorders. Among these compounds, the novel substituted triazinoindole derivatives cemtirestat (CMTI) and COTI, as well as the clinically employed epalrestat (EPA) and the pyridoindole-antioxidant stobadine (STB), were tested in both PC12 cells and BV2 microglia exposed to four different neurotoxic models.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
June 2020
Alcoholism leads to organ injury including mitochondrial defect and apoptosis with evidence favoring a role for autophagy dysregulation in alcoholic damage. Parkin represents an autosomal recessive inherited gene for Parkinson's disease and an important member of selective autophagy for mitochondria. The association between Parkinson's disease and alcoholic injury remains elusive.
View Article and Find Full Text PDFDoxorubicin (DOX) is one of the most effective antineoplastic drugs. However, its clinical application has been greatly limited due to the development of cardiotoxicity with DOX utilization. A number of theories have been postulated for DOX-induced cardiotoxicity with a pivotal contribution from unchecked (excess) mitophagy and mitochondrial fission.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
October 2018
Endothelin (ET)-1 is implicated in the pathophysiology of cardiovascular diseases although its role in obesity anomalies has not been fully elucidated. This study was designed to examine the impact of ET-1 receptor A (ET) ablation on obesity-induced changes in cardiac geometry and contractile function, as well as the mechanisms involved with a focus on autophagy. Cardiomyocyte-specific ET receptor knockout (ETAKO) and WT mice were fed either low-fat (10% calorie from fat) or high-fat (45% calorie from fat) diet for 24 weeks.
View Article and Find Full Text PDFObjectives: No valid treatment modality that will repair stroke damage and provide neurological recovery has yet been identified in literature. Studies demonstrated that adequate quality of life could be provided if post-stroke pain could be treated sufficiently and timely. Besides its pain relief effects, tramadol has oedema-reducing and anti-inflammatory properties.
View Article and Find Full Text PDFDiabetes is an important cause of morbidity and mortality worldwide. Management of blood glucose is critical for diabetic patients since diabetes carries a risk for many diseases and disorders. Although there are several antidiabetic agents in the markets for a long time, some of the agents have dose-limiting side effects, such as hypoglycemia and weight gain which limits their ability to reduce cardiovascular complications.
View Article and Find Full Text PDFAging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca properties were evaluated using echocardiography, IonOptix edge-detection and fura-2 techniques.
View Article and Find Full Text PDFCardiotoxicity is one of the major life-threatening effects encountered in cancer chemotherapy with doxorubicin and other anthracyclines. Mitochondrial aldehyde dehydrogenase (ALDH2) may alleviate doxorubicin toxicity although the mechanism remains elusive. This study was designed to evaluate the impact of ALDH2 overexpression on doxorubicin-induced myocardial damage with a focus on mitochondrial injury.
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