Inhibition of both NOX and TNF-α exerts substantial renoprotective effects in renal ischemia reperfusion injury rat model.

Background And Aims: Acute kidney injury (AKI) due to renal ischemia-reperfusion injury (RIRI) is associated with high morbidity and mortality, with no renoprotective drug available. Previous research focused on single drug targets, yet this approach has not reached translational success. Given the complexity of this condition, we aimed to identify a disease module and apply a multitarget network pharmacology approach.

Adrenergic receptors blockade alleviates dexamethasone-induced neurotoxicity in adult male Wistar rats: Distinct effects on β-arrestin2 expression and molecular markers of neural injury.

Background: Dexamethasone-induced neurotoxicity has been previously reported. However, the molecular mechanisms are still not completely understood.

Objectives: The current work aimed to investigate the modulatory effects of α- and β-adrenergic receptors on dexamethasone-induced neurotoxicity in rats focused on changes in β-arrestin2 and molecular markers of neural injury in cerebral cortex.

Hepatic β-arrestins: potential roles in liver health and disease.

Β-arrestins are intracellular scaffolding proteins that have multifaceted roles in different types of disorders. In this review article, we gave a summary about the discovery, characterization and classification of these proteins and their intracellular functions. Moreover, this review article focused on the hepatic expression of β-arrestins and their hepatocellular distribution and function in each liver cell type.

Carvedilol ameliorates dexamethasone-induced myocardial injury in rats independent of its action on the α1-adrenergic receptor.

The current study aimed to investigate the cardiotoxic effect of dexamethasone-high-dose in rats, the therapeutic effect of carvedilol and the role of α1-adrenergic receptor (α1AR). The experiment involved 6 groups: control, dexamethasone (10 mg/kg), carvedilol (10 mg/kg), phenylephrine (1 mg/kg), phenylephrine plus carvedilol and propranolol (30 mg/kg). Drugs and vehicles were given for 7 days.

Mitigation of dexamethasone-induced nephrotoxicity by modulating the activity of adrenergic receptors: Implication of Wnt/β-arrestin2/β-catenin pathway.

The present study aimed to investigate the role of α and β-adrenergic receptors (βARs) in mediation or modulation of the dexamethasone-induced nephrotoxicity by using different pharmacological interventions. Nephrotoxicity was induced by subcutaneous injection of dexamethasone (10 mg/kg) for 7 days in Wistar albino rats. Eight groups were used: control; dexamethasone; carvedilol; phenylephrine; carvedilol and phenylephrine; propranolol; doxazosin; propranolol and doxazosin.

Propranolol and low-dose isoproterenol ameliorate insulin resistance, enhance β-arrestin2 signaling, and reduce cardiac remodeling in high-fructose, high-fat diet-fed mice: Comparative study with metformin.

Aims: β-Arrestin2 signaling has emerged as a promising therapeutic target for the management of insulin resistance and related complications. Moreover, recent studies have shown that certain G protein-coupled receptor (GPCR) ligands can modulate β-arrestin2 signaling. The current study examined the effects of the β-blocker propranolol and a low dose of the agonist isoproterenol (L-D-ISOPROT) on β-arrestin2 signaling, insulin resistance, and cardiac remodeling in high-fructose, high-fat diet (HFrHFD)-fed mice.

Acute and chronic metabolic effects of carvedilol in high-fructose, high-fat diet-fed mice: implication of β-arrestin2 pathway.

We aimed to investigate the acute and chronic effects of carvedilol on insulin resistance in high-fructose, high-fat diet (HFrHFD) - fed mice and the implication of the β-arrestin2 pathway. The acute effect of carvedilol (10 mg/kg, i.p.

Quercetin and lithium chloride potentiate the protective effects of carvedilol against renal ischemia-reperfusion injury in high-fructose, high-fat diet-fed Swiss albino mice independent of renal lipid signaling.

Renal ischemia-reperfusion injury (R-IRI) is the main cause of acute renal failure. Carvedilol has been shown to protect against R-IRI. However, the underlying mechanisms are still not completely clarified.

Effect of omega-3 fatty acids on glucose homeostasis: role of free fatty acid receptor 1.

Insulin resistance is a worldwide health problem. This study investigated the acute effects of eicosapentanoic acid (EPA) on glucose homeostasis focusing on the role of free fatty acid receptor 1 (FFAR1) and the chronic effects of fish oil omega-3 fatty acids on insulin resistance. Insulin resistance was induced by feeding mice high-fructose, high-fat diet (HFrHFD) for 16 weeks.

Carvedilol Diminishes Cardiac Remodeling Induced by High-Fructose/High-Fat Diet in Mice via Enhancing Cardiac β-Arrestin2 Signaling.

Background: Insulin resistance (IR) is a well-known risk factor for cardiovascular complications. This study aimed to investigate the effect of a dietary model of IR in mice on cardiac remodeling, cardiac β-arrestin2 signaling, and the protective effects of carvedilol as a β-arrestin-biased agonist.

Methods And Results: Insulin resistance was induced by feeding mice high-fructose/high-fat diet (HFrHFD) for 16 weeks.

Effect of imidazoline-1 receptor agonists on renal dysfunction in rats associated with chronic, sequential fructose and ethanol administration.

Insulin resistance and chronic alcoholism are risk factors for renal dysfunction. This study investigated the therapeutic effects of two imidazoline-1 receptor (I1R) agonists on renal dysfunction in rats after chronic, sequential fructose and ethanol administration. Daily drinking water was supplemented with fructose (10%, w/v) for 12 weeks and then with ethanol (20%, v/v) for another 8 weeks.

Carvedilol protects against hepatic ischemia/reperfusion injury in high-fructose/high-fat diet-fed mice: Role of G protein-coupled receptor kinase 2 and 5.

Hepatic ischemia/reperfusion injury (H-IRI) is associated with irreversible liver damage. The current study aimed to investigate the protective effect of carvedilol against H-IRI in high-fructose high-fat diet (HFrHFD)-fed mice and the role of G protein-coupled receptor kinase 2 and 5 (GRK2 and GRK5). Mice were fed HFrHFD for 16 weeks; then mice were subjected to 30 min of ischemia followed by 1 h of reperfusion at the end of feeding period.

Hesperidin protects against stress induced gastric ulcer through regulation of peroxisome proliferator activator receptor gamma in diabetic rats.

Stress induced gastric ulcer is a serious health problem in diabetic patients. Some studies reported that hesperidin (HDN), a citrus bioflavonoid, can bind to and stimulate peroxisome proliferator-activator receptor-gamma (PPAR-γ) which may mediate its antidiabetic, anti-inflammatory and anti-oxidant effects. This work aims to study the possible protective effect of HDN against stress induced gastric ulcer in diabetic rats as well as the possible involvement of PPARγ in this effect.

Ameliorative effects of clonidine on ethanol induced kidney injury in rats: Potential role for imidazoline-1 receptor.

Chronic alcoholism is a risk factor for kidney injury. Clonidine is an α-adrenergic receptor/imidazoline-1 receptor agonist that can reduce blood pressure and maintain renal functions. This study aims to investigate the possible ameliorative effects of clonidine on ethanol induced kidney injury and its mechanism of action.

Sildenafil protects against bile duct ligation induced hepatic fibrosis in rats: Potential role for silent information regulator 1 (SIRT1).

Hepatic fibrosis is a potential health problem that may end with life-threatening cirrhosis and primary liver cancer. Recent studies point out to the protective effects of silent information regulator1 (SIRT1), against different models of organs fibrosis. This work aimed to investigate the possible protective effect of sildenafil (SIRT1 activator) against hepatic fibrosis induced by bile duct ligation (BDL).

GSK-3β heterozygous knockout is cardioprotective in a knockin mouse model of familial dilated cardiomyopathy.

Glycogen synthase kinase-3β (GSK-3β) plays a central role in both cardiac physiology and pathology. Herein we want to clarify the role of GSK-3β in familial dilated cardiomyopathy. We generated a mouse model carrying a heterozygous knockout mutation of GSK-3β (GSK-3β(+/-) KO), together with a ΔK210 knockin mutation in cardiac troponin T (ΔK210 cTnT KI), which was proved to be one of the genetic causes of familial dilated cardiomyopathy (DCM).

Ezrin, radixin, and moesin phosphorylation in NIH3T3 cells revealed angiotensin II type 1 receptor cell-type-dependent biased signaling.

β-Arrestin-biased agonists are a new class of drugs with promising therapeutic effects. The molecular mechanisms of β-arrestin-biased agonists are still not completely identified. Here, we investigated the effect of angiotensin II (AngII) and [Sar1,Ile4,Ile8] AngII (SII), a β-arrestin-biased agonist, on ezrin-radixin-moesin (ERM) phosphorylation in NIH3T3 cells (a fibroblast cell line) stably expressing AngII type 1A receptor.

β-arrestin-mediated signaling improves the efficacy of therapeutics.

β-Arrestins (β-arrestin-1 and β-arrestin-2) were first identified as proteins that have the ability to desensitize G protein-coupled receptors (GPCRs). However, it has recently been found that β-arrestins can activate signaling pathways independent of G protein activation. The diversity of these signaling pathways has also been recognized.