Solanum melongena L. Extract Promotes Intestinal Tight Junction Re-Assembly via SIRT-1-Dependent Mechanisms.

Tight junction disruption can lead to pathogenesis of various diseases without therapeutic strategy to recover intestinal barrier integrity. The main objective of this study is to demonstrate the effect of Solanum melongena L. extract (SMLE) on intestinal tight junction recovery and its underlying mechanism.

Vagus nerve stimulation and acetylcholinesterase inhibitor donepezil provide cardioprotection against trastuzumab-induced cardiotoxicity in rats by attenuating mitochondrial dysfunction.

Trastuzumab (Trz) is a targeted anticancer drug for human epidermal growth factor receptor 2 (HER2)-positive tumors, as Trz-induced cardiotoxicity (TIC) is commonly observed in Trz-treated patients. Since cardiac autonomic modulation with electrical vagus nerve stimulation (VNS) and acetylcholinesterase (AChE) inhibitors exerts cardioprotection against various heart diseases, the comparative effects of electrical VNS and an AChE inhibitor (donepezil) on cardiac and mitochondrial functions and programmed cell death pathways in TIC are not known. VNS devices were implanted in thirty-two male Wistar rats and were divided into 4 groups: (i) Control-Sham (CSham), (ii) Trz-Sham (TSham), (iii) Trz-VNS (TVNS), and (iv) Trz-donepezil (TDPZ).

Acetylcholinesterase inhibition protects against trastuzumab-induced cardiotoxicity through reducing multiple programmed cell death pathways.

Background: Trastuzumab (Trz)-induced cardiotoxicity (TIC) is one of the most common adverse effects of targeted anticancer agents. Although oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, and ferroptosis have been identified as potential mechanisms underlying TIC, the roles of pyroptosis and necroptosis under TIC have never been investigated. It has been shown that inhibition of acetylcholinesterase function by using donepezil exerts protective effects in various heart diseases.

Acetylcholine receptor agonists effectively attenuated multiple program cell death pathways and improved left ventricular function in trastuzumab-induced cardiotoxicity in rats.

Aims: Cardiotoxicity is a seriously debilitating complication of trastuzumab (TRZ) therapy in patients with cancer as a consequence of overexpression of the human epidermal growth factor receptor 2. Although most TRZ-induced cardiotoxicity (TIC) cases are reversible, some patients experience chronic cardiac dysfunction, and these irreversible concepts may be associated with cardiomyocyte death. Acetylcholine receptor (AChR) activation has been shown to exert cardioprotection in several heart diseases, but the effects of AChR agonists against TIC have not been investigated.

Effects of melatonin on cardiac metabolic reprogramming in doxorubicin-induced heart failure rats: A metabolomics study for potential therapeutic targets.

Using mass spectrometry-based targeted metabolomics, we aimed to determine the pattern of cardiac metabolic reprogramming and energetics in doxorubicin-induced heart failure. More importantly, we aimed to identify the potential effects of melatonin on cardiac metabolic reprogramming and energetics in doxorubicin-induced heart failure. Male Wistar rats (n = 18) were randomly divided into three groups (n = 6/group) to receive either (1) normal saline solution as a control, (2) 3 mg/kg/day of doxorubicin on Days 0, 4, 8, 15, 22, and 29, or (3) 3 mg/kg/day of doxorubicin on Days 0, 4, 8, 15, 22, and 29 plus 10 mg/kg/day of melatonin on Days 0-29.

Vagus nerve stimulation exerts cardioprotection against doxorubicin-induced cardiotoxicity through inhibition of programmed cell death pathways.

The aberration of programmed cell death including cell death associated with autophagy/mitophagy, apoptosis, necroptosis, pyroptosis, and ferroptosis can be observed in the development and progression of doxorubicin-induced cardiotoxicity (DIC). Vagus nerve stimulation (VNS) has been shown to exert cardioprotection against cardiomyocyte death through the release of the neurotransmitter acetylcholine (ACh) under a variety of pathological conditions. However, the roles of VNS and its underlying mechanisms against DIC have never been investigated.

Melatonin and metformin ameliorated trastuzumab-induced cardiotoxicity through the modulation of mitochondrial function and dynamics without reducing its anticancer efficacy.

Trastuzumab has an impressive level of efficacy as regards antineoplasticity, however it can cause serious cardiotoxic side effects manifested by impaired cardiac contractile function. Although several pharmacological interventions, including melatonin and metformin, have been reported to protect against various cardiovascular diseases, their potential roles in trastuzumab-induced cardiotoxicity remain elusive. We hypothesized that either melatonin or metformin co-treatment effectively attenuates trastuzumab-mediated cardiotoxicity through attenuating the impaired mitochondrial function and mitochondrial dynamics.

Melatonin and metformin counteract cognitive dysfunction equally in male rats with doxorubicin-induced chemobrain.

Melatonin (Mel) and metformin (Met) show beneficial effects in various brain pathologies. However, the effects of Mel and Met on doxorubicin (DOX)-induced chemobrain remain in need of elucidation. We aimed to investigate whether Mel and Met provide neuroprotective effects on glial dysmorphologies, brain inflammation, oxidative stress, brain mitochondrial dysfunction, apoptosis, necroptosis, neurogenesis, hippocampal dysplasticity, and cognitive dysfunction in rats with DOX-induced chemobrain.

Blood metabolomes as non-invasive biomarkers and targets of metabolic interventions for doxorubicin and trastuzumab-induced cardiotoxicity.

This study aimed to identify the alterations of blood metabolome levels and their association with cardiac dysfunction and cardiac injury following treatment with doxorubicin and trastuzumab. Eight-week-old male Wistar rats were divided into four groups (n = 6 per group) to receive intraperitoneal injection with either: (1) 1 mL of normal saline solution (NSS) at days 0, 4, 8, 15, 22, and 29 (control group for doxorubicin); (2) 3 mg/kg/day of doxorubicin at days 0, 4, 8, 15, 22, and 29 (doxorubicin group); (3) 1 mL of NSS at days 0-6 (control group for trastuzumab); or (4) 4 mg/kg/day of trastuzumab at days 0-6 (trastuzumab group). Four days after the last injected dose, cardiac function was determined.

Ranolazine alleviated cardiac/brain dysfunction in doxorubicin-treated rats.

Doxorubicin (Dox), a powerful chemotherapeutic agent, has been shown to cause cardiotoxicity and neurotoxicity. Ranolazine, a drug that is commonly used to treat patients with chronic angina, has been shown to reduce toxicity from Dox therapy. Therefore, the present study aims to investigate the mechanisms behind the protective effects of ranolazine on the heart and brain in Dox-treatment.

Promoting mitochondrial fusion in doxorubicin-induced cardiotoxicity: a novel therapeutic target for cardioprotection.

Changes in mitochondrial dynamics have been recognized as being one of the mechanisms related to cardiotoxicity following a high cumulative dose of doxorubicin (DOX). A mitochondrial division inhibitor-1 (Mdivi-1) and fusion promoter (M1) have been shown to be cardioprotective in a variety of cardiovascular settings, however, their anticardiotoxic efficacy against DOX therapy remains unclear. We therefore investigated whether treatment with Mdivi-1 and M1 protects the heart against DOX-induced cardiotoxicity via mitochondria-targeted pathways.

Acetylcholine receptor agonists provide cardioprotection in doxorubicin-induced cardiotoxicity via modulating muscarinic M and α7 nicotinic receptor expression.

The balance between cardiac sympathetic and parasympathetic activities has been intricately linked to mitochondrial function, cellular oxidative status, and immunomodulation in healthy and diseased myocardium. Cardiac autonomic neuropathy, along with the associated mitochondrial and cellular dysfunction, is an important pathophysiological feature of doxorubicin-induced cardiotoxicity (DIC). We tested the hypothesis that autonomic modulation by activation of acetylcholine receptors (AChR) effectively attenuates DIC.

Acetylcholinesterase inhibitor ameliorates doxorubicin-induced cardiotoxicity through reducing RIP1-mediated necroptosis.

Doxorubicin is an effective chemotherapeutic drug, but causes cardiotoxicity which limits its use. Oxidative stress, mitochondrial dysfunction, and inflammation are closely implicated in doxorubicin-induced cardiotoxicity (DIC). Necroptosis, a new form of programmed cell death, was also upregulated by doxorubicin, leading to cardiomyocyte death and cardiac dysfunction.

Cardioprotective effects of melatonin and metformin against doxorubicin-induced cardiotoxicity in rats are through preserving mitochondrial function and dynamics.

Doxorubicin (Dox) is widely used in chemotherapy regimens for several malignant conditions. Unfortunately, cumulative and irreversible cardiotoxicity of Dox is the most prominent adverse effect which limits its use. Several pharmacological interventions which exert antioxidant properties, including melatonin and metformin, have demonstrated beneficial effects against various cardiac pathological conditions.

A combination of an antioxidant with a prebiotic exerts greater efficacy than either as a monotherapy on cognitive improvement in castrated-obese male rats.

Previous studies by ourselves and others have demonstrated that both obesity and testosterone deprivation have been related to cognitive decline. We have also shown that a prebiotic and n-acetyl cysteine (NAC) improved cognitive dysfunction in obese rats and castrated-male rats. However, the effects of NAC, a prebiotic (inulin), and a combination of the two on cognition in castrated-obese rats has never been investigated.

The roles of resveratrol on cardiac mitochondrial function in cardiac diseases.

Left ventricular (LV) dysfunction is commonly associated with a variety of health conditions including acute myocardial infarction and obesity/diabetes. In addition, administration of several pharmacological agents such as anticancer, antiviral, and immunosuppressive drugs has been shown to be related with LV dysfunction. The molecular mechanism responsible for LV dysfunction has been extensively studied, and it has been proposed that the overproduction of reactive oxygen species (ROS) plays a crucial role in the regulation of this function.

N-acetyl cysteine, inulin and the two as a combined therapy ameliorate cognitive decline in testosterone-deprived rats.

Our previous studies reported that testosterone-deprived rats developed cognitive decline as a result of increased brain oxidative stress, microglia hyperactivity, and hippocampal dysplasticity. In addition, gut dysbiosis occurred in these rats. Previous studies demonstrated that n-acetyl cysteine (NAC) and a prebiotic (inulin) improved cognition in several pathological conditions.

Combined dipeptidyl peptidase-4 inhibitor with low-dose testosterone exerts greater efficacy than monotherapy on improving brain function in orchiectomized obese rats.

Both obesity and orchiectomy lead to the development of brain pathologies and cognitive decline. Testosterone replacement therapy (2 mg/kg/day TRT) and dipeptidyl peptidase-4 inhibitor (vildagliptin) improved cognition in orchiectomized rats, and obese rats. However, both had no beneficial effects in brain of orchiectomized-obese rats.

Combined low-dose testosterone and vildagliptin confers cardioprotection in castrated obese rats.

Although a physiological dose of testosterone replacement therapy (p-TRT) has been shown to improve left ventricular (LV) function, some studies reported that it increased the risk of myocardial infarction in testosterone-deprived men. We previously reported that vildagliptin might be used as an alternative to the p-TRT. In this study, we hypothesized that a combined low-dose TRT with vildagliptin exerts greater efficacy than single regimen in improving cardiometabolic function in obese-insulin resistant rats with testosterone deprivation.

Testosterone deprivation intensifies cognitive decline in obese male rats via glial hyperactivity, increased oxidative stress, and apoptosis in both hippocampus and cortex.

Aim: The study hypothesized that testosterone deprivation aggravates cognitive decline in obesity through increasing oxidative stress, glial activation, and apoptosis.

Methods: Male Wistar rats (n = 24) were fed with either normal-diet (ND) or high-fat diet (HFD) for 24 weeks. At week 13, ND-fed rats and HFD-fed rats were randomly assigned to two subgroups to receive either a sham-operation or bilateral-orchiectomy (ORX).

High-Saturated Fat High-Sugar Diet Accelerates Left-Ventricular Dysfunction Faster than High-Saturated Fat Diet Alone via Increasing Oxidative Stress and Apoptosis in Obese-Insulin Resistant Rats.

Scope: It has been hypothesized that a high-saturated-fat, high-sugar diet (HFHS) causes worse cardiometabolic dysfunction than a high-saturated-fat diet (HFD) due to severe mitochondrial dysfunction, oxidative stress, and apoptosis in obese insulin-resistant rats.

Methods And Results: Rats are divided into three groups to receive normal diet (ND), HFD, or HFHS for 24 weeks. Cardiometabolic parameters are determined at baseline and every 4 weeks until the end of the feeding protocol.