Nutraceuticals and Exercise against Muscle Wasting during Cancer Cachexia

Cancer cachexia (CC) is a debilitating multifactorial syndrome, involving progressive deterioration and functional impairment of skeletal muscles. It affects about 80% of patients with advanced cancer and causes premature death. No causal therapy is available against CC. In the last few decades, our understanding of the mechanisms contributing to muscle wasting during cancer has markedly increased. Both inflammation and oxidative stress (OS) alter anabolic and catabolic signaling pathways mostly culminating with muscle depletion. Several preclinical studies have emphasized the beneficial roles of several classes of nutraceuticals and modes of physical exercise, but their efficacy in CC patients remains scant. The route of nutraceutical administration is critical to increase its bioavailability and achieve the desired anti-cachexia effects. Accumulating evidence suggests that a single therapy may not be enough, and a bimodal intervention (nutraceuticals plus exercise) may be a more effective treatment for CC. This review focuses on the current state of the field on the role of inflammation and OS in the pathogenesis of muscle atrophy during CC, and how nutraceuticals and physical activity may act synergistically to limit muscle wasting and dysfunction.

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Inhibition of the Fission Machinery Mitigates OPA1 Impairment in Adult Skeletal Muscles

Cells ◽

10.3390/cells8060597 ◽

2019 ◽

Vol 8 (6) ◽

pp. 597 ◽

Cited By ~ 21

Author(s):

Vanina Romanello ◽

Marco Scalabrin ◽

Mattia Albiero ◽

Bert Blaauw ◽

Luca Scorrano ◽

...

Keyword(s):

Knockout Mice ◽

Skeletal Muscles ◽

Cancer Cachexia ◽

Muscle Wasting ◽

Premature Death ◽

Muscle Loss ◽

Mitochondrial Network ◽

Double Knockout ◽

Physiological Relevance ◽

Simultaneous Inhibition

The maintenance of muscle mass and its ability to function relies on a bioenergetic efficient mitochondrial network. This network is highly impacted by fusion and fission events. We have recently shown that the acute deletion of the fusion protein Opa1 induces muscle atrophy, systemic inflammatory response, precocious epithelial senescence, and premature death that are caused by muscle-dependent secretion of FGF21. However, both fusion and fission machinery are suppressed in aging sarcopenia, cancer cachexia, and chemotherapy-induced muscle wasting. We generated inducible muscle-specific Opa1 and Drp1 double-knockout mice to address the physiological relevance of the concomitant impairment of fusion and fission machinery in skeletal muscle. Here we show that acute ablation of Opa1 and Drp1 in adult muscle causes the accumulation of abnormal and dysfunctional mitochondria, as well as the inhibition of autophagy and mitophagy pathways. This ultimately results in ER stress, muscle loss, and the reduction of force generation. However, the simultaneous inhibition of the fission protein Drp1 when Opa1 is absent alleviates FGF21 induction, oxidative stress, denervation, and inflammation rescuing the lethal phenotype of Opa1 knockout mice, despite the presence of any muscle weakness. Thus, the simultaneous inhibition of fusion and fission processes mitigates the detrimental effects of unbalanced mitochondrial fusion and prevents the secretion of pro-senescence factors.

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The role of selected antioxidants in the development and treatment of Parkinson’s disease

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0013.5252 ◽

2019 ◽

Vol 73 ◽

pp. 516-528

Author(s):

Dominika Markowska ◽

Daria Malicka ◽

Jarosław Nuszkiewicz ◽

Karolina Szewczyk-Golec

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Modern Medicine ◽

Substantia Nigra Pars Compacta ◽

Current State ◽

And Oxidative Stress ◽

Significant Health

The widespread aging of societies results in the intensification of the development of neurodegenerative diseases associated with advanced age, including Parkinson’s disease. Unfortunately, modern medicine is not able to unequivocally determine the etiopathogenesis of the disease, which is why no causative treatment can be given. According to the current state of knowledge, in the course of Parkinson’s disease the substantia nigra pars compacta in the midbrain degenerates, leading to a decrease in dopamine levels in the patient’s brain. This results in neurotransmission disturbances and the development of undesirable effects. Neurodegenerative changes are supposedly caused by the combination of various factors, including genetic factors, chronic inflammation, the interaction of toxins, disturbances in protein metabolism, and oxidative stress. The therapeutic possibilities associated with the administration of antioxidants, which could alleviate increased oxidative stress and contribute to the better quality of life of the patient, are considered. Taking into account the studies on numerous antioxidants, such as coenzyme Q10, B vitamins, vitamin D, vitamin E and resveratrol, it cannot be unequivocally stated that this is an effective treatment, because experiments carried out on both humans and animals gave conflicting results. It is reasonable to say that antioxidant deficiencies should be avoided and the physiological levels should be sought, as this may be translated into significant health benefits.

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Sulfur – Containing Amino Acids in Seizures: Current State of the Art

Current Medicinal Chemistry ◽

10.2174/0929867324666170609090613 ◽

2018 ◽

Vol 25 (3) ◽

pp. 378-390 ◽

Cited By ~ 2

Author(s):

Dragan Hrncic ◽

Aleksandra Rasic-Markovic ◽

Duro Macut ◽

Dusan Mladenovic ◽

Veselinka Susic ◽

...

Keyword(s):

Oxidative Stress ◽

Amino Acids ◽

Experimental Models ◽

Neuroprotective Effects ◽

Homocysteine Thiolactone ◽

Current State ◽

Sulfur Containing ◽

And Oxidative Stress

Background: Homocysteine and taurine are non-proteinogenic sulfur-containing amino acids with numerous important physiological roles. Homocysteine and taurine are considered to be neurotransmitters and neuromodulators, the first showing clear hyperexcitability role, while the second is known by its inhibitory and neuroprotective properties. Objective: In this article we addressed the role of homocysteine and its related metabolite homocysteine thiolactone in the development of seizures, focusing on its experimental models in vivo, potential mechanisms of proepileptogenic activity via interactions with glutamatergic neurotransmission, sodium pump activity, oxidative stress, cholinergic system and NO-mediated neuronal signaling, as well as the pharmacological and non-pharmacological approaches to modulate its proconvulsive activity. Additionally, herein we will focus on taurine neuroprotective effects linked with its anticonvulsive properties and mediated by taurine interactions with GABA-ergic and glutamatergic system and oxidative stress.

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Impact of Cancer Cachexia on Cardiac and Skeletal Muscle: Role of Exercise Training

Cancers ◽

10.3390/cancers14020342 ◽

2022 ◽

Vol 14 (2) ◽

pp. 342

Author(s):

Cláudia Bordignon ◽

Bethânia S. dos Santos ◽

Daniela D. Rosa

Keyword(s):

Cardiac Remodeling ◽

Cancer Cachexia ◽

Muscle Wasting ◽

Clinical Evidence ◽

Premature Death ◽

Muscle Loss ◽

Multimodal Approach ◽

Progressive Loss

Cachexia is a multifactorial syndrome that presents with, among other characteristics, progressive loss of muscle mass and anti-cardiac remodeling effect that may lead to heart failure. This condition affects about 80% of patients with advanced cancer and contributes to worsening patients’ tolerance to anticancer treatments and to their premature death. Its pathogenesis involves an imbalance in metabolic homeostasis, with increased catabolism and inflammatory cytokines levels, leading to proteolysis and lipolysis, with insufficient food intake. A multimodal approach is indicated for patients with cachexia, with the aim of reducing the speed of muscle wasting and improving their quality of life, which may include nutritional, physical, pharmacologic, and psychological support. This review aims to outline the mechanisms of muscle loss, as well as to evaluate the current clinical evidence of the use of physical exercise in patients with cachexia.

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Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus

Current Pharmaceutical Design ◽

10.2174/1381612825666190926162229 ◽

2020 ◽

Vol 25 (40) ◽

pp. 4310-4317 ◽

Cited By ~ 4

Author(s):

Lichao Sun ◽

Shouqin Ji ◽

Jihong Xing

Keyword(s):

Oxidative Stress ◽

Brain Edema ◽

Severity Score ◽

Global Ischemia ◽

Signal Pathways ◽

Neurological Severity Score ◽

Tnf Α ◽

Transient Global Ischemia ◽

And Oxidative Stress

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

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LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

Current Neurovascular Research ◽

10.2174/1567202617666200727142019 ◽

2020 ◽

Vol 17 (4) ◽

pp. 394-401

Author(s):

Yuanhua Wu ◽

Yuan Huang ◽

Jing Cai ◽

Donglan Zhang ◽

Shixi Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Mechanisms ◽

Ischemia Reperfusion ◽

Critical Role ◽

Cell Activity ◽

Ht22 Cells ◽

Cerebral Ischemic ◽

Cerebral Ischemic Reperfusion ◽

And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

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The Concomitance of Hypertension and Diabetes Exacerbating Retinopathy: The Role of Inflammation and Oxidative Stress.

Current Clinical Pharmacology ◽

10.2174/1574884711308040002 ◽

2013 ◽

Vol 8 (4) ◽

pp. 266-277 ◽

Cited By ~ 5

Author(s):

Diego Duarte ◽

Kamila Silva ◽

Mariana Rosales ◽

José Lopes de Faria ◽

Jacqueline Lopes de Faria

Keyword(s):

Oxidative Stress ◽

And Oxidative Stress

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Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽

10.3390/cells10030629 ◽

2021 ◽

Vol 10 (3) ◽

pp. 629

Author(s):

Jorge Gutiérrez-Cuevas ◽

Ana Sandoval-Rodriguez ◽

Alejandra Meza-Rios ◽

Hugo Christian Monroy-Ramírez ◽

Marina Galicia-Moreno ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiac Dysfunction ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Peroxisome Proliferator ◽

White Adipocyte ◽

Peroxisome Proliferator Activated Receptors ◽

And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

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Neuroprotective Metabolites of Hericium erinaceus Promote Neuro-Healthy Aging

International Journal of Molecular Sciences ◽

10.3390/ijms22126379 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6379

Author(s):

Elisa Roda ◽

Erica Cecilia Priori ◽

Daniela Ratto ◽

Fabrizio De Luca ◽

Carmine Di Iorio ◽

...

Keyword(s):

Oxidative Stress ◽

Healthy Aging ◽

Molecular Layer ◽

Dietary Supplementation ◽

Purkinje Neurons ◽

Geriatric Syndrome ◽

Oral Supplementation ◽

Erinacine A ◽

And Oxidative Stress

Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.

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Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice

Journal of Translational Medicine ◽

10.1186/s12967-021-02814-5 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Shenhai Gong ◽

Yinglin Feng ◽

Yunong Zeng ◽

Huanrui Zhang ◽

Meiping Pan ◽

...

Keyword(s):

Oxidative Stress ◽

16S Rrna ◽

Gut Microbiota ◽

Gene Sequencing ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Metabolomic Analysis ◽

Rrna Gene Sequencing ◽

And Oxidative Stress

Abstract Background Gut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown. Methods We compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment. Results 16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity. Conclusions This study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.

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