scholarly journals Oxytocin Signaling as a Target to Block Social Defeat-Induced Increases in Drug Abuse Reward

2021 ◽  
Vol 22 (5) ◽  
pp. 2372
Author(s):  
Carmen Ferrer-Pérez ◽  
Marina D. Reguilón ◽  
José Miñarro ◽  
Marta Rodríguez-Arias
Keyword(s):  
Social Stress ◽  
Drugs Of Abuse ◽  
Negative Impact ◽  
Wide Spectrum ◽  
Initial Response ◽  
Stress Effect ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Clinical Literature

There is huge scientific interest in the neuropeptide oxytocin (OXT) due to its putative capacity to modulate a wide spectrum of physiological and cognitive processes including motivation, learning, emotion, and the stress response. The present review seeks to increase the understanding of the role of OXT in an individual’s vulnerability or resilience with regard to developing a substance use disorder. It places specific attention on the role of social stress as a risk factor of addiction, and explores the hypothesis that OXT constitutes a homeostatic response to stress that buffers against its negative impact. For this purpose, the review summarizes preclinical and clinical literature regarding the effects of OXT in different stages of the addiction cycle. The current literature affirms that a well-functioning oxytocinergic system has protective effects such as the modulation of the initial response to drugs of abuse, the attenuation of the development of dependence, the blunting of drug reinstatement and a general anti-stress effect. However, this system is dysregulated if there is continuous drug use or chronic exposure to stress. In this context, OXT is emerging as a promising pharmacotherapy to restore its natural beneficial effects in the organism and to help rebalance the functions of the addicted brain.

scholarly journals Crocin Improves Insulin Sensitivity and Ameliorates Adiposity by Regulating AMPK-CDK5-PPARγ Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Kai Fang ◽  
Ming Gu
Keyword(s):  
Protein Level ◽  
Biological Activities ◽  
Protective Effects ◽  
Metabolic Dysfunction ◽  
Ampk Activation ◽  
Diabetic Mice ◽  
Wild Type ◽  
Ampk Signaling ◽  
Beneficial Effects

Crocin is a carotenoid compound which possesses multiple biological activities. Our and other laboratory’s previous findings show that crocin alleviates obesity and type 2 diabetes-related complications. We have found that crocin activates AMP-activated protein kinase (AMPK) signaling and inhibition of AMPK suppresses crocin-induced protective effects. However, the causal role of AMPK activation in the biological role of crocin is still not verified. In the present study, we showed that crocin markedly inhibits the changes of glucose metabolic parameters and serum lipid profiles in wild type diabetic mice. In AMPKα KO diabetic mice, those protective effects of crocin against glucose and lipid metabolic dysfunction were abolished. These results demonstrated AMPK activation was responsible for the beneficial effects of crocin on metabolic dysfunction. Moreover, we have shown that the antiobese effect of crocin has been abolished by the deficiency of AMPKα. We also showed that crocin induced a significant decrease of CDK5 protein level in wild type diabetic mice, while this effect was abolished in AMPKα KO diabetic mice. The regulation of downstream targets of CDK5/PPARγ by crocin was abolished by the deficiency of AMPK. In conclusion, our study verified that activation of AMPK is involved in crocin-induced protective effects against glucose and lipid metabolic dysfunction. Activation of AMPK downregulates the protein level of CDK5, followed by the decrease of PPARγ phosphorylation, leading to the inhibition of adipose formation and metabolic dysfunction. Our study provides new insights into the mechanism of protective effects of crocin and interaction of AMPK and CDK5/PPARγ signaling.

scholarly journals Punicalagin protects H9c2 cardiomyocytes from doxorubicin-induced toxicity through activation of Nrf2/HO-1 signaling

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Mingfang Ye ◽  
Linlin Zhang ◽  
Yuanming Yan ◽  
Huizhong Lin
Keyword(s):  
Wide Spectrum ◽  
Critical Role ◽  
Antitumor Agent ◽  
Cytochrome C Release ◽  
Beneficial Effects ◽  
H9c2 Cardiomyocytes ◽  
Underlying Mechanisms ◽  
Interfering Rna

Abstract Doxorubicin (DOX) is a wide-spectrum antitumor agent, but its clinical application is largely limited by its cardiotoxicity. Therefore, identification of effective agents against DOX-induced cardiotoxicity is of critical importance. The present study aimed to determine the beneficial role of punicalagin (PUN), a polyphenol isolated from pomegranate, in DOX-induced cardiotoxicity in vitro and explored the underlying mechanisms. H9c2 cardiomyocytes were pretreated with different concentrations (50, 100 and 200 μM) of PUN prior to DOX exposure. The results showed that PUN pretreatment significantly increased cell viability, inhibited lactate dehydrogenase (LDH) release and suppressed cell apoptosis induced by DOX. Additionally, PUN pretreatment attenuated the loss of mitochondrial membrane potential and cytochrome c release. Besides, PUN further enhanced the expression of nuclear Nrf2 and HO-1 in DOX-treated H9c2 cells, and the aforementioned beneficial effects of PUN were partially abolished by small interfering RNA (siRNA)-mediated Nrf2 knockdown. Hence, our findings clearly revealed that PUN might be a promising agent for alleviating the cardiotoxicity of DOX, and Nrf2/HO-1 signaling might serve a critical role during this process.

scholarly journals Sirt1 Inhibits Oxidative Stress in Vascular Endothelial Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Weijin Zhang ◽  
Qiaobing Huang ◽  
Zhenhua Zeng ◽  
Jie Wu ◽  
Yaoyuan Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Protective Role ◽  
Vascular Endothelial ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Key Factor ◽  
Antioxidative Stress

The vascular endothelium is a layer of cells lining the inner surface of vessels, serving as a barrier that mediates microenvironment homeostasis. Deterioration of either the structure or function of endothelial cells (ECs) results in a variety of cardiovascular diseases. Previous studies have shown that reactive oxygen species (ROS) is a key factor that contributes to the impairment of ECs and the subsequent endothelial dysfunction. The longevity regulator Sirt1 is a NAD+-dependent deacetylase that has a potential antioxidative stress activity in vascular ECs. The mechanisms underlying the protective effects involve Sirt1/FOXOs, Sirt1/NF-κB, Sirt1/NOX, Sirt1/SOD, and Sirt1/eNOs pathways. In this review, we summarize the most recent reports in this field to recapitulate the potent mechanisms involving the protective role of Sirt1 in oxidative stress and to highlight the beneficial effects of Sirt1 on cardiovascular functions.

scholarly journals A Contribution of Beef to Human Health: A Review of the Role of the Animal Production Systems

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Dario Pighin ◽  
Adriana Pazos ◽  
Verónica Chamorro ◽  
Fernanda Paschetta ◽  
Sebastián Cunzolo ◽  
...  
Keyword(s):  
Human Health ◽  
Production Systems ◽  
Negative Impact ◽  
Meat Products ◽  
Global Food Security ◽  
Beneficial Effects ◽  
Health Quality ◽  
Negative Impacts ◽  
Global Food

Meat and meat products constitute important source of protein, fat, and several functional compounds. Although beef consumption may implicate possible negative impacts on human health, its consumption can also contribute to human health. Quality traits of beef, as well as its nutritional properties, depend on animal genetics, feeding, livestock practices, andpost mortemprocedures. Available data show that emerging beef production systems are able to improve both, quality and nutritional traits of beef in a sustainable way. In this context, Argentina’s actions are aimed at maximising beef beneficial effects and minimising its negative impact on human health, in a way of contributing to global food security.

scholarly journals Cardiovascular and Hepatic Toxicity of Cocaine: Potential Beneficial Effects of Modulators of Oxidative Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Manuela Graziani ◽  
Letizia Antonilli ◽  
Anna Rita Togna ◽  
Maria Caterina Grassi ◽  
Aldo Badiani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drugs Of Abuse ◽  
Special Focus ◽  
Therapeutic Effects ◽  
Hepatic Toxicity ◽  
Beneficial Effects ◽  
Xanthine Oxidase Inhibitors ◽  
Clinical Literature ◽  
Cocaine Toxicity ◽  
Superoxide Dismutase Mimetics

Oxidative stress (OS) is thought to play an important role in the pharmacological and toxic effects of various drugs of abuse. Herein we review the literature on the mechanisms responsible for the cardiovascular and hepatic toxicity of cocaine with special focus on OS-related mechanisms. We also review the preclinical and clinical literature concerning the putative therapeutic effects of OS modulators (such as N-acetylcysteine, superoxide dismutase mimetics, nitroxides and nitrones, NADPH oxidase inhibitors, xanthine oxidase inhibitors, and mitochondriotropic antioxidants) for the treatment of cocaine toxicity. We conclude that available OS modulators do not appear to have clinical efficacy.

scholarly journals The Role of Epoxyeicosatrienoic Acids in Cardiac Remodeling

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinsheng Lai ◽  
Chen Chen
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Diseases ◽  
Cardiac Remodeling ◽  
Therapeutic Strategy ◽  
Myocardial Hypertrophy ◽  
Epoxyeicosatrienoic Acids ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Related Drug

Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by cytochrome P450 (CYP) epoxygenases, which include four regioisomers: 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET. Each of them possesses beneficial effects against inflammation, fibrosis, and apoptosis, which could combat cardiovascular diseases. Numerous studies have demonstrated that elevation of EETs by overexpression of CYP2J2, inhibition of sEH, or treatment with EET analogs showed protective effects in various cardiovascular diseases, including hypertension, myocardial infarction, and heart failure. As is known to all, cardiac remodeling is the major pathogenesis of cardiovascular diseases. This review will begin with the introduction of EETs and their protective effects in cardiovascular diseases. In the following, the roles of EETs in cardiac remodeling, with a particular emphasis on myocardial hypertrophy, apoptosis, fibrosis, inflammation, and angiogenesis, will be summarized. Finally, it is suggested that upregulation of EETs is a potential therapeutic strategy for cardiovascular diseases. The EET-related drug development against cardiac remodeling is also discussed, including the overexpression of CYP2J2, inhibition of sEH, and the analogs of EET.

scholarly journals Neuraminidase1 Inhibitor Protects Against Doxorubicin-Induced Cardiotoxicity via Suppressing Drp1-Dependent Mitophagy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yating Qin ◽  
Chao Lv ◽  
Xinxin Zhang ◽  
Weibin Ruan ◽  
Xiangyu Xu ◽  
...  
Keyword(s):  
Mitochondrial Fission ◽  
Subsequent Development ◽  
Control Group ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
Myocardial Apoptosis ◽  
Sd Rats ◽  
Cardio Protection

Anthracyclines, such as doxorubicin (DOX), are among the effective chemotherapeutic drugs for various malignancies. However, their clinical use is limited by irreversible cardiotoxicity. This study sought to determine the role of neuraminidase 1 (NEU1) in DOX-induced cardiomyopathy and the potential cardio-protective effects of NEU1 inhibitor oseltamivir (OSE). Male Sprague–Dawley (SD) rats were randomized into three groups: control, DOX, and DOX + OSE. NEU1 was highly expressed in DOX-treated rat heart tissues compared with the control group, which was suppressed by OSE administration. Rats in the DOX + OSE group showed preserved cardiac function and were protected from DOX-induced cardiomyopathy. The beneficial effects of OSE were associated with the suppression of dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and mitophagy. In detail, the elevated NEU1 in cardiomyocytes triggered by DOX increased the expression of Drp1, which subsequently enhanced mitochondrial fission and PINK1/Parkin pathway-mediated mitophagy, leading to a maladaptive feedback circle towards myocardial apoptosis and cell death. OSE administration selectively inhibited the increased NEU1 in myocardial cells insulted by DOX, followed by reduction of Drp1 expression, inhibition of PINK1 stabilization on mitochondria, and Parkin translocation to mitochondria, thus alleviating excessive mitochondrial fission and mitophagy, alleviating subsequent development of cellular apoptotic process. This work identified NEU1 as a crucial inducer of DOX-induced cardiomyopathy by promoting Drp1-dependent mitochondrial fission and mitophagy, and NEU1 inhibitor showed new indications of cardio-protection against DOX cardiotoxicity.

scholarly journals Protective Effects of Morus nigra and Its Phytochemicals against Hepatotoxicity: A Review of Preclinical Studies

Pharmacology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Ahmad Ghorbani ◽  
Sara Hooshmand
Keyword(s):  
Wide Spectrum ◽  
Protective Effects ◽  
High Fat ◽  
Inherited Disorders ◽  
Beneficial Effects ◽  
The Core ◽  
Morus Nigra ◽  
Chemical Agents ◽  
Vital Functions ◽  
Different Parts

<b><i>Background:</i></b> Our liver has a variety of vital functions including removing poisons, storing energy, immunological roles, and secretory and excretory functions. It may face some kinds of diseases caused by viruses, hepatotoxic chemicals, drugs, alcohol, and inherited disorders. Oxidative stress and inflammation are in the core of mechanisms of liver damages induced by viruses or chemical agents. <b><i>Summary:</i></b> <i>Morus nigra</i> (<i>M. nigra</i>), generally known as black mulberry, exhibited wide-spectrum pharmacological effects including antidiabetic, antinociceptive, anticancer, and hepatoprotective activities. Different parts of this plant particularly the fruit and leaf have shown beneficial effects on hepatocytes in cell culture and animal models of liver damages induced by chemicals (e.g., CCl4), drugs (e.g., paracetamol), diet (e.g., high fat), diabetes, etc. The beneficial effects of <i>M. nigra</i> on the liver are attributed to the presence of considerable amounts of phenolic compounds such as anthocyanins, flavonols, and phenolic acids. The present review is aimed to focus on the hepatoprotective activities of <i>M. nigra</i> and its phytochemicals and the mechanisms responsible for these activities. <b><i>Key Messages:</i></b> The evidence reviewed in this study can help design clinical trials on <i>M. nigra</i> in patients with liver disorders and develop a hepatoprotective herbal medicine.

scholarly journals Vitamin D and Its Relationship with the Pathways Related to Thrombosis and Various Diseases

2021 ◽  
Author(s):  
Syed Mohd ◽  
Swati Sharma ◽  
Aastha Mishra ◽  
Mohammad Zahid Ashraf
Keyword(s):  
Vitamin D ◽  
Essential Role ◽  
Blood Clot ◽  
Coagulation Factor ◽  
Vital Role ◽  
Protective Effects ◽  
Close Link ◽  
Beneficial Effects ◽  
Calcium And Phosphorus

Vitamin D known for its vital role in diverse biological function such as calcium and phosphorus homeostasis, also exert an anticoagulant effect emphasizing its essential role in the thrombosis pathogenesis. Thrombosis is the formation and propagation of a blood clot or thrombus either in the arterial or the venous system resulting in several severe complications. Various studies have also reported the association of vitamin D deficiency with the increased incidences of thromboembolism. This may be in part due to its anticoagulant effects through upregulation of thrombomodulin, an anticoagulant glycoprotein, and downregulation of Tissue Factor, a critical coagulation factor. The protective effects of vitamin D and its receptor in endothelial cells may further explain some of the reported beneficial effects of vitamin D in the prevention or treatment of cardiovascular diseases. Additionally, the immunomodulatory role of vitamin D has been observed through its ability to alter the secretion of inflammatory cytokines that can induce a procoagulant milieu by multiple pathways. Therefore, it becomes pertinent to discuss the close link between vitamin D and human health and to improve our knowledge of the molecular pathways regulated or influenced by vitamin D and its associated metabolites.

scholarly journals Protective Effects of Necrostatin-1 in Acute Pancreatitis: Partial Involvement of Receptor Interacting Protein Kinase 1

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1035
Author(s):  
Yulin Ouyang ◽  
Li Wen ◽  
Jane A. Armstrong ◽  
Michael Chvanov ◽  
Diane Latawiec ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Protein Kinase ◽  
Pancreatic Acinar Cell ◽  
Protective Effects ◽  
Interacting Protein ◽  
Beneficial Effects ◽  
Protective Actions ◽  
Underlying Mechanisms

Acute pancreatitis (AP) is a severe and potentially fatal disease caused predominantly by alcohol excess and gallstones, which lacks a specific therapy. The role of Receptor-Interacting Protein Kinase 1 (RIPK1), a key component of programmed necrosis (Necroptosis), is unclear in AP. We assessed the effects of RIPK1 inhibitor Necrostatin-1 (Nec-1) and RIPK1 modification (RIPK1K45A: kinase dead) in bile acid (TLCS-AP), alcoholic (FAEE-AP) and caerulein hyperstimulation (CER-AP) mouse models. Involvement of collateral Nec-1 target indoleamine 2,3-dioxygenase (IDO) was probed with the inhibitor Epacadostat (EPA). Effects of Nec-1 and RIPK1K45A were also compared on pancreatic acinar cell (PAC) fate in vitro and underlying mechanisms explored. Nec-1 markedly ameliorated histological and biochemical changes in all models. However, these were only partially reduced or unchanged in RIPK1K45A mice. Inhibition of IDO with EPA was protective in TLCS-AP. Both Nec-1 and RIPK1K45A modification inhibited TLCS- and FAEE-induced PAC necrosis in vitro. Nec-1 did not affect TLCS-induced Ca2+ entry in PACs, however, it inhibited an associated ROS elevation. The results demonstrate protective actions of Nec-1 in multiple models. However, RIPK1-dependent necroptosis only partially contributed to beneficial effects, and actions on targets such as IDO are likely to be important.

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