Chronic ethanol consumption increases reactive oxygen species generation and the synthesis of pro-inflammatory proteins in the heart through TNFR1-dependent mechanisms

Nakashima, Marcelo A.; Silva, Carla B.P.; Gonzaga, Natália A.; Simplicio, Janaina A.; Omoto, Ana Carolina Mieko; Tirapelli, Luís Fernando; Tanus‐Santos, Jose E.; Tirapelli, Carlos Renato

doi:10.1016/j.cyto.2019.154734

Cited by 18 publications

(14 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Second, no obvious ESR signals of other ROS were detected due to the relatively low content and the complexity of the biological system. Although superoxide level can represent the ROS level, [ 69,70 ] they are not equal. Third, acute and chronic alcoholic liver injuries coexisted in the animal model, and we did not demonstrate the preventive effects of Lf embody in acute, chronic, or both.…”

Section: Discussionmentioning

confidence: 99%

Daily Dose of Bovine Lactoferrin Prevents Ethanol‐Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota

Liu

Qian

Yang

et al. 2021

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope Lactoferrin (Lf) possess a protective potential to liver, but whether it can prevent alcoholic liver injury (ALI) remains unclear. Methods and Results Four groups of male C57BL/6J mice are fed with different diets, namely, AIN‐93G diet for control (CON) and ethanol (EtOH) groups, and AIN‐93G diet with 0.4% and 4% casein replaced by Lf for low‐dose Lf (LLf) and high‐dose Lf (HLf) groups, respectively. ALI is induced by giving 20% ethanol ad libitum combined with four “binges”. Lf can remarkably decrease EtOH‐induced mortality. Lf promotes aldehyde dehydrogenase‐2 (ALDH2) expression and suppressing cytochrome P450 2E1 (CYP2E1) overexpression, resulting in the reduced hepatic superoxide and inflammation levels, which ultimately leads to the hepatic injury alleviation. However, HLf increases acetyl‐CoA carboxylase and fatty acid synthase protein levels, which suggests that excessive intake may weaken the beneficial effects of Lf. Moreover, LLf increases the relative abundances of Akkermansia and Lactobacillus. Additionally, the study shows that Lf likely exerts action in its digestive product forms rather than intact Lf molecular in normal condition. Conclusion LLf can ameliorate ALI, which is associated with the regulation of hepatic alcohol metabolism and the modulation of gut microbiota. However, excessive Lf intake may result in a diminished benefit.

show abstract

Section: Discussionmentioning

confidence: 99%

Daily Dose of Bovine Lactoferrin Prevents Ethanol‐Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota

Liu

Qian

Yang

et al. 2021

Molecular Nutrition Food Res

View full text Add to dashboard Cite

show abstract

“…Mice consuming increasing doses of ethanol over longer periods of time develop a specific type of alcoholic cardiomyopathy with fibrotic and structural changes in the left ventricle. In this model, mice showed TNFR1-dependent elevated serum levels of TNF-α, left ventricle dysfunction, and increased cardiac ROS and pro-inflammatory cytokine production [ 131 ]. Increased TNF-α levels have been also observed in a rat model of adriamycin-induced cardiomyopathy.…”

Section: Tnf-α In Animal Models Of Cardiovascular Diseasesmentioning

confidence: 99%

“…In cardiomyocytes TNF-α triggers a hypertrophic response and induces apoptosis [ 131 ]. Endogenous TNF-α contributes to increased protein synthesis and hypertrophy [ 142 ] through the NF-κB-mediated production of ROS [ 143 ].…”

Section: Cellular and Molecular Mechanisms Of Tnf-α Signaling In Cmentioning

confidence: 99%

Complexity of TNF-α Signaling in Heart Disease

Rolski

Błyszczuk

2020

JCM

102

View full text Add to dashboard Cite

Heart disease is a leading cause of death with unmet clinical needs for targeted treatment options. Tumor necrosis factor alpha (TNF-α) represents a master pro-inflammatory cytokine that plays an important role in many immunopathogenic processes. Anti-TNF-α therapy is widely used in treating autoimmune inflammatory disorders, but in case of patients with heart disease, this treatment was unsuccessful or even harmful. The underlying reasons remain elusive until today. This review summarizes the effects of anti-TNF-α treatment in patients with and without heart disease and describes the involvement of TNF-α signaling in a number of animal models of cardiovascular diseases. We specifically focused on the role of TNF-α in specific cardiovascular conditions and in defined cardiac cell types. Although some mechanisms, mainly in disease development, are quite well known, a comprehensive understanding of TNF-α signaling in the failing heart is still incomplete. Published data identify pathogenic and cardioprotective mechanisms of TNF-α in the affected heart and highlight the differential role of two TNF-α receptors pointing to the complexity of the TNF-α signaling. In the light of these findings, it seems that targeting the TNF-α pathway in heart disease may show therapeutic benefits, but this approach must be more specific and selectively block pathogenic mechanisms. To this aim, more research is needed to better understand the molecular mechanisms of TNF-α signaling in the failing heart.

show abstract

“…Hoyt et al (197) suggested that the activation of the NLRP3 inflammasome has an essential role in developing inflammation related to long-term exposure to ethanol. Of note, cardiac injury induced by ethanol consumption involves NF-κB activation (53). In addition, chronic ethanol exposure induces TLR4-mediated cytokine production (198).…”

Section: N-oxide-trimethylaminementioning

confidence: 99%

Ethanol: striking the cardiovascular system by harming the gut microbiota

Silva

Elias-Oliveira

McCarthy

et al. 2021

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Ethanol consumption represents a significant public health problem, and excessive ethanol intake is a risk factor for cardiovascular disease (CVD), one of the leading causes of death and disability worldwide. The mechanisms underlying the effects of ethanol on the cardiovascular system are complex and not fully comprehended. The gut microbiota and their metabolites are indispensable symbionts essential for health and homeostasis and therefore, have emerged as potential contributors to ethanol-induced cardiovascular system dysfunction. By mechanisms that are not completely understood, the gut microbiota modulates the immune system and activates several signaling pathways that stimulate inflammatory responses, which in turn, contribute to the development and progression of CVD. This review summarizes preclinical and clinical evidence on the effects of ethanol in the gut microbiota and discusses the mechanisms by which ethanol-induced gut dysbiosis leads to the activation of the immune system and cardiovascular dysfunction. The crosstalk between ethanol consumption and the gut microbiota and its implications are detailed. In summary, an imbalance in the symbiotic relationship between the host and the commensal microbiota in a holobiont, as seen with ethanol consumption, may contribute to CVD. Therefore, manipulating the gut microbiota, by using antibiotics, probiotics, prebiotics and fecal microbiota transplantation might prove a valuable opportunity to prevent/mitigate the deleterious effects of ethanol and improve cardiovascular health and risk prevention.

show abstract

Chronic ethanol consumption increases reactive oxygen species generation and the synthesis of pro-inflammatory proteins in the heart through TNFR1-dependent mechanisms

Cited by 18 publications

References 45 publications

Daily Dose of Bovine Lactoferrin Prevents Ethanol‐Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota

Daily Dose of Bovine Lactoferrin Prevents Ethanol‐Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota

Complexity of TNF-α Signaling in Heart Disease

Ethanol: striking the cardiovascular system by harming the gut microbiota

Contact Info

Product

Resources

About