scholarly journals Structure-Dependent Effects of Phthalates on Intercellular and Intracellular Communication in Liver Oval Cells

2020 ◽  
Vol 21 (17) ◽  
pp. 6069
Author(s):  
Lucie Čtveráčková ◽  
Daniel Jančula ◽  
Jan Raška ◽  
Pavel Babica ◽  
Iva Sovadinová
Keyword(s):  
Liver Toxicity ◽  
Daily Basis ◽  
Adverse Outcomes ◽  
Chronic Liver ◽  
Oval Cells ◽  
Gap Junctional Intercellular Communication ◽  
Cellular Effects ◽  
Adverse Health Outcomes ◽  
Gap Junctional ◽  
Homeostatic Mechanisms

Humans are exposed to phthalates released from plastics, cosmetics, or food on a daily basis. Phthalates have low acute liver toxicity, but their chronic exposures could induce molecular and cellular effects linked to adverse health outcomes, such as liver tumor promotion or chronic liver diseases. The alternation of gap junctional intercellular communication (GJIC) and MAPK-Erk1/2 pathways in liver progenitor or oval cells can disrupt liver tissue homeostatic mechanisms and affect the development and severity of these adverse outcomes. Our study with 20 different phthalates revealed their structurally dependent effects on liver GJIC and MAPK-Erk1/2 signaling in rat liver WB-F344 cell line with characteristics of liver oval cells. The phthalates with a medium-length side chain (3–6 C) were the most potent dysregulators of GJIC and activators of MAPK-Erk1/2. The effects occurred rapidly, suggesting the activation of non-genomic (non-transcriptional) mechanisms directly by the parental compounds. Short-chain phthalates (1–2 C) did not dysregulate GJIC even after longer exposures and did not activate MAPK-Erk1/2. Longer chain (≥7 C) phthalates, such as DEHP or DINP, moderately activated MAPK-Erk1/2, but inhibited GJIC only after prolonged exposures (>12 h), suggesting that GJIC dysregulation occurs via genomic mechanisms, or (bio)transformation. Overall, medium-chain phthalates rapidly affected the key tissue homeostatic mechanisms in the liver oval cell population via non-genomic pathways, which might contribute to the development of chronic liver toxicity and diseases.

Gap junctional intercellular communication as a target for liver toxicity and carcinogenicity

2009 ◽  
Vol 44 (4) ◽  
pp. 201-222 ◽  
Author(s):  
Mathieu Vinken ◽  
Tatyana Doktorova ◽  
Elke Decrock ◽  
Luc Leybaert ◽  
Tamara Vanhaecke ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Liver Toxicity ◽  
Gap Junctional Intercellular Communication ◽  
Gap Junctional

scholarly journals Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)—A Condition Associated with Heightened Sympathetic Activation

2021 ◽  
Vol 22 (8) ◽  
pp. 4241
Author(s):  
Revathy Carnagarin ◽  
Kearney Tan ◽  
Leon Adams ◽  
Vance B. Matthews ◽  
Marcio G. Kiuchi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Treatment Strategies ◽  
Adverse Outcomes ◽  
Metabolic Dysfunction ◽  
Sympathetic Activation ◽  
Beneficial Effects ◽  
Adverse Health Outcomes

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease affecting a quarter of the global population and is often associated with adverse health outcomes. The increasing prevalence of MAFLD occurs in parallel to that of metabolic syndrome (MetS), which in fact plays a major role in driving the perturbations of cardiometabolic homeostasis. However, the mechanisms underpinning the pathogenesis of MAFLD are incompletely understood. Compelling evidence from animal and human studies suggest that heightened activation of the sympathetic nervous system is a key contributor to the development of MAFLD. Indeed, common treatment strategies for metabolic diseases such as diet and exercise to induce weight loss have been shown to exert their beneficial effects at least in part through the associated sympathetic inhibition. Furthermore, pharmacological and device-based approaches to reduce sympathetic activation have been demonstrated to improve the metabolic alterations frequently present in patients with obesity, MetSand diabetes. Currently available evidence, while still limited, suggests that sympathetic activation is of specific relevance in the pathogenesis of MAFLD and consequentially may offer an attractive therapeutic target to attenuate the adverse outcomes associated with MAFLD.

Association between Frailty and 90-Day Outcomes amongst the Chinese Population: A Hospital-Based Multicentre Cohort Study

Gerontology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Jing Jiao ◽  
Na Guo ◽  
Lingli Xie ◽  
Qiaoyan Ying ◽  
Chen Zhu ◽  
...  
Keyword(s):  
Cohort Study ◽  
Adverse Outcomes ◽  
Hospital Ward ◽  
Adverse Health Outcomes ◽  
Multicentre Cohort Study ◽  
Older Inpatients ◽  
Ward Clustering ◽  
Clustering Effect ◽  
The Relationship ◽  
Multicentre Cohort

<b><i>Introduction:</i></b> Frailty has gained increasing attention as it is by far the most prevalent geriatric condition amongst older patients which heavily impacts chronic health status. However, the relationship between frailty and adverse health outcomes in China is far from clear. This study explored the relation between frailty and a panel of adverse health outcomes. <b><i>Methods:</i></b> We performed a multicentre cohort study of older inpatients at 6 large hospitals in China, with two-stage cluster sampling, from October 2018 to April 2019. Frailty was measured according to the FRAIL scale and categorized into robust, pre-frail, and frail. A multivariable logistic regression model and multilevel multivariable negative binomial regression model were used to analyse the relationship between frailty and adverse outcomes. Outcomes were length of hospitalization, as well as falls, readmission, and mortality at 30 and 90 days after enrolment. All regression models were adjusted for age, sex, BMI, surgery, and hospital ward. <b><i>Results:</i></b> We included 9,996 inpatients (median age 72 years and 57.8% male). The overall mortality at 30 and 90 days was 1.23 and 1.88%, respectively. At 30 days, frailty was an independent predictor of falls (odds ratio [OR] 3.19; 95% CI 1.59–6.38), readmission (OR 1.45; 95% CI 1.25–1.67), and mortality (OR 3.54; 95% confidence interval [CI] 2.10–5.96), adjusted for age, sex, BMI, surgery, and hospital ward clustering effect. At 90 days, frailty had a strong predictive effect on falls (OR 2.10; 95% CI 1.09–4.01), readmission (OR 1.38; 95% CI 1.21–1.57), and mortality (OR 6.50; 95% CI 4.00–7.97), adjusted for age, sex, BMI, surgery, and hospital ward clustering effect. There seemed to be a dose-response association between frailty categories and fall or mortality, except for readmission. <b><i>Conclusions:</i></b> Frailty is closely related to falls, readmission, and mortality at 30 or 90 days. Early identification and intervention for frailty amongst older inpatients should be conducted to prevent adverse outcomes.

scholarly journals Insights into preventing female genital mutilation/cutting in Sri Lanka: a qualitative interpretative study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Angela Dawson ◽  
Kumudu Wijewardene
Keyword(s):  
Sri Lanka ◽  
Complete Removal ◽  
Cultural Practice ◽  
Adverse Outcomes ◽  
Detailed Knowledge ◽  
The Sustainable Development ◽  
Genital Mutilation ◽  
Adverse Health Outcomes ◽  
Template Analysis ◽  
Role Of Religion

Abstract Background FGM/C is a cultural practice associated with adverse health outcomes that involves the partial or complete removal of the external female genitalia or injury to the genitalia. FGM/C is a form of violence against women and girls. There are no laws that specifically outlaw FGM/C in Sri Lanka and no national prevalence data. There is a lack of evidence about this practice to inform prevention efforts required to achieve the Sustainable Development Goal (SDG) target 5.3.2, which focuses on the elimination of all harmful practices, including FGM/C. Methods We undertook a qualitative interpretative study to explore the knowledge and perceptions of community members, religious leaders and professionals from the health, legal and community work sectors in five districts across Sri Lanka. We aimed to identify strategies to end this practice. Results Two-hundred-and twenty-one people participated in focus group discussions and key informant interviews. A template analysis identified five top-level themes: Providers, procedures and associated rituals; demand and decision-making; the role of religion; perceived benefits and adverse outcomes; ways forward for prevention. Conclusions This study delivered detailed knowledge of FGM/C related beliefs, perceptions and practitioners and provided opportunities to develop an integrated programming strategy that incorporates interventions across three levels of prevention.

Doxorubicin induces EGF receptor-dependent downregulation of gap junctional intercellular communication in rat liver epithelial cells

2005 ◽  
Vol 386 (3) ◽  
pp. 217-223 ◽  
Author(s):  
Kotb Abdelmohsen ◽  
Claudia von Montfort ◽  
Dominik Stuhlmann ◽  
P. Arne Gerber ◽  
Ulrich K.M. Decking ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Rat Liver ◽  
Intercellular Communication ◽  
Connexin 43 ◽  
Egf Receptor ◽  
Gap Junctional Intercellular Communication ◽  
Erk Activation ◽  
Liver Epithelial Cells ◽  
Rat Liver Epithelial Cells ◽  
Gap Junctional

Abstract Exposure of rat liver epithelial cells to doxorubicin, an anthraquinone derivative widely employed in cancer chemotherapy, led to a dose-dependent decrease in gap junctional intercellular communication (GJC). Gap junctions are clusters of inter-cellular channels consisting of connexins, the major connexin in the cells used being connexin-43 (Cx43). Doxorubicin-induced loss of GJC was mediated by activation of extracellular signal-regulated kinase (ERK)-1 and ERK-2, as demonstrated using inhibitors of ERK activation. Furthermore, activation of the epidermal growth factor (EGF) receptor by doxorubicin was responsible for ERK activation and the subsequent attenuation of GJC. Inhibition of GJC, however, was not by direct phosphorylation of Cx43 by ERK-1/2, whereas menadione, a 1,4-naphthoquinone derivative that was previously demonstrated to activate the same EGF receptor-dependent pathway as doxorubicin, resulting in downregulation of GJC, caused strong phos-phorylation of Cx43 at serines 279 and 282. Thus, ERK-dependent downregulation of GJC upon exposure to quinones may occur both by direct phosphorylation of Cx43 and in a phosphorylation-independent manner.

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