Membrane Remodeling as a Key Player of the Hepatotoxicity Induced by Co-Exposure to Benzo[a]pyrene and Ethanol of Obese Zebrafish Larvae

Imran, Muhammad; Sergent, Odile; Tête, Arnaud; Gallais, Isabelle; Chevanne, Martine; Lagadic‐Gossmann, Dominique; Podechard, Normand

doi:10.3390/biom8020026

Cited by 13 publications

(18 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various studies have shown that high levels of air pollutants including benzo(a)pyrene are linked with many adverse clinical complications comprising various organ injuries such as lungs, liver, and kidneys with increased mortality as well as morbidity [9,12,18,19]. However, the mechanisms accountable for such association have not been fully explained; few studies showed increased oxidative stress, inflammation, apoptosis, and impairment of cell cycle was due to exposure tobenzopyrene.…”

Section: Discussionmentioning

confidence: 99%

Curcumin, an Active Constituent of Turmeric Spice: Implication in the Prevention of Lung Injury Induced by Benzo(a) Pyrene (BaP) in Rats

et al. 2020

View full text Add to dashboard Cite

Benzo(a)pyrene (BaP) is a well-known carcinogen and enhances oxidative stress and apoptosis and also alters several molecular pathways. Curcumin is an active ingredient of Curcuma longa, and it has potent anti-inflammatory, antioxidant activity that defends cells from oxidative stress and cell death. The objectives of the present study were to explore the protective effects of curcumin against long-term administration of BaP induced disturbances in lungs of rats. Male rats were randomly divided into four groups: saline control, BaP only, BaP + curcumin, and curcumin only. Lung histopathology, electron microscopy, inflammatory cytokine release, antioxidant levels, apoptosis, and cell cycle were examined. Instillation of BaP significantly increased infiltration of inflammatory cells in alveolar space and inflammatory cytokine in blood. BaP induced lung tissue alterations including mild bronchitis, scant chronic inflammatory cell infiltrate in the wall of the respiratory bronchiole, and mild intra-alveolar haemorrhage. However, these alterations were found to be significantly less as mild inflammatory cell infiltrate in curcumin plus BaP treated group. Furthermore, electron microscopy results also showed necrotic changes and broken cell membrane of Type-II epithelial cell of alveoli in BaP group, which was reduced after adding curcumin treatment. In addition, we found BaP plus curcumin treatment effectively reduced inflammatory cytokines Tumour Necrosis Factor alpha (TNF-α), Interleukin 6 (IL-6), and C-reactive protein (CRP) levels in blood serum. Moreover, the levels of tunnel staining and p53 expression were significantly increased by BaP, whereas these changes were noticeably modulated after curcumin treatment. BaP also interferes in normal cell cycle, which was significantly improved with curcumin treatment. Overall, our findings suggest that curcumin attenuates BaP -induced lung injury, probably through inhibiting inflammation, oxidative stress and apoptosis in lung epithelial cells, and improving cell proliferation and antioxidants level. Thus, curcumin may be an alternative therapy for improving the outcomes of Benzo(a)pyrene-induced lung injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Curcumin, an Active Constituent of Turmeric Spice: Implication in the Prevention of Lung Injury Induced by Benzo(a) Pyrene (BaP) in Rats

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Finally, recent investigations of different experimental models of MAFLD suggested that benzo[a]pyrene exposure might even further aggravate the progression of steatosis to steatohepatitis induced by ethanol [176,[213][214][215]. Potential mechanisms involved in such progression include overproduction of ROS and nitric oxide [176,214], mitochondrial dysfunction [176], increased expression of proinflammatory cytokines [213] and plasma membrane remodeling [215].…”

Section: Ethanolmentioning

confidence: 99%

Xenobiotic-Induced Aggravation of Metabolic-Associated Fatty Liver Disease

Massart¹,

Begriche²,

Corlu³

et al. 2022

IJMS

View full text Add to dashboard Cite

Metabolic-associated fatty liver disease (MAFLD), which is often linked to obesity, encompasses a large spectrum of hepatic lesions, including simple fatty liver, steatohepatitis, cirrhosis and hepatocellular carcinoma. Besides nutritional and genetic factors, different xenobiotics such as pharmaceuticals and environmental toxicants are suspected to aggravate MAFLD in obese individuals. More specifically, pre-existing fatty liver or steatohepatitis may worsen, or fatty liver may progress faster to steatohepatitis in treated patients, or exposed individuals. The mechanisms whereby xenobiotics can aggravate MAFLD are still poorly understood and are currently under deep investigations. Nevertheless, previous studies pointed to the role of different metabolic pathways and cellular events such as activation of de novo lipogenesis and mitochondrial dysfunction, mostly associated with reactive oxygen species overproduction. This review presents the available data gathered with some prototypic compounds with a focus on corticosteroids and rosiglitazone for pharmaceuticals as well as bisphenol A and perfluorooctanoic acid for endocrine disruptors. Although not typically considered as a xenobiotic, ethanol is also discussed because its abuse has dire consequences on obese liver.

show abstract

“…Also, FluvaSt inhibited Fcγ receptor signaling in monocyte rafts, which was rescued by mevalonate, whereas the use of prenyl transferase inhibitors was without effect, thus indicating the involvement of these cholesterol-rich membrane domains [ 81 ]. Finally, PravaSt (at the low concentration of 0.5 μM) counteracted the deleterious effect of exposure to benzo( a )pyrene and ethanol of hepatic cells and of obese zebrafish larvae liver, which was mediated by membrane remodeling altering cholesterol-containing rafts that mediate inflammatory signaling [ 82 ].…”

Section: In-vitro Effects Of Statins On Cholesterol-enriched Membrane Microdomains: Rafts Can Be Altered By Statinsmentioning

confidence: 99%

Coronaviruses, cholesterol and statins: Involvement and application for Covid-19

2021

View full text Add to dashboard Cite

The infectious power of coronaviruses is dependent on cholesterol present in the membranes of their target cells. Indeed, the virus enters the infected cell either by fusion or by endocytosis, in both cases involving cholesterol-enriched membrane microdomains. These membrane domains can be disorganized in-vitro by various cholesterol-altering agents, including statins that inhibit cell cholesterol biosynthesis. As a consequence, numerous cell physiology processes, such as signaling cascades, can be compromised. Also, some examples of anti-bacterial and anti-viral effects of statins have been observed for infectious agents known to be cholesterol dependent. In-vivo , besides their widely-reported hypocholesterolemic effect, statins display various pleiotropic effects mediated, at least partially, by perturbation of membrane microdomains as a consequence of the alteration of endogenous cholesterol synthesis. It should thus be worth considering a high, but clinically well-tolerated, dose of statin to treat Covid-19 patients, in the early phase of infection, to inhibit virus entry into the target cells, in order to control the viral charge and hence avoid severe clinical complications. Based on its efficacy and favorable biodisposition, an option would be considering Atorvastatin, but randomized controlled clinical trials are required to test this hypothesis. This new therapeutic proposal takes benefit from being a drug repurposing, applied to a widely-used drug presenting a high efficiency-to-toxicity ratio. Additionally, this therapeutic strategy avoids any risk of drug resistance by viral mutation since it is host-targeted. Noteworthy, the same pharmacological approach could also be proposed to address different animal coronavirus endemic infections that are responsible for heavy economic losses.

show abstract

Membrane Remodeling as a Key Player of the Hepatotoxicity Induced by Co-Exposure to Benzo[a]pyrene and Ethanol of Obese Zebrafish Larvae

Cited by 13 publications

References 107 publications

Curcumin, an Active Constituent of Turmeric Spice: Implication in the Prevention of Lung Injury Induced by Benzo(a) Pyrene (BaP) in Rats

Curcumin, an Active Constituent of Turmeric Spice: Implication in the Prevention of Lung Injury Induced by Benzo(a) Pyrene (BaP) in Rats

Xenobiotic-Induced Aggravation of Metabolic-Associated Fatty Liver Disease

Coronaviruses, cholesterol and statins: Involvement and application for Covid-19

Contact Info

Product

Resources

About