Fatty Acid Amide Hydrolase (FAAH) Inhibition Plays a Key Role in Counteracting Acute Lung Injury

Genovese, Tiziana; Duranti, Andrea; D’Amico, Ramona; Fusco, Roberta; Impellizzeri, Daniela; Peritore, Alessio Filippo; Crupi, Rosalia; Gugliandolo, Enrico; Cuzzocrea, Salvatore; Paola, Rosanna Di; Siracusa, Rosalba; Cordaro, Marika

doi:10.3390/ijms23052781

Cited by 8 publications

(7 citation statements)

References 110 publications

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“…Radice and colleagues demonstrated that vinclozolin was able to induce lipid peroxidation in the Hep92 cell line [ 28 ]. As previously proven in other cell types, we found a significant increase in DNA damage, verified by the activation of PARP, a well-known marker of DNA damage, as well as an increase in lipid peroxidation, proven via an MDA level investigation [ 29 , 30 , 31 , 32 , 33 , 34 ]. Different studies demonstrated that vinclozolin administration induces granulosa cell apoptosis during follicular atresia in pigs, as well as apoptosis in testis [ 35 , 36 ].…”

Section: Discussionsupporting

confidence: 79%

Chronic Exposure to Endocrine Disruptor Vinclozolin Leads to Lung Damage via Nrf2–Nf-kb Pathway Alterations

D’Amico

Paola

Impellizzeri

et al. 2022

IJMS

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Endocrine-disrupting substances (EDS) are common and pervasive in our environment and pose a serious risk to both human and animal health. Endocrine-disrupting compounds (EDCs) have been associated with a variety of detrimental human health effects, including respiratory issues, as a result of their ability to disrupt cell physiology. Vinclozolin ((RS)-3-(3,5-Dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione) is a common dicarboximide fungicide used to treat plant diseases. Several studies have analyzed the effects of vinclozolin exposure on the reproductive system, but less is known about its effect on other organs such as the lung. Mice were exposed for 28 days to orally administered vinclozolin at a dose of 100 mg/kg. Vinclozolin exposure induced histological alterations and collagen depositions in the lung. Additionally, vinclozolin induced inflammation and oxidative stress that led to lung apoptosis. Our study demonstrates for the first time that the toxicological effects of vinclozolin are not limited to the reproductive system but also involve other organs such as the lung.

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Section: Discussionsupporting

confidence: 79%

Chronic Exposure to Endocrine Disruptor Vinclozolin Leads to Lung Damage via Nrf2–Nf-kb Pathway Alterations

D’Amico

Paola

Impellizzeri

et al. 2022

IJMS

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“…Fatty acid amide hydrolase (FAAH) is a transmembrane protein responsible for the hydrolysis of the endocannabinoid N-arachidonoylethanolamide (AEA) and other related amidated signaling lipids, such as N-oleoylethanolamide (OEA), linoleoylethanolamide (LEA), and palmitoylethanolamide (PEA) [ 148 ]. Inhibition of FAAH exhibits a protective role in the development of ALI by suppressing the activation of NF-κB pathway as well as the expression of pro-inflammatory cytokines in a dose-dependent manner [ 149 ]. N-acylethanolamine acid amidase (NAAA) is a cysteine hydrolase generally expressed in immune cells, which is also responsible for the hydrolysis of FAEs.…”

Section: The Impact Of Free Fatty Acids and Its Derivatives On Alimentioning

confidence: 99%

The role of fatty acid metabolism in acute lung injury: a special focus on immunometabolism

Lu,

Li,

Liu

et al. 2024

Cell. Mol. Life Sci.

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Reputable evidence from multiple studies suggests that excessive and uncontrolled inflammation plays an indispensable role in mediating, amplifying, and protracting acute lung injury (ALI). Traditionally, immunity and energy metabolism are regarded as separate functions regulated by distinct mechanisms, but recently, more and more evidence show that immunity and energy metabolism exhibit a strong interaction which has given rise to an emerging field of immunometabolism. Mammalian lungs are organs with active fatty acid metabolism, however, during ALI, inflammation and oxidative stress lead to a series metabolic reprogramming such as impaired fatty acid oxidation, increased expression of proteins involved in fatty acid uptake and transport, enhanced synthesis of fatty acids, and accumulation of lipid droplets. In addition, obesity represents a significant risk factor for ALI/ARDS. Thus, we have further elucidated the mechanisms of obesity exacerbating ALI from the perspective of fatty acid metabolism. To sum up, this paper presents a systematical review of the relationship between extensive fatty acid metabolic pathways and acute lung injury and summarizes recent advances in understanding the involvement of fatty acid metabolism-related pathways in ALI. We hold an optimistic believe that targeting fatty acid metabolism pathway is a promising lung protection strategy, but the specific regulatory mechanisms are way too complex, necessitating further extensive and in-depth investigations in future studies.

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“…(IV) Sham groups+URB878: animals received URB878 dissolved in a vehicle for 14 days at the dose of 5 mg/kg. Doses were chosen based on a work carried out in our lab in an experimental model of carrageenan-induced acute lung injury [52].…”

Section: Experimental Design and Groupsmentioning

confidence: 99%

Inhibition of Fatty Acid Amide Hydrolase (FAAH) Regulates NF-kb Pathways Reducing Bleomycin-Induced Chronic Lung Inflammation and Pulmonary Fibrosis

Genovese

Duranti

Monaco

et al. 2023

IJMS

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The deadly interstitial lung condition known as idiopathic pulmonary fibrosis (IPF) worsens over time and for no apparent reason. The traditional therapy approaches for IPF, which include corticosteroids and immunomodulatory drugs, are often ineffective and can have noticeable side effects. The endocannabinoids are hydrolyzed by a membrane protein called fatty acid amide hydrolase (FAAH). Increasing endogenous levels of endocannabinoid by pharmacologically inhibiting FAAH results in numerous analgesic advantages in a variety of experimental models for pre-clinical pain and inflammation. In our study, we mimicked IPF by administering intratracheal bleomycin, and we administered oral URB878 at a dose of 5 mg/kg. The histological changes, cell infiltration, pro-inflammatory cytokine production, inflammation, and nitrosative stress caused by bleomycin were all reduced by URB878. Our data clearly demonstrate for the first time that the inhibition of FAAH activity was able to counteract not only the histological alteration bleomycin-induced but also the cascade of related inflammatory events.

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Fatty Acid Amide Hydrolase (FAAH) Inhibition Plays a Key Role in Counteracting Acute Lung Injury

Cited by 8 publications

References 110 publications

Chronic Exposure to Endocrine Disruptor Vinclozolin Leads to Lung Damage via Nrf2–Nf-kb Pathway Alterations

Chronic Exposure to Endocrine Disruptor Vinclozolin Leads to Lung Damage via Nrf2–Nf-kb Pathway Alterations

The role of fatty acid metabolism in acute lung injury: a special focus on immunometabolism

Inhibition of Fatty Acid Amide Hydrolase (FAAH) Regulates NF-kb Pathways Reducing Bleomycin-Induced Chronic Lung Inflammation and Pulmonary Fibrosis

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