Targeting NLRP3 inflammasome via acetylsalicylic acid: Role in suppressing hepatic dysfunction and insulin resistance induced by atorvastatin in naïve versus alcoholic liver in rats

El-Kharashi, Omnyah A.; El-Waseef, Dalia Alaa El-Din Aly; Nabih, Enas Samir; Mohamed, Doaa I.

doi:10.1016/j.biopha.2018.08.032

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…They had dilated and distorted cisternae of the rER, mitochondria with destroyed cristae and cytoplasmic vacuoles. A similar pattern of rER was previously observed in hepatocytes due to chronic alcohol consumption, and was attributed to endoplasmic reticulum stress [28]. In the present study, treatment with alcohol and/or ATOR caused nearly similar effects on the neurons structure and glial cells in the frontal lobe of the brain tissue.…”

Section: Discussionsupporting

confidence: 90%

“…After acclimation for 6-7 days, the animals were treated with alcohol (10 g/kg; oral gavage) as a water solution (with solutions maximally containing 56% alcohol) for 10 weeks and treated with atorvastatin (10 mg/kg) alone and/or in combination with a dose of ASA (10 mg/kg) for the same duration. All rats had frequent standard rat chow available during the 6-week period [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…The pleiotropic mechanisms of action of ASA could aid in the prevention of cognitive dementia [ 27 ]. Recent studies showed that a low dose of ASA alleviates the hepatotoxic effects of alcohol by modulating the NLRP3 inflammasome pathway and IL-1β [ 28 , 29 ]. Further studies have showed that ASA improves the endothelial dysfunction by targeting NLRP3 inflammasome through the ROS/TXNIP pathway [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

et al. 2022

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Alcoholism is one of the most common diseases that can lead to the development of several chronic diseases including steatosis, and cognitive dysfunction. Statins are lipid-lowering drugs that are commonly prescribed for patients with fatty liver diseases; however, the exact effect of statins on cognitive function is still not fully understood. In the present study, we have investigated the molecular and microscopic basis of cognitive impairment induced by alcohol and/or Atorvastatin (ATOR) administration to male Wistar albino rats and explored the possible protective effect of acetylsalicylic acid (ASA). The biochemical analysis indicated that either alcohol or ATOR or together in combination produced a significant increase in the nucleotide-binding domain–like receptor 3 (NLRP3), interleukin-1β (IL-1β) miRNA155 expression levels in the frontal cortex of the brain tissue. The histological and morphometric analysis showed signs of degeneration in the neurons and the glial cells with aggregations of inflammatory cells and a decrease in the mean thickness of the frontal cortex. Immunohistochemical analysis showed a significant increase in the caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex. Interestingly, administration of ASA reversed the deleterious effect of the alcohol and ATOR intake and improved the cognitive function as indicated by biochemical and histological analysis. ASA significantly decreased the expression levels of miRNA155, NLRP3, and IL1B, and produced a significant decrease in caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex with a reduction in the process of neuroinflammation and neuronal damage. To further investigate these findings, we have performed an extensive molecular docking study to investigate the binding affinity of ASA to the binding pockets of the NLRP3 protein. Our results indicated that ASA has high binding scores toward the active sites of the NLRP3 NACHT domain with the ability to bind to the NLRP3 pockets by a set of hydrophilic and hydrophobic interactions. Taken together, the present study highlights the protective pharmacological effect of ASA to attenuate the deleterious effect of alcohol intake and long term ATOR therapy on the cognitive function via targeting miRNA155 and NLRP3 proteins.

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Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

et al. 2022

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“…Darwish, Raboh, and Mahdy (2012) reported that the serum levels of ALT, AST, and AKP in rat were increased after three weeks of ethanol administration, and histopathological examination showed inflammatory cell infiltration, steatosis, collagen accumulation, and necrotic injury. El‐Kharashi, El, Nabih, and Mohamed (2018) found that 6 g/kg/d alcohol gavage for 1 week and 8 g/kg/d for 5 weeks increased serum ALT, AST, and ALP levels as well as decreased liver GSH level in rat. In our study, we consulted previous study (Cai et al., 2016) to develop an ethanol‐induced rat liver damage model with a progressive increased ethanol dosage (2 ‒8 g/kg/d) for two weeks and lasted 8 g/kg/d for another four weeks.…”

Section: Discussionmentioning

confidence: 99%

Curcumin and Baicalin ameliorate ethanol‐induced liver oxidative damage via the Nrf2/HO‐1 pathway

et al. 2020

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One of the key mechanisms of alcoholic liver disease is oxidative stress. Both Curcumin and Baicalin exert antioxidant effects, but the mechanism of their combined effects of ethanol-induced liver injury is still unclear. This study was conducted to evaluate the dual antioxidant activity of Curcumin combined with Baicalin against ethanol-induced liver injury in rats. Rats were divided into five groups, a control, ethanol, ethanol + Curcumin (50 mg/kg), ethanol + Baicalin (50 mg/kg), and ethanol + Curcumin +Baicalin group with ten rats per group. The effects of ethanol on liver enzymes, oxidative stress indicators and the levels of Nrf2/HO-1 pathway related proteins and mRNA were observed along with liver histopathology in rats. Our results found that the serum ALT and AKP levels were increased in ethanol-treated rats, which also showed a rising trend of 8-OHdG and LPO levels while hydroxyl radical scavenging ability, T-AOC, and the activities of SOD and GSH-Px were decreased in liver. The mRNA levels of Nrf2 and HO-1, the ratio of p-Nrf2/Nrf2, the protein level of HO-1 were decreased while NQO1 mRNA level, Nrf2, p-Nrf2, and NQO1 protein levels were increased in ethanol-treated rats. Combination treatment of Curcumin and Baicalin significantly reversed the ethanol-induced liver oxidative damage and further activate the Nrf2/HO-1 pathway, which was more effective than each drug alone. In conclusion, evidence has shown for the first time in this study that Curcumin combined with Baicalin ameliorated ethanolinduced liver oxidative damage in rats and revealed liver-protection. Practical applications Many drugs for treating alcoholic liver disease are available commercially, but some adverse effects they have may cause secondary damage to the liver. At present, the combined treatment of different natural phytochemicals has attracted special attention in modern medicine. Curcumin, a kind of phytochemicals, is extracted from turmeric rhizome. Baicalin is one of the major active components of Scutellaria Baicalensis. The current research is to explore the antioxidant effect of Curcumin and Baicalin in ethanol-induced liver injury in rats. Our research proves that Curcumin combined with Baicalin on ethanol-induced liver oxidative damage is superior to single drug treatment. Therefore, the combination of Curcumin and Baicalin may provide a more prospective natural remedy to combat ethanol-induced liver injury. How to cite this article: Wang X, Chang X, Zhan H, et al. Curcumin and Baicalin ameliorate ethanol-induced liver oxidative damage via the Nrf2/HO-1 pathway.

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“…Finally, there is evidence that aspirin administration inhibits the activation of the NLP3 inflammasome [ [192] , [193] , [194] ]. In addition, this may be a specific property of aspirin and may underpin a significant improvement in endothelial function [ 192 , 194 ]. This data raises questions regarding the appropriate dose of aspirin for consideration in a trial of a treatment for COVID-19.…”

Section: Suggestions For Therapeutic Interventionmentioning

confidence: 99%

Preventing the development of severe COVID-19 by modifying immunothrombosis

Morris

Bortolasci

Puri³

et al. 2021

Life Sciences

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Background COVID-19-associated acute respiratory distress syndrome (ARDS) is associated with significant morbidity and high levels of mortality. This paper describes the processes involved in the pathophysiology of COVID-19 from the initial infection and subsequent destruction of type II alveolar epithelial cells by SARS-CoV-2 and culminating in the development of ARDS. Main body The activation of alveolar cells and alveolar macrophages leads to the release of large quantities of proinflammatory cytokines and chemokines and their translocation into the pulmonary vasculature. The presence of these inflammatory mediators in the vascular compartment leads to the activation of vascular endothelial cells platelets and neutrophils and the subsequent formation of platelet neutrophil complexes. These complexes in concert with activated endothelial cells interact to create a state of immunothrombosis. The consequence of immunothrombosis include hypercoagulation, accelerating inflammation, fibrin deposition, migration of NET producing neutrophils into the alveolar apace, activation of the NLRP3 inflammazome, increased alveolar macrophage destruction and massive tissue damage by pyroptosis and necroptosis Therapeutic combinations aimed at ameliorating immunothrombosis and preventing the development of severe COVID19 are discussed in detail.

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Targeting NLRP3 inflammasome via acetylsalicylic acid: Role in suppressing hepatic dysfunction and insulin resistance induced by atorvastatin in naïve versus alcoholic liver in rats

Cited by 7 publications

References 43 publications

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

Curcumin and Baicalin ameliorate ethanol‐induced liver oxidative damage via the Nrf2/HO‐1 pathway

Preventing the development of severe COVID-19 by modifying immunothrombosis

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