Hepatotoxicity prevention in Acetaminophen-induced HepG2 cells by red betel (Piper crocatum Ruiz and Pav) extract from Indonesia via antioxidant, anti-inflammatory, and anti-necrotic

Ginting, Chrismis Novalinda; Lister, I Nyoman Ehrich; Girsang, Ermi; Widowati, Wahyu; Yusepany, Dewani Tediana; Azizah, Alya Mardhotillah; Kusuma, Hanna Sari Widya

doi:10.1016/j.heliyon.2020.e05620

Cited by 18 publications

(11 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Considering the important role of apoptosis on alcohol-induced liver injury, we decided to further observe cell apoptosis by TUNEL staining. On the other hand, the Bcl-2 family is an important apoptotic protein in the death receptor-mediated pathway, consisting of anti-apoptotic and pro-apoptotic proteins [22]. The caspase family is the main mediator that activates cell apoptosis; Caspase-3, caspase-8, and caspase-9 are key nodes to control apoptosis in the regulatory network [23].…”

Section: Discussionmentioning

confidence: 99%

The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats

Chen

Huang

et al. 2022

Inflammation

View full text Add to dashboard Cite

The present study was to investigate the therapeutical effects and mechanisms of Asiatic acid from Potentilla Chinensis against alcoholic hepatitis. Rats were intragastrically fed with alcohol for 12 weeks to induce alcoholic hepatitis and then treated with various drugs for further 12 weeks. The results showed that Asiatic acid signi cantly alleviated liver injury caused by alcohol in rats, as evidenced by the improved histological changes and the lower levels of AST, ALT, and TBIL. Besides, Asiatic acid signi cantly enhanced the activity of ADH and ALDH, promoting alcohol metabolism. Asiatic acid suppressed CYP2E1 activity and NADP + /NADPH ratio, resulting in low ROS production. Further study revealed that Asiatic acid markedly reduced hepatocyte apoptosis by regulating the expression levels of the caspase and Bcl-2 families. Moreover, Asiatic acid could regulate the Keap1/Nrf2 and NF-κB signaling pathway, attenuating oxidative stress and in ammation as a result. Interestingly, the comprehensive analysis of transcriptomics and metabolomics indicated that Asiatic acid regulated the gene expression of Gpat4 and thereby affected the biosynthesis of the metabolites (1-acyl-Sn-glycerol-3-phosphocholine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine), regulating the glycerophospholipid metabolism pathway and ultimately ameliorating hepatocyte damage. In conclusion, this study demonstrates that Asiatic acid can ameliorate alcoholic hepatitis by modulating the NF-κB and Keap1/Nrf2 signaling pathways and the glycerophospholipid metabolism pathway, which may be developed as a potential medicine for the treatment of alcoholic hepatitis.

show abstract

Section: Discussionmentioning

confidence: 99%

The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats

Chen

Huang

et al. 2022

Inflammation

View full text Add to dashboard Cite

show abstract

“…Beclin-1 was observed in the plasma membrane of cancer cells by immunostaining, but no such effect was found in healthy cells [73]. In a study with HepG2 cell carcinoma cell lines by ELISA, an increase in TNF-α levels was found after acetaminophen exposure [74]. TNF-α as a tmTNF-α transmembrane protein in the form of stable homodimers, binding to its receptors TNFR1 and TNFR2, plays a role in the transmission of molecular signals such as inflammation and cell death [75,76].…”

Section: Acetaminophen (Paracetamol)mentioning

confidence: 95%

“…Figure 6 shows the impact of discussed drugs on gastrointestinal cancers cells membranes. [53,56], antigen on a cell surface (CD44) [53][54][55]65], Reactive Oxygen Species (ROS) [57,58,60], Ras-related C3 botulinum toxin substrate 1B (RAC1b) [61][62][63][64], Octamer-binding transcription factor 4 (OCT40) [65], Tumor necrosis factor α (TNF-α) [74][75][76], epidermal growth factor receptor (EGRF) [67,68], Fas ligand (FasL) [69,70], Beclin-1 protein [72,73].…”

Section: Acetaminophen (Paracetamol)mentioning

confidence: 99%

Effects of Non-Opioid Analgesics on the Cell Membrane of Skin and Gastrointestinal Cancers

Janicka

Sałek

Sawińska

et al. 2022

IJMS

View full text Add to dashboard Cite

Skin and gastrointestinal cancer cells are the target of research by many scientists due to the increasing morbidity and mortality rates around the world. New indications for drugs used in various conditions are being discovered. Non-opioid analgesics are worth noting as very popular, widely available, relatively cheap medications. They also have the ability to modulate the membrane components of tumor cells. The aim of this review is to analyze the impact of diclofenac, ibuprofen, naproxen, acetylsalicylic acid and paracetamol on skin and gastrointestinal cancers cell membrane. These drugs may affect the membrane through topical application, at the in vitro and in vivo level after oral or parenteral administration. They can lead to up- or downregulated expression of receptors, transporters and other molecules associated with plasma membrane. Medications may also alter the lipid bilayer composition of membrane, resulting in changes in its integrity and fluidity. Described modulations can cause the visualization of cancer cells, enhanced response of the immune system and the initiation of cell death. The outcome of this is inhibition of progression or reduction of tumor mass and supports chemotherapy. In conclusion, non-opioid analgesics may be used in the future as adjunctive therapy for the treatment of these cancers.

show abstract

“…Moreover, the anti-inflammatory and antioxidant properties of shikonin decreased interleukin (IL-6 and IL-1β), tumor necrosis factor-α (TNF-α), and CYP2E1 mRNA expression [ 44 ]. When APAP-challenged human hepatocellular carcinoma cells (HepG2) were treated with red betel leaf extract (from Indonesia) at 25 and 100 μg/mL, Ginting et al, showed hepatoprotective effects with elevated CYP2E1 and glutathione peroxidase gene expression [ 48 ]. Choi et al investigated the effects of the natural alkaloid, rutaecarpine, on APAP-induced liver injury in mice [ 49 ].…”

Section: The Role Of Hepatic Cyp2e1 In Causal Toxicity and Potential ...mentioning

confidence: 99%

Hepatic, Extrahepatic and Extracellular Vesicle Cytochrome P450 2E1 in Alcohol and Acetaminophen-Mediated Adverse Interactions and Potential Treatment Options

Kumar

Singla

Singh

et al. 2022

Cells

View full text Add to dashboard Cite

Alcohol and several therapeutic drugs, including acetaminophen, are metabolized by cytochrome P450 2E1 (CYP2E1) into toxic compounds. At low levels, these compounds are not detrimental, but higher sustained levels of these compounds can lead to life-long problems such as cytotoxicity, organ damage, and cancer. Furthermore, CYP2E1 can facilitate or enhance the effects of alcohol-drug and drug-drug interactions. In this review, we discuss the role of CYP2E1 in the metabolism of alcohol and drugs (with emphasis on acetaminophen), mediating injury/toxicities, and drug-drug/alcohol-drug interactions. Next, we discuss various compounds and various nutraceuticals that can reduce or prevent alcohol/drug-induced toxicity. Additionally, we highlight experimental outcomes of alcohol/drug-induced toxicity and potential treatment strategies. Finally, we cover the role and implications of extracellular vesicles (EVs) containing CYP2E1 in hepatic and extrahepatic cells and provide perspectives on the clinical relevance of EVs containing CYP2E1 in intracellular and intercellular communications leading to drug-drug and alcohol-drug interactions. Furthermore, we provide our perspectives on CYP2E1 as a druggable target using nutraceuticals and the use of EVs for targeted drug delivery in extrahepatic and hepatic cells, especially to treat cellular toxicity.

show abstract

Hepatotoxicity prevention in Acetaminophen-induced HepG2 cells by red betel (Piper crocatum Ruiz and Pav) extract from Indonesia via antioxidant, anti-inflammatory, and anti-necrotic

Cited by 18 publications

References 44 publications

The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats

The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats

Effects of Non-Opioid Analgesics on the Cell Membrane of Skin and Gastrointestinal Cancers

Hepatic, Extrahepatic and Extracellular Vesicle Cytochrome P450 2E1 in Alcohol and Acetaminophen-Mediated Adverse Interactions and Potential Treatment Options

Contact Info

Product

Resources

About