Quercetin reduced the formation of <i>N</i>‐acetyl‐<i>p</i>‐benzoquinoneimine, a toxic metabolite of paracetamol in rats and isolated rat hepatocytes

Pingili, Ravindrababu; Pawar, A. Krishnamanjari; Challa, Siva Reddy

doi:10.1002/ptr.6365

Cited by 13 publications

(12 citation statements)

References 74 publications

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“…Since hepatocytes are the prime liver parenchymal cells, L02 cell line, as an ideal cell line was incubated with ethanol to establish an in vitro model of ALD in our study [ 31 ]. In the liver, alcohol dehydrogenase (ADH) and CYP2E1 are the major oxidative pathways of alcohol metabolism, with a secondary pathway through peroxisome catalase [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Quercetin Protects Ethanol-Induced Hepatocyte Pyroptosis via Scavenging Mitochondrial ROS and Promoting PGC-1α-Regulated Mitochondrial Homeostasis in L02 Cells

Zhao

Wang

Dai

et al. 2022

Oxidative Medicine and Cellular Longevity

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Alcoholic liver disease (ALD) is a multifaceted process that involves excessive lipid, reactive oxygen species (ROS) production, unbalanced mitochondrial homeostasis, and ultimate cell death. Quercetin is a dietary phytochemical presented in various fruits and vegetables, which has anti-inflammatory and antioxidant effects. According to recent advances in pharmanutritional management, the effects of quercetin on various mitochondrial processes have attracted attention. In the study, we explored whether quercetin could attenuate ethanol-induced hepatocyte pyroptosis by maintaining mitochondrial homeostasis and studied its hepatoprotective effect and the underlying mechanism. We chose L02 cells to establish an in vitro model with ethanol-induced hepatocyte pyroptosis. Then, the cells at approximately 80% confluence were treated with quercetin (80, 40, and 20 μM). The cell viability (CCK-8) was used to investigate the effect of quercetin on ethanol-induced L02 cell proliferation. Relative assay kits were used to measure oxidative stress index ( OSI = TOS / TAS ), lipid peroxidation (LPO) release, and mitochondrial membrane potential ( δ Ψ m ). The morphology of mitochondria was characterized by transmission electron microscopy- (TEM-) based analysis. Mitochondrial dynamics (Mito Tracker Green), mitROS (MitoSOX Red Mitochondrial Superoxide) production, and nuclear DNA (nDNA) damage (γH2AX) markers were detected by immunofluorescence. The mRNA levels of mitochondrial function (including mitochondrial DNA (mtDNA) transcription genes TWNK, MTCO1, and MFND) and pyroptosis-related genes were detected by RT-qPCR, and the protein levels of NLRP3, ASC, caspase1, cleaved-caspase1, IL-18, IL-1β, and GSDMD-N were detected by western blot. The results showed that quercetin treatment downregulated redox status, lipid droplets, and LPO release, restored damaged mitochondrial membrane potential, and repaired mtDNA damage, PGC-1α nuclear transfer, and mitochondrial dynamics. The gene and protein expressions of NLRP3, ASC, cleaved-caspase1, IL-18, IL-1β, and GSDMD-N were decreased, which effectively inhibited cell pyroptosis. Therefore, the results indicated that quercetin protected ethanol-induced hepatocyte pyroptosis via scavenging mitROS and promoting PGC-1α-mediated mitochondrial homeostasis in L02 cells.

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Section: Discussionmentioning

confidence: 99%

Quercetin Protects Ethanol-Induced Hepatocyte Pyroptosis via Scavenging Mitochondrial ROS and Promoting PGC-1α-Regulated Mitochondrial Homeostasis in L02 Cells

Zhao

Wang

Dai

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…NAPQI stimulates oxidative stress after acute toxicity by exhaustion of the cellular antioxidants (e.g., GSH, CAT and GPx). In addition, NAPQI interacts with protein residues with formation of stable protein structures with marked damage of cellular proteins (27,28) . Concurrently, the immune response plays a significant role in the pathogenesis of the hepatorenal harmful effects due to acute paracetamol overdosage, and many cytokines (e.g., IL-1β, IL6, and IFN-γ) (29,30) .…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Ameliorates Oxidative and Inflammatory Effects of Hepatorenal Injury of Acute Paracetamol Toxicity: An experimental study

Elsaeed

Gawesh

Hammad

et al. 2020

SJMS

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Introduction and aim: An accidental or intentional paracetamol overdosage is a common condition, with hepatic injury as a common complication. Kidney could be injured in association with hepatic injury. Prevention and/or proper treatment is markedly important. The current study aimed to investigate the role of vitamin D (VD) in acute paracetamol-induced hepatorenal damage. Methodology: Fourty male Wister rats were divided into 4 equal groups. The negative control (NC), the positive control (PC) (received paracetamol 1200mg/kg), prophylactic group (received VD (1000 IU/Kg/day) before induction of toxicity and treatment continued after induction); and the treatment group with VD (2000 IU/Kg/day) for five successive days after induction of toxicity, for three successive cycles. VD levels, serum liver enzymes, total protein, albumin, serum urea and creatinine were estimated. The concentrations of interferon-γ (IFN- γ), interleukins (IL1β, IL4, IL10, and IL-17) in the tissue lysate were determined. The oxidative stress indicators and antioxidant enzymes (glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and Malonaldehyde (MDA)) were also measured. Results: Liver enzymes, serum urea and creatinine were increased in PC than NC groups, and were significantly reduced in prophylactic and treatment groups. But not return normal values, and prophylactic group is better. Total proteins and albumin significantly reduced by paracetamol toxicity and returned to near normal with VD supplementation. Vitamin-D levels were significantly reduced in PC than NC groups. However, it was significantly increased in prophylactic and treatment groups than NC and PC groups. IFN- γ, IL-1β, IL-17, and MDA were significantly increased, while IL-10, GPx, CAT, and GSH were significantly reduced in PC than NC groups. Prophylactic and treatment groups improved the values. However, SOD significantly reduced in PC than NC group. Vitamin D was significantly and inversely correlated with ALT, AST, ALP, albumin, creatinine, liver and kidney IFN-γ, IL-1β, IL-17 and MDA. But, it was proportionately and significantly correlated with liver and kidney IL-10. Conclusion: Acute paracetamol toxicity alters hepatic and renal VD homeostasis through oxidative stress and pro-inflammation. Vitamin D supplementation had an ameliorative action on hepatorenal injury, and the long duration of VD supplementation had better outcome.

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“…It can withhold the formation of N-acetyl-pbenzoquinone imine (NAPQI), which is a toxic metabolite of acetaminophen in rats and isolated rat liver cells, thereby preventing CYP2E1 and other CYPs mediated inhibition of paracetamol metabolism, and reducing the oxidative stress caused by paracetamol in the liver and kidneys. 64 Ethanol incubation of human primary hepatocytes results in sustained glutathion depletion, lipid peroxidation and membrane damage, whereas QUE-induced HO-1 correspondingly reduces ethanol-derived oxidative damage. HO-1 induction intercedes the protective effect of QUE via p38, especially via ERK/Nrf2 transduction pathway in human hepatocytes.…”

Section: Polyphenols Affect Metabolism Through Toxic Metabolitesmentioning

confidence: 99%

Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention

Yin

Ding

et al. 2022

Cell Proliferation

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Background Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation. Methods We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and liver cancer prevention. Results Targeting metabolic dysregulation in organisms prevents and resists the development of liver cancer, which has important implications for identifying new therapeutic strategies for the management and treatment of cancer. Polyphenols are a class of complex compounds composed of multiple phenolic hydroxyl groups and are the main active ingredients of many natural plants. They mediate a broad spectrum of biological and pharmacological functions containing complex lipid metabolism, glucose metabolism, iron metabolism, intestinal flora imbalance, as well as the direct interaction of their metabolites with key cell‐signalling proteins. A large number of studies have found that polyphenols affect the metabolism of organisms by interfering with a variety of intracellular signals, thereby protecting the liver and reducing the risk of liver cancer. Conclusion This review systematically illustrates that various polyphenols, including resveratrol, chlorogenic acid, caffeic acid, dihydromyricetin, quercetin, catechins, curcumin, etc., improve metabolic disorders through direct or indirect pathways to protect the liver and fight liver cancer.

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Quercetin reduced the formation of N‐acetyl‐p‐benzoquinoneimine, a toxic metabolite of paracetamol in rats and isolated rat hepatocytes

Cited by 13 publications

References 74 publications

Quercetin Protects Ethanol-Induced Hepatocyte Pyroptosis via Scavenging Mitochondrial ROS and Promoting PGC-1α-Regulated Mitochondrial Homeostasis in L02 Cells

Quercetin Protects Ethanol-Induced Hepatocyte Pyroptosis via Scavenging Mitochondrial ROS and Promoting PGC-1α-Regulated Mitochondrial Homeostasis in L02 Cells

Vitamin D Ameliorates Oxidative and Inflammatory Effects of Hepatorenal Injury of Acute Paracetamol Toxicity: An experimental study

Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention

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