Search Results (8)

N-acetyl para-aminophenol was suggested as a safer alternative to other drugs on the market for pain and fever in 1948. It was given the generic name “acetaminophen” in 1951 and the trade name “Tylenol” when it was put on the market in the USA in 1955 as a prescription drug to treat pediatric fever. It also received the generic name “paracetamol” in the UK where it was initially marketed in 1956 under the name “Panadol.” Toxicity from overdose of acetaminophen was reported in 1966. Research at the US National Institutes of Health uncovered the mechanisms of toxicity and proposed a treatment in a foundational series of papers in 1973 and 1974. A nomogram was developed in 1973 and published in 1975 to guide estimation of patient risk of hepatic toxicity. Rapid development followed utilizing acetylcysteine given both orally and intravenously. Various protocols and methods of administration have been employed over time with the primary use today of acetylcysteine intravenously as the therapeutic method. The nomogram has been revised over time to the current version, published in 2023, which allows stratification of patients to a high-risk group over 300 mg/L at 4 h and standard risk above 150 mg/L at 4 h, except in the UK where the standard risk is defined very conservatively with a line above 100 mg/L at 4 h. Adjunct therapy with fomepizole in patients with massive ingestions, delay until arrival in a health care facility or renal injury has been proposed. The mortality rate with treatment has been substantially reduced and recovery from hepatic injury is achieved in almost all patients. Full article

Background/Objectives: The most used antipyretic and pain relief treatment is paracetamol (acetaminophen), also known as N-acetyl-para-aminophenol (APAP). However, it is considered potentially hazardous if consumed repeatedly in large doses or over prolonged periods. This investigation explores the effectiveness of hesperidin (Hesp) and Hesp loaded on layered double hydroxide nanoparticles (Hesp-NPs) in inhibiting the progression of acute hepatotoxicity in rats induced by APAP. Methods: LDH-Hesp-NPs were prepared and characterized. Male Wistar rats were orally treated with Hesp and Hesp-NPs at the same adjusted dose (100 mg/kg) every other day for six weeks. After 2 h of the first doses of Hesp and Hesp-NPs, the rats received one oral dose of APAP (750 mg/kg). Results: Administering of Hesp and Hesp-NPs to APAP-treated rats significantly reduced oxidant parameter (malondialdehyde) and serum enzymes (ALT, AST, LDH, and ALP) associated with liver function. Antioxidant markers in the liver, such as catalase and glutathione, also increased notably. Moreover, Hesp and Hesp-NPs enhanced the mRNA expression of liver UGT1A6, IL-10, and HO-1. Conversely, the mRNA expressions of liver CYP1A1, KEAP1, TGF-β, P53, and BAX decreased. These improvements in biochemical and molecular markers were corroborated by liver histopathology. Conclusions: Hesp and Hesp-NPs protect significantly against APAP-induced hepatotoxicity in male Wistar rats. Hesp-NPs treatment was more potent. The protective effects may be mediated via modulation of APAP biotransformation, oxidative stress, inflammation and apoptosis. Full article

Emerging pollutants, such as N-acetyl-para-aminophenol, pose significant challenges to environmental sustainability, and Bi₂Fe₂O₂ (BFO) nanomaterials are an emerging class of piezoelectric materials. This study presents a novel piezoelectric-driven Fenton system based on Bi₂Fe₄O₉ nanosheets for the efficient degradation of organic pollutants. BFO nanosheets with varying thicknesses were synthesized, and their piezoelectric properties were confirmed through piezoresponse force microscopy and heavy metal ion reduction experiments. The piezoelectric electrons generated within the BFO nanosheets facilitate the in situ production of hydrogen peroxide, which in turn drives the Fenton-like reaction. Furthermore, the piezoelectric electrons enhance the redox cycling of iron in the Fenton process, boosting the overall catalytic efficiency. The energy band structure of BFO nanosheets is well-suited for this process, enabling efficient hydrogen peroxide generation and promoting Fe³⁺ reduction. The findings demonstrate that thinner BFO nanosheets exhibit superior piezoelectric activity, leading to enhanced catalytic performance. Additionally, the incorporation of gold nanodots onto BFO nanosheets further boosts their piezocatalytic efficiency, particularly in the reduction of Cr (VI). The system exhibited robust oxidative capacity, stability, and recyclability, with reactive oxygen species (ROS) verified via electron paramagnetic resonance spectroscopy. Overall, BFO nanosheets, with their optimal energy band structure, self-supplied hydrogen peroxide, and enhanced Fe³⁺ reduction, represent a promising, sustainable solution for advanced oxidation processes in wastewater treatment and other applications. Full article

Paracetamol, or acetaminophen (N-acetyl-para-aminophenol, APAP), is an analgesic and antipyretic drug that is commonly used worldwide, implicated in numerous intoxications due to overdose, and causes serious liver damage. APAP can cross the blood–brain barrier and affects brain function in numerous ways, including pain signals, temperature regulation, neuroimmune response, and emotional behavior; however, its effect on adult neurogenesis has not been thoroughly investigated. We analyze, in a mouse model of hepatotoxicity, the effect of APAP overdose (750 mg/kg/day) for 3 and 4 consecutive days and after the cessation of APAP administration for 6 and 15 days on cell proliferation and survival in two relevant neurogenic zones: the subgranular zone of the dentate gyrus and the hypothalamus. The involvement of liver damage (plasma transaminases), neuronal activity (c-Fos), and astroglia (glial fibrillar acidic protein, GFAP) were also evaluated. Our results indicated that repeated APAP overdoses are associated with the inhibition of adult neurogenesis in the context of elevated liver transaminase levels, neuronal hyperactivity, and astrogliosis. These effects were partially reversed after the cessation of APAP administration for 6 and 15 days. In conclusion, these results suggest that APAP overdose impairs adult neurogenesis in the hippocampus and hypothalamus, a fact that may contribute to the effects of APAP on brain function. Full article

The gut–liver axis is defined by dietary and environmental communication between the gut, microbiome and the liver with its redox and immune systems, the overactivation of which can lead to hepatic injury. We used media preconditioning to mimic some aspects of the enterohepatic circulation by treating the human Caco-2 intestinal epithelial cell line with 5, 10 and 20 mM paracetamol (N-acetyl-para-aminophenol; APAP) for 24 h, after which cell culture supernatants were transferred to differentiated human hepatic HepaRG cells for a further 24 h. Cell viability was assessed by mitochondrial function and ATP production, while membrane integrity was monitored by cellular-based impedance. Metabolism by Caco-2 cells was determined by liquid chromatography with tandem mass spectrometry. Caco-2 cell viability was not affected by APAP, while cell membrane integrity and tight junctions were maintained and became tighter with increasing APAP concentrations, suggesting a reduction in the permeability of the intestinal epithelium. During 24 h incubation, Caco-2 cells metabolised 64–68% of APAP, leaving 32–36% of intact starting compound to be transferred to HepaRG cells. When cultured with Caco-2-preconditioned medium, HepaRG cells also showed no loss of cell viability or membrane integrity, completely in contrast to direct treatment with APAP, which resulted in a rapid loss of cell viability and membrane integrity and, ultimately, cell death. Thus, the pre-metabolism of APAP could mitigate previously observed hepatotoxicity to hepatic tight junctions caused by direct exposure to APAP. These observations could have important implications for the direct exposure of hepatic parenchyma to APAP, administered via the intravenous route. Full article

Acetyl-para-aminophenol (APAP), a commonly used antipyretic analgesic, is becoming increasingly toxic to the liver, resulting in a high rate of acute hepatic failure in Europe and the United States. Excessive APAP metabolism in the liver develops an APAP–protein adduct, which causes oxidative stress, MPTP opening, and hepatic necrosis. HMGB-1, HSP, nDNA, mtDNA, uric acid, and ATP are DMAPs released during hepatic necrosis. DMAPs attach to TLR4-expressing immune cells such KCs, macrophages, and NK cells, activating them and causing them to secrete cytokines. Immune cells and their secreted cytokines have been demonstrated to have a dual function in acetaminophen-induced liver injury (AILI), with a role in either proinflammation or pro-regeneration, resulting in contradicting findings and some research confusion. Neutrophils, KCs, MoMFs, NK/NKT cells, γδT cells, DCs, and inflammasomes have pivotal roles in AILI. In this review, we summarize the dual role of innate immune cells involved in AILI and illustrate how these cells initiate innate immune responses that lead to persistent inflammation and liver damage. We also discuss the contradictory findings in the literature and possible protocols for better understanding the molecular regulatory mechanisms of AILI. Full article

Wheat (Triticum aestivum L.) is the oldest known food crop, and many studies have reported that wheat shoots (i.e., wheatgrass) possess anti-cancer, anti-inflammatory, and antioxidant activities. However, the potentially ameliorative effect of wheat shoots on hepatotoxicity caused by high doses of N-acetyl-para-aminophenol (acetaminophen, APAP) has yet to be reported. C57BL/6 mice received daily oral TAE (100 or 200 mg/kg), positive control (silymarin 100 mg/kg), or negative control (saline vehicle) treatments for 7 days prior to intraperitoneal APAP injection. Histological, serum (ELISA), Western blotting, and quantitative PCR analyses of excised liver tissues were then performed. Pre-treatment with TAE (100 or 200 mg/kg) ameliorated APAP-induced pathological damage (i.e., hepatotoxic lesions), reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and also ameliorated APAP-induced increases in oxidative stress, thereby inhibiting oxidative liver damage and reducing the expression of inflammatory cytokines. In addition, TAE pre-treatment inhibited the expression of Cytochrome P4502E1 (CYP2E1), which is a key enzyme in the onset of APAP-induced hepatotoxicity, suppressed the expression of the target proteins regulated by the antioxidant enzyme Nrf2, and suppressed hepatocyte apoptosis. These findings suggest that TAE is an attractive therapeutic candidate that exhibits potential hepatoprotective activity by inhibiting oxidative stress, inflammation, apoptosis, and liver damage. Full article