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The effect of oral administration of a 50% ethanol extract of Silene aprica (SA) on acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl₄) and acetaminophen. The results indicated that SA protected the liver from CCl₄- and acetaminophen-induced injury as judged by morphological and biochemical observations. An increase in both lipid peroxidation (LPO) and triglyceride concentrations occurred in the liver with CCl₄ injection , SA administration significantly reduced these changes.

Chai-Hu-Ching-Kan-Tang (CHCKT) is one of the traditional Chinese medicine prescriptions commonly used to treat liver diseases. In this study, we evaluated the hepatoprotective effects of aqueous CHCKT extract at various concentrations (125, 250 and 500 mg/kg body weight) on acetaminophen (APAP)-induced acute liver injury in rats. Results showed that CHCKT treatments significantly decreased the level of serum glutamic oxaloacetic transaminase (sGOT) and glutamic pyruvic transaminase (sGPT) in APAP-treated groups. CHCKT also significantly decreased the level of lipid peroxides and increased the activity of antioxidant enzymes (i.e. SOD and GPx). Histopathological observation further confirmed the hepatoprotective activity of CHCKT as indicated by the amelioration in the central necrosis and fatty changes of the liver after APAP induction. Interestingly, the hepatoprotective activity of CHCKT at concentrations 125~500 mg/kg appeared to be as good as 12.5 mg/kg silymarin (a commercial hepatoprotective agent). Taken together, these results suggest that aqueous extract of CHCKT possesses potent hepatoprotective effects agianst APAP-induced liver injury in rats.

The present study investigates the hepatoprotective activity of Myrica rubra Sieb. et Zucc. extract (MCE) against acetaminophen (AAP)-induced liver damage and elucidates the possible mechanisms behind the hepatoprotection observed. Serum alanine aminotransferase and serum aspartate aminotransferase activities were detected and liver histopathology was observed. Mitochondrial swelling, mitochondrial membrane potential, and voltage-dependent anion channel (VDAC) gene transcription were also investigated. The results showed that 50, 150, and 450 mg/kg MCE could restore AAP-induced changes in mice liver in a dose-dependent manner. The mechanisms behind the hepatoprotective effects of MCE may be related to the mitochondrial protection of liver cells, especially of VDAC, an important protein on the outer membrane of the mitochondria.

The present study investigated the anti-oxidative and hepatoprotective effects of Glossogyne tenuifolia (GT) Cassini, against acetaminophen-induced acute liver injury in BALB/c mice. The extracts of GT by various solvents (hot water, 50% ethanol and 95% ethanol) were compared for their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, reducing power, total phenolic content, and total anti-oxidant capacity. The results showed that hot water (HW) extracts of GT contained high levels of phenolics and exerted an excellent anti-oxidative capacity; thus, these were used in the animal experiment. The male BALB/c mice were randomly divided into control group, acetaminophen (APAP) group, positive control group and two GT groups at low (GT-L) and high (GT-H) dosages. The results showed that mice treated with GT had significantly decreased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). GT-H increased glutathione levels and the ratios of reduced glutathione and oxidized glutathione (GSH/GSSG) in the liver, and inhibited serum and lipid peroxidation. This experiment was the first to determine phenolic compounds, chlorogenic acid and luteolin-7-glucoside in HW extract of GT. In conclusion, HW extract of GT may have potential anti-oxidant capacity and show hepatoprotective capacities in APAP-induced liver damaged mice.

Apocynum venetum L. (A. venetum) has long been used in oriental folk medicine for the treatment of some liver diseases; however, the underlying mechanisms remain to be fully elucidated. Acetaminphen (APAP) is a widely used analgesic drug that can cause acute liver injury in overdose situations. In this study, we investigated the potential protective effect of A. venetum leaf extract (ALE) against APAP-induced hepatotoxicity. Mice were intragastrically administered with ALE once daily for 3 consecutive days prior to receiving a single intraperitoneal injection of APAP. The APAP group showed severe liver injury characterized by the noticeable fluctuations in the following parameters: serum aminotransferases; hepatic malondialdehyde (MDA), 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione (GSH). These liver damages induced by APAP were significantly attenuated by ALE pretreatments. A collective analysis of histopathological examination, DNA laddering and western blot for caspase-3 and cytochrome c indicated that the ALE is also capable of preventing APAP-induced hepatocyte death. Hyperoside, isoquercitrin and their derivatives have been identified as the major components of ALE using HPLC-MS/MS. Taken together, the A. venetum possesses hepatoprotective effects partially due to its anti-oxidant action.

Acetaminophen (APAP) overdose causes hepatocytes necrosis and acute liver failure. Baicalin (BA), a major flavonoid of Scutellariae radix, has potent hepatoprotective properties in traditional medicine. In the present study, we investigated the protective effects of BA on a APAP-induced liver injury in a mouse model. The mice received an intraperitoneal hepatotoxic dose of APAP (300mg/kg) and after 30min, were treated with BA at concentrations of 0, 15, 30, or 60mg/kg. After 16h of treatment, the mice were sacrificed for further analysis. APAP administration significantly elevated the serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity when compared with control animals. Baicalin treatment significantly attenuated the elevation of liver ALT levels, as well as hepatic MPO activity in a dose- dependent manner (15–60mg/kg) in APAP-treated mice. The strongest beneficial effects of BA were seen at a dose of 30mg/kg. BA treatment at 30mg/kg after APAP overdose reduced elevated hepatic cytokine (TNF-$\alpha$ and IL-6) levels, and macrophage recruitment around the area of hepatotoxicity in immunohistochemical staining. Significantly, BA treatment can also decrease hepatic phosphorylated extracellular signal-regulated kinase (ERK) expression, which is induced by APAP overdose. Our data suggests that baicalin treatment can effectively attenuate APAP-induced liver injury by down-regulating the ERK signaling pathway and its downstream effectors of inflammatory responses. These results support that baicalin is a potential hepatoprotective agent.

To investigate the hepatoprotective effect of Cymbopogon citratus or lemongrass essential oil (LGO), it was used in an animal model of acute liver injury induced by acetaminophen (APAP). Swiss mice were pretreated with LGO (125, 250 and 500mg/kg) and SLM (standard drug, 200mg/kg) for a duration of seven days, followed by the induction of hepatotoxicity of APAP (single dose, 250mg/kg). The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase were determined to evaluate the hepatoprotective effects of the LGO. The livers were used to determine myeloperoxidase (MPO) activity, nitric oxide (NO) production and histological analysis. The effect of LGO on leukocyte migration was evaluated in vitro. Anti-oxidant activity was performed by assessing the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro. LGO pretreatment decreased significantly the levels of ALT, AST and ALP compared with APAP group. MPO activity and NO production were decreased. The histopathological analysis showed an improved of hepatic lesions in mice after LGO pretreatment. LGO inhibited neutrophil migration and exhibited anti-oxidant activity. Our results suggest that LGO has protective activity against liver toxicity induced by paracetamol.

Thymoquinone (TQ) is a main aromatic component of Nigella sativa L. seeds or Agastache rugosa (Fisch. & C.A.Mey.) Kuntze. The protective mechanism of TQ against acute liver injury induced by acetaminophen (APAP), however, remains unclear. We aimed to investigated the hepato-protective mechanism of TQ on the development of APAP-induced acute liver injury. Male kunming mice were pretreated with TQ or N-acetylcysteine (NAC) before a single APAP injection. Human Chang liver cells were incubated with TQ, SP600125 or AICAR in presence of APAP for 24h. TQ pretreatment reduced levels of serum aminotransferases and increased hepatic glutathione and glutathione peroxidase activities via inhibiting CYP2E1 expression. TQ inhibited JNK, ERK and P38 phosphorylation induced by APAP. Meanwhile, TQ inhibited PI3K/mTOR signaling activation and activated AMPK phosphorylation. Moreover, TQ prevented APAP-induced hepatocytes apoptosis regulated by Bcl-2 and Bax. Furthermore, TQ inhibited STAT3 phosphorylation on APAP-induced acute liver injury. In addition, TQ significantly inhibited P2X7R protein expression and IL-1$\beta$ release. APAP-enhanced JNK phosphorylation and APAP-suppressed AMPK phosphorylation were also observed in Chang liver cells, and these changes were recovered by pretreatment with TQ, SP600125 and AICAR. Our findings suggest that TQ may actively prevent APAP-induced acute liver injury, and the effect may be mediated by JNK and AMPK signaling pathways.

Acute liver injury (ALI) induced by acetaminophen (APAP) is the main cause of drug-induced liver injury. Previous reports indicated liver failure could be alleviated by saponins (ginsenosides) from Panax ginseng against APAP-induced inflammatory responses in vivo. However, validation towards ginsenoside Rb1 as a major and marker saponin may protect liver from APAP-induced ALI and its mechanisms are poorly elucidated. In this study, the protective effects and the latent mechanisms of Rb1 action against APAP-induced hepatotoxicity were investigated. Rb1 was administered orally with 10mg/kg and 20mg/kg daily for 1 week before a single injection of APAP (250mg/kg, i.p.) 1h after the last treatment of Rb1. Serum alanine/aspartate aminotransferases (ALT/AST), liver glutathione (GSH) depletion, as well as the inflammatory cytokines, such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-1$\beta$ (IL-1$\beta$), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were analyzed to indicate the underlying protective effects of Rb1 against APAP-induced hepatotoxicity with significant inflammatory responses. Histological examination further proved Rb1’s protective effects. Importantly, Rb1 mitigated the changes in the phosphorylation of MAPK and PI3K/Akt, as well as its downstream factor NF-$\kappa$B. In conclusion, experimental data clearly demonstrated that Rb1 exhibited a remarkable liver protective effect against APAP-induced ALI, partly through regulating MAPK and PI3K/Akt signaling pathways-mediated inflammatory responses.

Excessive consumption of analgesic drug acetaminophen (APAP) can cause severe oxidative stress-mediated liver injury. Here, we investigated the protective effect and mechanism of aged citrus peel (Chenpi, CP), a Chinese herb usually used in foods in Asia, against APAP-induced hepatotoxicity. CP water (CP-WE), ethanolic (CP-EE), and water extraction residue ethanolic (CP-WREE) extracts were prepared. We found that CP-WREE contained higher content of bioactive flavonoids, including narirutin, nobiletin, and tangeretin, and more effectively enhanced the Nrf2 pathway in ARE-luciferase reporter gene transfected human HepG2-C8 cells. In mouse AML-12 hepatocytes, CP-WREE minimized APAP-induced damage and lipid peroxidation and increased mRNA and protein expressions of Nrf2 and its downstream defense enzymes (HO-1, NQO1, and UGT1A). CP-WREE also downregulated HDACs and DNMTs, upregulated KDMs, and increased the unmethylated Nrf2 promoter level. Additionally, CP-WREE blocked in vitro DNA methyltransferase activity. Taken together, CP-WREE might attenuate oxidative stress-induced hepatotoxicity through epigenetically regulating Nrf2-mediated cellular defense system.

Acetaminophen (APAP) overdose is the leading cause of acute liver failure (ALF) in the Western world, with limited treatment opportunities. 3,5,7,4$\prime$-Tetrahydroxyflavanone (Dihydrokaempferol, DHK, Aromadendrin) is a flavonoid isolated from Chinese herbs and displays high anti-oxidant and anti-inflammatory capacities. In this study, we investigated the protective effect by DHK against APAP-induced liver injury in vitro and in vivo and the potential mechanism of action. Cell viability assays were used to determine the effects of DHK against APAP-induced liver injury. The levels of reactive oxygen species (ROS), serum alanine/aspartate aminotransferases (ALT/AST), liver myeloperoxidase (MPO), and malondialdehyde (MDA) were measured and analyzed to evaluate the effects of DHK on APAP-induced liver injury. Western blotting, immunofluorescence staining, RT-PCR, and Transmission Electron Microscope were carried out to detect the signaling pathways affected by DHK. Here, we found that DHK owned a protective effect on APAP-induced liver injury with a dose-dependent manner. Meanwhile, Western blotting showed that DHK promoted SIRT1 expression and autophagy, activated the NRF2 pathway, and inhibited the translocation of nuclear p65 (NF-$\kappa$B) in the presence of APAP. Furthermore, SIRT1 inhibitor EX-527 aggravated APAP-induced hepatotoxicity when treating with DHK. Molecular docking results suggested potential interaction between DHK and SIRT1. Taken together, our study demonstrates that DHK protects against APAP-induced liver injury by activating the SIRT1 pathway, thereby promoting autophagy, reducing oxidative stress injury, and inhibiting inflammatory responses.

Constructing heterojunction photocatalyst is an effective method to enhance the separation of photogenerated electron and hole, which significantly improves ability of visible light response. In this study, calcination methods have been proposed to prepare highly efficient magnetic ternary photocatalyst g-C₃N₄/TiO₂-MnFe₂O₄ halloysite. It showed an enhanced photocatalytic degradation for dyes (crystal violet) and nonsteroidal anti-inflammatory drugs (acetaminophen) under vision light irradiation. Compared to pure g-C₃N₄, TiO₂, MnFe₂O₄ halloysite and binary g-C₃N₄-MnFe₂O₄ halloysite, the optimized ternary g-C₃N₄/TiO₂-MnFe₂O₄ halloysite displayed enhanced photodegradation efficiency with 91.1% removal of crystal violet (10ppm) in 90min under visible light irradiation, the optimized ternary g-C₃N₄/TiO₂-MnFe₂O₄ halloysite composite showed significantly enhanced photocatalytic activity with more than 79.1% removal of acetaminophen (10ppm) within 90min under visible light. The photocatalytic mechanism was identified through the free radical quenching experiment. The heterojunction photocatalyst could be easily recovered by an extra magnetic field and reused several times without any obvious deterioration in catalytic activity. Besides, the ternary heterojunction also exhibited antibacterial ability against Escherichia coli. The superior photocatalytic performance of composite should be mainly attributed to both the improvement of light harvesting as well as the enhanced separation and transfer efficiency. It is expected that this novel ternary visible-light responding composite would be a promising candidate material for organic pollutants degradation and bacteria inactivation.

Advanced oxidation technology based on PeroxyMonoSulfate (PMS) has become a research hotspot in the field of water treatment. To improve the activation efficiency of PMS, electrochemically assisted spinel type catalyst CoFe₂O₄ was used to activate PMS and achieve effective degradation of acetaminophen. The influence of single factor on degradation was explored to determine the best degradation process parameters of E/CoFe₂O₄/PMS system. Results show that under the optimum reaction conditions (DC voltage is 6V, the initial mass concentration of acetaminophen is 10mgL${}^{-1}$, the dosage of CoFe₂O₄ is 0.3gL${}^{-1}$, and the mass concentration of PMS is 1.5gL${}^{-1}$), the degradation rate of acetaminophen reaches up to 95% within 20min. CoFe₂O₄ catalyst showed a good stability, with only a 12% decrease in acetaminophen degradation after three cycles. Radical quenching tests show that $\cdot \mathrm{\text{OH}}$ and ${\mathrm{\text{SO}}}_4^{-}\cdot$ played predominant roles in the advanced oxidation process. This work provides a new strategy for more efficiency in PMS activation.

Ferro-alloys have been extensively studied in the field of electrochemical sensing due to their abundant earth reserves and excellent performances. In this work, serials of bimetallic Fe/Co nanoalloy@carbon composites (Fe/Co@C) were successfully prepared using Co-doped MIL-101(Fe) as templates and developed as excellent electrochemical sensors for acetaminophen (AP) detection. It was found that the atomic ratio of Fe/Co in the templates can significantly affect the electrochemical activity of the product. Among the prepared composites, Fe/Co@C-G2 (Fe/Co = 2:1) with high conductivity and large specific surface area presents the best electrochemical sensing performance. Under the optimal conditions, Fe/Co@C-G2 has a high sensitivity of 55.2 $\mu$A $\mu$${\text{M}}^{-1}$${\text{cm}}^{-2}$, a wide linear range of 0.29-407.15 $\mu$M, a low LOD of 0.09 $\mu$M, good selectivity, excellent stability, and good repeatability. In addition, Fe/Co@C-G2 can also be used for real sample testing. This work expands the application of Fe/Co@C-based composites in electrochemical sensing.

In this paper, ${\mathrm{\text{Cu(OH)}}}_2$ nanosheet arrays were directly grown in an upright manner on the surface of copper foam (CF) through a simple solvent reaction, followed by the successful reduction of ${\mathrm{\text{Cu(OH)}}}_2$ into ${\mathrm{\text{Cu}}}_2\mathrm{\text{O}}$ using hydrazine hydrate vapor, resulting in a binder-free ${\mathrm{\text{Cu}}}_2\mathrm{\text{O@CF}}$ array electrode. The in situ growth technique guarantees robust bonding between ${\mathrm{\text{Cu}}}_2\mathrm{\text{O}}$ and the conductive substrate, thereby enhancing electron transfer among various electrode components. Additionally, the vertically aligned array structures facilitate rapid penetration and transfer of the analyte, while also allowing for thorough exposure of the electroactive surfaces to the electrolyte. When utilized as an adhesive-free biosensor, the obtained ${\mathrm{\text{Cu}}}_2\mathrm{\text{O@CF}}$ array electrode exhibited sensitive catalytic oxidation activity toward acetaminophen (AP), providing a wide linear range of 2–200 $\mu$M and a low detection limit of 0.6 $\mu$M for AP detection. Furthermore, the developed ${\mathrm{\text{Cu}}}_2\mathrm{\text{O@CF}}$ array electrode was successfully utilized to detect AP in medicine samples. With its simple fabrication method, broad linear range, low detection limit, and excellent stability, this electrode holds significant promise for the detection of AP in pharmaceuticals.

Emission characteristics of Volatile Organic Compounds (VOCs) from typical pharmaceutical products (penicillin, amoxicillin, acetaminophen) were investigated in the main pharmaceutical industry in China. The results showed that the characteristic pollutants in the production process of penicillin industrial salt are butyl acetate and butanol. The characteristic pollutants of VOCs in the production process of amoxicillin are acetone, methylene chloride and triethylamine. The ethyl acetate and acetic acid are the main pollutants in the production process of acetaminophen.

In this paper, the HAP powder synthesized as drug material, use synthetic small size, uniform and well dispersed nano HAP powder, use acetaminophen as a drug load object, sustained-release test in simulated body fluid, for acetaminophen quality score of 69.97% at the time of 2h, at 12 h drug release rate is only reached 92.21 percent, play slow-release effect, which has a reduced frequency of administration, reducing the burden of the liver, expand clinical acetaminophen significance of applications.