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Objective To understand the changes of cytokines in acetaminophen-induced acute liver injury in rat models, and to provide ideas for clinical diagnosis and treatment. Methods A total of 12 male SD rats were equally divided into blank group and acetaminophen group (the experimental group), with six rats in each group. Each rat of experimental group was intraperitoneally injected with 750 mg/kg acetaminophen. After 12 hours, the model was successfully established. The degree of liver tissue injury of rats was observed. The blank group with nothing. The levels of serum interleukin-6 (IL-6), the expression of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), and the mRNA expression levels of TNF-a and CXCL- 10 (in two groups) were detected. Results The liver injury score of rats in the experimental group [(5.3± 0.8) scores was higher than that in the blank group (0 score), and the difference was statistically significant (P<0.01). The levels of AST and ALT in liver tissue of rats in the experimental group [(107.6±16.7), (35.1±5.2)U/g were lower than those in the blank group [(178.8±21.6),(58.9±6.8) U/g], and the differences were statistically significant (P<0.01). The expression level of IL-6 in serum of rats in the experimental group [(67.9±4.8)pg/mL] was significantly higher than that in the blank group [(4.8±0.4)pg/mL], and the difference was statistically significant (P<0.01). The expression levels of TNF-α and CXCL-10 in liver tissue of rats in the experimental group [(3.34±0.50) and (4.15±0.54), respectively were higher than those in the blank group [(1.00±0.14) and (1.00±0.15), respectively], and the differences were statitically significant (P<0.01). Conclusion Acetaminophen can cause drug-induced liver injury in rats. Detectting the changes of serum IL-6 level, the expression of AST and ALT in liver tissue and the mRNA expression of TNF-α and CXCL-10 are helpful for the diagnosis of the disease. [ABSTRACT FROM AUTHOR]

Liver regeneration plays a crucial role in the recovery after liver injury induced by N-acetyl-p-aminophenol (APAP) . After APAP overdose, the degree of regeneration increases with the extent of liver injury, leading to the resolution of liver injury and spontaneous recovery in most cases. However, severe APAP overdose can impair liver regeneration and result in uncontrolled liver injury, even failure to recover or death in severe cases. Following APAP-induced liver injury, interactions between cells in the liver are essential for regenerative response. Liver regeneration is jointly regulated by multiple proliferative signaling pathways, involving various kinases, nuclear receptors, transcription factors, and coactivators. Severe APAP overdose can inhibit the activation of proliferative signaling pathways, thereby causing cell cycle arrest and impairing liver regeneration. Although liver regeneration plays a critical role in the repair of APAP-induced liver injury, the underlying mechanisms remain unclear. This article reviews the research advances in the role of liver regeneration in APAP-induced liver injury, in order to provide a reference for further basic research in this area. [ABSTRACT FROM AUTHOR]

Objective: To study the best purification method of Perilla flavone (PF), and to investigate its protective effect and potential mechanism on Paracetamol (APAP) - induced acute liver injury. Methods: Single factor experiments were used to determine the optimal conditions for the purification of PF by macroporous resin. BALB/c male mice were randomly divided into 6 groups, blank control group (CON), model group (MOD), diphenylene dibenzoate group (DDB), low dose group of PF (L-PF, 12.5 mg/kg), middle dose group of PF (M-PF, 25 mg/kg), and high dose group of PF (H-PF, 50 mg/kg). DDB and PF were given by continuous intragastric administration for 15 days according to the dosage. After the last administration for 1 h, APAP was injected intraperitoneally to establish liver injury model in each group except CON group. The serum levels of AST and ALT of mice were determined, and the levels of MDA, SOD, GSH, and GSH-PX in the liver of mice were tested. HE staining of the livers was performed to observe pathological changes. The expressions of Nrf2, Keap1 and HO-1 proteins in the livers were detected by Western Blot. Results: The optimal purification conditions were as follows: 10 g of D101 resin, 2.0 mg/mL of up-sampling solution, up-sampling volume of 30 mL, 50 mL of 80% ethanol solution elution. After purification, the flavonoid content was 70.32%±1.49%. Compared with CON group, the expressions of AST and ALT in the serum were significantly higher in MOD group (P

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Objective: To investigate the protective effects of Ganoderma lucidum spore polysaccharide (GLSP) on liver injury caused by acetaminophen (APAP). Methods: Fifty mice were randomly divided into five groups: Blank group, model group, positive drug group, GLSP low-dose group and GLSP high-dose group, with 10 mice in each group. After each group was pre-administered according to the corresponding dose for 14 consecutive days, the liver index, serum indexes (glutamic oxalacetic transaminase (AST), glutamic-pyruvic transaminase (ALT)) and liver tissue plasma indexes (glutathione (GSH), malonaldehyde (MDA), superoxide dismutase (SOD), Caspase-3, Bax and Bcl-xl) were determined. Results: Compared with the blank group, ALT, AST, MDA and proapoptotic genes Caspase-3 and Bax were very significantly increased in the model group (P<0.01). The contents of SOD and GSH decreased very significantly (P<0.01), and HE staining showed that APAP treated mice showed typical lobular central necrosis of liver. Compared with model group, ALT and AST were very significantly decreased in polysaccharide dose group (P<0.01), SOD and GSH were significantly increased (P<0.05) and MDA was significantly decreased in polysaccharide low-dose group (P<0.05), SOD and GSH were very significantly increased (P<0.01) and MDA was very significantly decreased in polysaccharide high-dose group (P<0.01), and pro-apoptotic genes Caspase-3 and Bax were very significantly decreased in polysaccharide group (P<0.01), and the liver histopathological observation showed that the necrotic area of liver tissue decreased. Conclusion: Ganoderma lucidum spore polysaccharide can preprotect APAP liver injury, and its mechanism may be related to improving the antioxidant capacity of liver and inhibiting the occurrence of apoptosis. [ABSTRACT FROM AUTHOR]

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Objective To investigate whether Toll-like receptor 4（TLR4） inhibition affects liver regeneration during acetaminophen（APAP）-induced liver injury in mice, as well as the mechanism of TLR4 involved in liver regeneration. Methods A total of 78 male CD-1 mice were divided into nine groups using a random number table, i.e., three control groups（normal control group, solvent control group, inhibitor control group） with 6 mice in each group and six experimental groups（APAP 24-hour group, TAK-242+APAP 24-hour group, APAP 48-hour group, TAK-242+APAP 48-hour group, APAP 72-hour group, TAK-242+APAP 72-hour group） with 10 mice in each group. The mice in the experimental groups were given a single dose of intraperitoneally injected APAP（300 mg/kg）, and TAK-242 was intraperitoneally injected at a dose of 3 mg/kg at 3 hours before APAP administration. Serum and liver tissue samples were collected at different time points. The biochemical method was used to measure the serum level of alanine aminotransferase（ALT）; HE staining was used to observe liver pathological changes; RT-PCR, Western blot, and immunohistochemistry were used to measure the expression levels of Cyclin D1, PCNA, Ki-67, STAT3, and p-STAT3.The t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups. Results Compared with the normal control group, the APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT（both P＜0.05）, and the TAK-242+APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT than the APAP group at the same time point（both P＜0.05）. HE staining showed typical central lobular necrosis in the liver of APAP-treated mice, and the TAK-242+APAP 24-hour and 48-hour groups had a significantly larger necrotic area than the APAP group at the same time point（both P＜0.05）. RT-PCR, Western blot, and immunohistochemistry showed that the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had significantly lower mRNA and protein expression levels of Cyclin D1 than the APAP group at the same time point（all P＜0.05）; the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower mRNA expression level of PCNA than the APAP group at the same time point（all P＜0.05）, and the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower protein expression level of PCNA than the APAP group at the same time point（all P＜0.05）; the TAK-242+APAP 24-hour and 72-hour groups had a significantly lower mRNA expression level of Ki-67 than the APAP group at the same time point（all P＜0.05）, and the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower protein expression level of Ki-67 than the APAP group at the same time point（all P＜0.05）. In addition, the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower phosphorylation level of STAT3 than the APAP group at the same time point（both P＜0.05）. Conclusion TLR4 may promote liver regeneration by increasing the phosphorylation level of STAT3 during APAP-induced liver injury in mice. [ABSTRACT FROM AUTHOR]

Objective To assay the contents of acetaminophen with ultra high-performance liquid chromatography (UHPLC) method in the sustained-release tablets radiated by Gamma ray. Methods Acetaminophen sustained-release tablets were radiated by 60Co. UHPLC equipped with the Shim-pack GISS-C18（ 2.1 mm×50 mm, 1.9 μm） was used for the assay. The mobile phase was methanol-0.05 % ammonium acetate solution (15∶85). The flow rate was 0.3 ml/min with the detection wavelength at 245 nm. Results The acetaminophen showed good linear relationship within the range of 20-100 μg/ml (r=0.999 4). The RSD values of repeatability was 0.9 %. The average recovery was 97.9 %-104.9 %. Acetaminophen content was 96.2 %, 92.2 %, 91.8 %, 83.9 % at 0, 8, 50 and 80 kGy radiation, respectively. Conclusion This method is speedy and accurate. It can be used to assay the content of acetaminophen in the sustained-release tablets after radiation. The content of acetaminophen decreased after radiation. [ABSTRACT FROM AUTHOR]

A pharmaceutical co-crystal (named as APAP-NICO) was prepared at 25 °C by using acetaminophen (APAP) as the drug active ingredient and nicotinamide (NICO) as the eutectic substance. The monomer and eutectic were characterized by infrared spectrometer (IR), scanning electron microscope (SEM), X-ray powder diffractometer (XRD), high performance liquid chromatography (HPLC), and thermogravimetric (TG) analyzer. The stoichiometric ratio of APAP to NICO was determined to be 1:1 by two methods. This experiment involves a number of cutting-edge analysis methods that will help students to improve their hands-on ability and data analysis ability. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) is a type of necrotizing and inflammatory liver disease caused by certain commonly-used drugs, Chinese herbal medicines or dietary supplements. In severe cases, it may lead to acute liver failure. Without liver transplantation, the fatality could reach up to 80%. It is of significance to master the indications of liver transplantation. Several prognostic scoring systems have been developed to help clinicians to decide which patients need urgent liver transplantation, such as King's College criteria (KCC) and model for end-stage liver disease (MELD) scoring systems. However, these scoring methods have been developed for a long period of time and lack of modifications. Therefore, scholars have proposed several new scoring systems, such as acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scoring systems, which provide novel ideas for the evaluation of liver transplantation. As an important treatment measure for drug-induced acute liver failure, urgent liver transplantation has greatly improved the survival rate of patients. In this article, the classification, clinical diagnosis, liver transplantation evaluation and prognosis of DILI were summarized, aiming to provide reference for the treatment of DILI by liver transplantation. [ABSTRACT FROM AUTHOR]

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Copyright of Journal of Harbin Institute of Technology. Social Sciences Edition / Haerbin Gongye Daxue Xuebao. Shehui Kexue Ban is the property of Harbin Institute of Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To investigate the role of STA TI in hepatocyte proliferation after acetaminophen ( APAP) - induced hepatocellular injury in mice. Methods Normal mouse AML12 hepatocytes were cultured in vitro and were stimulated by APAP ( 1, 2. 5, 5, 10, and 20 mmoVL) for 12, 24 or 48 hours, and the hepatocytes treated with an equal volume of phosphate buffered saline were established as control group. After the optimal stimulation concentration and duration of action were screened out, AML12 hepatocytes were treated with AG490 (10, 50, and 100 µ,moVL). The CCK - 8 assay was used to measure the viability of AML12 hepatocytes; RT - PCR was used to measure the mRNA expression levels of PCNA, CyclinDl, and Ki67 in AML12 hepatocytes, and Western blot was used to measure the protein expression levels of STA TI, p - STA TI, PCNA, and CyclinDl. A one - way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t - t est was used for further comparison between two groups. Results After 24 and 48 hours of APAP treatment, compared with the control group, all concentration groups had a significant reduction in the viability of AML12 hepatocytes ( all P <0. 05), with a viability of 0. 717 ± 0. 0271 and 0. 752 ± 0. 0141, respectively, when the concentration of APAP was 2. 5 mmoVL, which was significantly different from that in the control group ( all P < 0. 05 ) and met the conditions of subsequent experiment. Compared with the control group, the 24 - hour APAP ( 2. 5 mmol/L) group had significant reductions in the mRNA expression of PCNA, CyclinDl, and Ki67 ( all P < 0. 01) ; compared with the 24 - hour APAP group, the 48 - hour APAP ( 2 . 5 mmoVL) group had significant increases in the mRNA expression of PCNA, CyclinDl, and Ki67 (all P <0. 01); therefore, a model of hepatocyte regeneration after in vitro AML12 hepatocyte injury was established by stimulation with APAP 2. 5 mmoVL for 48 hours. After the addition of AG490, there was no significant difference in viability between the control group and the 10 and 50 µ,moVL AG490 groups, and the other groups had a sigChemical and Drug Induced Liver Injury; STA TI transcription factor; Acetaminophen; Liver Regeneration. [ABSTRACT FROM AUTHOR]

Objective To investigate the ability of Ganshuang granule (a liver - protecting drug widely used in clinical practice)extract to reduce N - acetyl - p - aminophenol (APAP)- induced hepatotoxicity and possible mechanisms. Methods A total of five cell culture groups were set up in this experiment, i. e., normal control group, APAP injury group, and three injury protection groups treated with different concentrations of Ganshuang granule extract. Then 20 mmol/ L APAP was added to the cell culture medium and incubated for 24 hours to establish an in vitro model of drug - induced liver injury, and the injury protection groups were treated with different concentrations of Ganshuang granule extract (0. 2, 1, and 5 µg/ ml)in advance for 8 hours of incubation before APAP were added for 24 hours. Related markers were measured, including the markers for hepatocellular injury [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], the markers for mitochondrial injury [mitochondrial membrane potential, and glutamate dehydrogenase (GDH)], and antioxidant and oxidative stress markers [glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS)]. Related mechanism was discussed based on the experimental results. A one - way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t - test was used for further comparison between two groups. Results Ganshuang granule extract alleviated APAP - induced hepatotoxicity, improved cell viability (P < 0.001), and reduced the levels of AST, ALT, and LDH in supernatant (P < 0. 001, P < 0. 001, and P < 0. 05). Ganshuang granule extract inhibited APAP - induced hepatocellular oxidative stress, and compared with the APAP group, the Ganshuang granule extract groups had significant reductions in the oxidative stress indicators ROS and MDA (both P <0. 01). Ganshuang granule extract alleviated the loss of mitochondrial membrane potential induced by APAP (P <0. 05)and reduced the content of the mitochondrial injury marker GDH in supernatant (P <0. 001)in a dose - dependent manner. Ganshuang granule extract inhibited the expression of CYP2E1 /1A2 (both P < 0. 05) and increased the expression of phase II enzymes in hepatocytes. Ganshuang granule extract induced the expression of Nrf2 and its downstream genes NQO -1 and GCLC (all P <0. 05). Conclusion Ganshuang granule extract can prevent APAP - induced hepatocellular injury through two ways. The first way is that Ganshuang granule extract downregulates the expression of CYP2E1 /1A2 and thus reduces the production of NAPQI, a toxic product of APAP;the second way is that Ganshuang granule extract upregulates the expression of the detoxification pathway, which can activate Nrf2 to increase the expression of antioxidant enzymes (SOD and GSH)and phase ? enzymes and thus accelerate the harmless metabolism of APAP. [ABSTRACT FROM AUTHOR]

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Objective To investigate the protective effect of pinocembrin (PIN) in a mouse model of liver injury induced by acetaminophen (APAP). Methods A total of 50 healthy male C57BL/6J mice were randomly divided into blank group, PIN (50 mg/kg) group, APAP (300 mg/kg) model group, PIN (30 mg/kg)+APAP (300 mg/kg) experimental group, and PIN (50 mg/kg)+APAP (300 mg/kg) experimental group, with 10 mice in each group. The mice in the blank group and the model group were given an equal volume of normal saline by gavage, and those in the PIN group and the PIN+APAP groups were given PIN by gavage once a day, for 7 consecutive days. At 2 hours after the last administration, the mice in the model group and the PIN+APAP groups were given intraperitoneal injection of APAP 300 mg/kg once, and those in the blank group and the PIN group were given intraperitoneal injection of an equal volume of normal saline. Serum samples were collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); liver tissue homogenate was prepared to measure the biochemical parameters of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH); HE staining was used to observe liver histopathology. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with the blank group, the APAP (300 mg/kg) model group had significant increases in the activities of ALT and AST (P＜0.01), suggesting that a model was successfully established, while the PIN (30 mg/kg)+APAP (300 mg/kg) group and the PIN (50 mg/kg)+APAP (300 mg/kg) group had significant reductions in the levels of ALT and AST (P＜0.01). Compared with the blank group, the APAP (300 mg/kg) model group had a significant increase in the level of MDA and significant reductions in SOD activity and GSH level in the liver (P＜0.01); compared with the APAP (300 mg/kg) model group, the PIN (30 mg/kg)+APAP (300 mg/kg) group and the PIN (50 mg/kg)+APAP (300 mg/kg) group had a significant reduction in the level of MDA and significant increases in SOD activity and GSH level in the liver (P＜0.05). Histopathological observation showed that PIN significantly improved liver injury caused by APAP and helped to maintain normal liver histomorphology. Conclusion PIN exerts a marked protective effect on liver injury induced by APAP, possibly by inhibiting oxidative stress in the liver. [ABSTRACT FROM AUTHOR]

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This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1β), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1β, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1β, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1β, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.

Pharmaceuticals and personal care products (PPCPs) are a group of emerging contaminants causing detrimental effects on aquatic living organisms even at low doses. To investigate the contamination characteristics and ecological risks of PPCPs in drains flowing into the Yellow River of Ningxia, 21 PPCPs were detected and analyzed using solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry in this study. All 21 targeted compounds were detected in the drains, with total concentrations ranging from 47.52 to 1 700.96 ng·L -1 . Ciprofloxacin, acetaminophen, benzophenone-3, and diethyltoluamide were the more commonly detected compounds, with detection frequencies exceeding 80%. The five highest-concentration PPCPs were acetaminophen, diethyltoluamide, caffeine, benzophenone-3, and levofloxacin, with the maximum concentrations of 597.21, 563.23, 559.00, 477.28, and 473.07 ng·L -1 , respectively. Spatial analysis showed that the pollution levels of PPCPs in the drains of the four cities were different, with average concentrations of ∑PPCPs in the order of Yinchuan>Shizuishan>Wuzhong>Zhongwei. The total concentration of PPCPs before flowing into the Yellow River ranged from 124.82 to 1 046.61 ng·L -1 . Source analysis showed that livestock and poultry breeding wastewater was the primary source for sulfadiazine and oxytetracycline, whereas medical wastewater was the primary source for levofloxacin and ciprofloxacin. The primary sources of triclocarban and triclosan were domestic sewage and industrial wastewater, whereas the primary source of caffeine and diethyltoluamide was domestic sewage. The pollution of diciofenac, cimetidine, triclocarban, and triclosan in the drains was positively correlated with the regional population and economic development level. The ecological risk assessment indicated that levofloxacin, diclofenac, gemfibrozil, benzophenone-3, and triclocarban posed high risks to aquatic organisms in drains flowing into the Yellow River. It is worthwhile to consider the mixture risk of the PPCPs that exhibited high risk at most sampling sites.

Objective: To explore the association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and abnormal liver function-induced by acetaminophen (APAP) drugs. Methods: An ALDH2 gene knockout mouse model was constructed using CRISPR/Cas9 gene editing technology. The obtained heterozygous mice were mated with opposite sex of heterozygotes. Genomic DNA was extracted from the tail of the offspring mouse. The polymerase chain reaction (PCR) method was used to determine the ALDH2 genotype. APAP was further used to induce acute drug-induced liver injury models in wild-type and ALDH2 knockout mice. Blood and liver tissues of mice were collected for liver function index, HE staining, F4/80 immunohistochemistry, and other detections. The intergroup mean was compared using a one-way ANOVA. The LSD-  t test was used for pairwise comparison. Results: ALDH2 knockout mice were bred successfully. The genotyping of the offspring was segregated into the wild-type (ALDH2(+/+)), heterozygous mutant (ALDH2(+/-)), and homozygous mutant (ALDH2(-/-)), respectively. Biochemical and histological results after APAP modeling showed that the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) was not significantly increased in the blank control group ( P  < 0.05), while the ALT, AST,ALP, and TBil were all elevated in the APAP experimental group. The levels of ALT ( P   = 0.004), AST ( P  = 0.002), and TBil ( P  = 0.012) were significantly elevated among the mutant group compared to those in the wild-type group, and the expression levels of these indicators were also significantly elevated among the homozygous mutant group compared to those in the heterozygous mutant group ( P  = 0.003, 0 and 0.006). In addition, the ALP levels were higher in the heterozygous mutation group than those in the homozygous mutant group ( P  = 0.085) and wild-type group mice, but the difference was only statistically significant compared to wild-type mice ( P  = 0.002). HE staining results showed that mice in the APAP experimental group had hepatocyte degeneration, necrosis, and increased inflammatory cell infiltration, which was mostly evident in mutant mice. Simultaneously, the F4/80 immunohistochemical staining results showed that brown granules were visible in the liver tissue of APAP experimental group mice, and its expression levels were significantly enhanced compared to the blank control group. Conclusion: APAP-induced liver function abnormalities were associated with the ALDH2 gene polymorphism. The liver injury symptoms were increased in ALDH2 mutant mice following APAP modeling, and the ALDH2 gene defect may alleviate, to some extent, APAP-induced liver function abnormalities.

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Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Food Safety & Quality is the property of Journal of Food Safety & Quality Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

From January 2019 to December 2021, the clinical data of 151 patients with post craniotomy cervicogenic headache from Beijing Tiantan Hospital affiliated to Capital Medical University were retrospectively collected. The characteristics of cervicogenic headache were summarized, the numerical rating score (NRS) of patients before and after treatment of compound opioids and/or cervical nerve block was compared, and the occurrence of related adverse reactions and complications was counted. The onset of cervicogenic headache in 151 patients was on the (5.5±2.0) d after craniotomy, of which 131 (86.8%) had unilateral pain, pain in 127 (84.1%) could be induced by cervical activity, and 118 (78.1%) had limited neck movement. Of the 124 patients treated with compound capsule of oxycodone and acetaminophen, 85 (68.5%) patients had an NRS of (8.01±0.82) before treatment and 2.0 (1.0, 3.0) after treatment ( P <0.001). Thirty-nine patients who did not respond to medical therapy received cervical nerve block, and the NRS scores before and after receiving the nerve block were (7.49±1.12) and 2.0 (1.0, 2.5), respectively, with a statistically significant difference ( P <0.001). Twenty-seven patients who received cervical nerve block without medical treatment, and the NRS before and after treatment was (9.0±0.9) and 1.0 (1.0, 3.0), respectively, with a statistically significant difference ( P <0.001). Among the 124 patients receiving medication, 14 (11.3%) developed mild dizziness and nausea, which were resolved after stopping the drug, and no other drug-related adverse reactions were found. None of the patients who received nerve blocks saw complications associated with nerve block procedures. Compound capsule of oxycodone and acetaminophen are effective for most of patients with post craniotomy cervicogenic headache. Cervical nerve block is effective and safe for patients with or without drug resistance.

Objective: To establish a method for the rapid determination of acetaminophen (APAP) in human plasma by LC-MS/MS. Methods: The plasma samples were extracted by methanol and acetonitrile (1: 1) and purified directly. C(18) column was used for sample separation. The mobile phase were methanol (5 mmol/L ammonium acetate) and water (5 mmol/L ammonium acetate). Samples were analyzed by LC MS/MS with the electrospray ionization multi reaction monitoring (MRM) mode. Results: The calibration curves of APAP was linear in the concentration range of 0~10 mg/L, the correlation coefficient ( r ) was greater than 0.999 0. The relative standard deviation within and between batches was less than 10%. The recovery rate were 96.81%~101.7%. The detection limit of the method was 0.1 μg/L and the lower limit of quantification was 0.3 μg/L. Conclusion: This method has strong specificity, high sensitivity and reliable determination results. It is suitable for the rapid analysis of clinical plasma samples.

Ferroptosis is a type of regulated cell death driven by iron-dependent lipid peroxidation that has received extensive attention in recent years. A growing body of evidence suggests that ferroptosis contributes to the progression of drug-induced liver injury. Therefore, the role and mechanism of ferroptosis in the process of drug-induced liver injury deserve further extensive and in-depth exploration, which will aid in the discovery of novel biomarkers as well as the identification of potential approches of targeting ferroptosis to intervene in drug-induced liver injury.

Copyright of Chinese Journal of Contemporary Neurology & Neurosurgery is the property of Chinese Journal of Contemporary Neurology & Neurosurgery and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study aims to observe the effect of chlorogenic acid(CGA) on microRNA(miRNA) in the process of protecting against N-acetyl-p-aminophenol(APAP)-induced liver injury. Eighteen C57BL/6 mice were randomly assigned into a normal group, a model group(APAP, 300 mg·kg~(-1)), and a CGA(40 mg·kg~(-1)) group. Hepatotoxicity of mice was induced by intragastric administration of APAP(300 mg·kg~(-1)). The mice in the CGA group were administrated with CGA(40 mg·kg~(-1)) by gavage 1 h after APAP administration. The mice were sacrificed 6 h after APAP administration, and plasma and liver tissue samples were collected for the determination of serum alanine/aspartate aminotransferase(ALT/AST) level and observation of liver histopathology, respectively. MiRNA array combined with real-time PCR was employed to discover important miRNAs. The target genes of miRNAs were predicted via miRWalk and TargetScan 7.2, verified by real-time PCR, and then subjected to functional annotation and signaling pathway enrichment. The results showed that CGA administration lowered the serum ALT/AST level elevated by APAP and alleviate the liver injury. Nine potential miRNAs were screened out from the microarray. The expression of miR-2137 and miR-451a in the liver tissue was verified by real-time PCR. The expression of miR-2137 and miR-451a was significantly up-regulated after APAP administration, and such up-regulated expression was significantly down-regulated after CGA administration, consistent with the array results. The target genes of miR-2137 and miR-451a were predicted and verified. Eleven target genes were involved in the process of CGA protecting against APAP-induced liver injury. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment with DAVID and R language showed that the 11 target genes were enriched in Rho protein-related signal transduction, vascular patterning-related biological processes, binding to transcription factors, and Rho guanyl-nucleotide exchange factor activity. The results indicated that miR-2137 and miR-451a played an important role in the inhibition of CGA on APAP-induced hepatotoxicity.

Objectives: The purpose of this study was to determine students' knowledge, attitudes, and behavior regarding the correct use of analgesics and to examine the related factors. Methods: A probability-proportionate-to-size sampling method was used. Thirty-three senior/vocational high schools were randomly selected. A total of 2,910 students completed the online selfadministered questionnaire in 2013. Results: Greater than one-half of the students did not know that when taking pain medication containing acetaminophen, adults should not exceed 4,000 mg per day. Approximately 22.1% of the students were unaware of the hepatotoxicity risk associated with acetaminophen. Multiple regression analysis showed that students in higher grades who had greater levels of correct analgesic knowledge, attitude, and self-efficacy, take analgesic prescriptions and use other pain management techniques, such as hot/cold therapy, relaxation, and massage, and were more likely to demonstrate correct analgesic use behaviors if they had received pain management information from family members and had read the warning labels. In contrast, students taking analgesics from drug stores or family/friends were more likely to practice poor analgesic use behavior. Conclusions: The promotion of partnerships between schools and pharmacists is suggested, along with the implementation of teachers' training workshops, students' education programs, and parent-child activities in order to enhance correct analgesic use literacy. [ABSTRACT FROM AUTHOR]

An instrumental analysis experiment was introduced : simultaneous identification and quantitative determination of components in Paracetamol, Aminophenazone, Caffeine and Chlorphenamine Maleate Tablets using 1HNuclear Magnetic Resonance Spectroscopy. This paper introduces the purpose, procedure and effect of this experiment. Qualitative and quantitative analyses are based on resonance characteristics of the functional groups and the integral ratio of selected signals belonging to different compounds, respectively. This method covers the main points of nuclear magnetic resonance spectroscopy, which will help students learn this part better. [ABSTRACT FROM AUTHOR]

Objective: To explore the influencing factors of health-related quality of life (HRQoL) in patients with knee osteoarthritis, and to analyze the non-surgical treatment of knee osteoarthritis. Methods: Demographic variables, treatment modalities, imaging data, and 12-item short form health survey (SF-12) scores of patients with knee osteoarthritis in orthopedic outpatient departments of five hospitals in Beijing from December 2017 to November 2018 were collected to analyze influencing factors of HRQoL and non-surgical treatment. Results: A total of 2 034 patients were included. There were 530 males (26.1%) and 1 504 females (73.9%), with a mean age of (59.17±10.22) years. In terms of physical quality of life, female patients with knee osteoarthritis had lower physical components summary (PCS) compared with male patients (β=-0.521, P =0.036); patients aged ≥64 years had lower PCS than those aged<55 years (β=-0.636, P =0.026). Patients with an education of more than 12 years had higher PCS than those with less than 10 years (β=1.063, P <0.001). Compared to patients with mild clinical symptoms, the PCS of patients with moderate clinical symptoms was lower (β=-0.860, P =0.002), while the PCS of those with severe clinical symptoms was much lower (β=-1.126, P <0.001). Patients treated with combination therapy had higher PCS than untreated patients (β=0.731, P =0.005). In terms of mental quality of life, compared to patients engaged in sedentary work, the mental components summary (MCS) of patients engaged in mild manual labor jobs was lower (β=-0.712, P =0.015); Compared to patients with a Charson comorbidity index of 0, patients with a Charlson comorbidity index ≥ 2 had lower MCS (β=-1.183, P =0.007). In the past 12 months, 648 (31.9%), 143 (7.0%), 406 (20.0%), 680 (33.4%), 343 (16.9%), 681 (33.5%), 170 (8.4%) patients had used non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, glucosamine/chondroitin formulations, physical therapy, articular cavity puncture injection, traditional Chinese medicine treatment and exercise therapy, respectively. Total of 451 patients (22.2%) received monotherapy and 889 patients (43.7%) received combination therapy. Conclusions: The major non-surgical treatment methods for patients with knee osteoarthritis in Beijing are NSAIDs, physiotherapy and traditional Chinese medicine. Combination therapy is used more frequently than monotherapy. Physical quality of life is related to gender, age, education, severity of symptoms and treatment, while mental quality of life is related to occupational labor and comorbidities.

As one of the large dosages of pharmaceutical and personal care products (PPCPs), acetaminophen is widely present in the water environment and presents potential environmental risks. Therefore, it is necessary to study the removal mechanism of acetaminophen from the environment. Based on the high-value conversion demand of agricultural straw resources in China, straw-derived biochar prepared by pyrolysis has a good application prospect for the sorption and purification of acetaminophen in water. However, the sorption process and mechanism of straw-derived biochar for acetaminophen remain unclear. Four types of straw (rice, wheat, maize, and bean straw) were chosen as raw materials, and straw-derived biochars were prepared through the pyrolysis method at 400℃ and 500℃. The batch sorption experiments were used to study the sorption of acetaminophen to different sources and different pyrolysis temperature biochars. The effect of humic acid and pH on the sorption process was also studied. The results showed that:based on the Freundlich and site energy distribution models, the sorption of acetaminophen on biochar at 500℃ biochar was significantly higher than that at 400℃ biochar (the sorption coefficient K was 1.16-2.53 times higher), and 500℃ biochar had more high-energy sorption sites. For high-temperature pyrolysis biochar, the primary sorption mechanism was pore sorption and π-π effect; for low-temperature pyrolysis biochar, the primary sorption mechanism for removing acetaminophen was H-bonding. The presence of humic acid enhanced the sorption of acetaminophen, which was attributed to the strong interaction between the humic acid selected in the experiment and acetaminophen, thus promoting adsorption. The decrease in sorption capacity of biochar caused by the increasing pH was mainly attributed to the pore blockage resulting from the aggregation of acetaminophen molecules. The pore sorption and π-π interaction of acetaminophen on straw-derived biochar could be promoted by increasing pyrolysis temperature. These experiments on humic acid and pH show that straw-derived biochar is not affected by humic acid and has good sorption performance in a low pH environment.F was 1.16-2.53 times higher), and 500℃ biochar had more high-energy sorption sites. For high-temperature pyrolysis biochar, the primary sorption mechanism was pore sorption and π-π effect; for low-temperature pyrolysis biochar, the primary sorption mechanism for removing acetaminophen was H-bonding. The presence of humic acid enhanced the sorption of acetaminophen, which was attributed to the strong interaction between the humic acid selected in the experiment and acetaminophen, thus promoting adsorption. The decrease in sorption capacity of biochar caused by the increasing pH was mainly attributed to the pore blockage resulting from the aggregation of acetaminophen molecules. The pore sorption and π-π interaction of acetaminophen on straw-derived biochar could be promoted by increasing pyrolysis temperature. These experiments on humic acid and pH show that straw-derived biochar is not affected by humic acid and has good sorption performance in a low pH environment.

Salvianolic acid B(Sal B), tanshinone Ⅱ&#95;A(TSN Ⅱ&#95;A), and glycyrrhetinic acid(GA) lipid emulsion(GTS-LE) was prepared by the high-speed dispersion method combined with ultrasonic emulsification.The preparation process of the emulsion was optimized by single-factor method and D-optimal method with appearance, centrifugal stability, and particle size of the emulsion as evalua-tion indexes, followed by verification.In vitro release of Sal B, TSN Ⅱ&#95;A, and GA in GTS-LE was performed by reverse dialysis.In vivo pharmacokinetic evaluation was carried out in mice.The acute liver injury model was induced by acetaminophen.The effect of oral GTS-LE on the acute liver injury was investigated by serum liver function indexes and pathological changes in liver tissues of mice.The results showed that under the optimal preparation process, the average particle size of GTS-LE was(145.4±9.25) nm and the Zeta potential was(-33.6±1.45) mV.The drug-loading efficiencies of Sal B, TSN Ⅱ&#95;A, and GA in GTS-LE were above 95%, and the drug release in vitro conformed to the Higuchi equation.The pharmacokinetic results showed that the C&#95;(max) of Sal B, TSN Ⅱ&#95;A, and GA in GTS-LE was 3.128, 2.7, and 2.85 times that of the GTS-S group, and AUC&#95;(0-t) of Sal B, TSN Ⅱ&#95;A, and GA in GTS-LE was 3.09, 2.23, and 1.9 times that of the GTS-S group.After intragastric administration of GTS-LE, the activities of alanine aminotransferase and aspartate aminotransferase were significantly inhibited, the content of malondialdehyde was reduced, and the structure of hepatocytes recovered to normal.In conclusion, GTS-LE can delay the release of Sal B and promote the release of TSN Ⅱ&#95;A and GA.The encapsulation of three drug components in the emulsion can improve the oral bioavailability to varying degrees and can effectively prevent the acute liver injury caused by acetaminophen.

The N′-[ (E) -1 -( 5-Bromo-2-Hydroxyphenyl) ethylidene] benzohydrazide was synthesized by the reaction of 1- ( 5-bromo-2-hydroxyphenyl) ethanone and benzohydrazide. The crystal structure of the compound was characterized by X-ray diffraction. It was assigned to monoclinic crystal system, space group P2 (1)/n, cell data:α=0.737 61 (15) nm, α=90°, b=2.827 0(6)nm, β=116.928(12)°,c=0.860 89 (13) nm, γ=90°, V= 1.600 5(5) nm³, Z=4, μ=2.570 mm-1, Dc=1. 383mg/m³, F(000) =672, R1 =0.0676 [I>2σ(I)], wR2 =0. 187 7. [ABSTRACT FROM AUTHOR]

OBJECTIVE:To establish a method for the content determination of acetaminophen , doxylamine succinate , dextromethorphan hydrobromide in Soft capsule by HPLC .METHODS: Separation was carried out on a Agilent Zorbax C18 (4.6 mm ×150 mm,5 μm) column with mobile phase A of acetonitrile , mobile phase B of buffer solution(pH=3.0) in gradient elution at a flow rate of 1.2 ml/min, the detection wavelength was 275 nm, the column temperature was 35°C, and the injection volume was 20μl.RESULTS:The linearity range of acetaminophen , doxylamine succinate , dextromethorphan hydrobromide were 2.62-26.23 μg/ml ( r=0.999 9 ) , 2.51-25.14 μg/ml ( r=0.999 8 ) and 5.68-56.78 μg/ml ( r =0.999 9 ) , respectively .The average recovery rates were 100.6%, 101.1%and 100.2%, with RSD of 0.4%, 1.2%and 0.4%( n=9 ) , respectively .CONCLUSIONS:The method is simple, rapid, and accurate in the content determination of acetaminophen , doxylamine succinate , dextromethorphan hydrobromide in Soft capsule . [ABSTRACT FROM AUTHOR]

The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.

This study explored the protective effect of atractylenolide Ⅰ(AO-Ⅰ) against acetaminophen(APAP)-induced acute liver injury(ALI) in mice and its underlying mechanism. C57 BL/6 J mice were randomly divided into a control group, an APAP group(500 mg·kg~(-1)), a low-dose combination group(500 mg·kg~(-1) APAP + 60 mg·kg~(-1) AO-Ⅰ), and a high-dose combination group(500 mg·kg~(-1) APAP + 120 mg·kg~(-1) AO-Ⅰ). ALI was induced by intraperitoneal injection of APAP(500 mg·kg~(-1)). AO-Ⅰ by intragastric administration was performed 2 hours before APAP treatment, and the control group received the same dose of solvent by intragastric administration or intraperitoneal injection. The protective effect of AO-Ⅰ against APAP-induced ALI was evaluated by detecting alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels in the plasma and H&E staining in liver tissues of mice. The malondialdehyde(MDA) and glutathione(GSH) content and catalase(CAT) activity in mouse liver tissues were detected to evaluate the effect of AO-Ⅰ on APAP-induced oxidative stress in the liver. The proteins in the liver p38 mitogen-activated protein kinase(p38 MAPK), c-jun N-terminal kinase(JNK), and nuclear factor kappa-B p65(NF-κB p65) signaling pathways were measured by Western blot, and the liver inflammatory cytokines interleukin-1β(IL-1β) and interleukin-6(IL-6) were detected by real-time PCR. Compared with the APAP group, the combination groups showed reduced APAP-induced ALT level and liver MDA content, potentiated liver CAT activity, and elevated GSH content. Mechanistically, AO-Ⅰ treatment significantly inhibited APAP-up-regulated MAPK phosphorylation and NF-κB p65, and significantly reduced the transcriptional activities of IL-1β and IL-6, downstream targets of NF-κB p65. AO-Ⅰ can improve APAP-induced ALI and the underlying mechanism is related to the inhibition of the MAPK/NF-κB p65 signaling pathway in APAP-challenged mice.

Acetaminophen (APAP) is a widely used antipyretic and analgesic drug that is safe and effective in the therapeutic doses, but overdose may cause hepatotoxicity and even acute liver failure (ALF). Finding reliable biomarkers for APAP toxicity is not only a hot spot of current research, but also a problem that needs to be solved urgently. Clinicians should consider the existence of APAP hepatotoxicity when using APAP treatment, and explain that APAP may have a certain degree of dose dependence. This paper reviews the most promising biomarkers currently being evaluated, and expounds their application in the field of APAP hepatotoxicity, as well as the mechanism of mitochondrial damage and mitochondrial autophagy, thereby contributing to the diagnosis, prognosis, mechanism and research progress of therapeutic targets of APAP hepatotoxicity.

Objective: To investigate the protective effect of Colgalt2 gene deletion on acute liver injury induced by acetaminophen (APAP) in mice. Methods: Colgalt2(+/+) wild-type control mice and Colgalt2(-/-) mice (all C57BL/6J strains) were selected as the research subject. APAP solution was injected intraperitoneally to establish a mouse model of acute liver injury. The mouse were divided into four groups: Colgalt2(+/+) wild-type control group, Colgalt2(+/+) wild-type drug group (APAP 500 mg/kg), Colgalt2(-/-) control group, and Colgalt2(-/-) drug group (APAP 500 mg/kg). The survival rate was measured to plot survival curve. Liver function was evaluated by detecting serum ALT and AST levels. Liver histopathological changes were observed by HE staining to evaluate the condition of liver injury. Western blot was used to detect protein c-Jun N-terminal kinase (JNK)-related liver injury. Results: Compared with Colgalt2(+/+) mice, the survival rate was significantly increased after giving APAP to Colgalt2(-/-) mice (86.7% vs. 40%), and liver cell necrosis and inflammatory cell infiltrates of Colgalt2(+/+) mice were milder. Serum ALT, and AST level was significantly decreased [ALT: (5 291.9 ± 1 016.34) U/L vs. (1 616.9 ± 330.65) U/L, P = 0.000; AST: (4 978.0 ± 1 028.43) U/L vs. (1 851.0 ± 437.55) U/L, P = 0.000]. The expression level of JNK was significantly decreased in liver tissue. Conclusion: Colgalt2 gene deletion has a protective effect on acute liver injury induced by acetaminophen (APAP) in mice. Therefore, Colgalt2 may be a potential therapeutic option for acetaminophen-induced hepatotoxicity.

The aim of this study was to observe the protective effect of water extract from Sabia parviflora on mice with acute liver injury induced by acetaminophen, and investigate its possible mechanism. Fifty-eight Kunming mice were divided into 6 groups, 8 in the normal group, 10 in the model group, 10 in the biphenyl diester group, and 10 each in the low, medium and high dose groups. After adaptive feeding for one week, the mice in normal group were intragastrically administered with an equal volume of 0.5% sodium carboxymethylcellulose sodium(CMC-Na), and the mice in other groups were intragastrically administered with corresponding drugs at 20 mL·kg~(-1) once a day. Then acetaminophen(200 mg·kg~(-1)) was administered after the above drug administration except the normal group. The behavior and signs of the experimental animals were observed every day and the samples were taken for experiments on the next day of the final administration. The liver mass and mass index were calculated. The blood was collected from the abdominal aorta and centrifuged to obtain the serum for detecting aspartate aminotransferase(AST) activity and alanine aminotransferase(ALT) activity. The liver tissue homogenate was used to detect superoxide dismutase(SOD) activity, glutathione(glutathione, r-glutamyl cysteingl+glycine, GSH) activity and malondialdehyde(MDA) content. Liver tissue was analyzed for histological analysis. The results showed that S. parviflora could alleviate the lipid peroxidation damage in the liver caused by acetaminophen, reduce the ALT and AST activities in serum, increase the levels of SOD and GSH in liver tissue, decrease the content of MDA in liver tissue, and inhibit the apoptosis. S. parviflora could also improve the live histopathological profile, protect liver cells and restore liver function. Among them, the high dose had the most significant effect and showed dose-effect relationship. This study indicated that S. parviflora had a significant protective effect on acetaminophen-induced liver injury in mice, and its mechanism may be related to its anti-oxidation effect and inhi-bitory effect on apoptosis.

The study was aimed to investigate the protective effect and pharmacodynamic difference of the ethanol extracts of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus on the drug-induced liver injury induced by acetaminophen.The cell activations of LO2 cells treated by Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts were tested by CCK-8 essay.The effects of ethanol extracts on cell survival rate,the activities of ALT and AST in culture medium were detected based on the injury model of LO2 cells induced by APAP.Further,in purpose to observe the protective effect of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts on a mouse model of liver injury induced by intraperitoneal injectionof acetaminophen was established.Mice were randomly divided into control group,model group,positive drug group and Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts administration groups.The activities of ALT and AST in the serum and the levels of MDA,SOD,GSH and GSH-PX in the liver homogenate of the mice were detected by commercial kits.The HEstaining was used to observe the histopathological changes of liver tissue in each group and the TUNEL staining was used to observe the hepatocyte apoptosis.The results showed that the ethanol extracts at less than 1 g·L~(-1)did not affect the activity of LO2 cell.Compared with the model group,the cell survival rates of the Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract administration groups was significantly increased;the ALT and AST in the culture medium were distinct decreased(P<0.05 or P<0.01).The survival rate of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract from different batches were similar,while that of the Schisandrea Sphenatherae Fructus ethanol extract from different batches were quite different(P<0.05or P<0.01).Further,animal experiments showed that Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract administration groups could markedly inhibit the increase of ALT and AST levels in serum(P<0.01),decrease MDA content significantly(P<0.01),and increase GSH,GSH-PX and SOD activity significantly(P<0.01).Among them,compared with other groups,Schisandrae Sphenantherae Fructus ethanol extract-2 group showed the best effect(P<0.05 or P<0.01)while Schisandrae Sphenantherae Fructus ethanol extract-1 showed a poor effect(P<0.05 or P<0.01).In conclusion,both Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts have protective effect on APAP-induced drug-induced liver injury and there was a certain difference in the efficacy between Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts from different habitats.

Schisandra chinensis is a commonly used hepatoprotective medicine in clinic. Previous studies have showed that Schisandrae Chinensis Fructus has dual effects on the activity of CYPs. Short-term administration of Schisandrae Chinensis Fructus may inhibit CYP450s activity, while long-term administration may up-regulate CYP activity. High CYP450s activity level may increase the frequency of reactive metabolites-induced liver injury. It remains unclear how long-term administration of Schisandrae Chinensis Fructus may affect acetaminophen-induced acute hepatotoxicity. After oral administration of Schisandrae Chinensis Fructus extract (0.5-2.0 g·kg⁻¹) for 21 d, the activity of CYPs, Nrf2, HO-1, GST expressions, SOD and GST activity as well as glutathione level of SD rats were up-regulated. Besides, Schisandrae Chinensis Fructus extract ameliorated APAP (500 mg·kg⁻¹)-induced acute hepatotoxicity in a dose-dependent manner, as evidenced by decrease in ALT, AST, and MDA level and increase in GSH level ( P <0.05). What's more, the liver histopathology was alleviated, and cleaved caspase-3 expression was decreased. Besides, the increase of N-acetyl-p-benzoquinoneimine-GSH (reactive metabolite of acetaminophen) formation was observed in Schisandrae Chinensis Fructus extract groups. In conclusion, the present study indicated that the effects of Schisandrae Chinensis Fructuson acetaminophen-induced hepatotoxicity may rely on the Nrf2 signal pathway activation, and less depends on the increase in CYP450s activity., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The model of drug-induced liver injury (DILI) induced by acetaminophen (APAP) in mice was established to investigate the anti-oxidation and anti-ferroptosis mechanisms of Fuzheng Yanggan Mixture on DILI. C57BL/6 mice were randomly divided into five groups: control group, model group, positive group, and low and high-dose Fuzheng Yanggan Mixture groups (0.12, 0.24 g·kg⁻¹). Mice were intragastrically administration with Fuzheng Yanggan Mixture (0.12, 0.24 g·kg⁻¹) once per day for 21 consecutive days, and at the same time, mice were weighted every day. The mice were injected intraperitoneally with 600 mg·kg⁻¹ of APAP to establish a mouse model of acute DILI after 16 h from the last administration of Fuzheng Yanggan Mixture. After 6 h from APAP challenge, the experimental animals were weighted and sacrificed to collect blood and liver tissue samples. And then, the effect of Fuzheng Yanggan Mixture on liver weight and the liver weight ratio of mice were examined; the content of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum and the level of malondialdehyde (MDA), glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) in the liver tissue were measured. Prostaglandinendoperoxide synthase 2(ptgs2) mRNA level in liver tissues was detected by Q-PCR, and protein expression levels of SLC7A11 and GPX4 in liver tissues were detected by Western blot. Moreover, HE staining, immunohistochemical assay and TUNEL staining were used to observe pathological changes of the liver tissue sections. It is found that Fuzheng Yanggan Mixture could relieve APAP-induced liver enlargement and inhibit hepatic weight ratio increase. Compared with model group, the mice in Fuzheng Yanggan Mixture groups showed decreases in the content of ALT, AST and MDA, and increases in the content of GSH and NADPH. What is more, Fuzheng Yanggan Mixture could down-regulate ptgs2 mRNA level and up-regulate SLC7A11 and GPX4 protein levels. All of the results lead to a conclusion that Fuzheng Yanggan Mixture plays a protective effect on DILI in mice, which may be associated with the inhibition of ferroptosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To investigate the protective effects of Ginkgo biloba extract(GBE) on paracetamol(APAP)-induced acute hepatic injury in mice and its mechanism., Methods: Thirty mice were randomly divided into control group, model group, GBE low, medium and high-dose(50,100,and 200 mg·kg -1 )groups,with 6 mice in each group. All mice except control group were administered with APAP(300 mg/kg)for one time by intraperitoneal injection. The mice in GBE low, medium and high-dose groups were intragastric administered with GBE for 2 d consecutively, then samples were harvested for analysis. The appearance and pathology of liver were observed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and the levels of superoxide dismutase (SOD), myeloperoxidase(MPO), glutathione (GSH) and malondialdehyde (MDA) in hepatic tissue were measured. Western blot was used to detect the protein expressions of Nrf2 and HO-1., Results: Compared with control group, in model group, the appearance and pathology of liver were bad, the levels of ALT,AST,TNF-α and IL-6 in serum were increased significantly( P <0.01),the levels of GSH and SOD were decreased while the levels of MDA and MPO were increased in hepatic tissue( P <0.01), the expressions of Nrf2 and HO-1 were increased in hepatic tissue( P <0.05). Compared with model group, in GBE groups, the appearance and pathology of liver were improved, the levels of ALT,AST,TNF-α and IL-6 in serum were decreased significantly( P <0.01), the levels of GSH and SOD were increased while the levels of MDA and MPO were decreased in hepatic tissue( P <0.01), the expression of Nrf2 and HO-1 were increased in hepatic tissue( P <0.05). The high-dose of GBE possessed the most obvious treatment effect among them., Conclusions: GBE may play a protective role in APAP-induced acute hepatic injury through Nrf2/HO-1 pathway.

This paper was aimed to investigate the protective effects of luteolin (Lut) against acetaminophen（APAP）-induced damage in L02 liver cells. CCK-8 was used to detect the cell activation of L02 cells treated by different Lut. The concentration and time of APAP induced L02 cell damage was screened. The effect of Lut on APAP induced apoptosis of L02 cells was detected by cell morphological observation, CCK-8 assay and flow cytometry. The contents of MDA, GSH and SOD activity in cell supernatant were detected by colorimetric assay. The expression of apoptosis-related genes Bax, Bcl-2 and caspase-3 was detected by RT-PCR. The results showed that Lut in 2.5-40 μmol•L⁻¹ range does not affect the activity of L02 cells; 12 mmol•L⁻¹ APAP incubated with L02 cell 12 h to establish damage model. Compared with the model group, the cell status of Lut group was significantly improved, the cell body was increased, the adherence ability was recovered, and the apoptosis rate was obviously decreased. MDA content decreased significantly (P<0.05, P<0.01), GSH and SOD activity significantly increased (P<0.05, P<0.01), at the same time, it could up-regulate expression of Bcl-2 mRNA and down-regulate the expression of Bax and caspase-3 mRNA. In conclusion,Lut has protective effect on APAP induced L02 cell injury, and its mechanism may be related to the reduction of oxidative stress and inhibition of apoptosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To investigate the protective effects of hepatic fibrosis against a lethal dose of acetaminophen (APAP) and its underlying mechanisms using a carbon tetrachloride (CCl4)-induced mouse model of fibrosis., Methods: The experimental model of hepatic fibrosis was established by intraperitoneal injection of CC14 (in mineral oil), twice a week for 6 weeks; mice given a 6-week course of mineral oil injections served as normal controls. At the end of fibrosis induction, the expmimental (Fib group) and control (Norm group) mice were challenged with APAP (1 g/kg). Sera and liver tissues were harvested for analyses.To assess tolerance of the normal and fibrotic mice to the lethal dose of APAP, the survival rate,serum alanine aminotransferase (sALT) levels and hepatic histopathological changes were compared before and after the acute APAP challenge.HMGB 1 expression was analyzed by immunohistochemistry.One-way ANOVA test and Newman-Keuls test were used in statistical analysis., Results: The fibrotic liver was tolerant to the lethal dose of APAP,as evidenced by:(1) significantly higher survival rate in the Fib ± APAP group (80% vs. Norm+APAP group: 0%); (2) markedly lower sALT levels in the Fib+APAP group (6 437 ± 1 913 U/L vs. 12 456 ± 3 441 U/L), P=0.022; (3) remarkably well-preserved liver architecture in the Fib+APAP group.Immunohistochemical analysis showed high HMGB1 expression and cytoplasmic translocation in the Norm+APAP group,which was absent in the Fib+APAP group., Conclusions: CCl4-induced liver fibrosis protects mice against lethal dose of APAP, Possibly by a mechanism involving inhibition of the cytoplasmic translocation of HMGB1.

An analytical method has been developed and validated for the simultaneous determination of nine pharmaceuticals and personal care products (PPCPs) in water samples, including salicylic acid, naproxen, ibuprofen, paracetamol, clofibric acid, triclosan, diclofenac, ketoprofen, bisphenol A. The qualification and quantification of the target compounds were performed by gas chromatography-mass spectrometry in selected ion monitoring mode (GC-MS-SIM). The water samples were concentrated and purified through Oasis HLB cartridges after the pH value of the water was adjusted to 3, then derivatized with trimethyl sulfonium hydroxide (TMSH) at room temperature, and determined by GC-MS-SIM using 2,4,5-fenoprop as internal standard. The conditions for sample pretreatment (e. g. solid phase extraction and derivatization) were studied. Under the optimized conditions, the recoveries were ranged from 50.7% to 115.4% with the relative standard deviations lower than 10%. The limits of detection were in the range of 0.03-0.30 microg/L and the limits of quantification were in the range of 0.15-1.50 microg/L. The method has been successfully applied to monitor the occurrence of the PPCPs residues in agricultural irrigation water in Dongguan, Guangdong Province. The four compounds were detected at maximum mass concentration range of 0.176-0.998 microg/L. It proved that this analytical method is sensitive, reliable and acceptable.