ABSTRACT
Acetaminophen (APAP, also known as paracetamol)-induced liver injury is the leading cause of drug-induced liver injury in the world. Wuzhi Tablet (WZ, an ethanol extract of Schisandra sphenanthera) is widely used in clinical practice to protect liver function. Our previous studies have shown that pretreatment with WZ for 3 days can significantly protect against APAP-induced liver injury; however, the effect of different intervals between APAP and WZ treatment on APAP-induced liver injury remains unclear. In this study, the change in liver injury indexes, APAP metabolites, and the activity of cytochrome P450 (CYP450) enzymes after treatment with WZ and APAP at different intervals were determined. The animal experiment was reviewed and approved by the Animal Ethics Committee of Sun Yat-sen University. The results show that 0 h, 0.5 h, and 2 h pretreatment with WZ significantly protected against APAP-induced liver injury in mice, as evidenced by a significant decrease in biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malonaldehyde (MDA). WZ inhibited the metabolic activation of APAP mediated by CYP450 enzymes and reduced the formation of APAP metabolites. This study further demonstrates that pretreatment with WZ at different intervals (0 h, 0.5 h, and 2 h before APAP dosing) exerts a significant hepatoprotective effect against APAP-induced liver injury, and a single-dose of WZ inhibits the activity of CYP450 enzymes related to APAP metabolic activation, thereby protecting against APAP-induced hepatotoxicity.
ABSTRACT
Schisandrol B (SolB) is one of the active constituents from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. Our previous studies found that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. We further found that SolB significantly induces liver enlargement but the mechanisms remain unclear. The purpose of this study was to investigate the change of lipidome in liver tissues during SolB-induced hepatomegaly. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. Serum and liver samples of male C57BL/6 mice were collected after intraperitoneal injection of SolB (100 mg·kg-1·d-1) for 5 days. Lipidomics analysis was performed using Q Exactive UHPLC-MS/MS system. The results showed that SolB significantly promoted liver enlargement in mice without liver injury and inflammation. Lipid accumulation was observed in the liver tissues after SolB treatment. Thirty-five lipids were identified with significant change and triglycerides (TG) were found to have the most significant increase in SolB-treated group, indicating the increase of energy production during SolB-induced hepatomegaly. This study reveals the impact of SolB on lipid metabolism and provides a potential explanation for liver enlargement induced by SolB.
ABSTRACT
Cyclophosphamide (CPA) is one of the most commonly used alkylating agents in the treatment of malignant cancer. CPA is metabolized by cytochrome P450 enzymes into 4-hydroxycyclophosphamide in vivo which can exhibit anti-tumor activity. Metabolic activation of CPA can cause adverse reactions such as myelosuppression, cystitis, and liver injury. The aim of this study was to evaluate the dynamic changes of hepatic injury induced by CPA in mice. Male BALB/c mice were injected CPA (200 mg·kg-1) intraperitoneally. Both serum and liver samples were collected at 0, 2, 6, 12 and 24 hours after dosing. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. The results showed that hepatotoxicity was observed at 2 hours after CPA dosing, and the most serious liver injury was measured at 12 hours. The level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) was significantly increased, glutathione (GSH) level was significantly decreased, hepatocyte edema and vacuolar degeneration were widely observed in liver tissue, and began to recover 24 hours after dosing. In addition, due to oxidative stress damage caused by CPA, nuclear factor-erythroid 2-related factor 2 (NRF2) signaling pathway was activated and the mRNA and protein expression of its downstream targets such as quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate cysteine modifier subunit (GCLM) were up-regulated, which alleviated oxidative stress injury. In a summary, this study demonstrate the dynamic change of CPA-induced liver injury and the NRF2-mediated protective mechanisms, providing new insights into the CPA-induced liver injury.
ABSTRACT
Objective:To evaluate the relationship between large artery elastic function and coronary heart disease (CHD) or lower extremity arterial disease (LEAD) in patients with carotid plaque.Methods:A total of 491 patients with carotid plaque were enrolled into the study with complete data of arterial stiffness detection and blood test [male:208 and female:283,and mean age:(61.66 11.60) years].All the subjects were divided into 2 groups according to CHD or LEAD,namely non-CHD&LEAD group (neither CHD nor LEAD) and CHD/LEAD group (either CHD or LEAD).According to the mean age level (age ＜61.66 years or age ＞61.66 years),the independent association was analyzed between higher large arterial stiffness (carotid-femoral pulse wave velocity,CF-PWV,CF-PWV ＞ 9 m/s) and CHD/LEAD.Results:In the present research population,the mean level of arterial stiffness was high (the mean CF-PWV was 10.71 m/s),and 76.6％ of them had arteriosclerosis,and 36.9％ CHD/LEAD.The age,male and smoking proportion,systolic blood pressure (SBP),glycosylated hemoglobin (HbA1c),homocysteine (Hcy),creatinine (Cr),CF-PWV,prevalence rate of hypertension and diabetes mellitus,medication on hypertension,diabetes and hyperlipidemia were higher in CHD/LEAD group,and total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),and low density lipoprotein cholesterol (LDL-C) were lower in CHD/LEAD group than in non-CHD&LEAD group (all P ＜ 0.05).In multivariate Logistic regression analysis,the results showed that in the patients with age below 61.66 years,large artery stiffness (CF-PWV ＞ 9 m/s) was an independent risk factor of CHD/LEAD (OR =3.229,95％ CI 1.156-9.022,P ＜ 0.05);In the patients with age above 61.66 years,there was no independent association between large artery stiffness and CHD/LEAD (P ＞ 0.05).Conclusion:The large artery elasticity function in the patients with carotid plaque was poor.In the patients with carotid plaque and higher large artery stiffness below 61.66 years,the risk of the prevalence of CHD/LEAD was increased significantly than with normal arterial stiffness.In the patients with carotid plaque below or above 61.66 years,the independent influencing factors on the prevalence of CHD/LEAD were different.
ABSTRACT
The chemical constituents of Taxus chinensis var. mairei cell cultures were investigated by chromatographic methods, including silica gel column chromatography, Sephadex LH-20 and preparative HPLC. Thirteen compounds were isolated from the 80% ethanol extract of cultured cells and their structures were elucidated by spectral data and physicochemical properties, which were identified as 2α,4α,7β,9α,10β-pentaacetoxy-14β-hydroxytax-11-ene (1), 2α,4α,7β,9α,10β-pentaacetoxytax-11-ene (2), 1β-deoxybaccatin VI (3), 2α-acetoxytaxusin (4), taxuyunnanine C (5), yunnanxane (6), 2α,5α,10β-triacetoxy-14β-propionyloxy-4 (20), 11-taxadiene (7), 2α,5α,10β-triacetoxy-14β-isobutyryloxy-4 (20), 11-taxadiene (8), 2α,5α,10β-triacetoxy-14β-(2'-methyl)butyryloxy-4 (20), 11-taxadiene (9), 13-dehydroxylbaccatin III (10), 13-dehydroxy-10-deacetylbaccatin III (11), paclitaxel (12) and (13) β-sitosterol. Among them, compound 1 is a new compound, and compounds 2, 4, 10 and 11 are isolated from the cell culture of Taxus chinensis var. mairei for the first time.