Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A₂/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.     

Ketoprofen Versus Paracetamol in the Treatment of Acute Migraine

The efficacy and safety of ketoprofen and paracetamol were compared for the treatment of acute migraine in a randomized, double-blind study of 64 patients. Thirty-four patients received ketoprofen 100 mg intramuscularly, and 30 patients received paracetamol 500 mg intramuscularly. Partial or complete relief of pain and other symptoms was achieved 15 to 20 minutes after administration in the ketoprofen group and within 35 minutes in the paracetamol group. Complete relief of pain was achieved within 30 to 40 minutes after ketoprofen in 28 patients (82.5%) compared to 5 patients (17.5%) in the paracetamol group. Six of the patients treated with ketoprofen needed a second dose for complete relief of pain during the 4-hour follow-up period. Side effects were rare and minimal. Our findings suggest that ketoprofen produced statistically significant benefit in the treatment of acute migraine.     

丙氧氨酚与酮咯酸治疗癌痛的比较

晚期肿瘤疼痛病人３１例（男性１７例，女性１４例，年龄５０±５１４ａ），用丙氧氨酚２片，ｐｏ，ｔｉｄ，共７ｄ。相似病人３０例（男性１６例，女性１４例，年龄５１±１３ａ），用酮咯酸１０ｍｇ，ｐｏ，ｑｉｄ，共７ｄ。结果：疼痛强度（标尺法）２组均有降低；显效时间前组（丙氧氨酚）快于后组（酮咯酸）；药效维持时间后组长于前组；不良反应前组嗜睡多于后组，而胃肠道不适少于后组。     

紫外分光光度法测定对乙酰氨基酚泡腾片含量

本文用紫外分光光度法在２５７±１ｎｍ波长处测定对乙酰氨基酚泡腾片的含量，其浓度与吸收度的线性关系良好，相关系数ｒ＝０．９９９９８。平均回收率为９９．９４％，变异系数为０．２０％。本法简便、快速、结果准确。     

汉防己甲素对硫唑嘌呤致大鼠肝损伤的保护作用

研究汉防己甲素(Tet)对硫唑嘌呤(Aza)致大鼠肝损伤的保护作用。方法大鼠分为三组 :①对照组 ;②Aza组 ;③Aza Tet组。给药量分别为Aza25mg/kg·d。Tet30mg/kg·d,测定用药1wk和2wk时大鼠血清谷丙转氨酶(ALT)、碱性磷酸酶(AKP)、总蛋白(TP)和白蛋白(Alb)等肝功能指标以及血清中丙二醛(MDA)、超氧化物歧化酶(SOD)和全血谷胱甘肽含量(GSH) ,并作病理观察。结果用药1wk及2wk后 ,Aza组大鼠血清ALT、AKP、MDA含量均显著升高 ,TP、Alb、SOD、GSH含量均显著降低 ;合用Tet组则上述变化不明显 ,与对照组比较无显著性差异。病理学检查发现合用Tet组病理改变较轻微。结论Tet对Aza致大鼠肝损伤有保护作用 ,推测此作用与其抗脂质过氧化物、增加内源性解毒物质有关。     

Pollen extracts reduce the hepatotoxicity of paracetamol in mice

Cernitins are preparations obtained from plant pollen which contain numerous compounds of potential biological significance. This work deals with the influence of cernitins upon acute paracetamol toxicity in mice. The survival rate and indices of hepatic injury: aminotransferase and alkaline phosphatase activities, bilirubin level in serum, glutathione and cytochrome P-450 content in liver, liver weight, histopathologic picture of the liver and presence of glycogen and lipids in stained liver sections, under different experimental protocols, were determined. It was found that cernitins are able to increase the survival rate of mice and reduce liver injury in acute paracetamol poisoning. Cernitins are more effective when administered after, rather than before, a dose of paracetamol. The possible mechanism through which cernitins may act is discussed.     

扑苯黄片中三组分的HPLC测定

用ＨＰＬＣ同时测定扑苯黄片中三组分的含量。采用Ｓｐｈｅｒｉｓｏｒｂ ＣＮ柱，操作简单，结果准确。对乙酰氨基酚、盐酸伪麻黄碱、盐酸苯海拉明的回收率分别为１００．３％、９９．８％、９９．５％，ＲＳＤ分别为０．２９％、０．５１％、０．４５％。