Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria-caspase protease pathway.


BACKGROUND:Ketamine is widely used as an i.v. anaesthetic agent and as a drug of abuse. Hepatocytes contribute to the metabolism of endogenous and exogenous substances. This study evaluated the toxic effects of S-(+)-ketamine and possible mechanisms using human hepatoma HepG2 cells as the experimental model. METHODS:HepG2 cells were exposed to S-(+)-ketamine. Cell viability and the release of lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GPT) were measured to determine the toxicity of S-(+)-ketamine to HepG2 cells. Cell morphology, DNA fragmentation, and apoptotic cells were analysed to evaluate the mechanism of S-(+)-ketamine-induced cell death. Amounts of Bax, an apoptotic protein, and cytochrome c in the cytoplasm or mitochondria were quantified by immunoblotting. Cellular adenosine triphosphate levels were analysed using a bioluminescence assay. Caspases-3, -9, and -6 were measured fluorometrically. RESULTS:Exposure of HepG2 cells to S-(+)-ketamine increased the release of LDH and GPT, but decreased cell viability (all P<0.01). S-(+)-Ketamine time-dependently caused shrinkage of HepG2 cells. Exposure to S-(+)-ketamine led to significant DNA fragmentation and cell apoptosis (P=0.003 and 0.002). S-(+)-Ketamine increased translocation of Bax from the cytoplasm to mitochondria, but decreased the mitochondrial membrane potential and cellular adenosine triphosphate levels (all P<0.01). Sequentially, cytosolic cytochrome c levels and activities of caspases-9, -3, and -6 were augmented after S-(+)-ketamine administration (all P<0.001). Z-VEID-FMK, an inhibitor of caspase-6, alleviated the S-(+)-ketamine-induced augmentation of caspase-6 activity, DNA fragmentation, and cell apoptosis (all P<0.001). CONCLUSIONS:This study shows that S-(+)-ketamine can induce apoptotic insults to human HepG2 cells via a Bax-mitochondria-caspase protease pathway. Thus, we suggest that S-(+)-ketamine at a clinically relevant or an abused concentration may induce liver dysfunction possibly due to its toxicity to hepatocytes.


Br J Anaesth


Lee ST,Wu TT,Yu PY,Chen RM




Has Abstract


2009-01-01 00:00:00














  • Cardiovascular effects of 50% nitrous oxide in older adult patients anaesthetized with isoflurane or halothane.

    abstract::We have studied the cardiovascular effects of equipotent concentrations of halothane or isoflurane, with or without 50% nitrous oxide in oxygen, in 80 patients, aged 60 yr or more, during 20 min of stable equipotent anaesthesia. Non-invasive measurement techniques were used, with suprasternal Doppler ultrasonography f...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: McKinney MS,Fee JP

    更新日期:1998-02-01 00:00:00

  • Evaluation of postural stability after low-dose droperidol in outpatients undergoing gynaecological dilatation and curettage procedure.

    abstract:BACKGROUND:Low-dose droperidol is suggested to be cost-effective in preventing nausea and vomiting after ambulatory surgery. This clinical study evaluated patient postural stability using a computerized force platform after an i.v. dose of droperidol 0.625 mg in outpatients undergoing gynaecological dilatation and cure...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Song D,Chung F,Yogendran S,Wong J

    更新日期:2002-06-01 00:00:00

  • Comparison of midazolam and diazepam in doses of comparable potency during gastroscopy.

    abstract::The water soluble benzodiazepine midazolam was compared with diazepam, in doses of 0.07 mg kg-1 and 0.15 mg kg-1 respectively, administered i.v. to 100 patients undergoing gastroscopy. The degree of sedation, ease of endoscopy and recovery were comparable in the two groups. The effects of both drugs on arterial pressu...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Whitwam JG,Al-Khudhairi D,McCloy RF

    更新日期:1983-08-01 00:00:00

  • Gastric emptying in pregnancy.

    abstract::The rate of gastric emptying in pregnancy was measured indirectly using the rate of paracetamol absorption in four groups of 15 patients: non-pregnant controls, first trimester patients presenting for termination of pregnancy, second trimester patients presenting for prostaglandin termination of pregnancy, and patient...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Macfie AG,Magides AD,Richmond MN,Reilly CS

    更新日期:1991-07-01 00:00:00

  • Effect of diltiazem and dantrolene on the contractility of isolated malignant hyperpyrexia-susceptible porcine skeletal muscle.

    abstract::Diltiazem inhibited and antagonized the abnormal contractures induced by halothane, caffeine and potassium chloride in isolated skeletal muscle from pigs susceptible to malignant hyperpyrexia (MHS). Contractile responses to caffeine and electrical stimulation also were suppressed by diltiazem in control tissue. Simila...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Foster PS,Denborough MA

    更新日期:1989-05-01 00:00:00

  • Fentanyl and bupivacaine mixtures for extradural blockade.

    abstract::In a prospective double-blind study, single dose lumbar extradural blockade was instituted in 80 healthy male patients undergoing lower abdominal surgery. Patients were assigned randomly to one of four groups. Each group received treatment with 0.5% bupivacaine 20 ml containing adrenaline 1:200 000. To this solution w...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Rucci FS,Cardamone M,Migliori P

    更新日期:1985-03-01 00:00:00

  • Gastric and lower oesophageal sphincter (LOS) pressures in early pregnancy.

    abstract::Gastric (GP) and lower oesophageal sphincter pressures (LOSP) were measured in non-pregnant female volunteers (group I) and pregnant women with (group III) or without (group II) heartburn. Patients in early pregnancy had greater gastric pressures than group I. Mean barrier pressure (LOSP-GP) was significantly decrease...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Brock-Utne JG,Dow TG,Dimopoulos GE,Welman S,Downing JW,Moshal MG

    更新日期:1981-04-01 00:00:00

  • One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung: an experimental study.

    abstract:BACKGROUND:One-lung ventilation (OLV) increases mechanical stress in the lung and affects ventilation and perfusion (V, Q). There are no data on the effects of OLV on postoperative V/Q matching. Thus, this controlled study evaluates the influence of OLV on V/Q distribution in a pig model using a gamma camera technique ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Kozian A,Schilling T,Fredén F,Maripuu E,Röcken C,Strang C,Hachenberg T,Hedenstierna G

    更新日期:2008-04-01 00:00:00

  • Studies of the neuromuscular blocking effects of BW 403C65 in frog and cat muscle.

    abstract::BW 403C65, an isoquinolinium bisquaternary compound, was investigated for its neuromuscular blocking properties. In vitro in from preparations, low concentrations induced an increase in miniature endplate potentials (m.e.p.p.) frequency without altering their amplitude. With increasing concentrations m.e.p.p. frequenc...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Post EL,Sokoll MD,Gergis SD,Dretchen KL,Cronnelly R

    更新日期:1975-09-01 00:00:00

  • Histaminoid reactions associated with rocuronium.

    abstract::We describe three histaminoid reactions occurring on induction of anaesthesia. The patients were all resuscitated successfully and subsequent skin testing suggested sensitivity to rocuronium. In this hospital, the incidence of such reactions is of the order of 1 in 3000. This may be coincidental but suggests that ther...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Neal SM,Manthri PR,Gadiyar V,Wildsmith JA

    更新日期:2000-01-01 00:00:00

  • Differential B and C fibre block by an amide- and an ester-linked local anaesthetic.

    abstract::The relative sensitivity of sympathetic preganglionic and postganglionic axons, B and C fibres, respectively, to two structurally dissimilar local anaesthetics was examined. The concentration of amethocaine (ester-linked tertiary amine) or prilocaine (amide-linked secondary amine) required to reduce the B fibre compou...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Scurlock JE,Heavner JE,de Jong RH

    更新日期:1975-11-01 00:00:00

  • Comparison of intubating laryngeal mask airway and Bullard laryngoscope for oro-tracheal intubation in adult patients with simulated limitation of cervical movements.

    abstract:BACKGROUND:Intubation of a patient with limited cervical spine movement or in whom movement of the cervical spine is not desirable is always a challenge even to the most experienced anaesthesiologist. The intubating laryngeal mask airway (ILMA) and the Bullard laryngoscope (BL) are two instruments recommended for endot...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,随机对照试验


    authors: Nileshwar A,Thudamaladinne A

    更新日期:2007-08-01 00:00:00

  • Comparison between pressures measured from the proximal external jugular vein and a central vein.

    abstract::Mean venous pressures were measured in 20 patients in whom a catheter, inserted via the external jugular vein, failed to pass centrally. The catheter used had a rounded end and two side holes. Pressures were measured with the patient's head in three different positions. The pressures were compared with the central ven...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Shah MV,Swai EA,Latto IP

    更新日期:1986-12-01 00:00:00

  • Pharmacokinetics of Org NC45 (norcuron) in patients with and without renal failure.

    abstract::To determine the influence of renal failure on the pharmacokinetics and neuromuscular blockade of Org NC 45 (Norcuron), a new monoquaternary homologue of pancuronium, 13 patients under halothane and nitrous oxide anesthesia were studied. Org NC 45 was administered by 2-min infusion in doses of 0.28 mg kg-1 (normal ren...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Fahey MR,Morris RB,Miller RD,Nguyen TL,Upton RA

    更新日期:1981-10-01 00:00:00

  • Postoperative hypoxaemia: continuous extradural infusion of bupivacaine and morphine vs patient-controlled analgesia with intravenous morphine.

    abstract::We carried out a randomized prospective study in 60 patients who had undergone major abdominal surgery for cancer. For postoperative pain control, 30 patients received continuous extradural infusion of 0.125% bupivacaine 12.5 mg h-1 and morphine 0.25 mg h-1 (EXI group) and 30 received patient-controlled analgesia (PCA...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Motamed C,Spencer A,Farhat F,Bourgain JL,Lasser P,Jayr C

    更新日期:1998-06-01 00:00:00

  • Improvement in i.v. regional anaesthesia by re-exsanguination before surgery.

    abstract::A modification of an i.v. regional anaesthesia (IVRA) technique is described in which the arm is re-exsanguinated before surgery (re-IVRA). IVRA and re-IVRA were compared for quality of operative field, sensory and motor block, quality of analgesia and blood concentrations of prilocaine, lignocaine and mepivacaine in ...

    journal_title:British journal of anaesthesia

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Rawal N,Hallén J,Amilon A,Hellstrand P

    更新日期:1993-03-01 00:00:00

  • Thiopental to desflurane - an anaesthetic journey. Where are we going next?

    abstract::Development targets in anaesthetic pharmacology have evolved from minimizing harm caused by unwanted effects through an era in which rapid onset and offset of drug effect were prioritised. Today's anaesthetists have access to a library of effective drugs whose characteristics offer controllable hypnosis, analgesia and...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,评审


    authors: Sneyd JR

    更新日期:2017-12-01 00:00:00

  • Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study.

    abstract:BACKGROUND:The role of repeated prone positioning in intubated subjects with acute respiratory distress syndrome caused by COVID-19 remains unclear. METHODS:We conducted a retrospective observational cohort study of critically ill intubated patients with COVID-19 who were placed in the prone position between March 18,...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Weiss TT,Cerda F,Scott JB,Kaur R,Sungurlu S,Mirza SH,Alolaiwat AA,Kaur R,Augustynovich AE,Li J

    更新日期:2021-01-01 00:00:00

  • Randomized comparison of three transducer orientation approaches for ultrasound guided internal jugular venous cannulation.

    abstract:BACKGROUND:Ultrasound-guided internal jugular venous access increases the rate of successful cannulation and reduces the incidence of complications, compared with the landmark technique. Three transducer orientation approaches have been proposed for this procedure: short-axis (SAX), long-axis (LAX) and oblique-axis (OA...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,随机对照试验


    authors: Batllori M,Urra M,Uriarte E,Romero C,Pueyo J,López-Olaondo L,Cambra K,Ibáñez B

    更新日期:2016-03-01 00:00:00

  • Effect of atropine on the QT interval and T-wave amplitude in healthy volunteers.

    abstract::Prolongation of the QT interval of the ECG represents an imbalance in cardiac autonomic function and may predict cardiac arrhythmia. Vagal activity protects against prolongation of the QT interval which may be associated with flattening of the T-wave of the ECG. The changes in QT interval, T-wave amplitude and respira...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Annila P,Yli-Hankala A,Lindgren L

    更新日期:1993-11-01 00:00:00

  • Effects of inhalation anaesthetics on the release of acetylcholine in the rat cerebral cortex in vivo.

    abstract::By analysing the EEG, reticular multi-unit activity and behavioural changes, we have classified general anaesthetics into three groups: central nervous system (CNS) depressant, CNS excitant and epileptogenic agents. Changes in CNS neural activity are associated with alteration in transmitter release. We have attempted...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Shichino T,Murakawa M,Adachi T,Arai T,Miyazaki Y,Mori K

    更新日期:1998-03-01 00:00:00

  • Transoesophageal echocardiographic monitoring of pulmonary venous obstruction induced by sternotomy closure during infant heart transplantation.

    abstract::A case of an infant receiving orthotopic heart transplantation with over-sized donor heart was reported. Left lower pulmonary venous obstruction after sternotomy closure was detected by transoesophageal echocardiography (TOE) and the decision to delay sternal closure was made and the clinical outcome was very satisfac...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Lin CP,Chan KC,Chou YM,Wang MJ,Tsai SK

    更新日期:2002-04-01 00:00:00

  • Rapid pressure compensation by automated cuff pressure controllers worsens sealing in tracheal tubes.

    abstract:BACKGROUND:Cyclic redistribution of air within the cuff during respiratory pressure changes creates a self-sealing mechanism which allows tracheal sealing, despite tracheal airway pressure being above baseline cuff inflation pressure. The aim of the present study was to investigate the effect of continuous automated cu...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Weiss M,Doell C,Koepfer N,Madjdpour C,Woitzek K,Bernet V

    更新日期:2009-02-01 00:00:00

  • Lumbar extradural injection pressures in pregnant women. An investigation of relationships between rate of infection, injection pressures and extent of analgesia.

    abstract::Before the induction of labour in 34 pregnant women 1.5% lignocaine 10 ml was injected into the lumbar extradural space at constant rates between 0.143 and 0.333 ml s-1. Injection pressures and residual pressures were recorded and the extent of analgesia to pinprick was assessed. No significant correlation was found b...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Husemeyer RP,White DC

    更新日期:1980-01-01 00:00:00

  • Changes in cortical electrical activity during induction of anaesthesia with thiopental/fentanyl and tracheal intubation: a quantitative electroencephalographic analysis.

    abstract:BACKGROUND:There are regional differences in the effects of anaesthetics agents and perioperative stimuli on the EEG. We studied the topography of the EEG during induction of anaesthesia and intubation in patients receiving thiopental and fentanyl to document regional electrical brain activity. METHODS:EEG was recorde...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Rundshagen I,Schröder T,Prichep LS,John ER,Kox WJ

    更新日期:2004-01-01 00:00:00

  • Reduced cerebral embolic signals in beating heart coronary surgery detected by transcranial Doppler ultrasound.

    abstract::Cerebral emboli detected by transcranial Doppler imaging were recorded in 20 patients undergoing multiple-vessel coronary artery bypass surgery, either with or without cardiopulmonary bypass, in a prospective unblinded comparative study. Emboli were recorded continuously from the time of pericardial incision until 10 ...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Watters MP,Cohen AM,Monk CR,Angelini GD,Ryder IG

    更新日期:2000-05-01 00:00:00

  • Nociceptin/orphanin FQ in inflammation and sepsis.

    abstract::Nociceptin/orphanin FQ, N/OFQ, and its receptor NOP represent a non-opioid branch of the opioid superfamily that were first studied for their effects on pain responses. Both N/OFQ and NOP are involved in a wide range of 'non-pain' responses including immunomodulation and cardiovascular control. There is now growing in...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章,评审


    authors: Serrano-Gomez A,Thompson JP,Lambert DG

    更新日期:2011-01-01 00:00:00

  • Changes in intragastric pressure on induction of anaesthesia.

    abstract::Intragastric pressure was measured in 20 patients before, and immediately after, the induction of anaesthesia with thiopentone. Intragastric pressure decreased in patients whose weights were the same as or less than expected, and increased in five of seven patients whose weights were greater than expected (P = 0.0013)...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Drummond GB,Park GR

    更新日期:1984-08-01 00:00:00

  • Cardiovascular and neuromuscular effects of dimethyl tubocurarine in anaesthetized cats and rhesus monkeys.

    abstract::Intravenous dose-response relationships for dimethyl tubocurarine showed that vagal blockade only became appreciable (50-83%) at doses 8-16 times those sufficient for full neuromuscular paralysis in anaesthetized cats (0.0625 mg/kg) and rhesus monkeys (0.125 mg/kg); heart rate was unchanged. Sympathetic function was u...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Hughes R,Chapple DJ

    更新日期:1976-09-01 00:00:00

  • Paroxysmal electroencephalographic discharges during enflurane anaesthesia in patients with a history of cerebral convulsions.

    abstract::The electroencephalogram (EEG) was monitored through all phases of enflurane anaesthesia in dental outpatients with a history of cerebral convulsions which had been well controlled with anticonvulsant drugs. Abnormal EEG activity which differed from the background activity was observed in three patients. Their case re...

    journal_title:British journal of anaesthesia

    pub_type: 杂志文章


    authors: Yamashiro M,Sumitomo M,Furuya H

    更新日期:1985-10-01 00:00:00