A prospective randomized study comparing fibrin sealant versus suture for conjunctival wound closure in orbital wall fracture surgery.

The purpose of this randomized prospective study was to compare the clinical outcomes of orbital wall fracture surgery involving transconjunctival wound closure with fibrin sealant to the outcomes achieved with a conventional suture method. All surgeries were performed using the same technique, except that the conjunctival closure was achieved using either a buried 6-0 Vicryl suture (n=10) or fibrin sealant (n=10). The time to conjunctival closure and time required for complete wound healing were investigated. Postoperative discomfort in the two groups was compared at day 1, day 3, week 1, and week 4. Postoperative subconjunctival haemorrhage and peri-orbital ecchymosis were observed. The mean conjunctival closure time was significantly shorter in the fibrin group than in the suture group. All conjunctival wounds healed by the end of the first week. On postoperative days 1 and 3, the discomfort scores were significantly lower in the fibrin group. Subconjunctival haemorrhage and peri-orbital ecchymosis were less frequent in the fibrin group. Fibrin sealant proved to be as effective as sutures for conjunctival wound closure. Fibrin sealant allows a more comfortable early postoperative course and may be an excellent alternative for conjunctival wound closure in orbital wall fracture surgery.

Clinical and radiological outcomes of transoral endoscope-assisted treatment of mandibular condylar fractures.

Fractures of the mandibular condyle are one of the most common craniofacial fractures. However, the diagnosis and treatment of these fractures is controversial because of the multiple surgical approaches available. The purposes of this study were to identify surgery-related technical tips for better outcomes and to evaluate the results as well as complications encountered during 7 years of endoscope use to supplement the limited intraoral approach in the treatment of mandibular condylar fractures. Between 2005 and 2012, 50 patients with condylar fractures underwent endoscope-assisted reduction surgery. Postoperative facial bone computed tomography and panoramic radiography demonstrated adequate reduction of the condylar fractures in all patients. No condylar resorption was detected, and most patients displayed a satisfactory functional and structural recovery. There was no facial nerve damage or transitory hypoesthesia, and there were no visible scars after the surgery. Transoral endoscope-assisted treatment is a challenging but reliable method with lower morbidity and a rapid recovery.

Role of thalamic nuclei in the modulation of Fos expression within the cerebral cortex during hypertonic saline-induced muscle nociception.

It has been proposed that thalamic mediodorsal (MD) and ventromedial (VM) nuclei form thalamic 'nociceptive discriminators' in discrimination of nociceptive afferents, and specifically govern endogenous descending facilitation and inhibition. The present study conducted in rats was to explore the role of thalamic MD and VM nuclei in modulation of cerebral neuronal activities by means of detection of spatiotemporal variations of Fos expression within the cerebral cortex. Following a unilateral intramuscular injection of 5.8% saline into the gastrocnemius muscle, Fos expression within the bilateral, different areas of the cerebral cortex except S2 was significantly increased (P<0.05). Particularly, the increases in Fos expression within the cingulate cortex and the insular cortex occurred at 0.5h, 4h and reached the peak level at 4h, 16h, respectively. Electrolytic lesion of the contralateral thalamic MD and VM nuclei significantly blocked the 5.8% saline intramuscularly induced increases in Fos expression within the bilateral cingulate and insular cortices, respectively. Additionally, the 5.8% saline-induced Fos expression in the cingulate cortex and the insular cortex were dose-dependently attenuated by microinjection of µ-opioid antagonist ß-funaltrexamine hydrochloride into the thalamic MD and VM nuclei. It is suggested that (1) the neural circuits of 'thalamic MD nucleus - cingulate cortex' and 'thalamic VM nucleus - insular cortex' form two distinct pathways in the endogenous control of nociception, (2) mirror or contralateral pain is hypothesized to be related to cross-talk of neuronal activities within the bilateral cerebral cortices modulated by µ-opioid receptors within the thalamic MD and VM nuclei.

Randomised controlled clinical trial for autologous fibroblast-hyaluronic acid complex in treating diabetic foot ulcers.

OBJECTIVE: Diabetic foot ulcers (DFUs) often pose a treatment problem. Bioengineered skin substitutes have been reported to result in accelerated diabetic wound healing. The purpose of this clinical trial was to evaluate the efficacy and safety of the autologous fibroblast-hyaluronic acid complex for treating DFUs. METHOD: A stratified, randomised, controlled, multicentre study was carried out. Patients with DFUs were allocated to either a treatment group with grafting of an autologous fibroblast-hyaluronic acid complex or a control group with non-adherent foam dressing. Except for application of the fibroblast complex, treatment of the study ulcers was identical for patients in both groups. The maximum follow-up period for each patient was 12 weeks. RESULTS: Complete ulcer healing was achieved in 84% (26/31 patients) of the treatment group and 34% (11/32 patients) of the control group (p<0.05). The times required for complete healing were 36.4 ± 17.6 and 48.4 ± 13.1 days in the treatment and control groups, respectively (p<0.05). No adverse events related to treatment occurred. CONCLUSION: These results indicate that autologous fibroblast-hyaluronic acid complex may offer a safe and effective treatment for DFUs.

Development status of the 18 GHz superconducting electron cyclotron resonance ion source at National Fusion Research Institute.

A new superconducting 18 GHz electron cyclotron resonance ion source is being developed at the National Fusion Research Institute in South Korea. This source will be dedicated for future application of highly charged ions in the area of matter interaction, diagnostic imaging, and probing. In this paper, we describe the status of the source development consisting of a double electrode biased disk, sputtering systems for metal ion production, diagnostic ports for the extraction region, a variable gap extraction-Einzel lens system, and a low energy beam transport system.

Waveguide slot-excited long racetrack electron cyclotron resonance plasma source for roll-to-roll (scanning) processing.

We present a SLot-excited ANtenna (SLAN) long racetrack ECR plasma source that is utilized for roll-to-roll plasma processing such as thin film encapsulation of large-area OLED (organic light emitting diode) panel or modification of fabric surfaces. This source is designed to be long, and to operate under high density uniform plasma with sub-milli-torr pressures. The above features are accomplished by a slot-excited long racetrack resonator with a toroidal geometry of magnetic field ECR configuration, and reinforced microwave electric distributions along the central region of plasma chamber. Also, a new feature has been added to the source. This is to employ a tail plunger, which allows the microwave electric field and the uniformity of the plasma profile to be easily adjustable. We have successfully generated Ar plasmas operating with the microwave power of 0.5-3 kW in the pressure range of 0.2-10 mTorr. The plasma is uniform (<10%) in the direction of the straight track and has a Gaussian profile in the roll-to-roll (scanning) direction. In addition, it is shown that the tail plunger could adjust the plasma profile in order to obtain plasma uniformity. Furthermore, based on the results, we suggest a newly designed up-scaled racetrack-SLAN source.

Specific thalamic nuclei function as novel 'nociceptive discriminators' in the endogenous control of nociception in rats.

Recently, we hypothesized that supraspinal structures may have important functions in discriminating between noxious mechanically and heat mediated nociception through distinct functions: facilitation and inhibition. In this study, conducted in conscious rats, we explored the role of different thalamic nuclei: the mediodorsal (MD) nucleus, the central medial (CM) nucleus, the submedius (SM) nucleus, the ventralmedial (VM) nucleus and the ventral posterolateral (VPL) nucleus, in the descending control of secondary and contralateral mechanical hyperalgesia and heat hypoalgesia occurring in intramuscularly hypertonic (HT, 5.8%) saline-induced muscle nociception. We found that the MD nuclei participated in the descending facilitation of mechanical hyperalgesia, and that the VM nuclei were specifically involved in the descending inhibition of heat hypoalgesia. Neither descending facilitation nor descending inhibition was affected after electrolytic lesion of the thalamic CM, SM, and VPL nuclei. This descending facilitatory and inhibitory modulation of nociception was strengthened by glutamate, and weakened by GABA, microinjected into the thalamic MD and VM nuclei. It is suggested that (1) thalamic MD nucleus and VM nucleus form two distinct endogenous systems in the control of noxious mechanically and heat evoked responses, and (2) the strengthening of descending inhibition and the weakening of descending facilitation by means of up regulation and down regulation of appropriate receptor expression in the VM and MD nuclei may provide a new strategic policy in treating pathological pain.

The critical role of catalase in prooxidant and antioxidant function of p53.

The tumor suppressor p53 is an important regulator of intracellular reactive oxygen species (ROS) levels, although downstream mediators of p53 remain to be elucidated. Here, we show that p53 and its downstream targets, p53-inducible ribonucleotide reductase (p53R2) and p53-inducible gene 3 (PIG3), physically and functionally interact with catalase for efficient regulation of intracellular ROS, depending on stress intensity. Under physiological conditions, the antioxidant functions of p53 are mediated by p53R2, which maintains increased catalase activity and thereby protects against endogenous ROS. After genotoxic stress, high levels of p53 and PIG3 cooperate to inhibit catalase activity, leading to a shift in the oxidant/antioxidant balance toward an oxidative status, which could augment apoptotic cell death. These results highlight the essential role of catalase in p53-mediated ROS regulation and suggest that the p53/p53R2-catalase and p53/PIG3-catalase pathways are critically involved in intracellular ROS regulation under physiological conditions and during the response to DNA damage, respectively.

Dynamic variations of c-Fos expression in the spinal cord exposed to intramuscular hypertonic saline-induced muscle nociception.

BACKGROUND: Numerous studies focus on intramuscular (i.m.) injection of hypertonic saline-induced muscle pain and nociception. The spatio-temporal characteristics and dynamic variation of spinal neuronal activities elicited by i.m. hypertonic saline remain unknown. METHODS: The spatio-temporal variations of c-Fos expression in the lumbar spinal cord exposed to i.m. injection of 5.8% saline were investigated in male rats. RESULTS: After a unilateral i.m. 5.8% saline injection, c-Fos expression in dorsal horn of spinal L4-6 segments was significantly enhanced bilaterally (p < 0.05 and p < 0.001). These 5.8% saline-induced bilateral spinal Fos expression occurred rapidly 0.5 h following the i.m. injection, and reached the peak levels within 1 h, which declined gradually and returned to the control levels within 8 h. Compared with intact rats without i.m. insults, no significant influence of the spinalization on spinal c-Fos expression was found. However, the 5.8% saline-induced increases in Fos expression in intact and spinalized rats differed significantly. During muscle nociception, the c-Fos expression within the superficial layer (laminae I-II) and the deep layer (laminae V-VI) in spinalized rats were significantly lower and higher than that of in intact rats (p < 0.05 and p < 0.001). Fentanyl (20 µg/kg, intraperitoneal) completely attenuated the 5.8% saline intramuscularly induced increases in c-Fos expression in laminae III-VI (p < 0.001), but not laminae I-II. CONCLUSIONS: It is suggested that spinal nociceptive neuronal activities in superficial and deep layers may differently be modulated by endogenous descending facilitation and inhibition, respectively.

Design and fabrication of a superconducting magnet for an 18 GHz electron cyclotron resonance ion∕photon source NFRI-ECRIPS.

A superconducting magnet was designed and fabricated for an 18 GHz ECR ion∕photon source, which will be installed at National Fusion Research Institute (NFRI) in South Korea. The magnetic system consists of a set of four superconducting coils for axial mirror field and 36 pieces of permanent magnets for hexapolar field. The superconducting coils with a cryocooler (1.5 W @ 4.2 K) allow one to reach peak mirror fields of 2.2 T in the injection and those of 1.5 T in the extraction regions on the source axis, and the resultant hexapolar field gives 1.35 T on the plasma chamber wall. The unbalanced magnetic force between the coils and surrounding yoke has been minimized to 16 ton by a coil arrangement and their electrical connection, and then was successfully suspended by 12 strong thermal insulating supports made of large numbers of carbon fibers. In order to block radiative thermal losses, multilayer thermal insulations are covered on the coil windings as well as 40-K aluminum thermal shield. Also new schemes of quench detection and safety system (coil divisions, quench detection coils, and heaters) were employed. For impregnation of the windings a special epoxy has been selected and treated to have a higher breaking strength and a higher thermal conductivity, which enables the superconductors to be uniformly and rapidly cooled down or heated during a quench.

Inclined slot-excited annular electron cyclotron resonance plasma source for hyperthermal neutral beam generation.

An inclined slot-excited antenna (ISLAN) electron cyclotron resonance (ECR) plasma source is newly designed and constructed for higher flux hyperthermal neutral beam (HNB) generation. The developed ISLAN source is modified from vertical slot-excited antenna (VSLAN) source in two aspects: one is the use of inclined slots instead of vertical slots, and the other is a cusp magnetic field configuration rather than a toroidal configuration. Such modifications allow us to have more uniform arrangement of slots and magnets, then enabling plasma generation more uniform and thinner. Moreover, ECR plasma allows higher ionization rate, enabling plasma density higher even in submillitorr pressures, therefore decreasing the collision rate and∕or the reionization rate of the reflected atoms while passing through the plasma, and eventually getting higher flux of HNBs. In this paper, we report the design features and the plasma characteristics of the ISLAN source by doing plasma measurements and electromagnetic simulations. It was found that ISLAN source can be a high potential source for larger flux HNB generation; the source was found to give higher plasma densities and better uniformities than inductively coupled plasma source, particularly in low pressure ranges. Also, it is important that using ISLAN gives easier matching and better stability, i.e., ISLAN shows similar field patterns and good plasma symmetries irrespective of the variations of the mean diameter of the ring resonator and∕or the presence of a limiter or a reflector, and the operating pressures.

The p53-inducible gene 3 (PIG3) contributes to early cellular response to DNA damage.

The p53-inducible gene 3 (PIG3) is originally isolated as a p53 downstream target gene, but its function remains unknown. Here, we report a role of PIG3 in the activation of DNA damage checkpoints, after UV irradiation or radiomimetic drug neocarzinostatin (NCS). We show that depletion of endogenous PIG3 sensitizes cells to DNA damage agents, and impaired DNA repair. PIG3 depletion also allows for UV- and NCS-resistant DNA synthesis and permits cells to progress into mitosis, indicating that PIG3 knockdown can suppress intra-S phase and G2/M checkpoints. PIG3-depleted cells show reduced Chk1 and Chk2 phosphorylation after DNA damage, which may directly contribute to checkpoint bypass. PIG3 exhibited diffuse nuclear staining in the majority of untreated cells and forms discrete nuclear foci in response to DNA damage. PIG3 colocalizes with gamma-H2AX and 53BP1 to sites of DNA damage after DNA damage, and binds to a gamma-H2AX. Notably, PIG3 depletion decreases the efficient induction and maintenance of H2AX phosphorylation after DNA damage. Moreover, PIG3 contributes to the recruitment of 53BP1, Mre11, Rad50 and Nbs1 to the sites of DNA break lesions in response to DNA damage. Our combined results suggest that PIG3 is a critical component of the DNA damage response pathway and has a direct role in the transmission of the DNA damage signal from damaged DNA to the intra-S and G2/M checkpoint machinery in human cells.

Selective inhibitory effects of pregabalin on peripheral C but not A-delta fibers mediated nociception in intact and spinalized rats.

Effects of pregabalin (PGB, 20-80 mg/kg i.v. injection) on spinally-organized nociception were investigated in isoflurane-anesthetized intact and spinalized rats. Responses of single deep spinal dorsal horn (DH) (laminae IV-V) nociceptive-specific (NS) neurons receiving peripheral inputs from A-delta and C fibers to repetitive electrical stimulation (intensity: 3-5 mA; frequency: 1 Hz; pulse duration: 1 ms), mechanical/heat stimulation were recorded extracellularly during physiological condition and s.c. bee venom (BV) induced inflammation. PGB significantly inhibited C-fiber mediated spinal NS neurons' late responses including phenomena of wind-up (temporal summation) and after-discharge. However, the antinociceptive effects of PGB on nociception were not observed until 30 min after its administration. In contrast, no significant inhibitory effect of PGB on A-delta fiber mediated early responses was observed during the experiments. Compared with intact rats, the inhibitory effects of PGB upon nociception vanished in the spinalized animals. This suggests that PGB-induced selective antinociceptive effect on C-fiber mediated nociception is mainly central effects involving supraspinal centers via descending inhibitory controls. Furthermore, pre-treatment, but not post-treatment, with PGB (80 mg/kg) markedly inhibited s.c. BV elicited spontaneous neuronal responses, and noxious mechanical/heat stimuli evoked hyperactivities of spinal NS neurons, indicating that PGB has efficacy of pre-emptive analgesia on pathological pain associated with central sensitization.

Ribonucleotide reductase small subunit p53R2 suppresses MEK-ERK activity by binding to ERK kinase 2.

The p53-dependent RR small subunit (p53R2) protein, a newly identified member of the ribonucleotide reductase family, plays a key role in the p53-dependent cellular response to DNA. Several recent studies have suggested that p53R2 also plays an important role in suppressing the invasive potential of human cancer cells. However, the cellular mechanism that regulates invasiveness remains largely unknown. In this study, we show that p53R2 interacts with MEK2 (extracellular signal-regulated kinase (ERK) kinase 2-mitogen-activated protein kinase (MAPK) kinase 2), the molecule immediately upstream of ERK in the Ras-Raf-MAPK signaling cascade. In co-immunoprecipitation and immunofluorescence analyses, we found that p53R2 and MEK2 interact physically in cultured mammalian cells, and that the p53R2 segment comprising amino acids 161-206 is critical for this interaction. Moreover, serum-induced phosphorylation of MEK1/2 and ERK1/2 was greatly augmented in human cancer cells expressing small-interfering RNA against p53R2. On the other hand, phosphorylation of MEK1/2 and ERK1/2 in human cancer cells was markedly attenuated by overexpression of p53R2. Furthermore, MEK2 was required for p53R2 knockdown-induced enhancement of the invasive ability and anchorage-independent growth of human lung cancer H1299 cells. Taken together, these findings show that p53R2 negatively modulates serum-induced MEK-ERK activity and inhibits the MEK-ERK-mediated malignancy potential of human cancer cells.

Deduction of edge electron density with multiply charged ions in ORNL volume-type electron cyclotron resonance ion source.

The electron densities in the argon plasmas of the ORNL 6 GHz electron cyclotron resonance (ECR) ion source with a flat central magnetic field have been deduced from the ion branches of the electric probe current-voltage curves measured in the edge region of the plasmas. To overcome the difficulties due to unknown velocities of multiply charged ions at the sheath edge, a modified generalized Bohm criterion for the ion sheath velocity is introduced and the mean velocity of all ionic charge states at the sheath edge is assumed to be equal to the sound velocity of the system of particles. The calculated electron densities and temperatures for different plasmas optimized for four charge state distributions are discussed.

Sex differences in the responses of spinal wide-dynamic range neurons to subcutaneous formalin and in the effects of different frequencies of conditioning electrical stimulation.

The purpose of this study was to investigate sex-related differences in nociception elicited by s.c. injection of different concentrations (1-5%) of formalin. S.c. formalin-induced biphasic (early and late phases) persistent nociception was assessed by extracellularly recording the spontaneous activities of single spinal dorsal horn wide-dynamic range neurons in anesthetized male and female rats. The nociceptive responses of the dorsal horn wide-dynamic range neurons following s.c. injection of 5%, but not 1% and 2.5%, formalin in female rats were significantly stronger than the responses obtained in male rats. However, these concentration-dependent differences with respect to different sexes existed only in the late, but not the early, phase of formalin-induced nociception in intact, not spinal rats. The 5% formalin-induced late phase nociception in male rats was significantly depressed by 15 min of repeated conditioning electrical stimulation at a frequency of 5 Hz as well as 50 Hz during and after the period of conditioning electrical stimulation (intensity: 1 mA; pulse duration: 1 ms). In contrast, the inhibitory effect of 50 Hz conditioning electrical stimulation on the 5% formalin-elicited late phase response in female rats was markedly greater in magnitude and longer in duration than that of 5 Hz conditioning electrical stimulation. No significant depressive effects of 5 Hz conditioning electrical stimulation on formalin-induced nociception were found in female rats, indicating that the distinct effects of conditioning electrical stimulation at different frequencies are different in animals of opposite sexes. In conclusion, s.c. administration of different concentrations of formalin shows a distinct sex-related difference in its late tonic nociception of spinal nociceptive sensory neurons. Sex differences in formalin-induced tonic nociception are stimulus intensity dependent and related to the modulation from the supraspinal regions. S.c. formalin-induced late phase nociception in female rats is only sensitive to depression at a frequency of 50 Hz, but not 5 Hz, of conditioning electrical stimulation. This suggests that the involvement of the central mechanisms in the antinociceptive effects of conditioning electrical stimulation may be different at various frequencies of stimulation.

Differential antinociceptive effects induced by a selective cyclooxygenase-2 inhibitor (SC-236) on dorsal horn neurons and spinal withdrawal reflexes in anesthetized spinal rats.

The aim of present study was to examine the effect of a selective cyclooxygenase-2 (COX-2) inhibitor SC-236 (4 mg/kg) on the simultaneous responsiveness of spinal wide-dynamic range (WDR) neurons and single motor units (SMUs) from gastrocnemius soleus muscles to mechanical stimuli (pressure and pinch) and repeated suprathreshold (1.5xT, the intensity threshold) electrical stimuli with different frequencies (3 Hz, 20 Hz) under normal conditions and bee venom (BV, 0.2 mg/50 microl)-induced inflammation and central sensitization. During normal conditions, the responses of SMUs, but not WDR neurons, to mechanical and repeated electrical stimuli (3 Hz, wind-up) were depressed by systemic administration of SC-236 as well as its vehicle (100% dimethyl sulfoxide (DMSO)). The after-discharges of both the WDR neurons and the simultaneously recorded SMUs after electrical stimuli with 20 Hz were markedly depressed only by SC-236, indicating that the mechanisms underlying the generation of the C-fiber mediated late responses and the after-discharges may be different. The enhanced responsiveness of both WDR neurons and SMUs to mechanical pressure stimuli (allodynia) and pinch stimuli (hyperalgesia) in the BV experiments was apparently depressed by SC-236, but not its vehicle. For electrical stimulation, the enhanced late responses and after-discharges, but not early responses, of both the WDR neurons and the simultaneously recorded SMUs were markedly depressed only by SC-236. This indicates that different central pharmacological mechanisms underlie the generation of these enhanced early, late responses, and after-discharges during BV-induced inflammation. The data suggest that the COX-2 inhibitor SC-236 apparently depress the activities of both spinal cord dorsal horn neuron and spinal withdrawal reflex during BV-induced sensitization, indicating that COX-2 plays an important role in the maintenance of central sensitization.

Ursolic acid enhances nitric oxide and tumor necrosis factor-alpha production via nuclear factor-kappaB activation in the resting macrophages.

Ursolic acid (UA), a pentacyclic triterpene acid, is reported to have anti-tumor activities; however, the mechanism underlying its anti-tumorigenic effects is poorly understood. To further determine the mechanism of UA, we investigated the effects of UA on the release of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), and on the level of inducible nitric oxide synthase (iNOS) and TNF-alpha gene expression in mouse resting macrophages. We found that UA elicited a dose-dependent increase in NO and TNF-alpha production, and the level of iNOS and TNF-alpha mRNA. Transient expression and electrophoretic mobility shift assays with nuclear factor-kappaB (NF-kappaB) binding sites revealed that the increased level of iNOS mRNA and TNF-alpha mRNA induced by UA were mediated by the NF-kappaB transcription factor complex. These results demonstrate that UA stimulates NO and TNF-alpha release and is able to upregulate iNOS and TNF-alpha expression through NF-kappaB transactivation in the resting macrophages.

Effects of 6-arylamino-5,8-quinolinediones and 6-chloro-7-arylamino-5,8-isoquinolinediones on NAD(P)H: quinone oxidoreductase (NQO1) activity and their cytotoxic potential.

Synthesized 6-arylamino-5,8-quinolinediones 4a-4j and 6-chloro-7-arylamino-5,8-isoquinolinediones 5a-5g were evaluated for effects on NAD(P)H: quinone oxidoreductase (NQO1) activity with the cytosolic fractions derived from cultured human lung cancer cells and their cytotoxicity in cultured several human solid cancer cell lines. The 5,8-quinolinediones 4 and 5,8-isoquinolinediones 5 affected the reduction potential by NQO1 activity and showed a potent cytotoxic activity against human cancer cell lines. The tested compounds 4a, 5c, 5f, and 5g were considered as more potent cytotoxic agents. The compounds 4d, 5b, 5c, 5e and 5g were comparable modulators of NQO1 activity.

Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice.

The protective effects of an aqueous extract from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK), on acetaminophen (APAP)-induced hepatotoxicities and the possible protective mechanisms involved were investigated in mice. Pretreatment with CK prior to the administration of APAP significantly prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. APAP-induced hepatotoxicity was also essentially prevented as evidenced by liver histopathology. Hepatic glutathione levels and glutathione-S-transferase activities were not affected by treatment with CK alone, but pretreatment with CK protected the APAP-induced depletion of hepatic glutathione levels. The effects of CK on cytochrome P450 (P450) 1A2 and 2E1, the major isozymes involved in APAP bioactivation, were investigated. In microsomal incubations, CK effectively inhibited P450 lA2-dependent methoxyresorufin O-deethylase activities and the P450 2E1-dependent p-nitrophenol and aniline hydroxylase. The results suggest that the protective effects of CK against the APAP-induced hepatotoxicity may, at least in part, be due to its ability to block P450-mediated APAP bioactivation.