Biomedical subjects

S G Kim

Publications and source records attributed to S G Kim.

At least 37 records · Page 2Linked to original sources

PubMed2004

Simultaneous occurrence of an odontogenic keratocyst and giant cell granuloma-like lesion in the mandible.

An odontogenic keratocyst (OKC) and a giant cell granuloma (GCG) in the jaws are well-known entities, which have been reviewed extensively. However, there is no report in the literature of the simultaneous occurrence of these two lesions. A case of OKC in the mandible displaying foci of a GCG-like lesion is described. It is unclear whether the two lesions were just coincidental or were actually related to each other.

Child↗

PubMed2004

Incidence and risk factors of renal dysfunction after liver transplantation in Korea.

Renal dysfunction, one of the most common complications after liver transplantation, influences patient outcomes. Little is known, however, about it in Korea. The aims of this study were to determine the incidence and to identify the risk factors for renal dysfunction after liver transplantation. Sixty-two patients who survived over 6 months after transplantation were enrolled. Renal function was classified by creatinine clearance (Ccr, mL/min), which was estimated using the Cockcroft-Gault formula. Twenty-seven patients (44%) showed mild renal dysfunction (60 < or = Ccr < 90), and 27 patients (44%), moderate dysfunction (30 < or = Ccr < 60). The others were found to have normal function (Ccr > or = 90). None displayed severe dysfunction (Ccr < 30). Compared to a control group (Ccr > or = 60), the renal dysfunction group showed lower preoperative Ccr (91 +/- 28.6, 63 +/- 21.9, respectively, P < .01) and lower Ccr at 3 months after transplantation (72 +/- 17.1, 49 +/- 14.6, respectively, P < .05). Age, sex, immunosuppressive drug usage, serum tacrolimus levels, and the frequency of postoperative acute renal failure did not affect the postoperative renal dysfunction. Twenty-six patients received mycophenolate mofetil while reducing the dose of calcineurin inhibitors because of compromised renal function. With mycophenolate mofetil treatment, the renal function seemed to improve, although the difference was not statistically significant (P = .057). These data demonstrate that renal dysfunction is common after liver transplantation and that preoperative renal function is the important factor predicting postoperative renal dysfunction.

Adolescent↗

PubMed2004

Serum adiponectin concentrations predict the developments of type 2 diabetes and the metabolic syndrome in elderly Koreans.

OBJECTIVE: To determine whether low serum adiponectin concentrations are able to predict the future developments of type 2 diabetes and the metabolic syndrome using the National Cholesterol Education Programme (NCEP) criteria. We also investigated the stability of adiponectin levels and the relationships between baseline adiponectin levels and changes in the parameters related to the metabolic syndrome over a period of 3 years. PATIENTS AND MEASUREMENTS: This prospective cohort study included 372 elderly Koreans who participate in the SWS (South-West Seoul) study, which was conducted in 1999 and 2002 in Seoul, Korea. Fasting and postchallenge 2-h plasma glucose, body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid profiles and serum adiponectin data obtained in 1999 and 2002 were examined. RESULTS: The within-person variation between 1999 and 2002 of serum adiponectin was not significant (P = 0.61). Serum adiponectin was closely correlated with the risks factors of cardiovascular disease (CVD), that is negatively with BMI, WHR, blood pressure, triglyceride and blood glucose levels, and positively with high density lipoprotein (HDL)-cholesterol levels. Subjects with the metabolic syndrome showed lower serum adiponectin concentrations than those without the metabolic syndrome (P < 0.0001). Baseline adiponectin levels were found to be correlated with subsequent changes in WHR, low density lipoprotein (LDL)-cholesterol, fasting and postload 2-h glucose over the 3-year period, after adjusting for baseline values. Multiple logistic regression analysis showed that lower baseline serum adiponectin concentrations were significantly associated with the developments of type 2 diabetes and the metabolic syndrome after adjusting for age, sex, obesity, history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), hypertension and dyslipidaemia. CONCLUSIONS: Reduced concentrations of adiponectin were found to be independently associated with increased risk of both type 2 diabetes and the metabolic syndrome in elderly Koreans.

Adiponectin↗

PubMed2004

Plasma and urinary vascular endothelial growth factor and diabetic nephropathy in Type 2 diabetes mellitus.

AIMS: Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of diabetes mellitus. We determined whether alterations of plasma and urinary VEGF levels are related to diabetic nephropathy in Type 2 diabetic patients. METHODS: One hundred and seven patients and 47 healthy controls were studied. Study subjects were divided into four groups using urinary albumin-to-creatinine ratio (ACR): a non-diabetic healthy control group (n = 47), a normoalbuminuric diabetic group (n = 37), a microalbuminuric diabetic group (n = 37) and an overt proteinuric diabetic group (n = 33). VEGF levels were measured by enzyme-linked immunosorbent assay. RESULTS: (i) Urinary VEGF concentrations were significantly higher in the diabetic groups, even at the normoalbuminuric stage (log VEGF/Cr, normoalbuminuria; 4.33 +/- 1.06 vs. control; 3.53 +/- 0.79, P = 0.009). Urinary VEGF excretions increased as diabetic nephropathy advanced. (ii) Plasma and urinary VEGF levels were higher in hypertensive diabetic patients than in the normotensive individuals with diabetes. (iii) In those with diabetes, plasma VEGF levels were found to be positively correlated with plasma urea (r = 0.398, P = 0.039) and urinary ACR (r = 0.251, P = 0.044), and urinary VEGF to be positively correlated with urinary ACR (r = 0.645, P < 0.001), and creatinine (r = 0.336, P = 0.009), and to be negatively correlated with serum albumin (r = -0.557, P < 0.001). Urinary VEGF and serum creatinine were independently correlated with urinary ACR. CONCLUSIONS: Urinary excretion of VEGF increased during the earlier stage of diabetic nephropathy and was significantly correlated with urinary albumin excretion. This suggests that urinary VEGF might be used as a sensitive marker of diabetic nephropathy and for predicting disease progression.

Albuminuria↗

PubMed2004

The associations between plasma adiponectin, ghrelin levels and cardiovascular risk factors.

OBJECTIVE: Ghrelin is a recently discovered peptide, which is produced primarily in the stomach. This orexigenic peptide participates not only in the induction of mealtime hunger but also in long-term body weight regulation and energy homeostasis. Adiponectin is a protein secreted by adipocytes, and has been proposed to mediate obesity-related insulin resistance. Moreover, concentrations of adiponectin are reduced in individuals with obesity, insulin resistance and cardiovascular disease. However, human data are sparse about the direct relationship between adiponectin, ghrelin and cardiovascular risk factors including insulin resistance. DESIGN: Three hundred and thirty-eight elderly Korean women (mean age+/-s.d., 72.3+/-5.5 years) were included in the present study. METHODS: Plasma ghrelin and adiponectin levels were measured by RIA. Anthropometric measurements were taken and a 75 g oral glucose tolerance test performed. Fasting insulin and lipid profile were measured and insulin resistance was determined using the homeostasis model assessment insulin resistance index (HOMA-R) and the quantitative insulin sensitivity check index. RESULTS: Plasma adiponectin levels were negatively correlated with central obesity indices such as waist circumference (r=-0.27, P<0.001) and waist-to-hip ratio (WHR) (r=-0.32, P<0.001), and with insulin resistance indices such as fasting insulin (r=-0.17, P=0.004) and HOMA-R (r=-0.13, P=0.035). Plasma ghrelin levels were negatively correlated with WHR (r=-0.12, P=0.03), but plasma adiponectin and ghrelin levels were not correlated (r=0.03, P=0.66). Multiple regression analysis showed that adiponectin was associated with WHR, fasting insulin and fasting glucose levels. When ghrelin was used as a dependent variable, only WHR remained in the final fitted model. CONCLUSION: Fasting plasma adiponectin and ghrelin levels were found to be associated with central obesity or insulin resistance. However, plasma adiponectin and ghrelin concentrations were not associated with each other in elderly Korean women.

Adiponectin↗

PubMed2004

KNT-artificial neural network model for flux prediction of ultrafiltration membrane producing drinking water.

This paper describes the prediction of flux behavior in an ultrafiltration (UF) membrane system using a Kalman neuro training (KNT) network model. The experimental data was obtained from operating a pilot plant of hollow fiber UF membrane with groundwater for 7 months. The network was trained using operating conditions such as inlet pressure, filtration duration, and feed water quality parameters including turbidity, temperature and UV254. Pre-processing of raw data allowed the normalized input data to be used in sigmoid activation functions. A neural network architecture was structured by modifying the number of hidden layers, neurons and learning iterations. The structure of KNT-neural network with 3 layers and 5 neurons allowed a good prediction of permeate flux by 0.997 of correlation coefficient during the learning phase. Also the validity of the designed model was evaluated with other experimental data not used during the training phase and nonlinear flux behavior was accurately estimated with 0.999 of correlation coefficient and a lower error of prediction in the testing phase. This good flux prediction can provide preliminary criteria in membrane design and set up the proper cleaning cycle in membrane operation. The KNT-artificial neural network is also expected to predict the variation of transmembrane pressure during filtration cycles and can be applied to automation and control of full scale treatment plants.

Automation↗

PubMed2003

Is a 9-month treatment sufficient in tuberculous enterocolitis? A prospective, randomized, single-centre study.

BACKGROUND: Tuberculosis has increased in parallel with the acquired immunodeficiency syndrome epidemic and the use of immunosuppressive therapy, and the growing incidence of extra-pulmonary tuberculosis, especially with intestinal involvement, reflects this trend. However, the duration of anti-tuberculous therapy has not been clarified in intestinal tuberculosis. AIM: To compare the efficacy of different treatment durations in tuberculous enterocolitis in terms of response and recurrence rates. METHODS: Forty patients with tuberculous enterocolitis were randomized prospectively: 22 patients into a 9-month and 18 into a 15-month group. Diagnosis was made either by colonoscopic findings of discrete ulcers and histopathological findings of caseating granuloma and/or acid-fast bacilli, or by clinical improvement after therapeutic trial. Patients were followed up with colonoscopy every other month until complete response or treatment completion, and then every 6 months for 1 year and annually. Complete response was defined as a resolution of symptoms and active tuberculosis by colonoscopy. RESULTS: Complete response was obtained in all patients in both groups. Two patients in the 9-month group and one in the 15-month group underwent operation due to intestinal obstruction and perianal fistula, respectively. No recurrence of active intestinal tuberculosis occurred during the follow-up period in either group. CONCLUSIONS: Tuberculous enterocolitis can be managed by 9-month chemotherapy without disease recurrence. Further investigations are needed in immunocompromised patients.

Adult↗

PubMed2003

Relation between insulin resistance and hematological parameters in elderly Koreans-Southwest Seoul (SWS) Study.

In this study, we investigated the relation between insulin resistance and hematological parameters in elderly Koreans. This study included 1314 non-diabetic subjects over the age of 60, selected from a cross-sectional study, which was conducted in 1999 in Seoul, Korea. We measured fasting and post-load 2 h plasma glucose, insulin levels, lipid profiles, anthropometric measures, and hematological parameters. The degree of insulin resistance was assessed using the homeostasis model assessment (HOMA). We found a correlation between insulin resistance and hemoglobin concentrations in non-smoking men (r=0.20, P=0.0186). In non-smoking women, insulin resistance correlated with hemoglobin (r=0.10, P=0.0017) and with white blood cell (WBC) count (r=0.15, P=0.001). Hemoglobin concentrations and WBC counts were also associated with other components of the insulin resistance syndrome such as body mass index, blood pressure, lipid profiles and fasting plasma insulin levels (surrogate for insulin resistance). Furthermore, the group in the upper quartile for insulin resistance showed higher hemoglobin concentrations and WBC counts than the lower quartile, independent of smoking status and serum iron concentrations. Using HOMA-IR as a dependent variable in a multiple regression analysis, age, body mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure, HDL cholesterol, triglyceride, WBC count, hemoglobin, hematocrit and serum TIBC were significant. Our results provide support for a relation between insulin resistance/hyperinsulinemia and hematological parameters such as hemoglobin concentrations and WBC counts in elderly Koreans. This suggests that increased erythropoiesis and subclinical inflammation could be part of the metabolic syndrome in elderly Koreans.

Aged↗

PubMed2002

Effect of Helicobacter pylori eradication on duodenal ulcer scar in patients with no clinical history of duodenal ulcer.

BACKGROUND: Helicobacter pylori eradication has become the standard treatment for duodenal ulcer. However, there is no relevant evidence for antibacterial treatment of the white scar stage of duodenal ulcer (duodenal ulcer scar) in patients with no past history of duodenal ulcer. AIM: To investigate whether H. pylori eradication could decrease duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer. PATIENTS AND METHODS: We prospectively enrolled 66 patients with duodenal ulcer scar: 53 were H. pylori-positive and 13 were H. pylori-negative. H. pylori-positive patients were randomly assigned into two groups (two-to-one allocation): 36 patients were assigned to the treatment group and 17 to the follow-up group. Thirteen H. pylori-negative patients were followed up according to the study protocol. Follow-up endoscopy was performed to evaluate ulcer scar changes and H. pylori status 6 weeks after anti-H. pylori treatment and then every 6 months for up to 30 months. RESULTS: Active duodenal ulcer recurrence was identified in seven of 23 H. pylori-positive/non-cured patients (30%). There was no duodenal ulcer recurrence in 43 H. pylori-negative/cured patients (0%), which was significantly different in terms of duodenal ulcer recurrence (P=0.001). CONCLUSIONS: H. pylori eradication is effective at preventing active duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer.

Amoxicillin↗

PubMed2001

Potentiation of cadmium-induced cytotoxicity by sulfur amino acid deprivation through activation of extracellular signal-regulated kinase1/2 (ERK1/2) in conjunction with p38 kinase or c-jun N-terminal kinase (JNK). Complete inhibition of the potentiated toxicity by U0126 an ERK1/2 and p38 kinase inhibitor.

The mechanisms of cadmium-induced toxicity may include oxidative stress, altered redox homeostasis, and injuries to organelles. The current study was designed to study the effect of decreased cellular glutathione (GSH) content by sulfur amino acid deprivation on cadmium toxicity and to identify the signaling pathways responsible for the cytotoxicity. GSH content was increased by cadmium in H4IIE cells prior to cell death, which was prevented by excess GSH or cysteine. Cell viability, however, was not improved by GSH or cysteine complexation of cadmium. Cadmium-induced cytotoxicity was 40-fold potentiated in cells with decreased GSH by sulfur amino acid deprivation. Cadmium in combination with decreased GSH markedly increased apoptotic cell death. Mitogen-activated protein kinases including extracellular signal-regulated kinase 1/2, p38 kinase and c-Jun N-terminal kinase (JNK) were all activated 1-12 hr after sulfur amino acid deprivation. U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), which inhibited activation of extracellular signal-regulated kinase1/2 and p38 kinase in cells under sulfur amino acid deprivation, completely prevented potentiation in Cd-induced cytotoxicity and apoptosis. Potentiation of cadmium toxicity by sulfur amino acid deprivation was prevented in part by either PD98059 or SB203580, or in cells stably expressing dominant negative mutant of JNK1, and to greater extents by PD98059 in combination with either SB203580 or JNK1(-) transfection. These results demonstrated that decreased cellular GSH content potentiated cytotoxicity induced by cadmium at the level of human exposure, and that the potentiation of cytotoxicity resulted from activation of extracellular signal-regulated kinase1/2 in conjunction with p38 kinase or JNK.

Amino Acids↗

PubMed2001

Effects of cysteine on the pharmacokinetics of intravenous phenytoin in rats with protein-calorie malnutrition.

The effects of cysteine on the pharmacokinetics of phenytoin and one of its metabolites, 5-(p-hydroxyphenyl)-5-phenylhydantoin (pHPPH) were investigated after intravenous administration of phenytoin, 25 mg/kg, to control rats (4-week fed on 23% casein diet) and rats with PCM (protein-calorie malnutrition, 4-week fed on 5% casein diet) and PCMC (PCM with oral cysteine supplementation, 250 mg/kg, twice daily starting from the fourth week). In rats with PCM and PCMC, the phenytoin hydroxylation (to form pHPPH) activities were significantly smaller (164, 103 and 95.3 pmol/min per mg protein for the control rats, and rats with PCM and PCMC, respectively) than that in control rats. In rats with PCMC, the intrinsic clearance of phenytoin, CL(int) was significantly slower than those in control rats and rats with PCM (0.175, 0.131 and 0.044 ml/min). The above data suggested that the formation of pHPPH could be reduced in rats with PCM and PCMC. This was supported by significantly smaller 24-h urinary excretion of pHPPH (54.7, 35.6 and 32.5% of intravenous dose of phenytoin) in rats with PCM and PCMC than that in control rats. In rats with PCM, the maximum velocity (0.344, 0.203 and 0.196 microg/min), apparent volume of distribution in central compartment (44.4, 65.4 and 72.2 ml/kg) of phenytoin, and total area under the plasma concentration-time curve from time zero to time infinity (609, 714 and 1210 microg min/ml), renal clearance (20.5, 13.4 and 4.67 ml/min per kg) and 24-h urinary excretion (54.7, 35.6 and 32.5% of intravenous dose of phenytoin) of pHPPH were not returned to control levels by cysteine supplementation (rats with PCMC). This could be mainly due to the fact that the phenytoin hydroxylation activity in rats with PCMC was not returned to control level.

Algorithms↗

PubMed2001

Localized cerebral blood flow response at submillimeter columnar resolution.

Functional magnetic resonance imaging (fMRI) has been widely used for imaging brain functions. However, the extent of the fMRI hemodynamic response around the active sites, at submillimeter resolution, remains poorly understood and controversial. With the use of perfusion-based fMRI, we evaluated the hemodynamic response in the cat visual cortex after orientation-specific stimuli. Activation maps obtained by using cerebral blood flow fMRI measurements were predominantly devoid of large draining vein contamination and reproducible at columnar resolution. Stimulus-specific cerebral blood flow responses were spatially localized to individual cortical columns, and columnar layouts were resolved. The periodic spacing of orientation columnar structures was estimated to be 1.1 +/- 0.2 mm (n = 14 orientations, five animals), consistent with previous findings. The estimated cerebral blood flow response at full width at half-maximum was 470 microm under single-stimulus conditions without differential subtraction. These results suggest that hemodynamic-based fMRI can indeed be used to map individual functional columns if large-vessel contributions can be minimized or eliminated.

Animals↗

PubMed2001

8-Cl-cAMP induces cell cycle-specific apoptosis in human cancer cells.

8-Cl-cyclic adenosine monophosphate (8-Cl-cAMP) has been known to induce growth inhibition and differentiation in a variety of cancer cells by differential modulation of protein kinase A isozymes. To understand the anticancer activity of 8-Cl-cAMP further, we investigated the effect of 8-Cl-cAMP on apoptosis in human cancer cells. Most of the tested human cancer cells exhibited apoptosis upon treatment with 8-Cl-cAMP, albeit with different sensitivity. Among them, SH-SY5Y neuroblastoma cells and HL60 leukemic cells showed the most extensive apoptosis. The effect of 8-Cl-cAMP was not reproduced by other cAMP analogues or cAMP-elevating agents, showing that the effect of 8-Cl-cAMP was not caused by simple activation of protein kinase A (PKA). However, competition experiments showed that the binding of 8-Cl-cAMP to the cAMP receptor was essential for the induction of apoptosis. After the treatment of 8-Cl-cAMP, cells initially accumulated at the S and G2/M phases of the cell cycle and then apoptosis began to occur among the population of cells at the S/G2/M cell cycle phases, indicating that the 8-Cl-cAMP-induced apoptosis is closely related to cell cycle control. In support of this assumption, 8-Cl-cAMP-induced apoptosis was blocked by concomitant treatment with mimosine, which blocks the cell cycle at early S phase. Interestingly, 8-Cl-cAMP did not induce apoptosis in primary cultured normal cells and non-transformed cell lines, showing that 8-Cl-cAMP-induced apoptosis is specific to transformed cells. Taken together, our results show that the induction of apoptosis is one of the mechanisms through which 8-Cl-cAMP exerts anticancer activity.

3T3 Cells↗

PubMed2001

Atomic-scale dynamics of the formation and dissolution of carbon clusters in SiO(2).

Oxidation of SiC produces SiO(2) while CO is released. A "reoxidation" step at lower temperatures is, however, necessary to produce high-quality SiO(2). This step is believed to cleanse the oxide of residual C without further oxidation of the SiC substrate. We report first-principles calculations that describe the nucleation and growth of O-deficient C clusters in SiO(2) under oxidation conditions, fed by the production of CO at the advancing interface, and their gradual dissolution by the supply of O under reoxidation conditions. We predict that both CO and CO(2) are released during both steps.

Journal Article↗

PubMed2001

Activation of phosphatidylinositol 3-kinase by oxidative stress leads to the induction of microsomal epoxide hydrolase in H4IIE cells.

We have shown that PI3-kinase played an essential role in the ARE-mediated rGSTA2 induction by oxidative stress following SAAD (Mol. Pharmacol. 58 (2000) 1017). Microsomal epoxide hydrolase (mEH), which detoxifies a variety of epoxide intermediates produced from various xenobiotics, is inducible by oxidative stress. In the present study, we studied whether sulfur amino acid deprivation (SAAD) activated phosphatidylinositol 3-kinase (PI3-kinase)/Akt and induced mEH in H4IIE cells. The role of PI3-kinase activation on the mEH induction by SAAD was also investigated. PI3-kinase was activated from 10 min through 12 h after SAAD, the activity of which returned to control level at 24 h. The activation of PI3-kinase led to increases in the activity of Akt at the same time points. Northern and Western blot analyses revealed that the mEH mRNA level was four-fold increased at 48 h, which accompanied the induction of mEH protein. Wortmannin or LY294002, PI3-kinase inhibitors, completely inhibited the increases in mEH mRNA and protein by SAAD. These results demonstrated that SAAD activated the PI3-kinase/Akt pathway at early stages and induced mEH, presumably as an adaptive response, and that the PI3-kinase/Akt pathway played a crucial role in the induction of mEH.

Amino Acids, Sulfur↗

PubMed2001

Effects of cysteine on the pharmacokinetics and pharmacodynamics of intravenous and oral azosemide in rats with protein-calorie malnutrition.

The effects of cysteine on the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous (10 mg/kg) and oral (20 mg/kg) administration to male Sprague-Dawley rats fed on 23% protein diet (control rats), and 5% protein diet with (rats with PCMC) or without (rats with PCM) oral cysteine (250 mg/kg, twice daily for the fourth week) for 4 weeks. After intravenous administration to rats with PCMC, some pharmacokinetic parameters restored fully or more than the level of control rats; the time-averaged nonrenal clearance (2.70 versus 2.32 ml/min/kg) and apparent volume of distribution at steady state (160 versus 189 ml/kg) were comparable to those in control rats, however, the terminal half-life (34.7 versus 57.2 min) and mean residence time (73.3 versus 99.3 min) were significantly shorter, area under the plasma concentration-time curve from time zero to time infinity (AUC, 1930 versus 2680 microg min/ml) was significantly smaller, and time-averaged renal (2.24 versus 1.21 ml/min/kg) and total body (CL, 4.98 versus 3.65 ml/min/kg) clearances were significantly faster than those in control rats. This could be mainly due to significantly faster renal clearance and at least partly due to increased cytochrome P450 1A2 activity by cysteine supplementation. After intravenous administration to rats with PCMC, the total amount of 8-hr urinary excretion of unchanged azosemide was significantly greater (457 versus 305 microg/g body weight), however, the 8-hr urine output (15.3 versus 31.1 ml/g kidney) was not significantly different between control rats and rats with PCMC. This could be due to the fact that urine output seemed to reach an upper plateau from 10 mg/kg dose of azosemide in rats.

Administration, Oral↗

PubMed2001

Potentiation of arsenic-induced cytotoxicity by sulfur amino acid deprivation (SAAD) through activation of ERK1/2, p38 kinase and JNK1: the distinct role of JNK1 in SAAD-potentiated mercury toxicity.

Sulfur amino acid deficiency occurs in certain pathophysiological situations (e.g. protein-calorie malnutrition). Previous studies revealed that sulfur amino acid deprivation (SAAD) activated MAP kinases and potentiated cadmium-induced cytotoxicity by activation of ERK1/2 in conjunction with p38 kinase or JNK. The present study was designed to determine susceptibility of cells to a variety of heavy metals in combination with SAAD. Viability was assessed in H4IIE cells treated with sodium arsenite, mercuric chloride, sodium selenite, lead acetate, chromium trioxide or manganese chloride. SAAD potentiated the cytotoxicity of H4IIE cells by arsenic or mercury (i.e. EC50, 19 and 5 microM in SAAD vs. 401 and 42 microM in control medium, respectively). TUNEL assays revealed that the potentiated arsenic or mercury toxicity involved apoptotic cell death. Lead or selenite moderately elicited cell death, which was not enhanced by SAAD. Chromium or manganese caused no significant cytotoxicity. Treatment of cells with U0126 [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene] an ERK1/2 inhibitor or SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole] a p38 kinase inhibitor effectively prevented SAAD-potentiated arsenic toxicity. The potentiated arsenic toxicity was also inhibited in cells stably expressing a dominant negative mutant of c-Jun N-terminal kinase 1 [JNK1(-)]. The inhibitors of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 kinase failed to prevent mercury-induced toxicity enhanced by SAAD. JNK1(-) cells were minimally susceptible to mercury in SAAD medium. These results demonstrated that SAAD potentiated cytotoxicity induced by arsenic or mercury and that activation of ERK1/2, p38 kinase and JNK1 was responsible for the potentiated arsenic toxicity, whereas the mercury toxicity enhanced by SAAD was mediated with the activity of JNK1.

Amino Acids, Sulfur↗

PubMed2001

Mitochondrial dysfunction by gamma-irradiation accompanies the induction of cytochrome P450 2E1 (CYP2E1) in rat liver.

Multiple biological effects are induced by ionizing radiation through dysfunction of cellular organelles, direct interaction with nucleic acids and production of free radical species. The expression of cytochrome P450s was assessed in the livers of 60Co gamma-irradiated rats. Three gray (G) of gamma-irradiation caused CYP2E1 induction with a 3.6-fold increase in the mRNA at 24 h, whereas the expression of CYP1A2 and CYP3A was not changed. Pharmacokinetics of chlorzoxazone, a specific substrate of CYP2E1, was studied in 3 G-irradiated rats. The area under the plasma concentration-time curve from time zero to infinity of 6-hydroxychlorzoxazone and the amount of 6-hydroxychlorzoxazone excreted in 8 h urine were both significantly greater than those in control rats. Hepatic CYP2E1 was not induced in rats exposed to 0.5-1 G of gamma-rays. Rats irradiated at 6-9 G accumulated doses of gamma-rays exhibited smaller increases in the mRNA due to liver injury than those irradiated at a single dose of 3 G gamma-rays. The plasma glucose and insulin levels were not altered in rats with 3 G of gamma-irradiation. As the exposure level of gamma-irradiation increased, the activity of hepatic aconitase, a key enzyme in energy metabolism in mitochondria, was 30-90% decreased. The amount of mitochondrial DNA per gram of wet liver was 50% decreased in rats exposed to 3 G of gamma-rays. These results demonstrated that gamma-ray irradiation at the exposure level inducing organelle dysfunction induced CYP2E1 in the liver, which might be associated with mitochondrial damage, but not with alterations in glucose or insulin levels.

Aconitate Hydratase↗