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K C Mun

Publications and source records attributed to K C Mun.

At least 19 recordsLinked to original sources
PubMed2006

Apoptosis by cyclosporine in mesangial cells.

INTRODUCTION: The immunosuppressive agent cyclosporine (CsA) is widely used to treat allograft rejection and various autoimmune disorders. A major limiting factor in the use of CsA is chronic nephrotoxicity. The pathogenesis of CsA-induced nephrotoxicity is not fully understood. Several recent studies have suggested that CsA treatment directly induces apoptosis in several cell types. The present study was undertaken to investigate the effects of CsA on apoptosis of cultured rat mesangial cells (RMCs). METHODS: RMCs were treated with CsA at concentrations of 0.1 to 40 mumol/L. Cell viability was determined by MTT assay. Apoptotic protein expression was determined by Western blot analysis. RESULTS: Cell viability was decreased with increasing concentrations of CsA in dose-dependent manner. CsA produced dose-dependent induction of p53, caspase-6, and Bax protein expression. CsA treatment caused proteolytic cleavage of caspase-3 and induced the degradation of 116-kDa PARP into 89-kDa fragment. RMCs with CsA reduced Bcl-2 and cIAP expression. CONCLUSIONS: In this study, CsA induced apoptosis by up-regulating proapoptotic factors, caspase-3 and -6, p53, Bax, cleaving PARP, and down-regulating antiapoptotic factor, Bcl-2, and cIAP. These results suggested that the increased cell apoptosis exerted by CsA may be one of the mechanisms promoting CsA-induced nephrotoxicity.

Animals↗
PubMed2006

Effect of tacrolimus on the production of oxygen free radicals in hepatic mitochondria.

OBJECTIVES: Cyclosporine (CsA) causes side effects that occur mainly in the kidney but also in the liver. Several reports have strongly suggested that the production of oxygen free radicals (OFRs) is a common mechanism of CsA toxicity. However, tacrolimus is believed to suppress the production of OFRs. METHODS: We obtained the mitochondrial fraction with 96% purity from rat liver using a sucrose density gradient solution. Zero to 100 micromol/L tacrolimus was incubated with the mitochondrial fraction for 6 hours at 37 degrees C. OFRs were evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2,7-dichlorefluorescein using a VICTOR3 multilabel counter. RESULTS: The fluorescence units for OFR production were increased as the time of exposure to tacrolimus passed from 1 to 6 hours. The fluorescence units in 0.1 micromol/L tacrolimus were 6.0 x 10(5) at 1 hour, 7.8 x 10(5) at 2 hours, 9.0 x 10(5) at 3 hours, 10.0 x 10(5) at 4 hours, 11.1 x 10(5) at 5 hours, and 11.4 x 10(5) at 6 hours. However, the fluorescence units were similar although the tacrolimus concentration increases from 0.1 to 100 micromol/L. CONCLUSIONS: The results in this experiment suggested that tacrolimus induced the production of OFRs depending on the exposure time.

Animals↗
PubMed2006

Effects of cyclosporine and tacrolimus on the oxidative stress in cultured mesangial cells.

OBJECTIVES: Cyclosporine (CsA) and tacrolimus (Tac) are two primary immunosuppressive agents used for the prevention of graft rejection. However, their use is associated with significant side effects, most notably nephrotoxicity. The mechanisms of this toxicity are not fully understood, but they seem to be associated with increases in the production of oxygen free radicals (OFRs). This present work examined the effect of CsA and Tac on the production of OFRs in cultured rat renal mesangial cells (RMCs). METHODS: Varying concentrations of CsA and Tac (0 to 40 micromol/L) were added to RMCs and incubated for 60 minutes at 37 degrees C. The production of OFRs was evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2', 7'-dichlorofluorescin. RESULTS: At 60 minutes, the relative fluorescence units (RFU) for OFRs production in RMCs exposure to CsA were increased by 2.5%, 11.5%, 22.5%, 57.2%, and 174% at 2.5, 5, 10, 20, and 40 micromol/L, respectively. Tac increased the RFU by 15.9%, 13.6%, 14.8%, 13.2%, 21.4%, 13.2%, and 28.1% at 0.1, 1, 2.5, 5, 10, 20, and 40 micromol/L, respectively. In RMCs, the RFU produced by CsA was higher than that by Tac. CONCLUSIONS: The results of this experiment suggest that CsA and Tac induced renal injury by OFRs.

Animals↗
PubMed2006

Polyphenol (-)-epigallocatechin gallate protection from ischemia/reperfusion-induced renal injury in normotensive and hypertensive rats.

INTRODUCTION: The effect of epigallocatechin gallate (EGCG) in an in vivo renal model of ischemia with reperfusion (I/R) was compared between normotensive (WKR) and hypertensive (SHR) rats. METHODS: WKR (groups I, II, III) and SHR groups (groups IV, V, VI) were divided into three types. Groups I and IV were sham-operated animals; groups II and V were subjected to 45 minutes of renal I/R; and groups III and VI received 10 mg/kg EGCG intravenously at the time of reperfusion. Three days after renal I/R, we compared renal function markers, malondialdehyde (MDA), and histologic changes. RESULTS: Following renal I/R, levels of blood urea nitrogen (BUN) and serum creatinine (sCr) were increased and serum creatinine clearance (CrCl) decreased in group V compared to group II (P < .001). Those receiving EGCG treatment (groups III and VI) had decreased BUN and sCr compared to non-EGCG I/R groups (P < .001), but not surprisingly, higher than sham groups. CrCl was lowest in the SHR groups. The MDA was significantly decreased after EGCG treatment (P = .028 in group III, P = .002 in group VI). Following renal I/R, tissue necrosis was more severe among SHR (P < .001). However, the ratio of regeneration to damage significantly increased in SHR after EGCG treatment. CONCLUSIONS: The reperfusion injury was greater among SHR compared with WKR in terms of renal function, lipid peroxidation, and tissue damage. EGCG treatment significantly ameliorated renal impairment and promoted tissue regeneration following renal I/R.

Animals↗
PubMed2006

Total antioxidant status and oxygen free radicals during hepatic regeneration.

OBJECTIVES: The damage induced by oxygen free radicals (OFRs) is caused by an imbalance of the production of versus the antioxidant defenses against OFRs. METHODS: To understand hepatic damage induced by oxygen free radicals after hepatectomy in rats, total antioxidant status and total production of oxygen free radicals were serially measured in regeneration liver. At 1, 2, 3, 7, and 10 days after hepatectomy of Sprague-Dawley rats, blood was obtained into a capillary tube from a tail vein. Total antioxidant status and total production of oxygen free radicals were measured using the Randox kit, a colorimetric method, and the Free Radical Analytical System. We also measured the amount of malonyldialdehyde, which provides an indirect index of oxidative injury. RESULTS: The level of malonyldialdehyde after hepatectomy was higher compared with that before hepatectomy. The level of total oxygen free radicals after hepatectomy was higher compared with that before hepatectomy. Total antioxidant status after hepatectomy was lower compared with that before hepatectomy. CONCLUSIONS: The results suggested that the damage by OFRs to the regenerating liver was caused by increased production of OFRs and decreased antioxidant defense against OFRs.

Animals↗
PubMed2005

Effects of epigallocatechin gallate on the hemolysis induced by cyclosporine.

INTRODUCTION: Hemolysis is one of the side effects of cyclosporine (CsA) therapy, in part due to, increased production of free radical species by CsA. Epigallocatechin gallate (EGCG), which acts as a highly efficient free radical scavenger, may have a protective effect on CsA-induced hemolysis. In this study, we measured the degree of hemolysis of as well as the amounts of hydrogen peroxide level and malondialdehyde produced by normal human erythrocytes (RBCs) incubated with CsA and with EGCG. METHODS: Human RBCs were incubated as follows. In group 1, 4.2 x 10(6)/mL RBCs were incubated with Cremophore EL. In group 2, the RBCs were incubated with only 167 microg/mL EGCG. In group 3, the RBCs were incubated with 1.67 mg/mL CsA. In group 4, the RBCs were incubated with CsA plus EGCG. RESULTS: The degree of hemolysis in group 2 (53.8 +/- 3.8) was significantly higher than that in group 1 (7.0 +/- 1.0). The degree of hemolysis in group 3 (86.2 +/- 2.2) was significantly higher than that in group 1 and group 2. The degree of hemolysis in group 4 (74.9 +/- 2.9) was significantly higher than in group 1 and in group 2, but lower than that in group 3. The hydrogen peroxide and malondialdehyde levels paralleled the degree of hemolysis. CONCLUSIONS: These results suggest that CsA can induce free radical-mediated hemolysis, which can be partially prevented with EGCG.

Catechin↗
PubMed2004

Effect of epigallocatechin gallate on renal function in cyclosporine-induced nephrotoxicity.

INTRODUCTION: Nephrotoxicity is a clinically important side effect of cyclosporine (CsA). CsA-induced nephrotoxicity results from increased production of free radical species in the kidney. Epigallocatechin gallate (EGCG) acts as an antioxidant, thus, EGCG may have a protective effect on the alteration of renal function resultant from oxygen free radicals. The purpose of the present study was to investigate the protective effect of EGCG in a rodent model. METHODS: Experiments were performed on 3 groups. The normal control group (group 1) received normal saline solution. The CsA-treated group (group 2; 15 mg/kg body weight/d for 14 days) received subcutaneous injections. The EGCG-treated group (group 3) in addition received 25 mg of EGCG/kg body weight by intraperitoneal injection. RESULTS: There were significant increases in levels of blood urea nitrogen (BUN)(42.8 +/- 8.2 mg/dL; P < .001), serum creatinine (1.18 +/- 0.60 mg/dL; P < .05), and serum malondialdehyde (3.09 +/- 0.20 nmol/mL; P < .001), and a significant decrease in CCr(0.07 +/- 0.02 mL/min; P < .001) in group 2 compared with group 1. Levels of BUN (30.2 +/- 0.7 mg/dL; P < .01)and CCr (0.12 +/- 0.08 mL/min) were lower in group 3 than in group 2. Serum creatinine (0.71 +/- 0.04 mg/dL) and serum malondialdehyde level (2.13 +/- 0.15; P < .001 nmol/mL) were lower in group 3 than in group 2. There was no significant difference in CsA levels between group 2 (6.86 +/- 1.48 mug/mL) and group 3 (6.69 +/- 0.62 mug/mL). CONCLUSIONS: EGCG treatment significantly protected renal function and free radical-mediated injury in the kidney from CsA-induced changes.

Antioxidants↗
PubMed2004

Effect of melatonin on the malondialdehyde level of neutrophils in cyclosporine-treated rats.

INTRODUCTION: Cyclosporine (CsA) may contribute to oxygen free radical metabolism in neutrophils, thus resulting in the damage to these cells. This damage may be mitigated by antioxidants such as melatonin. In this study, we measured the malondialdehyde level, which was used as a marker of free radical-induced tissue damage from neutrophils in rats treated with CsA and melatonin. METHODS: The experiments included the following: (1) normal controls (group 1) that received Cremophor EL and 0.5 mL of 5% ethanol-saline solution; (2) CsA alone-treated (group 2) rats that received 15 mg/kg of body weight per day for 14 days by subcutaneous injection; and (3) melatonin-treated (group 3) rats received CsA as for group 2 plus melatonin (715 mug). RESULTS: Malondialdehyde level was significantly higher among group 2 (13.34 +/- 7.54 nmol/10(7) neutrophils) than group 1 animals (7.33 +/- 2.63 nmol/10(7) neutrophils; P < .05). The level was significantly lower in group 3 (5.58 +/- 1.59 nmol/10(7) neutrophils) than group 2 (P < .01). CsA levels were not significantly different between group 2 (6.25 +/- 1.60 mug/mL) and group 3 (6.09 +/- 2.01 mug/mL). CONCLUSIONS: In this experiment, the malondialdehyde level in neutrophils was increased after CsA treatment, suggesting that damage resulted from oxygen free radicals by CsA. This damage was reduced by melatonin. Thus, CsA-induced neutrophils oxidative damage may be protected by melatonin in transplant recipients.

Animals↗
PubMed2004

Effect of artificial cells on hepatic function after ischemia-reperfusion injury in liver.

BACKGROUND: The liver suffers from ischemia/reperfusion injury during transplantation. Reactive oxygen species generated by xanthine oxidase during reperfusion of the ischemic liver may be partially responsible for the hepatic injury. Oxygen free radicals are removed by antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. Using glutaraldehyde and lysine we constructed crosslinked hemoglobin, containing SOD and catalase, and assessed its ability to protect against ischemia/reperfusion injury during transplantation. METHODS: In contrast to the sham-operated control groups, blood was exchanged using crosslinked hemoglobin (polyHb) a PolyHb-SOD-catalase (PSC) group. After ischemia/reperfusion injury, several parameters of hepatic damage and oxygen free radicals were measured as well as microscopic examination. RESULTS: Alanine aminotransferase, aspartate aminotransferase, superoxide production, hydrogen peroxide, and malondialdehyde levels were higher among the PolyHb group than sham-operated controls. The PolyHb group revealed a few apoptotic bodies, some acute inflammatory infiltrates in the sinusoids, nuclear fragmentations, cell shrinkage, and chromatin clumping with formation of apoptotic bodies in the apoptotic cells under microscopic examination. Alanine aminotransferase, aspartate aminotransferase, superoxide production, and hydrogen peroxide levels were lower in the PSC than the PolyHb group. Hepatic structures were well preserved in the PSC group. CONCLUSIONS: Reactive oxygen species contribute to hepatic dysfunction with morphologic changes. PSC is effective to reduce hepatic damage by lowering oxygen free radical-mediated injury after ischemia/reperfusion in the liver.

Animals↗
PubMed2004

Effects of polyhemoglobin-antioxidant enzyme complex on ischemia-reperfusion in kidney.

INTRODUCTION: The kidney suffers ischemia-reperfusion (I/R) injury during transplantation. The purpose of the present study was to investigate the therapeutic effect of artificials cells on renal I/R injury through biochemical assays and histological examination. METHODS: We prepared artificial cells using cross-linked hemoglobin (Hb), superoxide dismutase (SOD), and catalase. Normal male Sprague-Dawley rats were divided into 6 groups: the sham-operated control group, the group treated with polyHb,and the group treated with polyHb-SOD-catalase (PSC) (per groups were subjected to ischemia for 1 hour or 2 hours). After reperfusion for 4 hours, kidney and blood samples were obtained. RESULTS: The levels of SOD and catalase in the PSC group were 15 and 50 times higher than those of the control group, respectively. In the polyHb group, the levels of blood urea nitrogen (BUN), serum creatinine, renal hydrogen peroxide, and renal malondialdehyde were increased. However, their levels were significantly decreased by PSC administration. Renal SOD activity did not show any significant changes in the polyHb group, but renal catalase activity was decreased by polyHb treatment in comparison with the control group. The activities of renal SOD and catalase were increased using PSC treatment. In the histological findings, the PSC group showed no evidence of acute tubular necrosis in proximal convoluted tubules; their microvilli and cytoplasmic microorganelles were relatively well preserved. CONCLUSIONS: These results show that PSC effectively reduces renal damage via diminished oxygen free radical-mediated injury after I/R.

Animals↗
PubMed2001

The effects of the melatonin on ultraviolet-B irradiated cultured dermal fibroblasts.

It has been reported that reactive oxygen species (ROS) and oxygen-derived free radicals are generated by ultraviolet (UV) radiation and various chemicals and their important roles in cellular damage and apoptosis are being increasingly recognized. Melatonin is a hormone with multiple functions in humans, produced by the pineal gland and stimulated by beta-adrenergic receptors. Melatonin has been shown to have photo protection properties, but there has been little progress toward identifying the specific mechanisms of its action. To clarify the role of melatonin as a free radical scavenger, in response to ultraviolet-B (UVB) irradiation, we investigated the effects of UVB and melatonin on cytotoxicity, lipid peroxidation, terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end-labeling (TUNEL) assay and alteration of cell cycle in cultured skin fibroblast. Cell survival curves after UVB irradiation showed dose dependent decrement pattern by trypan blue exclusion assay. Only 56% of dermal fibroblasts were survived at 140 mJ/cm2 UVB irradiation. The damage was associated with cell membrane lipid peroxidation, as shown by accumulation malondialdehyde (MDA). By pre-cultivation with melatonin (10(-9) M), a significant preventive effect was noted on the increase in the absolute number of surviving cells (up to 92.5% of cells were survived) and the levels of MDA were markedly decreased. These finding suggest significant correlation between an increase of lipid peroxide and cell viability. Morphological changes associated with apoptotic cell death were easily distinguished by TUNEL stain. Quantitative analysis of DNA content of skin fibroblasts was evaluated by flow cytometric analysis performed after vital staining with propidium iodide. UVB suppresses the G1 progression induced pre-G1 arrest leading to apoptotic changes of dermal fibroblast and those are blocked by melatonin pre-treatment. The results show the photodynamic effects of UVB that supposes the production of ROS and arrest the cell cycle. Melatonin, which have newly accepted as a potential UV protection properties, is effective membrane peroxidation inhibitor and prevent the pre-G1 arrest when present in relevant concentration during UVB irradiation.

Apoptosis↗