Kim, Ki-Young;Kim, Byeong-Gee;Kim, Sun-Ok;Yoo, Sung-Eun;Hong, Ki-Whan
The Korean Journal of Physiology and Pharmacology
/
v.5
no.5
/
pp.381-388
/
2001
This work describes the pharmacological inhibition by KR 31378 and its acetyl metabolite, KR 31612, of the apoptotic cell death induced by $H_2O_2$ in the A7r5 cells. Exposure of A7r5 cells to $H_2O_2$ (0.5 mM) induced a concentration-dependent cytotoxicity in association with oligonucleosomal DNA fragmentation. $H_2O_2-induced$ cell death was potently suppressed by KR 31378, KR 31612, ${\alpha}-tocopherol$ or trolox. Additionally, the apoptotic death of A7r5 cells (DNA ladders on electrophoresis) was also strongly suppressed by KR 31378 and KR 31612, but to a less degree by ${\alpha}-tocopherol$ and trolox. As a mechanistic study, incubation with $H_2O_2$ markedly showed a decreased Bcl-2 level and, in contrast, increased Bax protein and cytochrome C release, which were significantly and concentration-dependently reversed by KR 31378 and KR 31612 as well as by ${\alpha}-tocopherol$ and trolox. KR 31378 and ${\alpha}-tocopherol$ significantly reduced lipid peroxidation in accordance with reduced intracellular ROS and peroxyl radical. These results suggest that KR 31378 has a therapeutic potential against the apoptotic injury via mediation of anti- oxidative stress.
Objectives : Malondialdehyde (MDA), a lipid peroxidation by-product, has been widely used as an indicator of oxidative stress. Urinary 2-naphthol, a urinary PAH metabolite, is used as a marker of ambient particulate exposure and is associated with lung cancer and chronic obstructive pulmonary disease. However, the stability and intra-individual variation associated with urinary MDA and 2-naphthol have not been thoroughly addressed. The objective of this study was to assess the stability and intra-individual variation associated with urinary MDA and 2-naphthol. Methods : Urine samples were collected from 10 healthy volunteers (mean age 34, range $27{\sim}42$ years old). Each sample was divided into three aliquots and stored under three different conditions. The levels of urinary MDA and 2-naphthol were analyzed 1) just after sampling, 2) after storage at room temperature ($21^{\circ}C$) for 16 hours, and 3) after storage in a $-20^{\circ}C$ freezer for 16 hours. In addition, an epidemiological study was conducted in 44 Chinese subjects over a period of 3 weeks. The urinary MDA and 2-naphthol were measured by HPLC three times. Results : There was no difference in the levels of urinary MDA and 2-naphthol between the triplicate measurements (n=10, p=0.84 and p=0.83, respectively). The intra-class correlation coefficients (ICC) for urinary MDA and 2-naphthol were 0.74 and 0.42, respectively. However, the levels of PM2.5 in the air were well correlated with the levels of both MDA and 2-naphthol in the epidemiological study. Conclusions : These results suggest that urinary MDA and 2-naphthol remain stable under variable storage conditions, even at room temperature for 16 hours, and indicate that these markers can be used in epidemiological studies involving various sample storage conditions. The intra-CC of urinary 2-naphthol and MDA were acceptable for application to epidemiological studies.
The objective of this study was to evaluate the potential use of ginseng leaf as a cosmetic material. In this research, we employed enzymatic treated ginseng leaf by using Ultraflo L to improve the recovery of ginsenosides from the ginseng leaf and studied the biological activities and skin safety of the enzymatic treated ginseng leaf for use as a cosmetic material. The total ginsenoside contents of the non-enzymatic treated ginseng leaf (NEGL) and Ultraflo L treated ginseng leaf (UTGL) were 271 and 406 mg/g, respectively. The level of metabolite ginsenosides (sum of Rg2, Rg3, Rg5, Rk1, compound K, Rh1, Rh2, and F2) was higher in UTGL (93.1 mg) compared to NEGL (62.4 mg) in one gram ginseng leaf extract. The increase in amounts of ginsenoside types in UTGL compared to NEGL was generally 140% to 157%. UTGL exhibited relatively higher 2,2-diphenyl-2-picrylhydrazyl hydrate ($IC_{50}$, 2.8 mg/mL) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt ($IC_{50}$, 1.6 mg/mL) radical scavenging activities compared to NEGL (4.8 mg/mL and 2.2 mg/mL). The UTGL group showed normalized hydrogen peroxide, lipid peroxidation and visual wrinkling grade induced-UVB exposure. The UTGL did not induce any adverse reactions such as erythema and edema on intact skin sites; however, some guinea pigs treated with UTGL on abraded skin sites showed very slight erythema. The primary irritation index (PII) score of UTGL was 0.05 and it was classified as a practically non-irritating material (PII, 0 to 0.5). In skin sensitization tests with guinea pigs, UTGL had a positive rate of skin sensitization at 40%, and the mean evaluation score was 0.4.
To evaluate an effect of circadian variation on the xylene metabolizing enzyme activities, 50% m-xylene in olive oil(0.25 $m\ell$/100g body weight) was intraperitoneally administered to the rats every other day for 6 days both in the night; 24:00 and the day; 12:00. Then animals were sacrigiced at 8hr after last injection of m-xylene. Hepatic microsomal cytochrome p450 contents were more increased both in control and xylene treated rats of night phase than those of day phase. But the activity of hepatic alcohol dehydrogenase(ADH) in control of night phase showed the similar value with that in those of day phase and xylene treated rats of day phase showed an increasing tendency of hepatic ADH activity as those of night phase showing similar activity. Furthermore, control rats of night phase than those of day phase. And by xylene treatment, enzyme activities of rats of day phase were higher tendency in rats of control but those of night phase were somewhat inhibited. Besides, xylene-treated animals of night phase showed increasing tendency of urinary methylhippuric acid concentration compared with those of day phase. On the other hand, liver weight per body weight(%), hepatic lipid peroxide content and serum xanthine oxidase activity were higher in night phase. And the activities of hepatic oxygen free radical metabolizing enzymes such as xanthine oxidase, gluthathione S-transferase, and xylene-treated rats of night phase than those of day phase. In conclusion, it can be hypothesized on the basis of the results that the accumulation rate of m-xylene intermediate metabolite, i.e. m-methylbenzaldehyde in liver tissus may be higher in night phase than in day phase and it may be responsible for higher liver toxicity in bight phase than in day phase.
Carbon tetrachloride ($CCl_4$) has been used to treat a variety of parasitic infection in both large and small animals, including Fasciola hepatica. Recently, we can easily contest with carbon tetrachloride in air, food, water, rain and Industry area etc. and it is using in order to induce liver injury in laboratory. In this study. we investigated activitis of LDH, ALP, AST and ALT and amount of cholesterol, triacylglycerol, glucose and BUN in mice serum exposed to $CCl_4.$ The mice divided Into a Naive control(A), corn oil control(B) and experimental group(C, D). Naive control group(A) was given feed and water only. Corn oil control group(B) was given corn oil 1ml /100g of body weight(B.W). Experimental group(C) was given carbon tetrachloride 1ml /100g B.W. ($CCl_4$: corn oil=1:20(V /V) ), Experimental group(D) was given carbon teterachloride 1ml /100g B.W. ($CCl_4$: corn oil=1:10(V /V) ). The results obtained were summarized as follows : 1) The body weight was declined after the l0th day In mice exposed to carbon tetra-chloride. 2) The total protein level in serum was significantly in mice exposed to carbon tetra-chloride($P{\leq}0.05$). The albumin and A /G ratio was decresed significantly in mice exposed to carbon tetrachloride($P{\leq}0.01$) 3) All of the activity of LDH, AST, ALT and ALP in mice serum exposed to carbon tetra chloride inclosed significantly activity of LDH ($P{\leq}0.05$), inclosed significantly activity of AST($P{\leq}0.05, \;p {\leq}0.01$), inclosed significantly activityof ALT 3nd ALP($P {\leq}0.05,\;p {\leq}0.01$). 4) The amount of cholesterol and triacylglycerol, lipid metabolite products in serum was inclosed in case of cholesterol but did not change in case of triacylglycerol.
Kim, Ki-Woong;Won, Yong Lim;Ko, Kyung Sun;Heo, Kyung-Hwa;Chung, Yong Hyun
Toxicological Research
/
v.28
no.4
/
pp.269-277
/
2012
The purpose of this study was to understand the mechanism of cardiovascular disease (CVD) caused by exposure to hazardous chemicals. We investigated changes in the symptoms of metabolic syndrome, which is strongly related to CVD, and in levels of other CVD risk factors, with a special emphasis on the roles of catecholamines and oxidative stress. The results revealed that neither body mass index (BMI) nor waist and hip circumferences were associated with exposure to hazardous chemicals. Among metabolic syndrome criteria, only HDL-cholesterol level increased on exposure to hazardous chemicals. Levels of epinephrine (EP) and norepinephrine (NEP) were not influenced by exposure to hazardous chemicals; however, the total antioxidative capacity (TAC) reduced because of increased oxidative stress. Both hazardous chemical exposure level and metabolite excretion were related to EP, NEP, and the oxidative stress index (OSI). Logistic regression analysis with these factors as independent variables and metabolic syndrome criteria as dependent variables revealed that EP was associated with blood pressure, and NEP with metabolic syndrome in the chemical-exposed group. In conclusion, the results suggest that reactive oxygen species generated and oxidative stress due to exposure to hazardous chemicals act as mediators and cause changes in the physiological levels of EP and NEP to increase blood pressure. This ultimately leads to the development of CVD through increase in cholesterol, triglyceride, and blood glucose levels by lipid peroxidation.
Koldemir-Gunduz, Meliha;Aydin, Hasan Emre;Berikten, Derya;Kaymak, Gullu;Kose, Dursun Ali;Arslantas, Ali
Journal of Korean Neurosurgical Society
/
v.64
no.6
/
pp.864-872
/
2021
Objective : The aim of our study is to investigate the cytotoxic, antioxidant, and antimicrobial effects of newly synthesized boron compounds in U87MG glioblastoma cell treatment. Methods : We synthesized boron glycine monoester (BGM) and boron glycine diester (BGD) structures containing boron atoms and determined their cytotoxic activities on glioblastoma by the MTT method. The inhibitory concentration 50 (IC50) value was calculated with GraphPad Prism 5.0 program. The IC50 values were administered 48 hours on U87MG glioblastoma cell. Catalase (CAT), acid phosphatase (ACP) and alkaline phosphatase (ALP) enzyme activity, malondialdehyde (MDA), total glutathione (GSH), and total protein levels were detected using spectrophotometric methods. We determined the antimicrobial activities of BGM and BGD with the disc diffusion method. Results : After 48 hours of BGM and BGD application to U87MG glioblastoma cells, we found the IC50 value as 6.6 mM and 26 mM, respectively. CAT and ACP enzyme activities were decreased in BGM and BGD groups. MDA which is a metabolite of lipid peroxidation was increased in both boron compounds groups. GSH level was reduced especially in BGD group. BGM and BGD have been found to be antimicrobial effects. Conclusion : Boron compounds, especially the BGM, can provide a new therapeutic approach for the treatment of glioblastoma with their anticancer, antioxidant, and antimicrobial effects.
Moon, Su-Jin;Lee, Soo Hyun;Jung, Byung-Hwa;Min, Jun-Ki
Journal of Rheumatic Diseases
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v.24
no.4
/
pp.192-202
/
2017
Objective. Rebampide is a gastroprotective agent used to treat gastritis. It possesses anti-inflammatory and anti-arthritis effects, but the mechanisms of these effects are not well understood. The objective of this study was to explore mechanisms underlying the therapeutic effects of rebamipide in inflammatory arthritis. Methods. Collagen-induced arthritis (CIA) was induced in DBA/1J mice. DBA/1J mice were immunized with chicken type II collagen, then treated intraperitoneally with rebamipide (10 mg/kg or 30 mg/kg) or vehicle (10% carboxymethylcellulose solution) alone. Seven weeks later, plasma samples were collected. Plasma metabolic profiles were analyzed using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics study and metabolite biomarkers were identified through multivariate data analysis. Results. Low dose rebamipide treatment reduced the clinical arthritis score compared with vehicle treatment, whereas high dose rebamipide in CIA aggravated arthritis severity. Based on multivariate analysis, 17 metabolites were identified. The plasma levels of metabolites associated with fatty acids and phospholipid metabolism were significantly lower with rebamipide treatment than with vehicle. The levels of $15-deoxy-^{{\Delta}12,14}$ prostaglandin J2 and thromboxane B3 decreased only in high dose-treated groups. Certain peptide molecules, including enterostatin (VPDPR) enterostatin and bradykinin dramatically increased in rebamipide-treated groups at both doses. Additionally, corticosterone increased in the low dose-treated group and decreased in the high dose-treated group. Conclusion. Metabolomics analysis revealed the anti-inflammatory effects of rebamipide and suggested the potential of the drug repositioning in metabolism- and lipid-associated diseases.
Mi-Lim Kim;Soon-Ae Park;Min Ju Kim;Mi-Rae Shin;Seong-Soo Roh;Hae-Jin Park
The Korea Journal of Herbology
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v.39
no.3
/
pp.97-105
/
2024
Objective : This study examined the effects of yaksun recipe on the anti-fatigue and endurance enhancement properties in the forced swimming test (FST). Methods : The treatment groups were divided randomly into three groups: water-treated FST (control), 200 mg/kg of red ginseng-treated FST (RG200), 200 mg/kg of water extract of yaksun recipe-treated FST (YS200). After FST, an autopsy was performed, and the tissue and serum were collected. Results : The swimming exhaustion time in the RG200 and YG200 groups were significantly increased compared to the control group. The YG200 group fatigue indicators, D-Lactate, LDH(lactate dehydrogenase), creatine kinase, and ammonia content, significantly decreased compared to the control group. In addition, liver glycogen content significantly increased in the YG200 and tended to increase in RG200. Likewise, the glucose contents were significantly increased compared to the control group. The muscle damage indicators GPT (glutamic pyruvic transaminase) and BUN (blood urea nitrogen), a protein metabolite, in the YG200 group significantly decreased compared to the control group. Furthermore the concentration of liver lipid peroxidation, MDA(malondialdehyde) levels significantly decreased in the RG200 and YG200 compared to control group. Conclusions : These results suggest that YG200 can increase the endurance exercise capacity by decreasing the fatigue indicators, saving glycogen, and elevating the antioxidant defense system.
Journal of the Korea Academia-Industrial cooperation Society
/
v.19
no.12
/
pp.814-824
/
2018
This study was conducted to investigate VFA, monosaccharides and metabolites in rumen fluid according to feeding methods. Three castrated Hanwoo steers were used to the $3{\times}3$ Latin square design, 10 day for the diet adaptation period. VFA and monosaccharides which were not detected by HPLC and HPAEC however, those were detected by $^1H-NMR$. Among the metabolites measured by $^1H-NMR$ carbohydrate metabolites, pyruvate was detected only in the rumen fluid before feeding and succinate was detected before and after feeding rumen fluid. In amino acid total 9 metabolites were detected. In lipid metabolites, ethylene glycol was significantly higher (P<0.05) in before feeding Con group. In aliphatic acylic metabolite, trimethylamine N-oxide was no significant difference observed compare to Con group. In this study, many metabolites were observed in the rumen fluid by $^1H-NMR$, and it confirmed that rumen metabolic products were changed by feeding methods.
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