• 한국환경보건학회지
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• 제36권1호
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• pp.44-51
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• 2010

This study aimed to develop analytical method for 8-isoprostanes as biomarkers for oxidative stress with LC/MS/MS technique and to apply the method for human urine samples. Analyzed compounds for urinary oxidative stress markers were 7 stereo-isomers of prostaglandins and the internal standard (iso-$PGF_{2{\alpha}}-d_4$) was used to adjust the recovery rate. The method for determining urinary iso-$PGF_{2{\alpha}}$ consisted of solid phase extraction and LC/MS/MS detection. Separation of isomers of prostaglandins completed by porous graphitic carbon column and buffer solution. Detection limits for urinary markers of oxidative stress, iso-$PGF_{2{\alpha}}$ with LC/MS/MS were 0.01 ng/ml by S/N ratio 3 and 0.028 ng/ml by calculated as to FDA method. The recovery (92.8~101.9%) and precision (8.8~20.7%) of analysis were feasible for detecting iso-$PGF_{2{\alpha}}$ in real human urine samples. We detected 4 isomers of prostaglandins in human urine samples. Mean (standard deviation) of urinary iso-$PGF_{2{\alpha}}$ concentration were 0.231 (0.117) ng/mg creatinine for smoking group and 0.154 (0.082) ng/mg creatinine for non-smoking group.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.775-780
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• 2012

8-isoprostane (8-$isoPGF_{2{\alpha}}$) is a reliable marker and considered a gold standard for lipid peroxidation. There are very few reports of 8-isoprostane levels in cancer patients, and in patients undergoing chemotherapy. Oxidative stress is however expected and has been observed in patients with cancer. This study measured 8-isoprostane levels in urine by ELISA of 25 patients undergoing chemotherapy for advanced non-small cell lung cancer, at cycles 1, 2, and 3 of treatment. It considers the creatinine clearance of the patients, and correction of 8-isoprostane levels by creatinine clearance, and overnight urine volume methods. The average 8-isoprostane levels in urine increased more than 6 to 12 fold on chemotherapy treatment, from $532{\pm}587$ pg/mL at cycle $1,6181{\pm}4334$ at cycle 2, and $5511{\pm}2055$ at cycle 3. Similar results were obtained if 8-isoprostane levels were corrected for overnight urine volume, giving averages of $285{\pm}244{\mu}g$ at cycle $1,4122{\pm}3349$ at cycle 2, and $3266{\pm}1200$ at cycle 3. No significant difference was seen in average total overnight urine volume or number of urinations between chemotherapy cycles except for a large variation in urine volume between cycle 2 and 3. Creatinine levels were significantly different only between cycles 1 and 2 (p=0.016). In conclusion, cisplatin therapy has been shown to induce high levels of lipid peroxidation in lung cancer patients and can be assessed from the 8-isoprostane marker in overnight urine, with or without urine volume correction.

• Clinical and Experimental Pediatrics
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• 제46권9호
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• pp.865-870
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• 2003

목 적 : 지질 과산화의 주요 지표 중에 하나인 isoprostane($8-iso-PGF_{2{\alpha}}$)을 제대 동맥혈에서 측정하여 신생아에 산화손상을 유발 할 수 있는 주산기 위험인자 및 신생아기 주요 질환과의 관계를 규명하여, 제대 동맥혈 isoprostane이 신생아에서 산화손상의 지표로 사용할 수 있는지를 알아보고자 하였다. 방 법 : 2000년 6월부터 2001년 3월까지 단국대학교병원 신생아 중환자실 및 신생아실에 입원하였던 미숙아 33명과 만삭아 28명을 대상으로 제대 동맥혈에서 혈청을 분리하여 $-70^{\circ}C$에서 냉동 보관 후 isoprostane($8-iso-PGF_{2{\alpha}}$)과 malondialdehyde(MDA)를 측정하였다. 측정된 isoprostane과 MDA 농도를 미숙아와 만삭아에서 각각 비교하였고, 주산기-신생아기 위험인자와 주요 합병증과의 상관관계를 알아보았다. 결 과 : 평균 출생 체중은 미숙아 $1,771{\pm}445gm$, 만삭아 $3,200{\pm}567gm$이었고, 평균 재태 연령은 미숙아 $31.5{\pm}2.0$주, 만삭아 $39.0{\pm}2.0$주였다. 제대 동맥혈 isoprostane 농도는 미숙아 $704.7{\pm}635.6pg/mL$, 만삭아 $423.9{\pm}306.5pg/mL$로 미숙아에서 통계적으로 의미있게 높았으며(P<0.05), MDA도 미숙아 $44.0{\pm}22.9{\mu}M/L$, 만삭아 $28.2{\pm}10.7{\mu}M/L$로 미숙아에서 의미있게 높았다(P<0.05). 미숙아의 경우 isoprostane은 출생 후 24시간에 $478.6{\pm}580.6pg/mL$로 유의하게 감소하였다(P<0.05). 미숙아 제대 동맥혈 isoprostane은 둔위 분만, 양수 과소증, 신생아 가사와 통계적으로 유의한 상관관계가 있었고(P<0.05), 만삭아 제대 동맥혈 isoprostane은 임신성 고혈압과 유의한 상관관계를 보였다(P<0.05). 그러나 미숙아 제대 동맥혈 isoprostane은 신생아기의 주요 합병증과는 상관관계가 없었다. 결 론 : 미숙아에서 제대 동맥혈 isoprostane 농도는 만삭아에 비하여 높고, 일부 주산기-신생아기 위험인자와 연관이 있어서, 주산기-신생아기에 산화손상과 관련된 주요 지표 중에 하나로 사용될 가능성이 있음을 추측하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제11권3호
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• pp.129-133
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• 2007

There are growing evidences suggesting a pivotal role of oxidative stress in the pathophysiology of preeclampsia. We investigated oxidative stress in the rat model of preeclampsia, and in clinical cases. Pregnant female rats were injected intraperitoneally with deoxycorticosterone acetate (DOCA) and given 0.9% saline as drinking water during their pregnancy. We assessed plasma $F_2-isoprostane(8-iso-PGF_{2{\alpha})$ and malondialdehyde (MDA) in a rat model, and the same markers in the plasma of maternal blood and fetal cord blood in pregnant women with preclampsia. Blood samples from the umbilical arteries and veins were collected separately. The concentrations of MDA were increased in the preeclampsia groups of animal and humans, compared with the control group; it was significantly increased in the umbilical artery and vein of the preeclampsia group. The concentrations of $F_2-isoprostane$ were elevated in the preeclampsia groups of animal and humans, compared with the control group, and the increase in $F_2-isoprostane$ concentration was prominent in the umbilical vein than umbilical artery of the preeclampsia group. Therefore, it appears that the placenta has an important role in the pathophysiology of preeclampsia, and the $F_2-isoprostane$ of the umbilical vein may serve as a relatively reliable marker for ischemic/hypoxic injury to the fetus during the perinatal period.

• Nutrition Research and Practice
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• 제11권3호
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• pp.206-213
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• 2017

BACKGROUN/OBJECTIVES: Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. METHODS/MATERIALS: After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin $F2{\alpha}$ (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. RESULTS: Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly (P < 0.05) lower than those in the HF group without dose-dependent effect. Plasma TBARS concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly (P < 0.05) increased in the HF+BGE 1.0 and HF+BGE 1.5 groups compared to those of the HF group. The mRNA expression levels of hepatic Nrf2, NQO1, HO-1, and GSTA2 were significantly (P < 0.05) increased in the HF with BGE groups compared to those in the HF group. CONCLUSIONS: The improvements of blood glucose homeostasis and antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.