The Beneficial Effect of Trolox on Sepsis-Induced Hepatic Drug Metabolizing Dysfunction

Park, Sang-Won,Lee, Sun-Mee The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.2

Trolox is a hydrophilic analogue of vitamin E. The aim of this study was to investigate its effects on hepatic injury, especially alteration in cytochrome P450 (CYP)-dependent drug metabolism during polymicrobial sepsis. Rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). The rats were treated intravenously with Trolox (2.5 mg/kg) or vehicle, immediately after CLP. Serum aminotransferases and lipid peroxidation levels were markedly increased 24 h after CLP. This increase was attenuated by Trolox. Total CYP content and NADPH-P450 reductase activity decreased significantly 24 h after CLP. This decrease in CYP content was attenuated by Trolox. At 24 h after CLP, there was a significant decrease in the activity of these CYP isozymes: CYP1A1, 1A2, 2B1, and 2E1. However, Trolox differentially inhibited the decrease in CYP isozyme activity. Trolox had little effect on the decrease in CYP1A1 activity but Trolox significantly attenuated decreases in CYP1A2 and 2E1 activities. In fact, Trolox restored CYP2B1 activity to the level of activity found in control rats. Our findings suggest that Trolox reduces hepatocellular damage as indicated by abnormalities in hepatic drug-metabolizing function during sepsis. Our data also indicates that this protection is, in part, caused by decreased lipid peroxidation.

Effect of Trolox on Altered Vasoregulatory Gene Expression in Hepatic Ischemia/Reperfusion

Eum, Hyun-Ae,Lee, Sun-Mee The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.2

This study was designed to investigate the effect of Trolox, a hydrophilic analogue of vitamin E, on the alteration of vasoregulatory gene expression during hepatic ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia in vivo. The rats were treated intravenously with Trolox (2.5 mg/kg) or the vehicle as a control 5 min before reperfusion. Liver samples were obtained 5 h after reperfusion for a RT-PCR analysis on the mRNA for the genes of interest. These mRNA peptides are endothelin-1 (ET -1), potent vasoconstrictor peptide, its receptor $ET_A$ and $ET_B$, vasodilator endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and cyclooxygenase-2 (COX-2). It was seen that serum alanine aminotransferase and lipid peroxi-dation levels were markedly increased after I/R and Trolox significantly suppressed this increase. In contrast, the glutathione concentration decreased in the I/R group, and this decrease was inhibited by Trolox. ET-1 mRNA expression was increased by I/R, an increase which was prevented by Trolox. The mRNA levels for $ET_A$ receptor was significantly decreased, whereas ET$_{B}$ receptor transcript increased in the I/R group. The increase in $ET_A$ was prevented by Trolox. The mRNA levels for iNOS and HO-1 significantly increased in the I/R group and Trolox attenuated this increase. There were no significant differences in eNOS mRNA expression among any of the experimental groups. The mRNA levels for COX-2 and TNF-$\alpha$ significantly increased in I/R group and Trolox also attenuated this increase. Our findings suggest that I/R induces an imbalanced hepatic vasoregulatory gene expression and Trolox ameliorates this change through its free radical scavenging activity.y.

Paraquat로 처치한 백서에서 Melatonin과 수용성 비타민 E복합 투여가 지질과산화와 생존율에 미치는 영향

김진하 KOSIN UNIVERSITY COLLEGE OF MEDICINE 2006 高神大學校 醫學部 論文集 Vol.21 No.1

Objectives : Paraquat, an oxygen radical-generating agent, is a highly toxic compund for humans ans animals. This study was examined the effect of combined treatment of melatonin and Trolox^(®)(water-soluble analogue of α-tocopherol) in lipid peroxidation and mortality after paraquat intoxication in rats. Methods : Paraquat(20mg/kg) was injected i.p. into Spraque-Dawely rats. After the administration of paraquat, rats were treated with melatonin(10mg/kg), Trolox^(®)(100mg/kg), combined melatonin and Trolox^(®). All rats were killed by decapitation 24hours after paraquat administration and then examined the concentration of malonaldehye and 4-hydroxyalkenal (MDA + 4-HAE) as indices of lipid peroxidation in rat lung and liver. In a survival study, continous i.p. infusion of melatonin (50mg/kg/day) for 14 days using Alzet^(®) Osmotic pump (2ML2) and Trolox^(®)(100mg/kg/day) was injected i.p. after paraquat (20mg/kg) poisoning into rats for 14days. Results : Paraquat alone increased MDA + 4-HAE levels in lung, with this increase being reduced by melatonin and Trolox^(®), and also combined treatment with melatonin and Trolox^(®) completely reversed this effect. Paraquat at 20mg/kg did not induced any significant change in liver lipid peroxidation. In a result of survival analysis, percent survival was 100 % (8/8, control), 0 % (0/8, paraquat only), 62.5 % (5/8, paraquat + melatonin), 37.5 % (3/8, paraquat + Trolox^(®)), 75.0 % (6/8, paraquat + melatonin + Trolox^(®)) at 14 days after paraquat intoxication. Conclusions : These results indicate that melatonin and Trolox^(®) protect lipid peroxidation and increase survival time in paraquat intoxicated rats. Combined treatment with melatonin and Trolox^(®) seems to have more survival benefit than single agent treatment in paraquat intoxication.

Antioxidant effects and tyrosinase and elastase inhibitory activities of mountain ginseng adventitious roots extracts at different ethanol concentrations

고현민,엄태길,김경철,김철중,이재근,김주성 충남대학교 농업과학연구소 2018 Korean Journal of Agricultural Science Vol.45 No.3

To use mountain ginseng adventitious roots (MGAR), which is superior in functionality compared to ginseng, and to mass produce raw materials as a functional cosmetic material, the antioxidant and cosmeceutical activities of the extracts of MGAR at different ethanol concentrations (0, 20, 40, 60 and 80%) were compared and analyzed. At first, different ethanol concentrations were compared to determine the best solvent for the extraction of phenolic compounds from MGAR. An 80% ethanol extract with 10.07 mg of gallic acid equivalents/g sample and 0.94 mg of quercetin equivalents/g sample was the best solvent in the extraction of phenolic compounds. However, the 60% ethanol extract had the highest antioxidant activity, evident by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, Trolox equivalent antioxidant capacity (35.01 mM Trolox/g sample) and ferric reducing antioxidant power (460.94 mM FeSO4/g sample). However, the inhibitory activities of the 80% ethanol extract from the MGAR against tyrosinase and elastase were higher than those of the other extracts. The results of this study show that the extract of MGAR can be used as an easily accessible source of natural antioxidant and as a possible cosmetic ingredient in the cosmeceutical industry. However, the components responsible for the antioxidant and cosmeceutical activities of the MGAR extracts are currently unclear. Therefore, it is suggested that further studies should be carried out to isolate and identify the antioxidant and cosmeceutical components in MGAR.

고강도 트레드밀 운동에서 혈중 젖산과 산화스트레스의 상관관계

박혜미,한근호,성동준 한국웰니스학회 2022 한국웰니스학회지 Vol.17 No.1

본 연구의 목적은 30명의 남자 대학생을 대상으로 최대산소섭취량의 80% 운동 적용에 따른 젖산의 항산화 효과를 젖산과 산화스트레스의 상관관계를 통해 확인하는 데 있다. 본 연구에서는 휴식, 운동 5분, 운동 10분, 회복 3분에 젖산, 과산화수소(H2O2), 트롤록스의 항산화 활성을 측정하였다. 본 연구에서 적용한 운동강도에 따라 젖산과 H2O2가 유의하게 증가하였으나, trolox는 감소하는 경향을 보였고, 휴식과 회복 3분 사이에는 유의한 차이가 있었다. 또한 젖산과 H2O2 간에도 유의한 양의 상관관계가 있었다. 이러한 결과는 인간에 대한 연구에서 젖산의 항산화 효과가 미미함을 의미하며, 젖산과 산화 스트레스 사이의 기능적 상호 작용은 향후 연구를 통해 규명되어야 할 것이다.

Effect of Trolox C on Hypoxia/Reoxygenation-Induced Injury in Isolated Perfused Rat Liver

Lee, Sun-Mee,Cho, Tai-Soon The Pharmaceutical Society of Korea 1997 Archives of Pharmacal Research Vol.20 No.5

Livers isolated from 18 hours fasted rats were subjected to N$_{2}$ hypoxia (for 45 min) followed by reoxygenation (for 45 min). The perfusion medium used was Krebs-Henseleit bicarbonate buffer (KHBB, pH 7.4). Lactate and alanine were added as gluconeogenic and ureagenic substrates and Trolox C was also added to perfusate. Oxygen consumption, lactate dehydrogenase (LDH), alanine transaminase (ALT), total glutathione, oxidized glutathione, bile flow, glucose and urea were measured. After hypoxia oxygen consumption significantly dropped but Trolox C had no influence on this decrease. ALT and LDH were significantly increased by hypoxia/reoxygenation. This increase was markedly attenuated in the presence of Trolox C. The total glutathione and oxidized glutathione efflux increased following hypoxia, which were prevented by the treatment of Trolox C. Bile flow rate decreased following hypoxia/reoxygenation but did not continue to decrease in the reoxygenation phase by Trolox C. Following hypoxia/reoxygenation glucose and urea releases decreased. Trolox C had no influence on inhibition of glucose and urea production. These results suggest that Trolox C protected the liver cells against hypoxia/reoxygenation injury, yielding further evidence for a causative role of oxidative stress in this model.

Effect of Trolox C on Hypoxia/Reoxygenation-Induced Injury in Isolated Perfused Rat Liver

Lee, Sun-Mee,Cho, Tai-Soon 성균관대학교 약학연구소 1997 成均藥硏論文集 Vol.9 No.1

Livers isolated from 18 hours fasted rats were subjected to N_2 hypoxia (for 45 min) followed by reoxygenation (for 45 min). The perfusion medium used was Krebs-Henseleit bicarbonate buffer (KHBB, pH 7.4). Lactate and alanine were added as gluconeogenic and ureagenic substrates and Trolox C was also added to perfusate. Oxygen consumption, lactate dehydrogenase (LDH), alanine transaminase (ALT), total glutathione, oxidized glutathione, bile flow, glucose and urea were measured. After hypoxia oxygen consumption significantly dropped but Trolox C had no influence on this decrease. ALT and LDH were significantly increased by hypoxia/reoxygenation. This increase was makedly attenuated in the presence of Trolox C. The total glutathione and oxidized glutathione efflux increased following hypoxia, which were prevented by the treatment of Trolox C. Bile flow rate decreased following hypoxia/reoxygenation but did not continue to decrease in the reoxygenation phase by Trolox C. following hypoxia/reoxygenation glucose and urea releases decreased. Trolox C had no influence on inhibition of glucose and urea production. These results suggest that Trolox C protected the liver cells against hypoxia/reoxygenation injury, yielding further evidence for a causative role of oxidative stress in this model.

Trolox C Ameliorates Hepatic Drug Metabolizing Dysfunction After Ischemia/Reperfusion

Eum, Hyun-Ae,Lee, Sang-Ho,Lee, Sun-Mee The Pharmaceutical Society of Korea 2002 Archives of Pharmacal Research Vol.25 No.6

The present study was done to determine the effect of trolox C, a hydrophilic analogue of vitamin E, on hepatic injury, especially the alteration in cytochrome P-450 (CYP)-dependent drug metabolism during ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Rats were treated intravenously with trolox C (2.5 mg/kg) or vehicle (PBS, pH 7.4), 5 min before reperfusion. Serum alanine aminotransferase and lipid peroxidation levels were markedly increased after I/R. This increase was significantly suppressed by trolox C. Cytochrome P-450 content was decreased after I/R but was restored by trolox C. There were no significant differences in ethoxyresorufin O-dealkylase (CYP 1A1) and methoxyresorufin O-dealkylase (CYP 1A2) activities among any of the experimental groups. Pentoxyresorufin O-dealkylase (CYP 2B1) activity was decreased and aniline p-hydroxylase (CYP 2E1) activity was increased after I/R. Both these changes were prevented by trolox C. Our findings suggest that trolox C reduces hepatocellular damage as indicated by abnormalities in microsomal drug-metabolizing function during I/R, and that this protection is, in part, caused by decreased lipid peroxidation.

Trolox C Ameliorates Hepatic Drug Metabolizing Dysfunction After Ischemia/Reperfusion

Hyun-AeEum,이상호,이선미 대한약학회 2002 Archives of Pharmacal Research Vol.25 No.6

The present study was done to determine the effect of trolox C, a hydrophilic analogue of vitamin E, on hepatic injury, especially the alteration in cytochrome P-450 (CYP)-dependent drug metabolism during ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Rats were treated intravenously with trolox C (2.5 mg/kg) or vehicle (PBS, pH 7.4), 5 min before reperfusion. Serum alanine aminotransferase and lipid peroxidation levels were markedly increased after I/R. This increase was significantly suppressed by trolox C. Cytochrome P-450 content was decreased after I/R but was restored by trolox C. There were no significant differences in ethoxyresorufin O-dealkylase (CYP 1A1) and methoxyresorufin O-dealkylase (CYP 1A2) activities among any of the experimental groups. Pentoxyresorufin O-dealkylase (CYP 2B1) activity was decreased and aniline p-hydroxylase (CYP 2E1) activity was increased after I/R. Both these changes were prevented by trolox C. Our findings suggest that trolox C reduces hepatocellular damage as indicated by abnormalities in microsomal drug-metabolizing function during I/R, and that this protection is, in part, caused by decreased lipid peroxidation.

Synthesis, Cytotoxicity and Antitumor Activity of 2,3-Diarylcyclopent-2-ene-1-ones

Nguyen-HaiNam,YongKim,Young-JaeYou,Dong-HoHong,Hwan-MookKim,Byung-ZunAhn 대한약학회 2002 Archives of Pharmacal Research Vol.25 No.5

The present study was done to determine the effect of trolox C, a hydrophilic analogue of vitamin E, on hepatic injury, especially the alteration in cytochrome P-450 (CYP)-dependent drug metabolism during ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Rats were treated intravenously with trolox C (2.5 mg/kg) or vehicle (PBS, pH 7.4), 5 min before reperfusion. Serum alanine aminotransferase and lipid peroxidation levels were markedly increased after I/R. This increase was significantly suppressed by trolox C. Cytochrome P-450 content was decreased after I/R but was restored by trolox C. There were no significant differences in ethoxyresorufin O-dealkylase (CYP 1A1) and methoxyresorufin O-dealkylase (CYP 1A2) activities among any of the experimental groups. Pentoxyresorufin O-dealkylase (CYP 2B1) activity was decreased and aniline p-hydroxylase (CYP 2E1) activity was increased after I/R. Both these changes were prevented by trolox C. Our findings suggest that trolox C reduces hepatocellular damage as indicated by abnormalities in microsomal drug-metabolizing function during I/R, and that this protection is, in part, caused by decreased lipid peroxidation.