• Biomedical Science Letters
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• v.9 no.2
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• pp.75-84
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• 2003

To evaluate the influence of hepatic oxygen free radical systems on liver injury by topical p-phenylenediamine (PPD) application on rat skin, PPD (25 mg/16.5 $\textrm{cm}^2$) was topically applied to the abdominal region 5 times every other day and sacrificed. By PPD treatment, increasing rate of liver weight/body weight (%), serum activities of alanine aminotransferase and aspartate aminotransferase and decreasing rate of microsomal glucose-6-phosphatase activity were higher in the rats fed tungstate supplemented diet than those fed a standard diet. These findings indicate that group fed tungstate supplemented diet have more severe liver injury compared with group fed standard diet on topical PPD application. However, the activities of oxygen free radical generating enzymes such as xanthine oxidase (XO) and cytochrome P450 dependent aniline hydroxylase and those of oxygen free radical scavenging enzymes were not found to be different between these two animal groups. In the present study, a novel monitoring method to detect the generating of oxygen free radicals in liver extract was devised. Throughout this method, the oxidized PPD produced by oxygen free radicals was determined colorimetrically. The increasing rate of PPD oxidation by liver homogenate was higher in tungstate fed animals than in standard diet fed ones. Among the fractionations of liver extract, the mitochondrial and postmitochondrial fractions in the liver extract of tungstate fed animals led to a higher availability of PPD oxidation by PPD treatment compared with standard diet fed ones. In conclusion, these results suggest that an enhanced liver injury in tungstate fed animals treated with PPD may be due to oxygen free radicals produced in other systems except oxygen free radicals generating from cytosolic XO system. Especially, oxidative availability by PPD can be used for oxygen free radical detection in some tissue.

• Biomedical Science Letters
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• v.5 no.1
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• pp.51-58
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• 1999

To evaluate an effect of liver damage on the dermal oxygen free radical metabolizing enzyme activities, the $CCl_4$ (0.1 ml/ 100 g body wt., 50% $CCl_4$ in olive oil) was intraperitoneally given to the rats every other day for 2 weeks. Based on the histopathological findings, liver weight (%), serum alanine aminotransferase, xanthine oxidase activities and hepatic lipid peroxide contents, the animals were induced severe liver damage. In the present liver damaged animal, all the activities of dermal scavenging enzymes such as superoxide dismutase, catalase and glutathione peroxidase were significantly decreased compared with central. And under the cytochemical electron microscopy the more coarse granules of cerrous perhydroxide were found compared with the control. In conclusion, the $CCl_4$-induced liver damage may influence upon the activities of some dermal oxygen free radical scavenging enzymes.

• Journal of Environmental Health Sciences
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• v.28 no.2
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• pp.81-88
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• 2002

Effect of cyclohexanone treatment on the activities oxygen free radical and cyclohexanone metabolizing enzyme in acute liver damaged rats, was investigated. Acute liver damage was induced in rats with pretreatment of 50% $CCl_4$ in olive oil(0.1ml/100g body wt) intraperitoneally 3 times every other day. Cyclohexanone(1.56g/kg body wt, i.p.) was administered to the animals 24 hours after the last Pretreatment of CC1$_4$. Rats were sacrificed at 4 hours after injection of cyclohexanone. On the basis of liver weight/body weight(％), serum levels alanine aminotransferase activity and hepatic protein content, cyclohexanone treatment to acute liver damaged animals led to the more enhanced liver damage. On the other hand, injection of cyclohexanone to the rats led to the increased activities of hepatic cytochrome P-450 dependent aniline hydroxylase and xanthine oxidase. Furthermore, by treatment of cyclohexanone to the acute liver damaged rats hepatic xanthine oxidase activity was more increased than the $CCl_4$ treated rats. In case of oxygen free radical scavenging system, the hepatic glutathione content and the activities of hepatic glutathione S-transferase, catalase, superoxide dismutase were generally increased by injection of cyclohexanone to rats, and the hepatic glutathione content, catalase and alcohol dehydrogenase activities were more decreased in liver damaged rats by the treatment of cyclohexanone. In conclusion, the cyclohexanone treatment to acute liver damaged rats led to enhancement of liver damage that may be due to oxygen free radical together with cyclohexanone.

• The Journal of Korean Physical Therapy
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• v.11 no.3
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• pp.115-121
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• 1999

The effects of scald bum Injury ($40-45\%$ of total body surface area), there were not inhalation and secondary infection, on the histological changes and the levels of oxygen free radical generating and scavenging enzymes have been determined in liver tissue of rat models. It was found that dermal epithelium was left out with edema of dermis layer and hydorpic swelling of hepatocytes, Burn injury increased liver weight (L.W./B.W.) and serum aspartate aminotransferase content (pThe data of this study suggest that liver damage Induced by scald burn injury leads to dysbalance of oxygen free radical generating and scavenging enzymes.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.298-302
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• 1994

Wistar albino rats were injected subcutaneously with mercuric chloride (5 mg/kg) to define the early biochemical determinants that participate in the pathogenesis of mercuric chloride-induced hepatotoxicity, especially focusing on oxygen free radicals, we studied malondialdehyde(MDA) level and the activities of catalase and superoxide dismutase in the liver of rats at 24, 48 and 72 hr after the injection of mercuric chloride. MDA levels at 24, 48 and 72 hr after the injection of mercuric chloride increased as compared with that of control group. The activities of catalase and superoxide dismutase at 24, 48 and 72hr after the injection of mercuric chloride decreased as compared with that of control group. These results suggest that the depression of the activities of catalase and superoxide dismutase resulting from excessive oxygen free radicals is an important determinant in pathogenesis of mercuric chloride-induced hepatotoxicity.

• Biomedical Science Letters
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• v.7 no.3
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• pp.99-102
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• 2001

Toluene is mainly metabolized in liver by oxidative pathway. Oxigen free radicals occur through the process of toluene metabolism Therefore it causes tissue and cell min by the oxygen free radicals from the metabolism of toluene. Melatonin acts as a highly efficient free radical scavenger that protects cells from damage by oxygen free radicals. To test this hypothesis, toluene hepatotoxicity was induced by an abdominal injection of toluene. To see if the melatonin protects the rat's liver, melatonin was administrated orally, at the time of each toluene injection. Aspartate aminotransferase(AST), alanin aminotransferase(ALT), latic dehydrogenase(LDH) and alkaline phosphatase(ALP) levels in serum were measured to estimate hepatic function. Malondialdehyde(MDA), which gives an indirect index of oxidative injury was also measured. Hippuric acid is the last metabolic Production of toluene was measured by HPLC. There were significantly higher in AST, ALT, LDH, MDA and hippuric acid in toluene group, but there were no significant difference in melatonin group except ALT and hippuric acid. There was significantly lower in ALP level in toluene group, but there was no significant difference melatonin group, suggesting a significant hepatotoxicity due to oxygen free radicals through the process of toluene metabolism Melatonin treatment significantly protected hepatic function and free radical-mediated injury in the liver against toluene-induced changes. Accordingly, this study shows that melatonin is helpful in protecting liver injury by acute toluene intoxication.

• Biomedical Science Letters
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• v.9 no.3
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• pp.151-158
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• 2003

In the biological world, there are a number of ecological fights for survival between each organism such as plants, animals and microorganism In such events, an organism can use its natural bioactive products as defence agent against other organisms. Furthermore, natural bioactive products can be utilized for medicine or functional food. Recently, we investigate the effect of Monascus pigment extracted from a fungus, Monascus anke, on the alcohol metabolism and blood lipid profile. In the present study, it is observed that Monascus pigment supplemented dietary may have a hepatoprotective effect on rat's liver damage induced with $CCl_4$ . By treatment with $CCl_4$(3 times, I.P), liver damage was reduced more in the rats fed 2% Monascus pigment extract supplemented diet than those fed standard diet, based on the serum levels of alanine aminotransferase, microsomal glucose-6-phosphatse activity and hepaic malondialdehyde content. On the other hand, oxygen free radical generating enzymes, hepatic P-450 dependent aniline hydroxylase, xanthine oxidase, and oxygen free radical scavenging enzymes, hepatic glutathione S-transferase, catalase, superoxide dismutase activities were generally higher both in $CCl_4$ treated group and control fed 2% Monascus pigment extract supplemented diet than those fed standard diet. In conclusion, the rats fed 2% Monascus pigment extract supplemented diet showed more reduced liver damage than those fed standard diet, which may be due to the acceleration of oxygen free radical metabolism.

• The Journal of Korean Medicine
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• v.17 no.1 s.31
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• pp.21-36
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• 1996

This study was undertaken to examine the effect of Jwagyuyeum and Woogyuycum, being known to reinforce Kidney-yin and yang, on the activities of endogenous antioxidant enzymes and the production of oxygen free radicals in the liver and kidney tissues, Alterations in enzyme activities were observed after in vivo treatment in rats, Jwagyuyeum and Woogyuyeum caused a significant increase in the activities of superoxide dismutase(SOD) and catajase Jwagyuyeum significantly increased the activity of glutathione peroxidase in both liver and kidney, but the enzyme activity was not significantly altered by Woogyuyeum. Treatment in vitro of Jwagyuyeum and Woogyuyeum decreased the production of oxygen free radicals in a dose-dependent fashion. These results suggest that Jwagyuyeum and Woogyuyeum stimulate the activities of antioxidant enzymes and inhibit directly the production of oxygen free radicals. These effects of both herbs may contribute to prevent the oxygen free radical-induced impairment of cell function.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.5
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• pp.911-913
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• 2002

Rubi Fructus (fruit of Rubus coreanus Miq.), oriental medicine, has been used for remedy of the liver diseases and for tonic. In order to investigate the oxygen free radical, a harmful factor of aging, in liver of rats fed diets supplemented with the Rubi Fructus water extract(RX), Sprague-Dawley male rats have been fed a diet supplemented with 3% or 5% RX for a month. In rats fed 3% RX supplemented diet, hepatic cytochrome P-450 contents appeared to be increased, and catalase and superoxide dismutase activities were significantly increased compared with the control. There was no difference in glutathione peroxide and glutathione-S-transferase activities between the rats fed RX supplemented diets and the control diet. In conclusion, it is likely that rats fed a diet supplemented with RX may have the oxygen free radicals detoxication potential.

• Archives of Pharmacal Research
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• v.18 no.3
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• pp.189-194
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• 1995

The focus of this study was to investigate the influences of enzymatic scavengers of active oxygen metabolites and phospholipase $A_2$ inhibitor on hepatic secretory and microsomal function during hepatic ischemia/reperfusion. Rats were pretreated with free radical scavengers such as superoxide dismutase (SOD), catalase, deferoxamine and phospholipase $A_2$ inhibitor such as quinacrine and then subjected to 60 min. no-flow hepatic ischemia in vivo. After 1, 5 hr of reperfusion, bile was collected, blood was obtained from the abdominal aorta, and liver microsomes were isolated. Serum aminotransferase (ALT) level was increased at 1 hr and peaked at 5 hr. The increase in ALT was significantly attenuated by SOD plus catalase, deferoxamine and quinacrine especially at 5 hr of reperfusion. The wet weight-to-dry weight ratio of the liver was significantly increased by ischemia/reperfusion. SOD and catalase treatment minimized the increase in this ratio. Hepatic lipid peroxidiltion was elevated by ischemia/reperfusion, and this elevation was inhibited by free radical scavengers and quina crine. Bile flow and cholate output, but not bilirubin output, were markedly decreased by ischemia/reperfusion and quinacrine restored the secretion. Cytochrome $P_{450}$ content was decreased by ischemia/reperfusion and restored by free radical scavengers and quinacrine to the level of that of the sham operated group. Aminopyrine N-demethylase activity was decreased and aniline p-hydroxylase was increased by ischemia/reperfusion. The changes in the activities of the two enzymes were prevented by free radical scavengers and quinacrine. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory functions as well as microsomal drug metabolizing systems by increasing lipid peroxidation, and in addition to free radicals, other factors such as phospholipase $A_2$ are involved in pathogenes of hepatic dysfunction after ischemia/reperfusion.