• Natural Product Sciences
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• v.15 no.1
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• pp.37-43
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• 2009

Oxidative stress is caused by an imbalance between the production of reactive oxygen and an ability of a biological system, to readily detoxify the reactive intermediates or easily repair the resulting damage. It has been suggested that developmental alloxan-induced liver damage is mediated through increases in oxidative stress. The anti-diabetic effect and antioxidant activity of Phaleria macrocarpa (PM) fractions were investigated in alloxan-induced diabetic rats. After two weeks administration of PM, the liver antioxidant enzyme and hyperglycemic state were evaluated. The results showed that oral administration of PM treatments reduced blood glucose levels in diabetic rats by oral administration (P < 0.05). Serum glutamic-oxaloacetic transaminase (sGOT) and serum glutamic-pyruvate-transaminase (sGPT) were also diminished by PM supplementation. The superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx) activities, and glutathione (GSH) level in the alloxan-induced diabetic rats were significantly decreased (P < 0.05) compared to those in the normal rats but were restored by PM treatments. PM fractions also repressed the level of malondialdehyde (MDA) in the liver. Glutathione reductase (GR), glutathione-S-transferase (GST) and $\gamma$-glutamylcysteine synthase (GCS) were also reduced in alloxan-induced diabetic rats. PM fractions could restore the GR and GST activities, but the GCS activity was not affected in rat livers. From the results of the present study, the diabetic effect of the butanol fraction of PM against alloxan-induced diabetic rats was concluded to be mediated either by preventing the decline of hepatic antioxidant status or due to its indirect radical scavenging capacity.

• Journal of Environmental Health Sciences
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• v.27 no.2
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• pp.10-16
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• 2001

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.

• Archives of Pharmacal Research
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• v.27 no.3
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• pp.340-345
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• 2004

Our work in this study was made in the microsomal fraction to evaluate the lipid peroxidation by measuring superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) and to elucidate the preventive role of CS in the $CCl_4$-induced oxidative stress. The excessive lipid peroxidation by free radicals derived from $CCl_4$ leads to the condition of oxidative stress which results in the accumulation of MDA. MDA is one of the end-products in the lipid peroxidation process and oxidative stress. MDA, lipid peroxide, produced in this oxidative stress causes various diseases related to aging and hepatotoxicity, etc. Normal cells have a number of enzymatic and nonenzymatic endogenous defense systems to protect themselves from reactive species. The enzymes in the defense systems, for example, are SOD, CAT, and GPx. They quickly eliminate reactive oxygen species (ROS) such as superoxide anion free radicalㆍO$^{[-10]}$ $_2$, hydrogen peroxide $H_2O$$_2$ and hydroxyl free radicalㆍOH. CS inhibited the accumulation of MDA and the deactivation of SOD, CAT and GPx in the dose-dependent and preventive manner. Our study suggests that CS might be a potential scavenger of free radicals in the oxidative stress originated from the lipid peroxidation of the liver cells of $CCl_4$-treated rats.

• Applied Microscopy
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• v.31 no.1
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• pp.37-47
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• 2001

In order to investigate a pathogenesis of liver damage induced by skin burn, thermal injury was induced by scald burn on entirely dorsal surface in rats (total burn surface area $20\sim25\%$) except for inhalated injury. At 5 and 24 h after scald burn, biochemical assay and morphological changes in serum and liver tissue were examined. Skin burn increased liver weight (% of body weight, p<0.05) and the activity of serum aniline amino-transferase (ALT, p<0.05), in addition, the activity of xanthine oxidase (XO), an enzyme of oxygen free radical generating system, was elevated (p<0.01) in serum, but not in skin and in liver. Postburn treatment of allopurinol intraperitoneally decreased liver weight, serum ALT activity and serum XO activity. Scald burn induced ultrastructurally swelling of endoplasmic reticulum, ribosome detachment, accumulation of lipid, dilatation of bile canaliculi and intercellular space, neutrophil infiltration, activation of Kupffer's cells and degeneration of hepatocytic microvilli. Futhermore , thermal injury decreased not only the protein concentration in plasma but also the number of intravascular leukocytes, that indicates induction of edema formation with protein exudation and inflammation by neutrophil infiltration into the internal organs. However allopurinol injection after burn inhibited post burn ultrastructural changes. These data suggest that acute dermal scald burn injury leads to liver damage, that is related to elevation of xanthine oxidase activity in serum. Xanthine oxidase may be a key role in the pathogenesis of liver damage induced by skin burn.

• YAKHAK HOEJI
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• v.46 no.2
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• pp.129-136
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• 2002

The pathogenesis of cholestatic liver injury as well as the modulation of hepatic fibrogenesis is causally associated with involvement of reactive oxygen species (ROS) and free radical reactions. In this study, we investigated whether dried extracts of oriental medicine (LH) have antioxidant and antifibrotic effect under the biliary liver fibrosis (cirrhosis) c ondition. The female Sprague-Dawley rats were divided in six groups (Normal, N-LH, op-2, op-4, opLH-2, opLH-4) and were observed in 2 weeks or 4 weeks. For this purpose the rats were operated by bile duct ligation/scission (BDL/S), which induced to liver fibrosis and cirrhosis. After surgery, the prepared LH was administered p.o. 2 mι/day/rat in 2 weeks or 4 weeks for opLH groups. During the observation period, jaundices appeared in eyes, ears and tail of all BDL/S operated rats. And at the time of sacrifice, cholestasis was observed in proximal bile duct, especially the color of bile juice and urine in opLH-4 group showed more clear than op-2, op-4 and opLH-2 group. The value of clinical parameters and product of lipid peroxidation (MDA) in sera and the hydroxyproline (hyp) content in liver tissue were significantly increased in all liver fibrosis (cirrhosis) developed rats (p＜0.001~0.05). Among the clinical parameters of sera, value of BUN, ALP in opLH-4 group showed significantly lower than in op-4 group (p＜0.05, p＜0.001). The content of hyp in opLH-2, opLH-4 group (478.0 $\pm$ 134.3 $\mu\textrm{g}$/g 897.5 $\pm$ 118.2 $\mu\textrm{g}$/g) showed lower than in op-2, op-4 group (528.9 $\pm$ 220.7 $\mu\textrm{g}$/g, 1023.8 $\pm$ 277.1 $\mu\textrm{g}$/g) and then the value of MDA in opLH-4 was also significantly reduced to 59.4% of that in op-4 group (p＜0.001). The histological change (bile duct proliferation, fibrosis, collagen bundle) was similarly observed in op-2 group and in opLH-2 group, but the weak fibrosis and bile duct proliferation were observed in opLH-4 group compared with in op-4 group. Our data indicate that the 4 weeks treatment with LH extract suppressed lipid peroxidation and inhibited fibrotic (cirrhosis) process, and experimental cholestatic liver disease is associated with increased lipid peroxidation in BDL/S operated rats. Hence we concluded that the measurement of MDA and hyp can be useful monitor for the screening of antioxidant and antifibrotic effect in experimental liver fibrosis (cirrhosis), and LH has been shown to have hepatoprotective effect, antifibrotic effect and antioxidant effect.

• Natural Product Sciences
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• v.9 no.4
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• pp.235-240
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• 2003

Tectorigenin has an apoptosis-inducing ability and immunosuppressive activity. We investigated the effect of tectorigenin on Phase I and II enzyme activities to elucidate the pharmacological action of the immunosuppressive tectorigenin in the diabetic rat. This compound was obtained from the hydrolysis of tetoridin isolated from the flower of Pueraria thumbergiana (Leguminosae). This crude drug (Puerariae Flos) has been used as a therapeutic for diabetes mellitus in traditional Korean medicine. Tecotrigenin inhibited the formation of malondialdehyde (MDA) and hydroxy radicals in serum and liver but promoted superoxide dismutase (SOD) activity. Low MDA contents and low xanthine oxidase and aldehyde oxidase activities were observed in the tectorigenin-treated rats, suggesting that such Phase I enzyme activities are the major source of lipid peroxidation. However, tectorigenin increased Phase II enzyme activities such as SOD, glutathione peroxidase and catalase, suggesting the activation of free radical-scavenging enzymes. The activities of tectorigenin were comparable to those of glibenclamide, which was employed as a positive control. These results suggest that tectorigenin may share some biological properties with glibenclamide in insulin-dependent-diabetes mellitus (IDDM).

• Advances in Traditional Medicine
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• v.9 no.3
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• pp.225-231
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• 2009

The present study deals with the amelioration by Lagerstroemia speciosa Linn. leaf extract against hepatotoxicity induced by carbon tetrachloride ($CCl_4$), which was evaluated in terms of serum marker enzymes like serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, serum total bilirubin, total protein levels along with concomitant hepatic and antioxidants like superoxide dismutase, catalase, glutathione, glutathione peroxidase and lipid peroxidation enzymes were monitored. These biochemical parameters altered by the single dose level of $CCl_4$ (0.75 ml/kg body weight, i.p). Pre treatment with L. speciosa prior to the administration of $CCl_4$, at the doses of 50 and 250 mg/kg. body weight/day, p.o. for 7 days, significantly restored all the serum and liver tissue parameters near to the normal levels, respectively. Silymarin was used as a reference standard, prior to the administration of $CCl_4$ to rats. These findings indicate the protective potential of L. speciosa against hepato toxicity which possibly involve mechanism related to its ability of selective inhibitors of (reactive oxygen species like antioxidants brought about significant inhibition of TBARS suggesting possible involvement of $O_2{\cdot}-$, $HO_2{\cdot}$, and ${\cdot}OH$. In conclusion, the amelioration may be attributed to the synergistic effects of its constituents rather than to any single factor as the leaves are rich in tannins, sterols, flavonoids, saponins etc.

• Korean Journal of Plant Resources
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• v.22 no.5
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• pp.425-430
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• 2009

The objective of this study was to investigate the antioxidative capacity of oregano extracts. Amount of oregano extract at which DPPH radical scavenging activity was inhibited by 50% was $21.8{\mu}g$ as compared to 100% by pyrogallol as a reference. Total antioxidant status was examined by total antioxidant capacity against potent free radical reactions. Total antioxidant capacities of oregano extract at the amounts of 7.5 and $15{\mu}g$ were 15.1 and 31.4 nmol Trolox equivalents, respectively. Oxygen radical absorbance capacities of oregano extract at the amounts of 0.2 and $0.4{\mu}g$ were 1.4 and 2.4 nmol gallic acid equivalents, respectively. Total phenolic contents of oregano extract at the amounts of 30 and $75{\mu}g$ were 40.5 and 83.9 nmol gallic acid equivalents, respectively. The inhibitory effect of oregano extract on lipid peroxidation was examined using rat liver mitochondria induced by $FeSO_4$/ascorbic acid. Oregano extracts at the amounts of 20 and $50{\mu}g$ decreased TBARS level by 20 and 64%, respectively. Thus strong antioxidant effects of oregano extract seem to be due to, at least in part, the prevention against free radicals-induced oxidation, followed by inhibition of lipid peroxidation.

• Journal of Pharmacopuncture
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• v.11 no.1
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• pp.109-118
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• 2008

Objective : The objective of this study was to compare the antioxidant effects of hot pepper extract and capsaicin. Methods : In vitro, antioxidant activities were examined by DPPH radical scavenging activity, total antioxidant capacity(TAC), oxygen radical scavenging capacity(ORAC), inhibition of induced lipid peroxidation using liver mitochonria and total phenolic contents. Results : 1. DPPH free radical scavenging activities at the concentrations of both 1 and $10mg/m{\ell}$ were 1.2 to 1.9 times higher in capsaicin than in hot pepper extract. The concentration of capsaicin required for 50% radical scavenging was lower than that of hot pepper extract(3.9 vs $5.9mg/m{\ell}$), indicating that capsaicin had higher DPPH radical scavenging activity than hot pepper extract. 2. Total antioxidant capacities of capsaicin at the concentrations of 0.1 and 1mg/ml(13.8 and 41.3 nmol Trolox equivalent) were not significantly different from those at the concentrations of 1 and $10mg/m{\ell}$(11.4 and 41.2nmol Trolox equivalent), indicating that capsaicin showed 10 times higher ABTS radical scavenging activity compared to hot pepper extract. 3. ORAC of capsaicin at the concentrations of 1, 5, 10 and 100 mg/ml were 0.04, 0.17, 0.29 and 1.74nmol gallic acid equivalent, respectively. On the other hand, ORAC of hot pepper extract at the concentrations of 1, 5, 10 and $100{\mu}g/m{\ell}$ were 0.15, 0.44, 0.75 and 2.49nmol gallic acid equivalent, respectively, indicating that capsaicin showed higher peroxyl radical scavenging activity than hot pepper extract. 4. Inhibition of lipid peroxidation caused by hot pepper extract at the concentrations of 1 and $10mg/m{\ell}$ were 12.2 and 61.4%, respectively. Inhibition of lipid peroxidation caused by capsaicin at the concentrations of 1 and $10mg/m{\ell}l$ were 64.0 and 96.8%, respectively. Thus capsaicin showed 10 times stronger effect in inhibiton of lipid peroxidation than hot pepper extract. 5. Total phenolic contents of hot pepper extract at the concentrations of 0.1 and $1mg/m{\ell}$ were 1.4 and 20.8nmol gallic acid equivalent, respectively. Total phenolic contents of capsaicin at the concentrations of 0.1 and $1mg/m{\ell}$ were 6.1 and 55.4 nmol gallic acid equivalent, respectively, indicating that capsaicin had 2.7 to 4.3 times higher total phenolic contents than hot pepper extract. Conclusions : In summary, the results of this study demonstrate significant antioxidant activity of hot pepper extract, although the activity was lowered compared to capsaicin, suggesting that hot pepper extract play a role in prevention of oxidative-related diseases.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.4
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• pp.301-314
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• 2005

Objective: Rebamipide is a propionic acid derivative that has an action of the inhibition of superoxide production and removal of hydroxyl radical with the sperm incubation and cryopreservation. In the present study, to investigate whether rebamipide is useful to treat male infertility and sterility, the author observed the antioxidative effects in patient with male infertility and also examined its absorption and distribution in rat genital organ. Methods: To measure the distribution of rebamipide in reproductive organ in the rat, carbon indicated rebamipide, $^{14}C-OPC-12759$, was orally administered to 10 Spraque-Dawley rats and its organ concentration in serum, liver, kidney, stomach, duodenum, colon, urinary bladder, seminal vesicle, epididymis and testicle were measured each time after 0.5, 1, 2, 4, 8 and 24 hours by using HPLC fluorescent method. The concentrations in semen were measured by HPLC fluorescent method in a sample of 50 infertile males who took 900 mg of rebamipide daily for 3 months. To measure the antioxidative effect and fertility rate for 3 months, each month before and after the treatment, sperm motility, vitality, the oxygen free radical formation, level of peroxidation, fetilizing capacity of semen sample which were obtained from infertile male patients by masturbation after at least 48 hours abstinence were analyzed by computer assisted semen analyzer, eosin-nigrosin stain, chemiluminescence, thiobarbituric acid method and hypo-osmotic swelling test. Simultaneously in a sample that wanted baby, both pregnancy and delivery were researched. Results: The $^{14}C-OPC-12759$ concentration in the body of white rats was highest in gastrointestinal organ like stomach, smal intestine and duodenum and followed by genital organ like seminal vesicle, testis and epididymis. The rebamipide concentration in semen of infertile males was $220.77{\pm}327.84ng/mL$ (SD) which showed a large deviation but it was higher than serum which was $126{\pm}76ng/mL$ (SD). In the infertile males, after the treatment with rebamipide, the level of seminal reactive oxygen species (ROS) and lipid peroxidation have significantly decreased in duration of the treatment (p<0.05) and sperm vitality and fertilizing capacity except sperm motility significantly improved on post treatment of 2~3 months (p<0.05). Out of the 41 cases who hoped for pregnancy, 15 cases (36.6%) became pregnant and 12 cases had childbrith, 2 cases had miscarriage and one case is ongoing. The side effect was observed in 1 case (2%) which experienced diarrhea but it was lost spontaneously. Conclusions: We conclude from this study that rebamipide showed relatively high tendancy of absorption and excretion in the genital organ. In infertile males who had elevated ROS in semen, by specifically inhibiting the cell damage from the antioxidation, a way to preserve sperm motility, vitality and fertilizing capacity was confirmed.