• 한국자원식물학회지
• /
• 제30권6호
• /
• pp.647-653
• /
• 2017

Hepatic ischemia-reperfusion injury (HIRI) is linked with high mortality rate. Several agents have been developed so far to reduce the risk of HIRI. In this study, we investigated the effects of Acanthopanax senticosus extract (AS) on hepatic ischemia-reperfusion. To explore the protective effects of A. senticosus extract injection (ASI) on hepatic ischemia-reperfusion injury rats animal model were used. After the development of HIRI by using clamping method rats were then randomly divided into five groups. Different doses of AS were administered in HIRI rat model. The level of ALT, AST, and MDA content in serum were detected in sham and HIRI groups. The activity of SOD, MPO and $Ca^{2+}-ATPase$, content of MDA, and cAMP in hepatic tissue were also measured. Expression of Bcl-2 and Bax protein were detected by immunohistochemical staining method. Compared with sham group, ASI has the protective effect on the HIRI model in rats. Blood levels of ALT, AST, SOD, MPO, and MDA were significantly lower in ASI group compared with HIRI. Indeed SOD and $Ca^{2+}-ATPase$ activities, MDA content, and cAMP level were improved in ASI group. Furthermore, Bcl-2 and Bax protein were improved in ASI group compared with only HIRI group. These results suggest that AS may provide potential ameliorative therapy by inhibiting the damage signaling mechanism in hepatic ischemia/reperfusion injury model.

• 한국산업보건학회지
• /
• 제17권3호
• /
• pp.181-191
• /
• 2007

With the 2-Butanethiol, which is an unidentified inhalation toxic material, acute inhalation toxicity was tested with SD rats. The $LC_{50}$ was evaluated to be 2,500 ppm (9.22 mg/L) or higher which falls under the criteria of acute toxicity Category 3 (500<$LC_{50}$<2,500 ppm) in the Industrial Safety and Health Act. In the subchronical inhalation toxicity test by 0, 25, 100, and 400 ppm, 6 hours a day, 5 days a week, for 13 weeks repeated exposure, though no death or particular clinical presentation was observed, in the female 25 and 400 ppm group, including weight change, and in each concentration group including 400 ppm, change of feed rate, eye stimulation, motility change in male group, and lesions in blood and blood biochemical were observed. In the internal organs weight, 25, 100, and 400 ppm groups in male and 400 ppm group in female showed significant (p<0.05) changes in kidney, liver, thymus, and lung. In the pathological tissue test, severe cortical tubular hyaline droplets were observed in the male 400 ppm group, and all male rats of 400 ppm group and 2 female individuals showed tubular degeneration/regeneration accompanied with pigmentation, showing that the target organs of inhalation exposure of 2-Butanethiol are spleen, kidney, nasal cavity, and adrenal. Through the tests, the NOEL of 2-Butanethiol was evaluated to be 25 ppm (0.092 mg/L) or less for both male and female.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권5호
• /
• pp.2931-2936
• /
• 2013

Background: Doxorubicin is an anthracycline antibiotic commonly used to treat a variety of cancers as a most effective antitumor. However, its clinical use is associated with the toxic effects in numerous healthy tissues. Here we investigated the pretreatment effect of regular aerobic exercise on oxidative stress in rats acutely exposed to DOX-induced hepatotoxicity. Materials and Methods: Forty-eight Wistar male rats were randomly divided into 2 groups: control and training. The training protocol included treadmill running between 25 to 54 min/day and 15 to 20m/min, 5 days/week for 6 weeks. At the end of the exercise training protocol, rats from the control and trained groups were again randomly separated into 3 subgroups: DOX10mg/kg, DOX20mg/kg and saline. All treatments were carried 24 h after the last exercise bout and animals were sacrificed 24 h after DOX and saline injections. Results: Administration of DOX (10 and 20 $mg.kg^{-1}$) resulted in imbalance in biomarkers related to oxidants and antioxidants in liver tissue, as compared to control groups. Six weeks of pretreatment training led to a significant increase in nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPX) as compared to the control+DOX 10 mg/kg group. Training before DOX 20 mg/kg administration also led to a significant increase in NO and SOD, and a significant decrease in malondialdehyde (MDA). In addition, there was a significant difference between DOX 10 mg/kg and DOX 20 mg/kg treatments in MDA levels, only. Conclusions: The results of the present study indicate that pretreatment with aerobic exercise induces positive adaptations and has a potential protective effect against doxorubicin (DOX)-induced hepatotoxicity with doses of 10 and 20 mg.kg.

• Journal of Nutrition and Health
• /
• 제34권3호
• /
• pp.253-264
• /
• 2001

This study was carried out to examine a part of the mechanism for the etiology of diabetic complications. Thirty normal and forty streptozotocin(STZ)-induced diabetic rats were used as the animal models. The animals were sacrificed at the time points of 3 days, 1,2,4 and 6 weeks after STZ-injection and a time course changes in the concentrations of thiobarbituric acid-reactive substances(TBARS) in blood, urine, and tissues, along with the levels of conjugated dienes in tissues were measured as indices of in vivo lipid peroxidation. The activities of antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase and the levels of blood retinol and alpha-tocopherol were also measured. The diabetic rats maintained a slightly higher plasma TBARS level throughout the experiment. The urinary TBARS level was significantly higher in diabetic group and gradually increased with time. Concentrations of TBARS in liver, heart, and kidney tissues from diabetic animals were higher than those from the normal group. An increase of conjugated dienes was also observed in the all tissues examined. The kidney tissue of diabetic animals revealed more significant lipid peroxidation state than any other organ tissues. The activities of hepatic antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase were higher in diabetic animals compared to the control ones and increased with the duration of diabetes mellitus. The plasma levels of vitamin A and E were loser in diabetic animals than in normal controls throughout the experimental period. The level of vitamin E in diabetic animals was significantly decreased with the duration of the disease. The results of this study suggest that an effective regimen to suppress the adverse changes in lipid peroxidation and antioxidant defense system is required from the early stage of the disease to prevent the development of diabetic complications. (Korean J Nutrition 34(3) : 253∼264, 2001)

• Journal of Nutrition and Health
• /
• 제29권2호
• /
• pp.232-241
• /
• 1996

This study was designed to compare the effect of different dietary fats on plasma lipids, the degree of lipid peroxidation and the activity of antioxidant enzymes in RBC and liver rats treated with or wighout 1, 2-dimethylhydrazing (DMH). Male Sprague Dawley rats, at 7 weeks-old, were divided into control and DMH-treated grous, and each group was again subdivided into four were perilla oil (PO), blend fat (BF) containing ten different kinds of dietary oil, beef tallow (BT), corn oil (CO). At the same time, each rat was injected intramusculary with saline(for control) or DMH twice a week for 6 weeks to give total dose of 180 mg/kg body weight. Compared with BT feeding, BF reduced plasma total choesterol level and PO and Co reduced plasma TG levels (p<0.05). DMH injection decreased plasma cholesterol in all dietary groups. However, PO decreased tocopherol levels and increased TBARS levels in RBC compared to BT. The degree of hemolysis in PO group was higher than that of BT group (p<0.05 only in control group. Fatty acid composition of hepatic microsome was reflected by dietary fatty acid profile. The peroxidizability index and TBARS level in hepatic micorsome were significantly increased but tocopherol level was lowered in PO group compared to BT group. Activites of superoxide dismutase and glutathione peroxidase in RBC and hepatic cytosol were not influenced y dietary fats and DMH treatment(p<0.05). Overall, perilla oil rich in $\omega$3 $\alpha$-linolenic acid could be a very important dietary source in reducing plasma lipids and blend fat was also good dietary oil mixture in reducing plasma cholesterol. However, the degree of lipid peroxidation was greater in tissue by perilla oil feeding and it is very difficult to use only perilla oil as oil source for meal preparation, so that it could be suggested to use more perilla oil and fish to give an equal effect of blend fat in order to reduce the risk factors against cardiovascular disease.

• 약학회지
• /
• 제42권6호
• /
• pp.589-597
• /
• 1998

Effects of Mori Folium Ethanol Soluble Fraction (MFESF) on mRNA expression of glucose transporters, acetyl-CoA carboxylase (ACC) and leptin were examined in db/db mice. 500 and 1000mg/kg dose for MFESF (designated by SY 500 and SY 1000, respectively) and 5mg/kg dose for acarbose were administered for 6 weeks. Quantitations of glucose transporters (GLUT-2 and GLUT-4), ACC and leptin mRNA were performed by RT-PCR and in vitro transcription with co-amplification of rat ${\beta}$-actin gene as an internal standard. Muscular GLUT-4 mRNA expression in MFESF-treated groups were increased dose dependently. On the other hand, MFESF caused the GLLT-4 and leptin mRNA expressions in adipose tissue to decrease dose dependently, which means that triglyceride synthesis in adipocytes might be decreased and consequently signals adipocytes to inhibit the synthesis and release of leptin. Hepatic ACC mRNA expression in MFESF-treated groups was also decreased. and this may result in lowering of serum triiglyceride level. In contrast, liver GLUT-2 mRNA expressions in MFESF-treated and acarbose groups were increased. Higher rate of glucose uptake into hepatocytes is known to inhibit a phosphoenolpyruvate carboxykinase (PEPCK)-catalyzed reaction, which is a rate-limiting step in gluconeogenesis.

• 한국발생생물학회지:발생과생식
• /
• 제21권4호
• /
• pp.441-448
• /
• 2017

Bisphenol-A(BPA) is a member of alkylphenol family, and shows adverse effects including reduced fertility, reproductive tract abnormalities, metabolic disorder, cancer induction, neurotoxicity and immunotoxicity. In the present study, we conducted Hershberger assay to evaluate whether the two candidates to replace BPA have androgenic or antiandrogenic activity. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were BPA, isosorbide (ISO) and cyclohexanedimethanol (CHDM). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and three androgen-insensitive tissues (kidney, spleen and liver) were measured. All test materials including BPA did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was CHDM > BPA > ISO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of BPA group as well as ISO group. In CHDM group, high dose treatment exhibited most severe weight reduction in all measured tissues. There was no statistical difference in androgen-insensitive tissue measurements, except BPA groups. Since the effects of ISO treatment on the accessory sex organs were much less or not present at all when compared to those of BPA, ISO could be a strong candidate to replace BPA. CHDM treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of BPA substitute selection.

• 한국발생생물학회지:발생과생식
• /
• 제22권1호
• /
• pp.19-27
• /
• 2018

In the present study, we employed Hershberger assay to determine possible androgenic or antiandrogenic activities of three di-2-ethylhexyl phthalate (DEHP) substitute candidates. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were DEHP, 2-ethylhexyl oleate (IOO), 2-ethylhexyl stearate (IOS) and triethyl 2-acetylcitrate (ATEC). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, coagulating glands, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and four androgen-insensitive tissues (kidney, adrenal glands, spleen and liver) were measured. All test materials including DEHP did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was ATEC < DEHP < ISO < IOO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of all replacement candidate groups. In DEHP groups, high dose treatment exhibited significant weight gains in LABC and Glan Penis. There was no statistical difference in androgen-insensitive tissue measurements. Since the effects of ATEC treatment on the accessory sex organs were much less or not present at all when compared to those of DEHP, ATEC could be a strong candidate to replace DEHP. IOO treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of DEHP substitute selection.

• The Korean Journal of Physiology and Pharmacology
• /
• 제12권1호
• /
• pp.7-12
• /
• 2008

OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium $(K_{ATP})$ channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of $K_{ATP}$ channels, insulin receptor ${\beta}$-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that $K_{ATP}$-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on $K_{ATP}$ channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects.

• Nutrition Research and Practice
• /
• 제2권4호
• /
• pp.218-226
• /
• 2008

The present study evaluated the effects of various dosages of soybean isoflavone extract on lipid profiles, lipid peroxidation and antioxidant activities in streptozotocin-induced diabetic rats. The one normal control group was fed an AIN-76-based experimental diet and four diabetic groups were fed the same diet, supplemented with four different levels of soybean isoflavone extract for seven weeks. The daily dosages of pure isoflavone for four diabetic groups were set to be 0 mg (diabetic control), 0.5 mg (ISO-I), 3.0 mg (ISO-II) and 30.0 mg (ISO-III) per kilogram of body weight, respectively. The plasma total cholesterol levels and the TBA-reactive substances contents in the liver and kidney were significantly lowered in ISO-II and ISO-III groups compared to those in the diabetic control group. The levels of plasma HDL-cholesterol, plasma vitamin A and hepatic superoxide dismutase were significantly increased in those two groups compared with the diabetic control group. The present study demonstrated the possibility that the diets supplemented with 3.0 mg and 30.0 mg of soybean isoflavone extract may have beneficial effects on the plasma lipids, tissue lipid peroxidation and partly on antioxidant system in diabetic animals and there were no significant differences between the ISO-II and ISO-III groups. The results suggest that the effective daily dosage level of isoflavone for improving lipid metabolism in diabetic rats may be above 3.0 mg per kilogram body weight.