This study evaluated the effectiveness of different arsenical sources on inducing fatty liver, on changes in lipid metabolism and on liver function in mule ducks. Sixty twelve-week-old mule ducks were selected and randomly divided into five treatments, including the control group and four different arsenical sources; Roxarsone (300 mg/kg), arsanilic acid, $As_2O_5$ or $As_2O_3$, containing 85.2 mg/kg arsenic were included in the basal diet. The ducks were fed the medicated basal diet for 3 weeks followed by a one-week drug withdrawal. The results showed Roxarsone treatment decreased body weight, feed intake, liver weight and abdominal fat weight (p<0.05), while it increased the relative liver weight (p<0.05) during medication period ($3^{rd}$ week). The $As_2O_5$ treatment decreased abdominal fat weight and relative abdominal fat weight when compared to the control (p<0.05). Only Roxarsone among the treatment groups increased feed intake, liver weight and relative liver weight, while the $As_2O_3$ group showed the lightest liver weight and relative liver weight among treatment groups during the withdrawal period ($4^{th}$ week). The Roxarsone group decreased (p<0.05) NADP-malic dehydrogenase (MDH) and acetyl-CoA carboxylase (ACC) activities and increased (p<0.05) cholesterol concentration during the medication period, and elevated the MDH and ACC activities during the withdrawal period. All four arsenical treatment groups showed lymphocytic infiltration in liver tissue, while the Roxarsone and $As_2O_3$ treatments showed an increase in aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities (p<0.05). During the withdrawal period, arsenical treatments resulted in liver vacuoles. However, the arsenicals differed in effectiveness and mechanisms of inducing fat vacuoles.
Jang, Young Eun;Park, Ji Ha;Roh, Seong Soo;Koo, Jin Suk;Seo, Bu Il
The Korea Journal of Herbology
/
v.30
no.3
/
pp.77-82
/
2015
Objectives : The Korean medical doctors use PMR(Polygoni Multiflori Radix) for nourishing the liver-kidney, loosing the bowel to relieve constipation, recovering from malaria, and clearing away heat and eliminating toxin, etc. But, this study was performed to investigate the effect of water extracts from PMR on prevention of hyperlipidemia and liver damage induced by alcohol. Methods : Except for the normal group, we fed rat on 25% alcohol for 55 days. And the extract was administrated for the same period. We measured the serum components in rat's blood, body weight and weight of liver. Results : At first, we observed effects of PMR on prevention of hyperlipidemia induced by alcohol. PMR group showed significant decrease of total cholesterol and triglyceride in comparison with those of the control group. PMR group showed significant increase of body weight in comparison with those of the control group in 4weeks and 8weeks. At second, we observed effects of PMR on prevention of liver damage induced by alcohol. PMR group showed significant decrease of GOT, GPT, ALP, and LDH in comparison with those of the control group. PMR group showed significant increase of liver weight in comparison with those of the control group. Conclusions : Reviewing these experimental results, it appears that water extracts from PMR have pharmaceutical efficacy on prevention of hyperlipidemia and liver damage induced by alcohol. Therefore further additional study should be conducted to elucidate in depth the pharmaceutical efficacy of these.
Seo, Bu-Il;Park, Ji-Ha;Choi, Hong-Sik;Kim, Seung-Mo;Gu, Deok-Mo;Kim, Mi-Ryeo;Park, Jin-Hyun
The Korea Journal of Herbology
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v.23
no.1
/
pp.9-15
/
2008
Objectives : This study was performed to investigate the effect of water extracts from Lagocephalus wheeled with several herbs(LW) on hyperlipemia and liver damage induced by alcohol. Methods : Except for the normal group, we fed rat on 25% alcohol for 55 days. And each extract was administrated for the same period. We measured the serum component in rat's blood, body weight and weight of liver. Results : At first, we observed effects of LW on hyperlipemia induced by alcohol. LW group didn't show significant increase of total cholesterol in comparison with those of the control group. LW group didn't show significant increase of HDL(High-Density lipoprotein) cholesterol in comparison with those of the control group. LW group showed significant decrease of triglyceride in comparison with those of the control group. LW group showed significant increase of body weight in comparison with those of the control group in 4weeks and 8weeks. LW group showed significant increase of liver weight in comparison with those of the control group. At second, we observed effects of LW on liver damage induced by alcohol. LW group showed significant decrease of ALP, GOT, GPT and LDH in comparison with those of the control group. Conclusions : Reviewing these experimental results, it appears that water extracts from Lagocephalus wheeleri with several herbs have pharmaceutical efficacy on hyperlipidemia and liver damage induced by alcohol. Therefore further additional study should be conducted to elucidate in depth the pharmaceutical efficacy of this.
Objectives : This study was performed to investigate the effect of water extracts from Phyllostachys Folium(PF) on hyperlipiderma and liver damage induced by alcohol. Methods : Except for the normal group, we fed rat on 25% alcohol for 55 days. And extract was administrated for the same period. We measured the serum component in rat's blood, body weight and weight of liver. Results : At first, we observed effects of PF on hyperlipidemia induced by alcohol. PF group didn't show significant change of total cholesterol in comparison with those of the control group. PF group showed significant increase of HDL(High-Density lipoprotein) cholesterol in comparison with those of the control group. PF group showed significant decrease of triglyceride in comparison with those of the control group. PF group showed significant increase of body weight in comparison with those of the control group at 4weeks and 8weeks. At second, I observed effects of PF group on liver damage induced by alcohol. PF group showed significant decrease of GOT, GPT, ALP and LDH in comparison with those of the control group. PF group showed significant increase of liver weight in comparison with those of the control group. Conclusions : Reviewing these experimental results, it appears that water extracts from Phyllostachys Folium(PF) have pharmaceutical efficacy on hyperlipidemia and liver damage induced by alcohol. Therefore further additional study should be conducted to elucidate in depth the pharmaceutical efficacy of these.
Yoo Jae Myung;Lee Youn Sun;Choi Heon Kyo;Lee Yong Moon;Hong Jin Tae;Yun Yeo Pyo;Oh Seik Wan;Yoo Hwan Soo
Archives of Pharmacal Research
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v.28
no.3
/
pp.311-318
/
2005
Oxidative stress has been reported to elevate ceramide level during cell death. The purpose of the present study was to modulate cell death in relation to cellular glutathione (GSH) level and GST (glutathione S-transferase) expression by regulating the sphingolipid metabolism. LLCPK1 cells were treated with H$_2$O$_2$ in the absence of serum to induce cell death. Subsequent to exposure to H$_2$O$_2$, LLC-PK1 cells were treated with desipramine, sphingomyelinase inhibitor, and N-acetylcysteine (NAC), GSH substrate. Based on comparative visual observation with H202-treated control cells, it was observed that 0.5 $\mu$M of desipramine and 25 $\mu$M of NAC exhibited about 90 and $95\%$ of cytoprotection, respectively, against H$_2$O$_2$-induced cell death. Desipramine and NAC lowered the release of LDH activity by 36 and $3\%$ respectively, when compared to $71\%$ in H$_2$O$_2$-exposed cells. Cellular glutathione level in 500 $\mu$M H202-treated cells was reduced to 890 pmol as compared to control level of 1198 pmol per mg protein. GST P1-1 expression was decreased in H$_2$O$_2$-treated cells compared to healthy normal cells. In conclusion, it has been inferred that H$_2$O$_2$-induced cell death is closely related to cellular GSH level and GST P1-1 expression in LLC-PK1 cells and occurs via ceramide elevation by sphingomyelinase activation.
Kim, Myung-Hwan;Namgoong, Hoon;Jung, Bae-Dong;Kwon, Myung-Sang;Choi, Yeon-Shik;Shin, Taekyun;Kim, Hyoung-Chun;Wie, Myung-Bok
Korean Journal of Veterinary Research
/
v.57
no.1
/
pp.1-7
/
2017
Parkinson's disease (PD) is an irreversible neurological disorder with related locomotor dysfunction and is characterized by the selective loss of nigral neurons. PD can be experimentally induced by 6-hydroxydopamine (6-OHDA). It has been reported that reactive oxygen species, which deplete endogenous glutathione (GSH) levels, may play important roles in the dopaminergic cell death characteristic of PD. Fucoidan, a sulfated algal polysaccharide, exhibits anti-inflammatory and anti-oxidant actions. In this study, we investigated whether fucoidan can protect against 6-OHDA-mediated cytotoxicity in SH-SY5Y cells. Cytotoxicity was evaluated by using MTT and LDH assays. Fucoidan alleviated cell damage evoked by 6-OHDA dose-dependently. Fucoidan reduced the number of apoptotic nuclei and the extent of annexin-V-associated apoptosis, as revealed by DAPI staining and flow cytometry. Elevation of lipid peroxidation and caspase-3/7 activities induced by 6-OHDA was attenuated by fucoidan, which also protected against cytotoxicity evoked by buthionine-sulfoximine-mediated GSH depletion. Reduction in the glutathione/glutathione disulfide ratio induced by 6-OHDA was reversed by fucoidan, which also inhibited 6-OHDA-induced disruption of mitochondrial membrane potential. The results indicate that fucoidan may have protective action against 6-OHDA-mediated neurotoxicity by modulating oxidative injury and apoptosis through GSH depletion.
The purpose of this study was designed to observe the effects of the feeding Cynanchum wilfordii extract on the improvement of the blood glucose, lipid components in the serum of dietary hyperlipidemic and streptozotocin(STZ) -induced diabetic rats(S.D. strain, ♂) fed the experimental diets for 5 weeks. Concentrations of total cholesterol, atherosclerotic index, LDL, LDL-Cholesterol, free-cholesterol. cholesteryl ester, TG, PL and blood glucose in serum were significantly higher in the cholesterol administration groups((group 2(cholesterol+water), 4(cholesterol+Cynanchum WIlfordii 3.5g% extract)) than those in the control group (group1 , basal diet+water). But the concentrations of total cholesterol. atherosclerotic index, LDL, LDL- cholesterol. free-cholesterol, cholesteryl ester, TG, PL and blood glucose in serum were remakably lower in the group 4 than those in the group 2. In the STZ(55mg/kg B.W.)-induced diabetic groups((group 3(STZ, IP.)+water), 5(STZ(IP.)+Cynanchum WIlfordii 3.5g% extract? the serum total cholesterol, atherosclerotic index, LDL, LDL-cholesterol, free-cholesterol. cholesteryl ester, TG, PL and blood glucose concentrations actions were rather lower in the group 5 than those in the group 3. In the ratio of HDL -cholesterol concentration to total cholesterol and HDL-cholesterol concentration, Cynanchum wilfordii extract administration groups were higher percentage than III the groups 2 and 3. The activities of aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase (ALP) and lactate dehydrogenase(LDH) in serum were rather lower in the Cynanchum wllfordii extract administration groups (group 4,5) than in the cholesterol diet group(group 2) and STZ-induced diabetic group (group 3). From the above research, the physiological activity substances in Cynanchum wllfordii were effective on the improvement of the blood glucose, lipid compositions in serum of dietary hyperlipidemic and STZ-induced diabetic rats. And particularly, physiological activity substance in Cynanchum wilfordii was more effective therapeutic regimen for the control of metabolic derangements in adult disease.
To investigate the immunomodulatory roles of cyclic AMP (CAMP) on macrophage- and T lymphocyte-mediated immune responses, CAMP elevating agents were employed and carefully re-examined under the activation conditions of the cells. Various inhibitors tested dose-dependently blocked tumor necrosis factor (TNF)-${\alpha}$ production with IC$_{50}$ values ranged from 0.04 to 300 ${\mu}$M. Of the inhibitors, cAMP-elevating agents showed lower cytotoxicity assessed by lactate dehydrogenase (LDH) release, suggesting less toxic and more selective. In particular co-treatment of dbcAMP with a protein kinase C inhibitor staurosporine displayed the synergistic inhibition of TNF-${\alpha}$ production. The modulatory effect of dbcAMP on TNF-${\alpha}$ and nitric oxide (NO) was significantly affected by treatment time of dbcAMP. Thus, post-treatment of dbcAMP (three hours before LPS) abrogated dbcAMP's inhibitory activity and rather enhanced TNF-${\alpha}$ level up to 60%. In contrast, additional NO production was shown at the co-treatment of dbcAMP with LPS. Unlike simultaneous treatment of phorbol 12-myristate 13-acetate (PMA) and interferon (IFN)-${\gamma}$co-treatment, the combination of dbcAMP with other NO-inducing stimuli did not show drastic overproduction of NO. cAMP elevating agents also diminished splenocyte proliferation stimulated by concanavalin (Con) A, phytohemaglutinin A (PHA) and lipopolysaccharide (LPS). In addition, dbcAMP but not rolipram strongly suppressed CD8$^+$ T cells (CTLL-2). Finally, cAMP elevating agents were differentially involved in regulating CD98-mediated cell-cell adhesion. Thus, dbcAMP and rolipram significantly enhanced the cell-cell adhesion, whereas forskolin blocked. Therefore, our results suggest that CAMP elevating agents participate in various immune responses mediated by macrophages and T cells with a different fashion depending on cellular environments and activation signals.
Studies on the effect of quinones on cardiac function has been conducted with normal hearts. But not with injured hearts, I.e. ischemia/reperfusion-injured heart. Quinone compounds are known to produce oxygen free radicals during metabolism, and for this reason, quinones are implicated in the aggravation of ischemia/reperfusion injury or cardioprotection, as in the case of ischemic preconditioning depending on the experimental conditions. The present study was carried out to examine the effect of 2-chloro-3-(4-cyanophenylamino)-1.4-naphthoquinone (NQ-Y15) on cardiac function of ischemic/reperfused and normal rat hearts. In isolated perfused hearts, various functional parameters such as left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (EDP) and maximum positive and negative dP/dt ($[\pm}dP/dt_{max}$), time to contracture, heart rate (HR) and coronary flow rate (CFR) were measured before and 30 min after dosing and following 25 min ischemia/30min reperfusion. NQ-Y15 increased LVDP, +dP/$d_{max}$and -dP/$dt_{min}$ by 18%. 30%, and 40%, respectively. There were no significant changes in other haemodynamic parameters. After ischemia/reperfusion injury, pretreatment with NQ-Y15 induced a significant decrease in LVDP and $[\pm}dP/dt_{max}$, but an increase in EDP. LDH-release was not significantly increased. These results suggested that NQ-Y15 may augment the ventricular contractility but it makes hearts more vulnerable to ischemia/reperfusion injury.
Myocardial ischemia-reperfusion injury is a medical problem occurring as damage to the myocardium following blood flow restoration after a critical period of coronary occlusion. Oxygen free radicals (OFR) are implicated in reperfusion injury after myocardial ischemia. The antioxidant enzyme, Cu, Zn-superoxide dismutase (Cu, Zn-SOD, also called SOD1) is one of the major means by which cells counteract the deleterious effects of OFR after ischemia. Recently, we reported that a PEP-1-SOD1 fusion protein was efficiently delivered into cultured cells and isolated rat hearts with ischemia-reperfusion injury. In the present study, we investigated the protective effects of the PEP-1-SOD1 fusion protein after ischemic insult. Immunofluorescecnce analysis revealed that the expressed and purified PEP-1-SOD1 fusion protein injected into rat tail veins was efficiently transduced into the myocardium with its native protein structure intact. When injected into Sprague-Dawley rat tail veins, the PEP-1-SOD1 fusion protein significantly attenuated myocardial ischemia-reperfusion damage; characterized by improving cardiac function of the left ventricle, decreasing infarct size, reducing the level of malondialdehyde (MDA), decreasing the release of creatine kinase (CK) and lactate dehydrogenase (LDH), and relieving cardiomyocyte apoptosis. These results suggest that the biologically active intact forms of PEP-1-SOD1 fusion protein will provide an efficient strategy for therapeutic delivery in various diseases related to SOD1 or to OFR.
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