• Development and Reproduction
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• v.14 no.3
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• pp.199-205
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• 2010

A neurotoxin, 6-hydroxydopamine (6-OHDA) has been widely used to create animal model for Parkinson's disease (PD). The present study was undertaken to examine whether depletion of brain dopamine (DA) stores with 6-OHDA can make alteration in the activities of the testicular steroidogenesis in adult rats. Young adult male rats (3 months old) were received a single dose of 6-OHDA (200 ${\mu}g$ in 10 ${\mu}{\ell}$/animal) by intracerebroventricular (icv) injection, and sacrificed after two weeks. The mRNA levels of steroidogenesis-related enzymes were measured by qRT-PCRs. Serum testosterone levels were measured by radioimmunoassay. Single icv infusion of 6-OHDA significantly decreased the mRNA levels of CYP11A1 (control:6-OHDA group=$1:0.68{\pm}0.14$ AU, p<0.05), CYP17 (control:6-OHDA group=$1:0.72{\pm}0.13$ AU, p<0.05). There were no changes in the mRNA levels of $3{\beta}$-HSD (control:6-OHDA group=$1:0.84{\pm}0.08$ AU) and $17{\beta}$-HSD (control: 6-OHDA group=$1:0.63{\pm}0.20$ AU), though the levels tended to be decreased in the 6-OHDA treated group. Administration of 6-OHDA decreased significantly the mRNA level of StAR when compared to the level of saline-injected control animals (control:6-OHDA group=$1:0.72{\pm}0.08$ AU, p<0.05). Treatment with single dose of 6-OHDA remarkably lowered serum testosterone levels compared to the levels of control group (control:6-OHDA group=$0.72{\pm}0.24:0.13{\pm}0.03ng/m{\ell}$, p<0.05). Taken together with our previous study, the present study demonstrated that the activities of hypothalamus-pituitary-testis hormonal axis could be negatively affected by blockade of brain DA biosynthesis, and suggested the reduced reproductive potential might be resulted in the animals. More precise information on the testicular steroidogenic activities in PD patients and PD-like animals should be required prior to the generalization of the sex steroid hormone therapy to meet the highest standards for safety and efficacy.

• Nutrition Research and Practice
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• v.16 no.5
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• pp.589-603
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• 2022

BACKGROUND/OBJECTIVES: Previous studies have reported that protein supplementation contributes to the attenuation of inflammation. Serious trauma such as burn injury usually results in the excessive release of inflammatory factors and organs dysfunction. However, a few reports continued to focus on the function of protein ingestion in regulating burn-induced inflammation and organ dysfunction. MATERIALS/METHODS: This study established the rat model of 30% total body surface area burn injury, and evaluated the function of blended protein (mixture of whey and soybean proteins). Blood routine examination, inflammatory factors, blood biochemistry, and immunohistochemical assays were employed to analyze the samples from different treatment groups. RESULTS: Our results indicated a decrease in the numbers of white blood cells, monocytes, and neutrophils in the burn injury group administered with the blended protein nutritional support (Burn+BP), as compared to the burn injury group administered normal saline supplementation (Burn+S). Expressions of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6 [IL-6]) and chemokines (macrophage chemoattractant protein-1, regulated upon activation normal T cell expressed and secreted factor, and C-C motif chemokine 11) were dramatically decreased, whereas anti-inflammatory factors (IL-4, IL-10, and IL-13) were significantly increased in the Burn+BP group. Kidney function related markers blood urea nitrogen and serum creatinine, and the liver function related markers alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were remarkably reduced, whereas albumin levels were elevated in the Burn+BP group as compared to levels obtained in the Burn+S group. Furthermore, inflammatory cells infiltration of the kidney and liver was also attenuated after burn injury administered with blended protein supplementation. CONCLUSIONS: In summary, nutritional support with blended proteins dramatically attenuates the burn-induced inflammatory reaction and protects organ functions. We believe this is a new insight into a potential therapeutic strategy for nutritional support of burn patients.

• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.138-143
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• 2009

Ischemia/reperfusion injury(I/RI) is the major cause of acute renal failure and delayed graft function(DGF) unavoidable in renal transplantation. Enormous studies on ischemia damage playing a role in activating graft rejection factors, such as T cells or macrophages, are being reported. Present study was performed to determine whether ischemia time would play an important role in activating rejection-related factors or not in rat models of I/RI. Male Sprague-Dawley rats were submitted to 30, 45, and 60 minutes of warm renal ischemia with nephrectomy or control animals underwent sham operation(unilateral nephrectomy). Renal function and survival rates were evaluated on day 0, 1, 2, 3, 5 and 7. Immunofluorescence staining of dendritic cells(DCs), natural killer(NK) cells, macrophages, B cells, CD4+ and CD8+ T cells were measured on day 1 and 7 after renal I/RI. Survival rates dropped below 50% after day 3 in 45 minutes ischemia. Histologic analysis of ischemic kidneys revealed a significant loss of tubular architecture and infiltration of inflammatory cells. DCs, NK cells, macrophages, CD4+ and CD8+ T cells were infiltrated from a day after I/RI depending on ischemia time. Antigen presenting cells(DCs, NK cells or macrophages) and even T cells were infiltrated 24 hours post-I/RI, which is at the time of acute tubular necrosis. During the regeneration phase, not only these cells increased but B cells also appeared in more than 45 minutes ischemia. The numbers of the innate and the adaptive immune cells increased depending on ischemia as well as reperfusion time. These changes of infiltrating cells resulting from each I/RI model show that ischemic time plays a role in activating rejection related immune factors and have consequences on progression of renal disease in transplanted and native kidneys.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.97-105
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• 1993

Adenosine receptors in rat adipose tissues have been reported to be of $A_{1}$ subclass, and their stimulation leads to inhibition of adenylyl cyclase, resulting in inhibition of lipolysis. In the present study we investigated changes in $A_{1}$ adenosine receptor-adenylyl cyclase system of adipocytes following induction of experimental diabetes in rats. One week following experimental diabetes were induced by intravenous injection of streptozotocin (50 mg/kg body wt.), adipocytes from rats $(170{\sim}230g)$ fed ad libitum were isolated using collagenase. When adipocytes were incubated for 1 h with 1 unit/ml adenosine deaminase and $1\;{\mu}M$ isoproterenol, and assayed for glycerol formation, it was found that the inhibition of lipolysis in diabetic adipocytes by $(-)-N^{6}-(R-phenylisopropyl)adenosine$ (PIA), an $A_{1}$, adenosine receptor agonist, was twice that of control adipocytes. In an effort to delineate the mechanism(s), $[^{3}H]PIA$ binding to adipocytic membranes from diabetic and control rats were determined. Neither the affinities nor numbers of $A_{1}$ adenosine receptor were significantly different from each other (Best fit parameters for the one-site model are: $K_{d}=0.51{\pm}0.09nM$ and $B_{max}=1.60{\pm}0.12\;pmoles/mg$ protein for control membranes; $K_{d}=0.54{\pm}0.21\;nM$ and $B_{max}=1.72{\pm}0.31\;pmoles/mg$ protein for diabetic membranes). However, the inhibiton by PIA of the isoproterenol-stimulated adenylyl cyclase activities was found to be 1.9 times higher in adipocytic membranes from diabetic rats than those from controls. These results suggest that the increased sensitivity of inhibition of lipolysis to PIA in adipocytic membranes from diabetic rats is due to changes in signal transduction pathways, rather than alterations of $A_{1}4 adenosine receptor molecules themselves.

• Korean Journal of Food Science and Technology
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• v.26 no.3
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• pp.213-220
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• 1994

Gastrodia (G) Rhizoma has been used clinically as an oriental herbal medicine with sedative, anticonvulsive, and depressor effects. The present study tested effects of G. Rhizoma extracts on the coronary circulation and myocardial oxygen consumption in perfused rat hearts. Sprague Dawley rats (SD) and spontaneously hypertensive rats (SHR) were employed as experimental animals and nonworking Langendorff heart perfusion technique introduced for heart experiments. G. Rhizoma extracts were prepared from grinding G. Rhizoma into powder, extracting in water and 50% ethanol for 4 or 16 hr and diluting with Krebs-Henseleit bicarbonate perfusion buffer to be 70%. Hearts were perfused with bicarbonate buffer oxygenated with 95% $O_{2}:$ 5% $CO_{2}$ at constant coronary perfusion pressure of $90cmH_{2}O$. The diluted extracts were infused into coronary arteries in a concentration of $1{\sim}5\;{\mu}M$ for $7{\sim}8 min. While in SD water- or ethanol-extracts of G. Rhizoma extracted for 16 hr increased coronary perfusate flow (CPF) and decreased coronary vascular resistance (CVR), ethanol-extracts in SHR produced coronary vasoconstriction associated with enhanced CVR. G. Rhizoma extracts-induced increase in CPF reduced myocardial oxygen extraction, and thus myocardial oxygen consumption ($MVO_{2}$) remained at that observed prior to infusion of extracts. In SD and SHR 16 hr-water-extracts markedly altered coronary venous effluent pH and $Pco_{2}$ and evoked metabolic acidosis, which could be a coronary vasodilator mechanism decreasing CVR. In this study, the extracts decreasing CVR in SD and SHR did not augment the lactate production. Therefore, although the effects of the extracts on cardiac function and coronary circulation depended on solvents and duration for extraction, the 16hr-water-extracts, at least, exhibited coronary vasodilation in SD and SHR. Conversely, ethanol-extracts constricted coronary arteries in SHR. G. Rhizoma extracts-induced vasodilation might be due to the metabolic acidosis rather than due to the increased lactate production. The results indicate that G. Rhizoma extracts obtained from proper extracting procedures can be used as a safe and clinically applicable herbal medicine in the cardiovascular diseases such as coronary artery disease and hypertension for vasodilatory and antihypertensive actions.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.5
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• pp.631-640
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• 2014

The inhibitory effects of Boswellia serrata (BW) extracts on degenerative osteoarthritis were investigated in primary-cultured rat cartilage cells and a monosodium-iodoacetate (MIA)-induced osteoarthritis rat model. To identify the protective effects of BW extract against $H_2O_2$ ($800{\mu}M$, 2 hr) in vitro, cell survival was measured by MTT assay. Cell survival after $H_2O_2$ treatment was elevated by BW extract at a concentration of $20{\mu}g/mL$. In addition, BW extract treatment significantly reduced and normalized the productions of pro-inflammatory factors, nuclear transcription factor ${\kappa}B$, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interleukin-6 at a concentration of $20{\mu}g/mL$. Treatment of chondrocytes with BW extract significantly reduced 5-lipoxygenase activity and production of prostaglandin E2, especially at a concentration of $10{\sim}20{\mu}g/mL$. For the in vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats. Consumption of a diet containing BW extract (100 and 200 mg/kg) for 35 days significantly inhibited the development and severity of osteoarthritis in rats. To determine the genetic expression of arthritic factors in articular cartilage, real-time PCR was applied to measure matrix metalloproteinases (MMP-3, MMP-9, and MMP-13), collagen type I, collagen type II, and aggrecan, and BW extract had protective effects at a concentration of 200 mg/kg. In conclusion, BW extract was able to inhibit articular cartilage degeneration by preventing extracellular matrix degradation and chondrocyte injury. One can consider that BW extract may be a potential therapeutic treatment for degenerative osteoarthritis.

• Journal of Life Science
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• v.15 no.5 s.72
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• pp.819-825
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• 2005

The Antioxidative accvities of the cell free extracts containing high glutathione by Saccharomyces cerevisiae FF-8 were tested in vitro experimental models : DPPH method for radical scavenging activity, ferric TBA method and ferric thiocyanate method using linoleic acid and tissue microsome for lipid peroxidation inhibitions. The concentration of intercellular glutathione by cultivating S. cerevisiae FF-8 in the YM optimal medium obtained $204\mug/ml$, which was increased by 2.76-fold from $74\mug/ml$ in the YM basal medium. A comparition between the YM basal medium and the YM optimal medium on antioxidative substance produced by S. cerevisiae FF-8 was investigated. In DPPH ($\alpha, \alpha-diphenyl-\beta-picrylhydrazyl$) method, the electron donating activity of the glutathione produced by S. cerevisiae FF-8 cultured in the YM optimal medium was as high as that of BHT ($ 0.05\%w/v $). The antioxidative a.tivity was measured by inhibition against lipid peroxidation of rat tissues' microsomes. The results of anti-oxidant activity of the cell free extracts by S. rerevisiae FF-8 cultured in the YM optimal medium was shown in the following order . $ liver 60.98\% > kidney 56.43\% > heart 52.91\% > brain 52.13\% > testis 45.57\% > spleen 42.95\% $. In antioxidative activities determined by ferric thiocyanate method and TBA methods against lipid peroxidation, the lipid peroxidation in the control mixture increased more rapidly than the typical peroxidation curve of linoleic acid from one day. The antioxidative activity of the cell free extracts by cultivating S. cerevisine FF-8 in the YM optimal medium were higher than that of the YM basal medium. These data indicate that the cell free extracts containing a high intercellular glutathione of S. cerevisiae FF-8 cultured in YM optimal medium showed strong antioxidative capacities by DPPH radical scavenging activity and ferric thiocyanate and TBARS measurements.

• The korean journal of orthodontics
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• v.28 no.5 s.70
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• pp.699-716
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• 1998

This study was designed to evaluate the expression of non-collagenous protein in periodontal tissue during the experimental movement of rat incisors, by LSAB(labelled streptavidine biotin) immunohistochemical staining for osteonectin and osteocalcin. Twenty seven Sprague-Dawley rats were divided into a control group(3 rats) and 6 experimental groups(24 rats) where 75g of force was applied from helical springs across the maxillary incisors. Rats of experimental groups were sacrificed at 12 hours, 1, 4, 7, 14 and 28 days after force application, respectively. And the tissues of a control group and experimental groups were studied immunohistochemically and histologically. The results were as follows : 1. Until 28 days after force application, periodontal fibers had been strectched on tension side and compressed in pressure side of all the experimental groups, and the arrangement of periodontal fibers had not been recovered yet. 2. The expression of osteonectin in control group was rare in dentin, cementum and osteocyte, and was mild in odontoblasts and matrix of alveolar bone. 3. The expression of osteocalcin in control group was negative in gingiva, osteoblasts, osteocyte and cementum, and was rare in predentin, capillaries in pulp and periodontal ligament and the matrix of alveolar bone. 4. There was no difference in the expression of osteocalcin or osteonectin in dentin, cementum, pulp, odontoblasts, between of control and of experimental groups. 5. The expression of osteonectin in intermaxillary suture got the peak in 7-day and was declined after 14-day. The expression of osteocalcin remained in a same degree since it became mild in 14-day. 6. The expression of osteonectin in pressure side of periodontal ligament of experimental group was rare, which was similar to control group. But in tension side, it was increased until 14-day aftrer which it was declined. 7. The expression of osteocalcin in periodntal ligament was rare in 12-hour to 14-day, but became severe in 28-day, which was greater in tension side than in pressure side, and in the periodontal fiber next to alveolar bone than to tooth surface. 8. The expression of osteocalcin in alveolar bone was rare until 14-day in pressure side, but became moderate in 28-day. The expression of osteonectin was increased from 7-day by time dependency, which was greater in tension side than in pressure side.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.321-330
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• 1994

The protective effect of 'ischemic preconditioning (PC)' on ischemia-reperfusion injury of heart has been reported in various animal species, but without known mechanisms in detail. In an attempt to investigate the cardioprotective mechanism of PC, we examined the effects of PC on the myocardial oxidative injuries and the oxygen free radical production in the ischemia-reperfusion model of isolated Langendorff preparations of rat hearts. PC was performed with three episodes of 5 min ischemia and 5 min reperfusion before the induction of prolonged ischemia (30 min)-reperfusion(20 min). PC prevented the depression of cardiac function (left ventricular pressure x heart rate) observed in the ischemic-reperfused heart, and reduced the release of lactate dehydrogenase during the reperfusion period. On electron microscopic pictures, myocardial ultrastructures were relatively well preserved in PC hearts as compared with non-PC ischemic-reperfused hearts. In PC hearts, lipid peroxidation of myocardial tissue as estimated from malondialdehyde production was markedly reduced. PC did not affect the activity of xanthine oxidase which is a major source of oxygen radicals in the ischemic rat hearts, but the myocardial content of hypoxanthine (a substrate for xanthine oxidase) was much lower in PC hearts. It is suggested from these results that PC brings about significant myocardial protection in ischemic-reperfused heart and this effect may be related to the suppression of oxygen free radical reactions.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.181-192
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• 1999

Background: Nitric oxide, a vasodilator synthesized from L-arginine by vascular endothelial cells, accounts for the biological activity of endothelium derived relaxing factor. Previous studies demonstrated that nitric oxide inhibitor, $N^{\omega}$-Nitro-L-Arginine(NNA) diminished the hyperdynamic splanchnic and systemic circulation in portal hypertensive rats The present study was done to determine the role of nitric oxide in the development of hyperdynamic circulations in the prehepatic portal hypertensive rat model produced by partial portal vein ligation. Methods: The portal hypertensive rats were divided into water ingestion group and NNA ingestion group. After partial portal vein ligation, NNA ingestion group and water ingestion group received NNA 1mg/kg/day and plain water through the mouth for 14 days, respectively. Cardiac output, mean arterial pressure, organ blood flow and porto-systemic shunting were measured by radioisotope labeled microsphere methods. Vascular resistances were calculated by standard equation. Results: There were significant decreases in mean arterial pressure, increases in cardiac output and cardiac index, and decreases in total systemic and splanchnic vascular resistance in portal hypertensive rats compared to normal control group (p<0.01). Compared to the water ingestion group, significantly increased mean arterial pressure with decreased cardiac output and cardiac index were developed in the NNA ingestion group. Total systemic and splanchnic vascular resistance were significantly increased in the NNA ingestion group compared to water ingestion group (p<0.05). But, there was no significant difference in portal pressure between the two groups. Conclusion: The hemodynamic results of this study indicate that hyperdynamic circulation in prehepatic portal hypertensive rat mode1 was attenuated by ingestion of NNA. Nitric oxide may play an important role in the development of hyperdynamic circulation with splanchnic vasodilation in chronic portal hypertension.