• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.1
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• pp.41-64
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• 2014

Objectives: This study was to evaluate the effect of Jaeumkanghwa-tang (JEKHT) on the propylthiouracil (PTU)-induced rat hypothyroidism. Methods: Six groups, each of 8 rats per group were used in the present study - intact vehicle control, PTU control, Levothyroxine ($LT_4$), JEKHT 500, 250 and 125 mg/kg treated groups. JEKHT were administered once a day for 42 days as an oral dose of 500, 250 and 125 mg/kg, and hypothyroidism was induced by daily subcutaneous treatment of PTU 10 mg/kg for 28 days. The changes on the body and organ weight, serum hormone and lipid profiles, liver and testis antioxidant defense factors were observed with histopathology of organs. Results were compared with $LT_4$ 0.5 mg/kg intraperitoneally treated rats in this experiment. Results: PTU treatment, marked decrease of body weight, increases of thyroid weight, decreases of liver, testis, epididymis and prostate weights, decreases of serum Tri-iodothyronine ($T_3$), and Thyroxine ($T_4$) level with increase of serum Thyroid-stimulating hormone (TSH) level, decreases of serum testosterone and dihydrotestosterone (DHT) level with increases of serum Follicular stimulating hormone (FSH) level, increases of serum High density lipoprotein (HDL), decrease of triglyceride content, increase of serum Aspartate aminotransferase (AST) level, decreases of liver and testis antioxidant defense factors were observed. In addition, marked hyperplasia of follicular cells with decreases of follicular colloid contents and diameters was additionally demonstrated with the decrease of hepatocyte numbers per unit area due to hypertrophy of hepatocytes related to lipid droplet depositions, increase of a/oligospermatic epididymal tubules with epididymal atrophic changes, seminiferous tubular atrophy with decrease of stage I~II seminiferous tubules in testis, prostate tubular atrophic changes at histopathological inspections. However, these PTU induced hypothyroidism and related hepatic and male reproductive organ damages were favorably and dose-dependently inhibited by treatment of JEKHT 500, 250 and 125 mg/kg, and JEKHT also effectively regulated the PTU-induced abnormal antioxidant defense factor changes in the both liver and testis. Conclusions: JEKHT 500, 250 and 125 mg/kg dose-dependently inhibited PTU-induced hypothyroidism and related liver and male reproductive organ damages in rats.

• Journal of Life Science
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• v.31 no.7
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• pp.631-640
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• 2021

Houttuynia cordata Thunberg has been studied for a variety of pharmacological actions in traditional oriental medicine. In this study, we investigated the effects of Houttuynia cordata ethanol extract (HCE) on benign prostatic hyperplasia (BPH) models induced by castration and testosterone propionate (TP) injection. Thirty rats were divided into six groups. One group was used as a normal control, and the other groups were castrated and had intraperitoneal injections of TP for 14 days to induce BPH. A positive control group was given daily doses of finasteride (5 mg/kg) to the BPH model. Rats administered HCE (0.5, 1 or 2 mg/kg) instead of finasteride were compared with controls as experimental groups. There was no statistical significance in terms of prostate weight based on 100 g of body weight. The concentrations of 5-α reductase and dehydroxytestosteronre (DHT) were determined via ELISA tests, and there was a significant decrease in all experimental groups. The 0.5 mg/kg HCE group had the lowest level of 5-α reductase, and the 2 mg/kg HCE group had the lowest level of DHT. In the histopathological observation of prostates, the control and the 2 mg/kg HCE groups had normal cell shapes and no swelling. However, in the negative control group and the 1 mg/kg HCE group, the cells were swollen, and the gap between the cells was narrowed. In particular, in the 0.5 mg/kg HCE group, some cells were bursting. Therefore, the administration of more than 2 mg/kg of HCE is suitable to protect against BPH.

• Korean Journal of Food Science and Technology
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• v.50 no.6
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• pp.629-635
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• 2018

In this study, the safety aspect of Maesil-cheongs with reduced amygdalin levels was investigated in terms of toxicokinetics and repeated oral toxicity. Plasma or UVC treatment was utilized to obtain Maesil-cheongs with reduced amygdalin levels. The toxicokinetic study demonstrated that the oral absorption of amygdalin decreased remarkably after a single-dose oral administration of both plasma- and UVC-treated Maesil-cheongs. The fourteen-day repeated oral toxicity study revealed that plasma- or UVC-treated Maesil-cheongs did not cause changes in body weight, food intake, water consumption, and absolute and relative organ weights. No significant effects on hematological and serum biochemical parameters were found. Histopathological examination showed no abnormality or toxicological change. These findings suggest that plasma- and UVC-treated Maesil-cheongs have no toxicity potential, and these processes will be useful to obtain products with safe, reduced amygdalin levels.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.3
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• pp.370-378
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• 2019

The hepatic ischemic model has recently been widely used for the epidemiological study of ischemic reperfusion injury. This study was carried out to investigate the protective effect of vanillin, which is known to have antioxidant and anti-inflammatory effects, against hepatic and renal injury using an ischemia-reperfusion rat model, and we also investigated the mechanism related to vanillins' protective effect. The test material was administered at a concentration of 100 mg/kg for 3 days, followed by ligation of the liver for 60 minutes to induce ischemia reperfusion. As control groups, there was a negative control, sham control and ischemia-reperfusion-only ischemia reperfusion control, and the controls groups were compared with the drug administration group. In the vanillin group, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly inhibited compared with the AST and ALT activities of the ischemia-reperfusion group, and histopathological examination showed significant reduction of both inflammation and necrosis. The malondialdehyde (MDA) and superoxide dismutase (SOD) levels were significantly different from the ischemia-reperfusion group. In conclusion, vanillin showed a hepatocyte protective action by alleviating the cellular inflammation and cell necrosis caused by hepatic ischemia-reperfusion, and vanillin mitigated inflammatory changes in the kidney glomeruli and distal tubules. The protective effect is considered to be caused by vanillin's antioxidant function. Further studies such as on cell death and possibly vanillin's same effect on damaged tissue will be necessary for clinical applications such as organ transplantation.

• Journal of Environmental Health Sciences
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• v.46 no.6
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• pp.667-675
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• 2020

Objectives: Exposure to fine dust (PM10) could contribute to the occurrence of cardiovascular disease or respiratory abnormalities. Since garlic is known to possess an anti-oxidative stress effect, the present study was performed to evaluate the effect of garlic intake on fine dust-mediated pulmonary toxicity. Methods: Rats were intratracheally instilled with fine dust at 15 mg/kg body weight (BW)/day for five days following five-day intragastric intubation of garlic at 0.7 or 1.4 g/kgBW/day, or 13.1 mg/kgBW/day S-allyl-cysteine (SAC) as a reference component in garlic. Blood and bronchoalveolar lavage fluid (BALF) were collected. Results: Deposit of fine dust was visually and histopathologically observed in the lungs. Body weight gain during the instillation period was significantly lowered in all the groups instilled with fine dust. Neutrophil numbers in blood were significantly elevated in the fine dust alone group, but this alteration was diminished in the groups administered with garlic. Levels of serum glutathione were lower in the rats instilled with fine dust alone, and this decrease in the glutathione level seems dose-dependently compensated among the groups administered with garlic. Similar findings were observed in the BALF with statistical significance. Typical pulmonary histopathological observation related with inflammation was demonstrated in the lungs of the rats exposed to fine dust alone, whereas such histopathologic findings were not improved in the groups administered with garlic. Conclusion: The present study suggests that garlic intake could alleviate fine dust-mediated pulmonary or systemic toxicities. Further investigation is necessary to delineate the mechanism of garlic-mediated effects on pulmonary function.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.408-419
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• 2021

Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

• The Korea Journal of Herbology
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• v.28 no.3
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• pp.17-24
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• 2013

Objectives : This study was to evaluate the single dose toxicity of Persicae Semen (PS) in ICR mice. Methods : Aqueous extracts of PS (Yield = 18.60%) were administered as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) guidelines (2009-116, 2009). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. Results : Amygdalin contents in PS aqueous extracts were detected as $32.50{\pm}5.96{\mu}g/ml$. We could not find any PS extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations up to 2,000 mg/kg in both female and male mice, except for transient and slight loss of locomotion detected in female and male mice treated with 2,000 mg/kg. In addition, pharmacological immunomodulatory effects related findings were also demonstrated in 2,000mg/kg treated female and male mice as hypertrophy and hyperplasia of lymphoid cells in the submandibular lymph nodes. Conclusions : Based on the results of this experiment, the approximate lethal dose (ALD) of PS extracts after single oral treatment in female and male mice were considered above 2,000 mg/kg, respectively. It should be carefully used in clinics because the possibilities of respiratory or neurological disorders were observed when administered over 2,000 mg/kg of PS extract related to amygdalin.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.5
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• pp.353-375
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• 2022

No systematic review to date has examined histopathological parameters in relation to native liver survival in children who undergo the Kasai operation for biliary atresia (BA). A systematic review and meta-analysis is presented, comparing the frequency of native liver survival in peri-operative severe vs. non-severe liver fibrosis cases, in addition to other reported histopathology parameters. Records were sourced from MEDLINE, Embase, and CENTRAL databases. Studies followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and compared native liver survival frequencies in pediatric patients with evidence of severe vs. non-severe liver fibrosis, bile duct proliferation, cholestasis, lobular inflammation, portal inflammation, and giant cell transformation on peri-operative biopsies. The primary outcome was the frequency of native liver survival. A random effects meta-analysis was used. Twenty-eight observational studies were included, 1,171 pediatric patients with BA of whom 631 survived with their native liver. Lower odds of native liver survival in the severe liver fibrosis vs. non-severe liver fibrosis groups were reported (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.08-0.33; I²=46%). No difference in the odds of native liver survival in the severe bile duct destruction vs. non-severe bile duct destruction groups were reported (OR, 0.17; 95% CI, 0.00-63.63; I²=96%). Lower odds of native liver survival were documented in the severe cholestasis vs. non-severe cholestasis (OR, 0.10; 95% CI, 0.01-0.73; I²=80%) and severe lobular inflammation vs. non-severe lobular inflammation groups (OR, 0.02; 95% CI, 0.00-0.62; I²=69%). There was no difference in the odds of native liver survival in the severe portal inflammation vs. non-severe portal inflammation groups (OR, 0.03; 95% CI, 0.00-3.22; I²=86%) or between the severe giant cell transformation vs. non-severe giant cell transformation groups (OR, 0.15; 95% CI, 0.00-175.21; I²=94%). The meta-analysis loosely suggests that the presence of severe liver fibrosis, cholestasis, and lobular inflammation are associated with lower odds of native liver survival in pediatric patients after Kasai.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1213-1227
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• 2023

Fetal growth restriction (FGR) is a prevalent obstetric condition. This study aimed to investigate the role of Toll-like receptor 9 (TLR9) in regulating the inflammatory response and gut microbiota structure in FGR. An FGR animal model was established in rats, and ODN1668 and hydroxychloroquine (HCQ) were administered. Changes in gut microbiota structure were assessed using 16S rRNA sequencing, and fecal microbiota transplantation (FMT) was conducted. HTR-8/Svneo cells were treated with ODN1668 and HCQ to evaluate cell growth. Histopathological analysis was performed, and relative factor levels were measured. The results showed that FGR rats exhibited elevated levels of TLR9 and myeloid differentiating primary response gene 88 (MyD88). In vitro experiments demonstrated that TLR9 inhibited trophoblast cell proliferation and invasion. TLR9 upregulated lipopolysaccharide (LPS), LPS-binding protein (LBP), interleukin (IL)-1β and tumor necrosis factor (TNF)-α while downregulating IL-10. TLR9 activated the TARF3-TBK1-IRF3 signaling pathway. In vivo experiments showed HCQ reduced inflammation in FGR rats, and the relative cytokine expression followed a similar trend to that observed in vitro. TLR9 stimulated neutrophil activation. HCQ in FGR rats resulted in changes in the abundance of Eubacterium_coprostanoligenes_group at the family level and the abundance of Eubacterium_coprostanoligenes_group and Bacteroides at the genus level. TLR9 and associated inflammatory factors were correlated with Bacteroides, Prevotella, Streptococcus, and Prevotellaceae_Ga6A1_group. FMT from FGR rats interfered with the therapeutic effects of HCQ. In conclusion, our findings suggest that TLR9 regulates the inflammatory response and gut microbiota structure in FGR, providing new insights into the pathogenesis of FGR and suggesting potential therapeutic interventions.

• Korean Journal of Radiology
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• v.21 no.6
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• pp.647-659
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• 2020

Objective: The occurrence of intramyocardial hemorrhage (IMH) and microvascular obstruction (MVO) in myocardial infarction (MI), known as severe ischemia/reperfusion injury (IRI), has been associated with adverse remodeling. APT102, a soluble human recombinant ecto-nucleoside triphosphate diphosphohydrolase-1, can hydrolyze extracellular nucleotides to attenuate their prothrombotic and proinflammatory effects. The purpose of this study was to temporally evaluate the therapeutic effect of APT102 on IRI in rats and to elucidate the evolution of IRI in the acute stage using cardiovascular magnetic resonance imaging (CMRI). Materials and Methods: Fifty-four rats with MI, induced by ligation of the origin of the left anterior descending coronary artery for 60 minutes, were randomly divided into the APT102 (n = 27) or control (n = 27) group. Intravenous infusion of APT102 (0.3 mg/kg) or placebo was administered 15 minutes before reperfusion, and then 24 hours, 48 hours, 72 hours, and on day 4 after reperfusion. CMRI was performed at 24 hours, 48 hours, 72 hours, and on day 5 post-reperfusion using a 7T system and the hearts were collected for histopathological examination. Cardiac function was quantified using cine imaging and IMH/edema using T2 mapping, and infarct/MVO using late gadolinium enhancement. Results: The extent of infarction (p < 0.001), edema (p < 0.001), IMH (p = 0.013), and MVO (p = 0.049) was less severe in the APT102 group than in the control group. IMH size at 48 hours was significantly greater than that at 24 hours, 72 hours, and 5 days after reperfusion (all p < 0.001). The left ventricular ejection fraction (LVEF) was significantly greater in the APT102 group than in the control group (p = 0.006). There was a negative correlation between LVEF and IMH (r = -0.294, p = 0.010) and a positive correlation between IMH and MVO (r = 0.392, p < 0.001). Conclusion: APT102 can significantly alleviate damage to the ischemic myocardium and microvasculature. IMH size peaked at 48 hours post reperfusion and IMH is a downstream consequence of MVO. IMH may be a potential therapeutic target to prevent adverse remodeling in MI.