• Journal of Periodontal and Implant Science
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• 제30권2호
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• pp.359-374
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• 2000

Cyclosporine A(CsA) is a widely used immunosuppressant for transplant patients and is also used for the treatment of a wide variety of systemic diseases with immunologic disorders. However, its use is frequently limited because of complications such as nephrotoxicity or gingival hyperplasia. Although several hypotheses have been postulated for CsA-induced gingival hyperplasia, i.e. various cytokine effects of inflammatory cells, existence of plaque or CsA itself, but its pathogenesis is still unclear. For experimental chronic CsA toxicity, salt depletion has been shown to increased susceptibility of rodents to the effects of CsA, and this maneuver facilitates production of arteriolopathy and interstitial fibrosis in kidney that mimic the changes found in human. The purpose of this study was to evaluate pathogenesis of CsA-induced gingival hyperplasia by comparing changes between CsA administration groups of normal standard diet and those of low salt diet group. Specific pathogen-free, 20 to 25 days old(120 to 150 g), male Fisher-344 rats(KIST, Korea), 120 to 150g of body weight, were assigned to four groups of six animals each after one week of adaptation period for powder food. Group 1 received olive oil($300{\mu}l/g\;of\;diet$) with normal standard diet(0.4% of sodium)(NSD). Group 2 received CsA(Cypol-N, Jonggundang, Korea; $300{\mu}g/g\;of\;diet$) with normal standard diet(NSD+CsA). Group 3 received same amount of olive oil with low salt diet(0.05 % of sodium, Teklad Premier, U.S.A.)(LSD). Group 4 received same dose of CsA with low salt diet(LSD+CsA). Rats were pair fed and were sacrificed after six weeks. Renal histologic lesions associated with CsA, consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles and the impairment of renal function including increase of serum creatinine and decrease of glomerular filtration rate was more severe in low salt diet group. These were proved as the results of activated of renin-angiotensin system in the kidney by low salt condition. Meanwhile the degree of gingival hyperplasia at incisor and molar tooth was less severe in low salt diet group compared with normal sodium diet group. Hyperplastic gingiva showed mild epithelial hyperplasia and expanded underlyng stroma which consisted of matrix increasement, capillary proliferation and dilatation. While the number and the activation of fibroblasts were increased, inflammatory cells were rare in the stroma. The immunohistochemistry for TGF-${\beta}_1$ in the kidney and gingiva revealed stronger positive in LSD+CsA in kidney but in gingiva of NSD+CsA. These results suggested followings; Gingival hyperplasia can be developed without inflammatory cells infiltration and seemed not induced by CsA by itself. The major role for gingival hyperplasia by CsA would be the secondary effect of TGF-${\beta}$, which maybe upregulated by CsA administration. Low salt diet can attenuate this hyperplasia perhaps by decreasing the activation of $TGF-{\beta}$.

• Laboraroty Animal Research
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• 제33권2호
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• pp.57-67
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• 2017

The inhibitory effects of Asparagus cochinchinensis against inflammatory response induced by lipopolysaccharide (LPS), substance P and phthalic anhydride (PA) treatment were recently reported for some cell lines and animal models. To evaluate the hepatotoxicity and nephrotoxicity of A. cochinchinensis toward the livers and kidneys of ICR mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed in male and female ICR mice after oral administration of 150, 300 and 600 mg/kg body weight/day saponin-enriched extract of A. cochinchinensis (SEAC) for 14 days. The saponin, total flavonoid and total phenol levels were found to be 57.2, 88.5 and 102.1 mg/g in SEAC, respectively, and the scavenging activity of SEAC gradually increased in a dose-dependent manner. Moreover, body and organ weight, clinical phenotypes, urine parameters and mice mortality did not differ between the vehicle and SEAC treated group. Furthermore, no significant alterations were measured in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and the serum creatinine (Cr) in the SEAC treated group relative to the vehicle treated group. Moreover, the specific pathological features induced by most toxic compounds were not observed upon liver and kidney histological analysis. Overall, the results of the present study suggest that SEAC does not induce any specific toxicity in the livers and kidneys of male and female ICR mice at doses of 600 mg/kg body weight/day.

• Journal of Applied Biological Chemistry
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• 제63권4호
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• pp.413-420
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• 2020

알코올성 간손상을 유발한 마우스 모델에서 새싹인삼 지상부 추출물(HGE)의 간 보호 효과를 확인하였다. 알코올성 간손상 모델은 25% 알코올을 마우스에 5 g/kg의 농도로 경구 투여하여 이루어졌고, HGE를 투여한 군에는 알코올을 투여하기 3일전부터 경구투여를 시작하여 10일간 마우스 개체 당 4와 12 mg/kg의 농도로 경구투여 하였다. HGE를 투여한 그룹에서는 알코올만 처리한 대조군에 비해 AST 및 ALT 수치가 농도의존적으로 낮아진 것을 확인하였다. 또한, 간손상에 의해 증가된 LDH 수치는 대조군과 유사하게 감소하였다. 새싹인삼 지상부 추출물로 부터 ginsenoside F5, F3, F1, 및 F2의 정량분석 결과는 각각 2.5, 4.4, 1.4, 및 23.3 mg/g으로 확인하였다.

• 한국식품위생안전성학회지
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• 제30권1호
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• pp.120-125
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• 2015

본 연구는 Sprague-Dawley 계통의 4주령 랫드에서 MSG의 반복경구투여 독성평가와 행동실험을 통해 어린랫드의 인지능력과 불안감에 미치는 영향을 평가하기 위해서 시행하였다. 시험군은 MSG 대신 distilled water를 투여한 대조군(Control, n = 4), MSG를 3 g/kg을 투여한 군(Low, n = 4), MSG를 5 g/kg을 투여한 군(High, n = 4)으로 나누어 4주 동안 주5회 경구투여를 하였다. MSG의 안정성을 확인하기 위해 다음과 같은 관찰 및 검사를 하였다. 검사항목으로는 체중의 변화, 임상증상, 행동실험인 T-maze, Elevated-plus-maze와 혈액학적 검사, 혈청생화학적 검사, 병리조직학적 검사를 관찰한 결과 모든 투여군 및 대조군에서 특이할 만한 임상증상과 체중변화는 관찰되지 않았으며, 폐사 및 빈사 동물은 시험 전 기간을 통하여 발견되지 않았다. 행동실험인 T-maze 결과 MSG 고용량 투여군에서 움직이는 횟수가 감소하다 증가하는 양상을 보였고, Elevated-plus-maze 실험에서는 MSG 고용량 투여군의 Open arm의 출입빈도가 증가하는 등 유의적인 변화가 나타났다. 혈액학적 검사 및 혈청생화학적 검사에서는 대조군과 비교 시 유의적인 변화가 관찰되었지만 그 수치가 정상범위 안에 포함되기 때문에 이상을 나타내지 않았다. 병리조직검사 또한 약간의 염증발생 소견이 나왔지만 정상범위 안에 포함되기 때문에 이상을 나타내지 않았다고 판단했다. 따라서, 어린랫드를 이용한 MSG의 반복투여 독성시험 결과 특이할만한 신체적인 변화는 나타나지 않았으나 고용량의 MSG 투여는 어린랫드에서 인지능력의 저하 및 행동의 불안을 유발할 가능성이 있다고 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7367-7369
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• 2013

Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-${\beta}$) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

• 한국가축번식학회지
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• 제24권3호
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• pp.241-248
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• 2000

본 연구는 생약제재가 dioxin의 연속투여시 생식독성 완화에 미치는 영향을 구명하고저 30 $\mu\textrm{g}$/kg의 dioxin을 5일간 연속투여 후 생약제재를 3주간격일로 경구투여 했을 때 정자수, 정자활력, 정소중량 및 정소조직에 미치는 영향을 조사하였다. 1. Dioxin 10~20 $\mu\textrm{g}$/kg을 5일간 연속투여한 군의 정자수는 90.7$\pm$3.6~l18.5$\pm$3.6$\times$$10^{6}$$m\ell$, 30~40 $\mu\textrm{g}$/kg투여군의 정자수는 67.3$\pm$4.1~88.2$\pm$3.3$\times$$10^{6}$$m\ell$로서 대조군의 119.3$\pm$3.4~120.2$\pm$4.7$\times$$10^{6}$$m\ell$에 비해 현저히 감소된 정자수를 나타냈다(p<0.05). 2. dioxin 10~20 $\mu\textrm{g}$/kg 투여군의 정자활력은 77.0$\pm$4.7~89.5$\pm$3.6%, 30~40$\mu\textrm{g}$/kg 투여군은 66.5$\pm$3.3~79.9$\pm$3.8%로서 대조군의 93.6$\pm$3.8~94.9$\pm$3.4%에 비해 현저히 감소된 정자활력을 나타냈다(p<0.05). 3. Dioxin 30 $\mu\textrm{g}$/kg을 5일간 연속투여 후 녹차, 홍삼, 구기자, 오메 추출물을 격일로 3주간 투여했을 때 정자수는 각각 77.4$\pm$3.2~90.9$\pm$3.4$\times$$10^{6}$$m\ell$, 78.0$\pm$3.3~105.0$\pm$4.2$\times$$10^{6}$$m\ell$, 76.2$\pm$2.8 ~84.4$\pm$3.5$\times$$10^{6}$$m\ell$, 75.4$\pm$3.3~80.2$\pm$3.3$\times$$10^{6}$$m\ell$이었다. 4. Dioxin 30 $\mu\textrm{g}$/kg을 5일간 연속투여 후 녹차, 홍삼, 구기자, 오메 추출물을 격일로 3주간 투여했을 때 정자활력은 대조군의 119.3$\pm$3.4~120.2$\pm$4.7$\times$$10^{6}$$m\ell$와 93.0$\pm$3.5~96.1$\pm$3.5%에 비해 홍삼추출물 투여군에서는 회복이 현저하였고(p<0.05), 녹차는 다음이었으며, 구기자, 오메는 회복이 미미하였다. 5. Dioxin 30 $\mu\textrm{g}$/kg을 5일간 연속투여 후 녹차, 홍삼, 구기자, 오메 추출물을 각각 격일로 3주간 투석했을 때 정소중량은 대조군의 0.15$\pm$0.01~0.16$\pm$0.01g에 비해 낮은 치를 나타냈으며 홍삼추출물 투여군에서는 회복효과가 현저하였다. 6. Dioxin 30 $\mu\textrm{g}$/kg을 5일간 연속투여 후 녹차, 홍삼, 구기자, 오메를 각각 3주간 격일로 경구 투여했을 때 간, 비장 및 정소조직은 대조군에 비해 심한 손상이 관찰되었으며, 정소는 홍삼 투여군에서 많은 회복이 관찰되었다.