성인의 급성 설사에 대한 로페라미드 옥사이드의 효과: 위약과의 무작위 이중 맹검 비교 다시설 시험

박영태,정희진,박중원,이계희,김나영,임선희,윤병철,한동수,이오영 大韓消化器病學會 1998 大韓消化器病學會誌 Vol.31 No.5

제주산 참다래가 Loperamide로 유도된 변비에 미치는 영향

김동건,진영건,진주연,김상철,김성철,한창훈,이영재 한국자원식물학회 2011 한국자원식물학회지 Vol.24 No.1

Loperamide-induced constipation reduced gastric emptying, small-intestinal and colonic motility, and these effects were prevented by Actindia chinensis(Gold Kiwi Fruit, GKF). In this study, the effects of Actindia chinensis on constipated male Sprague-Dawley rats induced by loperamide(2 mg/kg, s.c.,5 days) were investigated. Rats were randomly assigned to the normal control rats(regular diet), constipated rats(regular diet plus loperamide), constipated rats treated with 2.5% GKF(regular diet supplemented with 2.5% GKF plus loperamide), constipated rats treated with 5% GKF (regular diet supplemented with 5% GKF plus loperamide). There was less fecal excretion and lower fecal water content in loperamide-treated rats than in control rats. Oral administration of GKF blocked the decrease of fecal excretion and fecal water content in the loperamide-treated rats. Mucus production of crypt cell and mucus contents at fecal and mucosa surface were reduced by loperamide-treated rat. But colonic crypt cell contained increased mucin in the GKF treated group and mucus layer stained with alcian blue was significantly thicker in GKF treated rats compared with in loperamide-treated rats. In isolated rat ileum, loperamide produced inhibition of ileal motility. Pretreatment with methanolic extracts of GKF in isolated rat ileum prevented inhibition by loperamide. These findings indicated that the GKF was effective for alleviation of inhibition of colonic peristalsis by loperamide and that GKF might be of value in the prevention of constipation. 참다래 동결건조물을 2.5%, 5% 농도로 사료와 혼합하여 실험동물에 투여하고 실험 5일간 loperamide(2 mg/kg/ day, s.c.)로 변비를 유도하여 참다래의 변비치료 및 예방효과를 측정하였다. Lopermide를 단독 투여한 군은 정상 대조군과 비교하여 변의 개수 및 중량이 유의적으로 감소하였으며 원위 결장 내 변 잔류의 증가 및 cecocolonic segment의 무게가 증가하였다. 참다래 동결건조물 및 loperamide를 투여한 군은 loperamide를 단독 투여한 군과 비교하여 변의 개수 및 중량이 유의적으로 증가하였으며 원위 결장 내 잔류 변 및 cecocolonic segment의 무게도 감소하였다. 이러한 결과는 참다래가 in vivo에서 변비 개선 효과가 있음을 보여준다. 변의 수분 함량에서도 loperamide로 변비를 유발시킨 군에서 감소하는 경향을 보였고 참다래 동결건조물 투여군에서 농도 의존적으로 증가하는 것을 확인 할 수 있었다. 조직학적 검사에서도 참다래 동결건조물 투여군의 원위 대장관에서 crypt cell내 점액의 증가와 장관내 분변의 점액질의 증가도 관찰되었다. In vitro 실험결과, 회장 적출 절편에서 참다래 동결건조물 (2.5 mg/ml)을 전 처리 시 loperamide에 의한 장력과 진폭 억제가 부분적으로 차단되었으며 이러한 결과는 참다래 동결건조물의 변비 개선효과가 장의 운동성 촉진과 대장관내 점액분비 증가에 의한 대장관 내용물의 이동성증가와 관련이 있음을 시사한다.

표고버섯 추출액이 loperamide로 유도된 변비에 미치는 영향

박민경(Min-Kyung Park),진영건(Young Gun Jin),김동건(Dong Gun Kim),진주연(Ju Yeon Jin),이영재(Young Jae Lee) 한국식품과학회 2007 한국식품과학회지 Vol.39 No.1

표고버섯 추출액을 10, 20 및 40%로 30일간 음용수에 섞어 실험동물에 투여하고 실험 28-30일애 loperamide(4 ㎎/㎏/day, s.c.)로 변비를 유도한 뒤 표고버섯 추출액의 변비 예방효과를 측정하였다. Loperamide를 단독 투여한 군은 정상 대조군과 비교하여 변의 개수 및 중량이 유의적으로 감소하였으며 원위 결장 내 변 잔류의 증가 및 cecocolonic segment의 무게가 증가하였다. 표고버섯 추출액 및 loperamide를 투여한 군은 loperamide를 단독 투여한 군과 비교하여 변의 개수 및 중량이 유의적으로 증가하였으며 원위 결장 내 잔류 변 및 cecocolonic segment의 무게도 감소하였다. 이러한 결과는 표고버섯 추출액이 in vivo에서 변비 개선효과가 있음을 보여준다. 변의 수분함량은 실험군 간의 유의한 차이가 없었지만 loperamide에 의한 변비 유발 시 감소하는 경향이 있었으며, 표고버섯 추출액 투여군에서는 변의 수분함량 감소가 다소 완화되었다. 한편, 혈 중 WBC, RBC, HGB, HCT, PLT, MCV, MCH, MCHC치 및 혈청 ALT, AST, ALP, BUN 및 creatinine 수치는 정상 대조군, loperamide 처리군 및 표고버섯 추출액 처리군 사이에서 차이가 없었다. In vitro 실험결과, 회장 적출 절편에 표고버섯 추출액 동결건조물(0.5 ㎎/㎖)을 전 처리 시 loperamide에 의한 장력과 진폭 억제가 부분적으로 차단되었으며, atropine에 의해 유도된 진폭의 억제도 효과적으로 차단되었다. 이러한 결과는 표고버섯 추출물의 변비 개선효과가 장의 운동성 촉진과 관련이 있음을 시사한다. The preventive effect of Lentinus edodes extract (LE) against constipation was studied in rats. Rats were pretreated with LE contained in drinking water at the concentration of 10%, 20% and 40% over 30 days. Constipation was induced by subcutaneous injection of loperamide (4 ㎎/㎏/day) 3 days prior to sacrifice. Treatment of loperamide resulted in decreases in the number and wet weight of fecal pellets, and increase in the number of fecal pellet in the distal colon and cecocolon weight. In contrast, the number and wet weight of fecal pellets were increased, and the number of fecal pellet in the distal colon and the cecocolon weight were decreased in LE-pretreated groups compared to the loperamide-treated group. Blood parameters such as white blood cell, red blood cell, hemoglobin, hematocrit, platelet, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, and serum alanine transaminase, aspartate aminotransferase and alkaline phosphatase activities, and blood urea nitrogen and creatinine values were not significantly different between the groups. In addition, LE (0.5 ㎎/㎖) increased spontaneous contractile activity, which was reduced by atropine or loperamide in isolated rat ileum. Theses results suggest that the improvement of constipation symptoms in LE-pretreated rats resulted from a stimulatory effect of LE on intestine contractile activity.

Loperamide로 유도된 변비 증상에 유산균 제제가 미치는 영향

김은영,조경애,안소현,박성선,손흥수,한성희,Kim, Eun Young,Jo, Kyungae,Ahn, So Hyun,Park, Sung Sun,Son, Heung Soo,Han, Sung Hee 한국식품영양학회 2015 韓國食品營養學會誌 Vol.28 No.6

Loperamide를 통해 변비가 유발된 실험동물에 유산균 투여가 미치는 영향을 알아보기 위하여 14일 동안 저농도($10^7CFU/mL$ per kg of body weight)의 유산균과 고농도($10^9CFU/mL$ per kg of body weight)의 유산균을 투여한 후, 변비개선 효과를 측정하였다. 그 결과, 변비 유발 후 유산균을 투여한 실험군들의 경우, 대조군(CON)에 비하여 변의 개수, 변 중량 및 수분 함량이 유의적으로 증가하였다. 또한 소화관 이동률을 조사한 결과, 대조군(CON)에 비하여 변비 유발 후 유산균을 투여한 군에서 정상대조군(NOR)인 군과 유사한 이동성을 보이는 것을 확인하였다. 변비가 유발된 실험동물의 혈청 중성지방, 총 콜레스테롤 함량, HDL-콜레스테롤 함량에는 유산균 투여 유무 및 유산균의 농도에 대한 영향을 크게 받지 않은 것으로 보여진다. 고농도의 유산균을 섭취시킨 실험동물군(HIG)의 경우, 분변으로 유도된 아세트산과 프로피온산의 함량이 유의적으로 높게 나타났다. 또한 헤마톡실린 및 에오신 염색을 통한 장내 상피세포 관찰을 통해 유산균 분말 투여시 장 점막의 길이와 넓이가 유의적으로 증가하는 것을 확인하였다. 메타지노믹스 유전자 분석을 통한 미생물 분포의 상동성을 비교해 본 결과, 고농도의 유산균 투여군(HIG)이 정상대조군(NOR)과 가장 흡사한 분포 특성을 가지고 있음을 보여주었다. 이상의 결과에 따라 유산균 제제는 변비 개선 효과가 있다고 볼 수 있다. Probiotics is known improve the microenvironment of colon; however, the metagenomic DNA study of its lactic acid bacteria in constipation induced by loperamide is not clearly understood. In the present study, we investigated the reduction of the lactic acid bacteria in case of constipation, in normal and loperamide-induced rat. Lactic acid powder (lactic acid bacteria 19) was prepared from Chong Kun Dang Pharmaceutical Corporation. After 2 weeks of oral administration, the group treated with the higher concentration of lactic acid bacteria ($10^9CFU/mL$ per kg of body weight) following loperamide treatment was the most effective in increasing number, weight, and water content of feces. A similar but significant increase was found in the group treated with lower concentration of lactic acid bacteria ($10^7CFU/mL$ per kg of body weight) after loperamide treatment. The concentrations of acetic acid and propionic acid in feces in the loperamide-induced rat with high concentration lactic acid, were significantly higher than that of others. Furthermore, gastrointestinal transit ratio as well as the length and area of intestinal mucosa were significantly increased after treatment with lactic acid bacteria in loperamide-induced rat. Metagenomics DNA analysis indicated that the microorganism homology in cecum was similar between the groups of normal (NOR) and HIG. Our results show that lactic acid bacteria were effective in improving the constipation.

Metabolomics approach to serum biomarker for loperamide-induced constipation in SD rats

Ji-Eun Kim,Young-Ju Lee,Moon-Hwa Kwak,Go Jun,Eun-Kyoung Koh,Sung-Hwa Song,Ji-Eun Seong,Ji Won Kim,Kyu-Bong Kim,Suhkmann Kim,Dae-Youn Hwang 한국실험동물학회 2014 Laboratory Animal Research Vol.30 No.1

Loperamide has long been known as an opioid-receptor agonist useful as a drug for treatment of diarrhea resulting from gastroenteritis or inflammatory bowel disease as well as to induce constipation. To determine and characterize putative biomarkers that can predict constipation induced by loperamide treatment, alteration of endogenous metabolites was measured in the serum of Sprague Dawley (SD) rats treated with loperamide for 3 days using ¹H nuclear magnetic resonance (¹H NMR) spectral data. The amounts and weights of stool and urine excretion were significantly lower in the loperamide-treated group than the Notreated group, while the thickness of the villus, crypt layer, and muscle layer was decreased in the transverse colon of the same group. The concentrations of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatinine (Cr) were also slightly changed in the loperamide-treated group, although most of the serum components were maintained at a constant level. Furthermore, pattern recognition of endogenous metabolites showed completely separate clustering of the serum analysis parameters between the Notreated group and loperamide-treated group. Among 35 endogenous metabolites, four amino acids (alanine, glutamate, glutamine and glycine) and six endogenous metabolites (acetate, glucose, glycerol, lactate, succinate and taurine) were dramatically decreased in loperamide-treated SD rats. These results provide the first data pertaining to metabolic changes in SD rats with loperamide-induced constipation. Additionally, these findings correlate the changes in 10 metabolites with constipation.

Antioxidant and laxative effects of taurine-xylose, a synthetic taurine-carbohydrate derivative, in loperamide-induced constipation in Sprague-Dawley rats

( Hee Geun Jo ),( Min Ji Kim ),( Bo Yeong Moon ),( Sun Hee Cheong ) 한국운동영양학회 2019 Physical Activity and Nutrition (Phys Act Nutr) Vol.23 No.4

[Purpose] In this study, we examined the in vitro anti­oxidant activities and laxative effects of taurine-xylose (T-X), a synthetic taurine-carbohydrate derivative, in a rat model of constipation induced by loperamide. [Methods] The animals were divided into four treat­ment groups: normal untreated rats (NOR group), lop­eramide- treated control rats (CON group), loperamide and taurine-xylose (15 mg/kg)-treated rats (T-X group), and loperamide and commercial Dulcolax S (5.5 mg/ kg)-treated rats (DS group). [Results] In the present study, T-X exhibited potent reducing power and free radical scavenging activities for DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS+ (2,2′-azino-bis (3-ethylbenzothiazoline 6-sulfonic acid ammonium salt) radicals. The laxative effects of T-X were dependent on food, body weight, fecal properties, gastrointestinal transit (GIT) ratio, and serum metabolic parameters. In the T-X group, the number, wet weight, and water content of fecal pellets were noticeably increased compared to those in the loperamide-induced group. T-X treatment significantly increased the activities of hepatic antioxidant enzymes, including those of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT), relative to those in loperamide-induced constipated rats. Furthermore, the GIT ratio and loperamide-induced metabolic parameters in serum, including gastrin (GAS), motilin (MTL), and somatostatin (SS) levels, were significantly improved by T-X treatment. [Conclusion] These results suggest that taurine-xy­lose exerts antioxidant activities and laxative effects on loperamide-induced constipation by promoting gastrointestinal motility.

Antioxidant and laxative effects of taurine-xylose, a synthetic taurine-carbohydrate derivative, in loperamide-induced constipation in Sprague-Dawley rats

조희근,김민지,문보영,정선희 한국운동영양학회 2019 Physical Activity and Nutrition (Phys Act Nutr) Vol.23 No.4

[Purpose] In this study, we examined the in vitro antioxidant activities and laxative effects of taurine-xylose (T-X), a synthetic taurine-carbohydrate derivative, in a rat model of constipation induced by loperamide. [Methods] The animals were divided into four treatment groups: normal untreated rats (NOR group), loperamide-treated control rats (CON group), loperamide and taurine-xylose (15 mg/kg)-treated rats (T-X group), and loperamide and commercial Dulcolax S (5.5 mg/kg)-treated rats (DS group). [Results] In the present study, T-X exhibited potent reducing power and free radical scavenging activities for DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS+ (2,2′-azino-bis (3-ethylbenzothiazoline 6-sulfonic acid ammonium salt) radicals. The laxative effects of T-X were dependent on food, body weight, fecal properties, gastrointestinal transit (GIT) ratio, and serum metabolic parameters. In the T-X group, the number, wet weight, and water content of fecal pellets were noticeably increased compared to those in the loperamide-induced group. T-X treatment significantly increased the activities of hepatic antioxidant enzymes, including those of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT), relative to those in loperamide-induced constipated rats. Furthermore, the GIT ratio and loperamide-induced metabolic parameters in serum, including gastrin (GAS), motilin (MTL), and somatostatin (SS) levels, were significantly improved by T-X treatment. [Conclusion] These results suggest that taurine-xylose exerts antioxidant activities and laxative effects on loperamide-induced constipation by promoting gastrointestinal motility.

구멍쇠 미역의 변비 완화 효과 및 혈액지방에 미치는 영향

박성진 ( Sung Jin Park ),김봄 ( Bom Kim ),김민정 ( Min Jeong Kim ),김영언 ( Young Eon Kim ),박성혜 ( Sung Hye Park ),박태길 ( Tae Gil Park ) 한국식품조리과학회(구 한국조리과학회) 2013 한국식품조리과학회지 Vol.29 No.2

구멍쇠 미역의 변비 개선 효능을 검정한 결과, 흰쥐의 사료섭취량과 체중 변화는 정상군에 비해 구멍쇠 미역 투여군이 유의적으로 식욕억제와 비만예방에 효과가 있을 것으로 사료된다. 장통과시간은 대조구 853.1분이었고, 구멍쇠 미역 5% 급이군에서 789.7분으로 감소하였다. 변비를 유발시키면서 식이섬유를 급이한 흰쥐의 체중 대비 간의 무게는 모든 실험군에서 정상군과 차이가 없었으며, 신장의 무게도 각 실험군에서 차이가 나타나지 않았다. 또한, 소장 및 대장의 길이는 변비의 유무와 식이섬유 급원에 따른 군간 유의적인 차이가 없었다. 분변량을 측정한 결과 정상군의 1일 평균 분변량은 2.84 g, 대조군은 1.34 g, 구멍쇠 미역 5% 급이군은 1.57 g, 구멍쇠 미역 10% 급이군은 2.02 g으로 구멍쇠 미역의 섭취가 변비 증상 호전 효과가 있을 것으로 판단된다. 분변의 수분 함량 측정 결과, loperamide를 단독 투여한 대조군 분변의 수분함량이 정상군에 비해 유의적으로 감소하여 loperamide 투여로 인해 변비가 유발된 것을 확인하였으며, 구멍쇠미역 5% 및 10%가 함유된 사료를 급이한 군은 정상군에 비해 분변의 수분함량이 각각 1.6배 및 2.1배 증가하였다. 구멍쇠 미역을 급이한 흰쥐의 혈청 중 cholesterol 및 triglyceride 함량 변화 측정 결과, 혈청 중 total cholesterol 함량은 구멍쇠 미역 5% 급이군에서 loperamide로 변비를 유발한 대조군에 비해 3.5% 감소하였으나 유의적인 차이는 없었으며, 구멍쇠 미역 10% 급이군은 40.21 mg/dL로 33.5% 감소하여 구멍쇠 미역의 섭취량이 높아질수록 흰쥐의 혈중 cholesterol 함량이 감소하였다. GOT 및 GPT는 각 실험군에서 차이가 나타나지 않았으나, BUN 농도는 대조군에 비해 구멍쇠 미역 10% 급이군에서 낮게 나타났으며, 혈중 포도당 농도는 각 실험군 간에 유의적인 차이가 없었다. 간 조직 내의 총콜레스테롤 분석 결과, 구멍쇠 미역 급이군 모두 정상군 및 대조군에 비해 총콜레스테롤 함량이 감소하였으며, loperamide 투여에 의해 감소되었던 HDL-콜레스테롤은 구멍쇠 미역 급이 시 대조군에 비해 증가 하였으나 유의적인 차이는 없었다. 또한, 중성지방 함량은 총 콜레스테롤과 마찬가지로 구멍쇠 미역 급이군이 정상군과 대조군에 비해 감소하였다. 이와 같은 결과로 보아 구멍쇠 미역은 장 이동률을 증가시켜 장운동을 촉진하리라 생각되며, 변비 해소 작용도 나타내어 장 기능 개선에 효과가 있을 것으로 판단된다. The present study was conducted to evaluate the effects of Agarum cribrosum on weight change and defecation states in rats with constipation induced by loperamide. Food intake and body weight both decreased in the 5% Agarum cribrosum and loperamide-treated group (SD5) and 10% Agarum cribrosum and loperamide-treated group (SD10), whereas fecal water contents increased by 1.6 and 2.1-fold in the SD5 and SD10 groups, respectively. The concentrations of total-cholesterol, HDL-cholesterol and triglyceride in the sera of the SD5 and SD10 groups were lower than those in the control (C) group. However, the biochemical parameters, GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), and glucose levels, were not affected by the level of Agarum cribrosum. In addition, the concentrations of total-cholesterol and triglyceride in the livers of the SD5 and SD10 groups were also lower than those in the control group. The results of the present study demonstrated that Agarum cribrosum might ameliorate constipation symptoms, and lower lipid concentrations in the blood and liver.

解谿(ST41) 유침 및 전침의 전ㆍ후처치가 loperamide로 억제된 흰쥐의 장운동에 미치는 영향

김경민(KyungMin Kim),이현(Hyun Lee),임윤경(YunKyoung Yim) 대한한의학회 2012 대한한의학회지 Vol.33 No.3

Effects of Bifidus Enhancer Yogurt on Relief from Loperamide-induced Constipation

최진희,정승환,조영훈,조윤경,Hae-Yeon Choi,김순임 한국축산식품학회 2012 한국축산식품학회지 Vol.32 No.1

This study investigated the effects of bifidus enhancer yogurt (BEY) on loperamide-induced constipation in rats. The bifidus enhancer, made of rice-DDGS (Dried Distillers Grains with Solubles), improved proliferation of bifidobacteria (BB-12). Male SD rats were induced with constipation using loperamide and were then used to test the effectiveness of BEY in relieving constipation. The rats were divided into four groups: normal group (NOR), loperamide-treated group (LOP), bifidus enhancer yogurt and loperamide-treated group (L-BEY), and commercial yogurt and loperamide-treated group (L-CY). Treatment of loperamide reduced the wet weight and water content of fecal pellets, but increased the number of fecal pellets in the distal colon. Meanwhile, the fecal weight of the L-BEY group showed an increase of 43% and 23% versus the LOP and L-CY group, respectively. Also, the fecal water content in the L-BEY group was 14.5% and 6.8% higher than that in the LOP and L-CY group, respectively. In addition, the L-BEY group had the fewest fecal pellets in the distal colon. In the serum lipid parameters, the LOP group had a HDL/total cholesterol ratio that was 43% lower than the NOR group, but the L-BEY group had 27% lower than NOR group. These results suggest that bifidus enhancer yogurt has superior effects when it comes to relieving loperamide-induced constipation in rats.