Mouse에서의 quercetin 경구투여 후의 체내 농도 및 대사체 isorhamnetin의 농도변화

박관하,주종재,최선남,Park, Kwan-Ha,Choo, Jong-Jae,Choi, Sun-Nam 한국식품과학회 2005 한국식품과학회지 Vol.37 No.1

Quercetin을 50 및 100mg/kg의 용량으로 mouse에 경구투여 후 흡수, 대사 및 조직내 농도를 조사하였으며 일부의 시험은 비교를 위해 rat에서도 수행하였다. Quercetin은 mouse에서 신속히 흡수되어 l시간 후면 최고 혈장내 농도에 도달하였으며 4시간 후에는 현저하게 농도가 감소하였다. 주요 대사체인 isorhamnetin의 혈장내 농도도 신속하게 증가하였으나 quercetin 보다는 높은 농도로 유지되는 시간이 길었다. Rat에서 알려진 현상과 같이 quercetin이나 isorhamnetin 모두 유리상태로 존재하지 않고 대부분 glucuronide/sulfate의 포합체 형태로 존재하였다. Quercetin 및 isorhamnetin의 조직내 농도는 투여 1시간 및 6시간 콩히 간장>신장>비장>혈장의 순이었으며 이 순서는 rat에서도 마찬가지였다. 이 연구결과를 통해 mouse에서 quercetin이 경구투여 후 실제로 흡수되며 사람이나 다른 동물종에서 관찰된 것과 같이 quercetin은 신속하게 전환됨을 관찰하였다. 또한 이 결과는 mouse를 이용한 실험에서 지금까지 규명된 quercetin의 다양한 약리효과를 설명하는 데 필요한 자료의 역할을 할 수 있을 것이다. Absorption, metabolism, and tissue concentrations of quercetin were examined and compared in mice and rats after oral administration of quercetin at 50 or 100 mg/kg. Quercetin was absorbed quickly in mice and reached maximum plasma concentration in I hr post-administration, and declined sharply after 4 hr. Plasma concentration of isorhamnetin, a major metabolite, also increased sharply, indicating rapid metabolic conversion, but elevated level was maintained longer than that of quercetin. Quercetin and isorhamnetin were found predominantly in glucuronide/sulfate-conjugate forms in both mice and rats. Tissue concentrations of quercetin and isorhamnetin in mice and rats were in the order of liver>kidney>spleen>plasma both 1 and 6 hr postadministration. These results show that quercetin is absorbed in mice after oral feeding and quickly metabolized into isorhamnetin as demonstrated in humans and other animal species. The results also can be used to explain various pharmacological activities reported in mouse models.

수산동물에서의 nitric oxide(NO)의 생리적 및 병리적 역할과 미래의 연구과제

박관하(Kwan Ha Park),김경호(Kyong-Ho Kim),김강전(Kang-Jeon Kim),최민순(Min-Soon Choi),최상훈(Sang-Hoon Choi),최선남(Sun-Nam Choe) 군산대학교 수산과학연구소 1997 水産科學硏究 Vol.- No.13

A tremendous amount of data has been accumulated with regard to the pathological and physiological role of the highly elusive endogenous substance citric oxide(NO). Despite the extensive investigation on No by numerous researchers in mammals including humans, the information on the existence and significance of No in aquatic animals is quite rare. In view of the fact that No production is likely to be stimulated with Gram negative pathogenic bacteria in certain fishes, its participation in the pathological process of aquatic animal diseases should be clarified. The aim of this article is to review the known roles of No in aquatic animals, and to suggest future research directions related to its pathophysiological role.

잉어(Cyprinus carpio)에서 어류 구충제에 대한 N-acetylcysteine(NAC)의 독성 저감 효과

박관하 ( Kwan Ha Park ) 한국수산과학회(구 한국수산학회) 2011 한국수산과학회지 Vol.44 No.5

This study examined whether N-acetylcysteine (NAC), a glutathione precursor, could attenuate toxic effects of three fish anti-parasitic agents, trichlorfon, hydrogen peroxide (H2O2) and formalin, all of which are known to exert side effects through free radical production. Common carp Cyprinus carpio were fed with NAC (approx. 50 mg/kg/ day) for 3 consecutive days prior to anti-parasite bathing for a 24 hr period. Mortality rates were examined during this 24 hr bathing period, and selected hematological and biochemical parameters were also assessed at the termination of anti-parasite exposure. The mortality rates and plasma glucose elevations caused by all three anti-parasitics were significantly reduced by NAC pretreatment. Trichlorfon, but not H2O2 or formalin, elevated plasma levels of aspartatetransaminase (AST) and alanine-transaminase (ALT), and these elevations were attenuated by NAC. There was no change in hematocrit values in any treatment. The results provide evidence for the attenuating effects of NAC against toxicity caused by anti-parasite agents that act through free radical-producing properties. The results found in this study also suggest that NAC may be administered to fish to minimize toxicity in fish parasiticide use.

해양생물로부터 의약품의 개발

박관하(Kwan-Ha Park) 군산대학교 수산과학연구소 2004 군산대학교 수산과학연구소 연구논문집 Vol.4 No.-

Numerous marine organisms represent promising candidates for the development of pharmacologically active drugs. Countries such as USA, Australia, Japan and France have been administering national mammoth projects to screen out active marine compounds applicable to intractable diseases like cancer, acquired immune deficiency syndrome, or resistant bacterial infection. Due to the recent progress of supportive fields, especially chemical analysis techniques, to marine natural product research, the discovery of noble marine substances is greatly facilitated. In view of the species variety and biomass richness of unutilized marine organisms, the importance and necessity of research on this area is discussed.

해양생물로부터 의약품의 개발

박관하(Kwan-Ha Park) 군산대학교 수산과학연구소 2000 水産科學硏究 Vol.- No.16

Numerous marine organisms represent promising candidates for the development of pharmacologically active drugs. Countries such as USA, Australia. Japan and France have beenadministering national mammoth projects to screen out active marine compounds applicable tointractable diseases like cancer, acquired immune deficiency syndrome, or resistant bacterialinfection. Due to the recent progress of supportive fields, especially chemical analysis techniques,to marine natural product research, the discovery of noble marine substances is greatly facilitated.In view of the species variety and biomass richness of unutilizded marine organisms, the importance and necessity of research on this area is discussed.

항산화물질 N-acetylcysteine (NAC)이 메기에서 비특이적 면역지표인 화학발광 반응에 미치는 영향

박관하 ( Kwan Ha Park ),이한나 ( Han-na Lee ),안재영 ( Jae-young An ),배준성 ( Jun Sung Bae ),이채원 ( Chae Won Lee ),양찬영 ( Chan Young Yang ),최상훈 ( Sang-hoon Choi ) 한국어병학회 2019 한국어병학회지 Vol.32 No.1

It has been reported that various anti-oxidant substances stimulate non-specific immune responses in fishes. In this study it was examined whether N-acetylcysteine (NAC), a precusor for anti-oxidant glutathione (GSH) synthesis, can modulate non-specific immune function in Far Eastern catfish Silurus asotus. Immune functions were assessed using the respiratory burst activity monitored by chem-iluminescence (CL) responses in isolated leucocyte. NAC stimulated CL responses with doses of 10 or 100 mg/kg, but not with 1 mg/kg after 48 hr injection. It was observed with 10 mg/kg NAC that CL activity continued to elevate from 24 hr through 96 hr post-dosing, and returned to the near preinjection level by 10 days. To understand whether NAC can also activate CL activity in vitro, NAC was directly added to isolated catfish leucocytes. It was observed, however, that NAC can not stimulate CL at reasonable concentration ranges in vitro. As NAC is a precursor for the strong anti-oxidant glutathione (GSH), a putative immune stimulator, it was assessed whether GSH can also stimulate CL responses. Observed results show that GSH activated CL both in vivo and in vitro. The data obtained collectively support the proposition that NAC indirectly stimulates non-specific immune functions in catfish by enhancing GSH biosynthesis, but not by direct action of NAC. Such effects may have beneficial significance in aquaculture for practical utilization.

아질산 노출이 이스라엘잉어 혈장내 아질산 농도 및 간장 약물대사효소에 미치는 영향

박관하(Kwan-Ha Park 외 5명),최상훈,김영길,김용호,최선남,김종배 환경독성보건학회 2003 환경독성보건학회지 Vol.18 No.2

Effects of ambient nitrite, NO₂^-, at 1, 3, 10 and 30 mg/l, on the changes of plasma nitrite/nitrate and on hepatic drug-metabolizing enzyme activity were examined in the juvenile Israeli carp, Cyprinus carpio. When the fish were exposed to 1 and 3 mg/l NO₃^-, there was an exposure duration-dependent increase in plasma NO₂^- over the 96-hr period reaching 6~7 fold excess the ambient concentration. In the fjsh exposed to 10 mg/l, a plateau concentration of less than 2-fold of the environment was attained in 12hr. With 30 mg/l, however, the maximal plasma NO₂^- was 41.25 mg/l at 12hr followed by a gradual decline. There was a concentration-dependent increase in methemoglobin(metHb) level in an N0₂^--exposed groups and a significant decrease in hematocrit value in 30mg/l group after 96-hr exposure. Apart from the blunted increase in plasma NO₂^- with higher NO₂^-(10 and 30mg/l) exposure, the ratio of plasma NO₃^- to NO₂^- was significantly higher in these groups compared to 1 and 3 mg/l. The imbalance in the plasma NO₃^-/NO₂^- at higher NO₂^- exposure suggests a possible accelerated conversion of NO₂^- to NO₃^-. Nitrite exposure did not affect the hepatic drugmetabolic activitjes in juvenile Israeli carp. All these data indicate that disposition of NO₂^- differ dependjng upon exposed concentration and that metHb production may not be the exclusive toxic mechanism in carp.

Dehydroepiandrosterone ( DHEA ) 의 투여에 의한 rat 흉대동백의 반응성 변화

박관하(Kwan Ha Park) 한국응용약물학회 2001 Biomolecules & Therapeutics(구 응용약물학회지) Vol.9 No.2

In order to determine the role of dehydroepiandrosterone (DHEA), the important sex-steroid hormone precursor, in vascular reactivity in rats, animals were treated for two weeks with DHEA or sex hormones, and the vascorelaxant and contractile responses of isolated aorta were examined. DHEA diminished the acetylcholine (ACh)-induced relaxation in female rats, while the drug was without effect in males. Testoterone lowered the vasorelaxant activity to ACh in either sex. 17β-Estradiol enhanced ACh-induced vasorelaxation in male rats, but this female sex hormone did not influence in females. In male rats, the androgen receptor antagonist flutamide also enhanced vasorelaxant action of ACh. When the male rat aorta was incubated in vitro with a nitric oxide (NO) synthase inhibitor L-NAME, phenylephrine-induced contraction was greatly potentiated in DHEA-pretreated rats compared to control ones. The present results suggest that DHEA stimulates mainly androgen in female, but both androgen and estrogen in male rats. The participation of NO in the modulation of vascular reactivity with pretreated DHEA was also considered.

수산동물에서의 nitric oxide(NO)의 생리적 및 병리적 역할과 미래의 연구과제

박관하(Kwan Ha Park),김경호(Kyong-Ho Kim),김강전(Kang-Jeon Kim),최민순(Min-Soon Choi),최상훈(Sang-Hoon Choi),최선남(Sun-Nam Choe) 군산대학교 수산과학연구소 2004 군산대학교 수산과학연구소 연구논문집 Vol.3 No.-

A tremendous amount of data has been accumulated with regard to the pathological and physiological role of the highly elusive endogenous substance nitric oxide (NO). Despite the extensive investigation on NO by numerous researchers in mammals including humans, the information on the existence and signi ficance of NO in aquatic animals is quite rare. In view of the fact that ~O production is likely to be stimulated with Gram negative pathogenic bacteria in certain fishes, its participation in the pathological process of aquatic animal diseases should be clari fied. The aim of this article is to review the known roles of NO in aquatic animals, and to suggest future research directions related to its pathophysiological role.

Dehydroepiandrosterone(DHEA)의 투여에 의한 rat 흉대동맥의 반응성 변화

박관하(Kwan Ha PARK) 군산대학교 수산과학연구소 2004 군산대학교 수산과학연구소 연구논문집 Vol.5 No.-

여성은 동일 연령의 남성과 비교하여 관상동맥질환과 같은 순환기질환의 발생 율이 낮은 것으로 알려져 있다(Barret-Connor, 1994; Castelli, 1988). 이런 차이를 유발하는 과정에서 여성호르몬인 estrogen의 혈중농도를 높이면 혈관 내피세포의존성 이완(endothelium-dependent relaxation)이 증진하는 것이 실험동물의 적출혈관계에서 증명되었다(Gisclard et al., 1988; Williams et al., 1988). 또한 같은 맥락에서 인위적으로 실험동물에 estrogen을 투여하면 혈관수축물질에 대한 수축반응은 감소한다고 알려져 있다(Karanian and Ramwell. 1996; Sintetos et. al., 1978). 이때 초래되는 혈관반응성의 변화는 estrogen이 혈관내피세포에서 유리되는 nitric oxide(NO)의 생성을 증진하기 때문인데, 그 증거로서 출산기 여성의 혈중 17β-estradiol 농도와 NO의 파괴산물 (nitrite/nitrate) 농도가 상관관계가 있음 (Rosseli et al., 1994)과 난소를 제거한 영장류에서는 내피세포의 존성 혈관이완반응이 estrogen 투여에 의해 증진되는 현상(Williams et al., 1994)이 제시되어 있다. 인간의 부신에서 Dehydroepiandrosterone(DHEA)은 base형태 또는 황산염(DHEA-sulfate)으로 생성ㆍ분비되어 다양한 말초 장기(전립선, 정낭, 유선, 피부, 신장, 자궁 등)로 이동한 뒤 androgen이나 estrogen으로 쉽게 전환된다.(Labrie, 1991; Labre et al., 1988). 노령화에 따른 혈중 DHEA농도 감소가 동맥경화(Barrett-Connor et al., 1986), 유방암 (Rose et al., 1977; Schwarts, 1979), 비만(Coleman et al., 1984), 자가 면역질환 (Thoman and Weigle, 1989) 등 다양한 질병의 원인이 된다는 가설이 제시되어 많은 관심과 논란을 불러일으키고 있다. 이와 같이 DHEA가 다양한 질병의 발생에 관여할 가능성 때문에 최근 이 물질의 남용이 국내에서는 사회적 문제가 된 바도 있다. DHEA는 NO의 생성을 유도하는 성호르몬의 중요한 선구물질로서의 역할을 하나 이 물질 자체가 인간이나 동물에서 NOD의 생성에 어떤 영향을 미치는지에 대해서는 연구결과 거의 없으며, 현재까지 보고된 결과가 시사하는 바는 NO 생성의 촉진(Hayashyi et al., 2000; Manabe et al., 1999), 억제(Barger et al., 2000; Wang et al., 2001), 또는 영향이 없을 가능성(Kipper-Galperin et al., 1999)등 모든 가능성을 제시하고 있다. 특히 혈관의 이완 및 수축물질에 대한 반응성은 NO의 생성능에 의해 크게 영향(Moncada et al., 1991)을 받지만 DHEA가 혈관의 반응성에 미치는 영향이나 혈관에서의 NO의 생성에 미치는 효과에 대해서는 알려진 바가 없다. 따라서 본 연구에서는 estrogen 및 androgen의 전구물질로 작용하는 DHEA를 생식연령에 이른 정상 암ㆍ수 rat에 2주간 반복 투여하였을 때 혈관의 내피의존성 이완작용과 혈관수축물질에 대한 반응성에 어떤변화가 나타나느 가를 검토하였다. In order to determine the role of dehydroepiandrosterone(DHEA). the important sex-steroid hormone precursor, in vascular reactivity in rats, animals were treated for two weeks with DHEA or sex-steroid hormones, and the vascorelaxant and contractile responses of isolated aorta were examined. DHEA diminished the acetylcholine (ACh)-induced relaxation in female rats, while the drug was without effect in males. Testoterone lowered the vasorelaxant activity to ACh in either sex. 17β-Estradiol enhanced ACh-induced vasorelaxation in male rats, but this female sex hormone did not influence in females. In male rats, the androgen receptor antagflutamide also enhanced vasorelaxant action of ACh. When the male rat aorta was incubated in vitro with a nitric oxide (NO) synthase inhibitor L-NAME, phenylephrine-induced contraction was greatly potentiated in DHEA-pretreated rats compared to control ones. The present results suggest that DHEA stimulates mainly androgen in female. but both androgen and estrogen in male rats. The participation of NO in the modulation of vascular reactivity with pretreated DHEA was also considered.