Endotoxin에 의해 생성된 혈관의 nitric oxide가 교감신경계에 미치는 영향

박관하 한국독성학회 1996 Toxicological Research Vol.12 No.2

Endotoxic shock causes death in humans and animals via extreme hypoperfusion of peripheral organs. A massive production of nitric oxide (NO) both from the endothelical cells and smooth muscle cells has been proposed as a possible mechanism in this process. Since NO attenuated the contractility to vasoconstricting agents such as norepinephrine (NE) by directly acting on the smooth muscle cells, this mechanism was considered mainly as a postsynaptic mechanism. In this research it was investigated whether NO, thus released, also participates in the presynaptic events for the regulation of vascular tone in endotoxic shock. The role of NO was studied by adding NO donors or NO synthase inhibitor $N^\omega $methyl-L-arginine (NMA) in stimulated sympathetic nerves of the mesenteric vascular bed and the Langendorff heart of rats. Sodium nitroprusside (SNP), an NO donor, reduced the pressor responses of isolated mesenteric artery either to electrical stimulation or exogenously administered phenylephrine (PE). In this mesentery, although neither agent influenced NE release, in the presence of the adrenergic $\alpha_2$-receptor antagonist yohimbine, elecrical stimulation-evoked NE release was augumented by SNP. In the heart SNP facilitated the NE release induced by electrical stimulation, while NMA had no effect. From these results it is proposed that there exists a local reflex phenomenon in the junction between the sympathetic nerve terminals and the smooth muscle of resistance blood vessels; by which sympathetic responses are reduced by NO at the postjunctional level while NO facilitates NE release contributing to augumentation of sympathetic tone. All these facts suggest that NO produced during endotoxic shock has dual effects: whereas NO blunts the vasoconstrictive activity of NE at the postsynaptic level, NO presynaptically facilitates the release of NE from sympathetic nerve terminals.

조피볼락(Sebastes schlegeli)에서 다환성방향족탄화수소 fluoranthene의 축적과 배설

박관하 환경독성보건학회 2005 환경독성보건학회지 Vol.20 No.3

Gametogenic Cycle by Quantitative Statistical Analysis and the Biological Minimum Size in Protothaca (Notochione) jedoensis (Bivalvia: Veneridae) in Western Korea

박관하,정의영,이창훈,김성한,김성연,서원재,류동기 한국패류학회 2011 The Korean Journal of Malacology Vol.27 No.3

The gametogenic cycle and the spawning season in female and male Protothaca (Notochione) jedoensis were investigated by quantitative statistical analysis and sexual maturity was studied by qualitative histological analysis. In females, monthly changes in the percents of the ovarian tissue area to total tissue area, the percents of the follicle area to total tissue area, the percents of the follicles area to the ovarian tissue area, and the percents of the oocyte area to the ovarian tissue area increased in February and reached the maximum in April, and then gradually decreased from May to July, with the spawning peak between June and July. In males, monthly changes in the percents of the testicular tissue area to total tissue area, and the percents of the spermatogenic stage area to the testicular tissue area increased in February and reached the maximum in April and then showed a rapid decrease from May to July. From these data, it is apparent that the number of spawning seasons in female and male P. (N.) jedoensis occurred once a year, from May to July, with the spawning peak between June and July. Therefore, P. (N.) jedoensis in both sexes showed a unimodal gametogenic cycle during the year. Compared the gametogenic cycle by quantitative statistical analysis in 2007 with the previous qualitative results (Chung and Ryou, 2000) in female and male P. (N.) jedoensis, the results of the gametogenic cycle calculated by quantitative statistical analysis showed some differentiations between two spawning seasons in comparisons of results evaluated by the gonad index by qualitative histological analysis (through individual subjective assessment) including several errors. The spawning season evaluated by quantitative statistical analysis was from May to July, and that evaluated by histological gonad index was June to July. The interval of beginning of two spawning seasons showed one month between them. Therefore, the spawning season of this species should be checked in detail by quantitative analysis because this species has been noted as a target organism for aquaculture. The percentages of sexual maturities of female and male clams ranging from 30.1 to 35.0 mm in length by qualitative histological analysis of this species were 53.3% and 61.1%, respectively, and 100% for clams over 45.1 mm length. The biological minimum size (considering to 50% of group sexual maturity) in female and male clams by quantitative analysis of this species are 32.01 mm in shell length in females and 30.58 mm in males, respectively. According to the growth curves for the mean shell length fitted to von Bertalanffy’s equation by Kim et al.(2003b), individuals ranging from 25.1 to 30.0 mm in shell length were considered to be two years old because Kim et al.(2003) reported that 30.58 and 32.01 mm in shell length were considered to be two years old. Therefore, we assume that both sexes of this population begin reproduction from two years of age. In terms of natural resource management, the present study suggests that harvesting clams less than 30.6 mm in shell length (< 2 years old) can potentially lead to a drastic reduction in recruitment.

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.

콜린성 및 아드레날린성 신경전달물질에 의한 이스라엘잉어 복대동맥의 혈관긴장도 조절기능

박관하 한국어류학회 2000 韓國魚類學會誌 Vol.12 No.1

Depending on the fish species the vascular tone is distinctively regulated by numerous vasoactive substances. In most fish species the regulatory role of autonomic neurotransmitters and other vasoactive substances are not well defined. This research was designed to delineate the regulatory role of various endogenous autonomic neurotransmitters known to be important in mammalian vascular systems on isolated Israeli carp ventral aorta. Acetylcholine(ACh) contracted the aorta regardless of the pre-existing level of vascular tone, and the contraction was almost completely abolished by a cholinergic-muscarinic antagonist atropine. Endogenous, multiple receptor(α and β)-acting adrenergic agonist epinephrine(Epi) relaxed the vessel in the presence and absence of the pre-existing tones. Another endogenous multiple receptoracting agonist norepinephrine(NE) weakly contracted the aorta in non-preconstrcted state, but the response was reversed to relaxation when preconstricted. Isoproterenol, α β adrenergic receptor agonist, was a potent vasodilator whereas an α₁ agonist phenyephrine was a contractor. The α₂ adrenergic receptor agonist clonidine has not any significant effect in altering the vascular tone. The vasorelaxing action of Epi, NE and isoproterenol was significantly attenuated by β receptor antagonist propranolol. These results imply that ACh may primarily play a contractor role via muscarinic receptor activation while adrenergic agonists, Epi and NE, are relaxants through activation of β adrenergic receptors in vivo.

아질산 노출이 이스라엘잉어 혈장내 아질산 농도 및 간장 약물대사효소에 미치는 영향

박관하,최상훈,김영길,김용호,최선남,김종배 한국환경독성학회 2003 환경독성보건학회지 Vol.18 No.2

Effects of ambient nitrite, N0₂^(-), 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 N0₂^(-), there was an exposure duration-dependent increase in plasma N0₂- over the 96-hr period reaching 6~7 fold excess the ambient concentration, In the fish exposed to 10 mg/l, a plateau concentration of less than 2-fold of the environment was attained in 12 hr. With 30 mg/l, however, the maximal plasma NOf was 41.25 mg/1 at 12 hr followed by a gradual decline. There was a concentration increase in methemoglobin (metHb) level in all N02^(-)-exposed groups and a significant decrease in hematocrit value in 30 mg/l group after 96-hr exposure. Apart from the blunted increase in plasma N0₂^(-) with higher N0₂^(-)(10 and 30 mg/1) exposure, the ratio of plasma N0₃^(-) to N0₂^(-) was significantly higher in these groups compared to 1 and 3 mg/l. The imbalance in the plasma N0₃^(-)/N0₂^(-) at higher N0₂^(-) exposure suggests a possible accelerated conversion of N0₂^(-) to N0₃^(-). Nitrite exposure did not affect the hepatic drug-metabolic activities in juvenile Israeli carp. All these data indicate that disposition of N0₂- differ depending upon exposed concentration and that metHb production may not be the exclusive toxic mechanism in carp

Alteration of hepatic anti-oxidant systems by 4-nonylphenol, a metabolite of alkylphenol polyethoxylate detergents, in Far Eastern catfish Silurus asotus

박관하 환경독성보건학회 2015 환경독성보건학회지 Vol.30 No.-

Objectives This study aimed to estimate the effects of 4-nonylphenol (NP), a ubiquitously present surfactant in aquatic environments, on the anti-oxidant systems of the liver in the Far Eastern catfish Silurus asotus. Methods Changes in biochemical parameters involved in glutathione (GSH)-related and other anti-oxidant systems were analyzed following 4 weeks of 4-NP administration (0.1 and 1.0 mg/kg diet) via a formulated diet to catfish. Results 4-NP exposure induced an elevation in hepatic lipid peroxide levels and an accompanying decrease in reduced state GSH after 2 weeks, suggesting pro-oxidant effects of the chemical in catfish. This oxidative stress was associated with an inhibition of the GSH-utilizing enzyme glutathione peroxidase at the same time point. This inhibition was restored after 4 weeks. The activities of other anti-oxidant enzymes, i.e., glutathione reductase, superoxide dismutase and catalase were increased after 4 weeks. These enzyme increases occurred more strongly at the higher 4-NP concentration (1.0 mg/kg diet). Conclusions 4-NP given to catfish at 0.1 to 1.0 mg/kg diet, concentrations relevant to environmental levels, depletes the endogenous anti-oxidant molecule GSH and temporarily inhibits GSH-related anti-oxidant enzymes. Such declines in anti-oxidant capacity and elevated oxidative stress seem to be compensated eventually by subsequent activation of various anti-oxidant enzyme systems.

Sodium Hypochlorite (NaOCl)의 해산어류에 대한 단기노출의 영향

박관하,한조희 한국환경독성학회 2002 환경독성보건학회지 Vol.17 No.2

넙치는 단기간 NaOCl에 대한 노출에 대해 2ppm 이하에서는 육안적으로 관찰시 심각한 이상 증상이 관찰되지 않았으며, 조피볼락에서는 2.5ppm까지 급성적으로 안전하였다. 넙치와 조피볼락에서의 1시간 LC_50은 각각 3.24ppm 및 7.58ppm이었다. 조피볼락을 NaOCl로 1시간 노출시키고 혈액학적 및 혈장생화학적 변수를 측정하였을 때 2ppm 이상의 농도에서 glucose의 농도가 현저히 상승한 부분을 제외하고는 생화학적 변수에도 이상이 발견되지는 않았다. Glucose의 거의 모든 종류의 stress에 의해서 신속히 증가하는 변수로서 이 시험에서 발견된 증가현상도 NaOCl이 가진 냄새 또는 화학적 자극성에 의한 stress의 결과로 나타난 것으로 추정된다. Sodium hypochlorite (NaOCI) has been demonstrated to he effective against algae that cause red tides. To secure the environmental safety of this chemical for practical use, toxic effects of NaOCI were evaluated in two important aquaculture fishes, flounder and rockfish. At concentrations above 2.5 and 5 ppm for I hr, mortality occurred in flounder and rockfish, respectively. Flounder, however, did not die at 2 ppm up to an 8 hr exposure, nor did lipid peroxide level change at the same concentration in 1 hr. Plasma glucose level significantly increased in 1 hr with more than 2 ppm exposure. The results indicate that NaOCI may not induce persistent severe toxicity in flounder and rockfish at the algicidal concentration, 0.5 ppm.

In vitro 에서 Levamisole 이 양식뱀장어의 면역조절작용에 미치는 영향

박관하,최민순,윤성호,정경민,심현빈 한국어병학회 1999 한국어병학회지 Vol.12 No.1

Levamisloe(LMS)이 뱀장어의 면역반응에 미치는 영향을 측정하기 위해서 뱀장어의 혈액 및 신장으로부터 백혈구를 분리하여, 림프구의 증식능, MIF 생산능, 자연살해세포활성능, 탐식세포의 탐식능, superoxide anion, hydrogen peroxide 및 lysozyme 활성능 등을 측정하였다. LMS는 T-cell 마이토젠인 Con A 및 PHA 처리시에는 LMS 농도에 비례감소를 보인 반면에 B-cell 마이토젠인 LPS에는 LMS 처리와는 무관하게 큰 차이를 보이지 않았다. 한편 MIF 및 MAF의 생성에는 LMS 처리 농도에 비례 증가되었다. NK 세포의 활성은 LMS 첨가농도에 비례 증가하였는데, 이는 표적세포에 대한 결합율을 증가시킨 결과 NK 세포의 활성이 증가된 것으로 보인다. LMS는 백혈구의 탐식능, superoxide anion의 생성능, hydrogen peroxide 생성능 및 Iysozyme의 활성을 증가시켰다. 이러한 결과로부터 LMS가 어체의 면역작용에 관여하는 작용기전은 면역 작동세포수의 증가를 촉진시키기보다는 분화를 촉진시켜서 cytokine의 방출증가 및 세포의 기능활성을 증강시킴을 알수 있다. The immunomodulatory effects of levamisole (LMS) were evaluated in leucocytes of eels in vitro. Proliferation of lymhocytes treated with T-cell mitogen (Con A or PHA) was markedly inhibited by LMS in a dose dependent manner. B cell mitogen (LPS), in contrast, slightly increased the proliferaion. On the other hand, production of MIF and MAF when treated with Con A was increased in a dose-dependent way. NK cell activities were somewhat increased when LMS was pretreated and this augmentation was due to an increase in binding capacity of effector-target cell, but not due to the target cell lytic activity of effector cells. Phagocytic activity, superoxide anion formation, hydrogen peroxide formation and lysozyme activity of leucocytes were enhanced by LMS in a dose related-manner. These results suggest that LMS might modulate the immmune responses by activation of cytokine production and by augmentation of leukocyte activity but not by increment of immunocompetent cell numbers.

말라카이트그린, 수산업계를 울리다.

박관하,Park, Gwan-Ha 한국단미사료협회 2005 피드저널 Vol.3 No.12