• Preventive Nutrition and Food Science
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• 제20권4호
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• pp.266-275
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• 2015

Exposure to cadmium (Cd) has harmful effects on the liver and kidney. Resveratrol (RES) is an herbal substance that functions as a protective mediator. This study aimed to investigate the effects of RES on the histology of liver and kidney in Cd-exposed mice. Male mice were divided into 4 groups daily receiving normal saline (1 mL normal saline/d), Cd (1 mg/kg/d), RES (20 mg/kg/d), and Cd plus RES, respectively. After 4 weeks, the liver and kidney components were evaluated using stereological methods. The total volume and number of hepatocytes, and volume of fibrous tissue were respectively increased by 34%, 58%, and a 3-fold in the Cd-exposed mice in comparison to the control animals (P<0.03). On the other hand, the volume of the main vasculature (sinusoids and central veins) was decreased by 36% in the Cd group compared to the control mice (P<0.03). Considering the kidney, the results showed a 3-fold increase in the total glomeruli volume and a 7-fold increase in fibrous tissue in the Cd-treated group compared to the control mice (P<0.03). After Cd treatment, a 32% reduction was observed in the volume and length of the proximal and distal convoluted tubules. RES-treatment alone did not induce any structural changes. In comparison to the Cd group, an increase in the normal components of the liver and kidney and a decrease in the formation of the fibrous and degenerated tissues were observed in the Cd+RES-treated mice (P<0.03).

• Applied Microscopy
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• 제32권3호
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• pp.205-211
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• 2002

본 연구의 목적은 납 중독된 쥐의 신장에서 키토산 효과를 연구하고자 하였다. 납(30 mg/kg)은 1주 2회 복강투여하고, 0.1% 키토산(1 mg/ml) 수용액은 음용수를 통해 자유자재로 공급하였다. 실험 후, 4주, 8주째에 각각의 신장을 적출해서 투과전자 현미경으로 관찰하였다. 실험군의 경우 Group 1은 납 중독 후 키토산용액을 처치하지 않은 군, Group 2는 납 중독 후 키토산용액을 처치한 군으로 각 군당 10마리의 쥐를 사용하였다. 실험 결과는 다음과 같다. 납 단독투여군의 경우 세뇨관 세포에서 미세융모의 소실이 나타났으며 용해소체가 증가되었다. 사립체 및 과립형질내세망 수조 내강의 팽대와 과립형질내세망으로부터 리보솜의 탈락이 관찰되었다. 납-키토산 투여군의 경우 세뇨관 세포에서 미세융모의 변화는 없었으며 용해소체의 수가 감소되었다. 기다란 모양의 사립체와 리보솜이 부착된 과립형질내세망이 정상적인 상태로 관찰되었다. 결론적으로, 키토산이 쥐의 신장에 미치는 납의 독성을 감소시키는데 효과가 있는 것으로 사료된다.

• Applied Microscopy
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• 제34권3호
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• pp.185-197
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• 2004

본 연구의 목적은 납중독에 의한 신장 기능 손상에 대한 스쿠알렌의 효과를 관찰하고자 하였다. ICR계 건강한 생쥐를 사용하여 납과 스쿠알렌을 복강 투여한 후, NO와 조직학적 변화를 관찰하였다. 실험군 설정은 다음과 같다. 실험군 1은 정상군, 실험군 2는 납 (30 mg/kg)만 처치한 군, 실험군 3은 납을 처치하고 스쿠알렌 (180 mg/kg)도 함께 처치한 군으로 각 실험군 당 생쥐 10마리를 사용하였다. 결과는 다음과 같다. 실험군 2의 경우, 미토콘드리아 신장, 사립체내막의 파괴, 소포체에서 리보소옴의 탈락이 24, 48시간동안 관찰되었고, 72시간부터 서서히 회복 되는 것을 관찰할 수 있었다. 실험군 3의 경우 실험군 2에 비해 손상 정도가 덜 하였으며, 48시간 이후부터 정상군과 유사한 소견을 보였다. NO의 경우 실험군 2에서는 NO 수치가 감소하였다. 하지만, 실험군 3의 경우 정상군보다 NO가 증가하였을 뿐만 아니라 납에 의한 NO 수치 감소에 대해 회복 효과를 보였다. 위와 같은 결과로 보아, 스쿠알렌이 신장 근위세뇨관에 미치는 납 독성을 감소시키면서 빠른 회복에 효과가 있을 것으로 사료된다.

• 대한이식학회지
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• 제28권3호
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• pp.135-143
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• 2014

Background: Kidney injury molecule-1 (KIM-1) is known as a good ancillary marker of acute kidney injury (AKI) and its expression has also been observed in acute rejection and chronic graft dysfunction. We tested usefulness of KIM-1 as an indicator of acute and chronic renal graft injury by correlating KIM-1 expression with renal graft function and histology. Methods: A total of 133 zero-time biopsies and 42 follow-up biopsies obtained within 1 year posttransplantation were selected. Renal tubular KIM-1 staining was graded semiquantitatively from 0 to 3 and the extent of staining was expressed as the ratio of KIM-1 positive/CD10 positive proximal tubules using Image J program. Results: KIM-1 was positive in 39.8% of zero-time biopsies. KIM-1 positive cases were predominantly male and had received grafts from donors with older age, deceased donors, and poor renal function at the time of donation, compared with KIM-1 negative cases. KIM-1 expression showed correlation with delayed graft function and acute tubular necrosis. In comparison of KIM-1 expression between stable grafts (n=23) and grafts with dysfunction (n=19) at the time of repeated biopsy, the intensity/extent of KIM-1 staining and renal histology at zero-time did not differ significantly between the two groups. Histologically, KIM-1 expression was significantly increased with both acute and chronic changes of glomeruli, tubules and interstitium, peritubular capillaritis, and arteriolar hyalinosis. Conclusions: KIM-1 can be used as an ancillary marker of AKI and a nonspecific indicator of acute inflammation and tubulointerstitial fibrosis. However, KIM-1 expression at zero-time is not suitable for prediction of long-term graft dysfunction.

• 한국동물학회지
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• 제16권2호
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• pp.79-96
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• 1973

붕어(Carassius carassius)에 미치는 동의 영향을 밝히기 위하여 다음과 같은 연구를 하였다. 1) 셀루로오스 아세테이트 전기영동법에 의한 젖산수소이탈효소 아이소자임 상, 2) 분광비색법에 의한 LDH활성과 LDH효소계에 대한 동의 영향, 3) 한천 박층 전기영동법에 의한 에스테라아제 아이소자임 상, 4) 전분 겔 전기영동법에 의한 혈색소 상, 및 5) 조직 학적 연구. 1. LDH 아이소자임 영동대는 정상 붕어의 아가미에 2개 (LDH-3 및 LDH-5), 간에 3개(LDH-2, LDH-4, 및 LDH-5), 그리고 근육에서 2개 (LDH-3 및 LDH-4) 나타났다. LDH-1은 이상의 세가지 조직에서 나타나지 않았다. 동을 처리한 붕어의 간에서는 LDH-3이 나타났고 근육에서는 LDH-5가 나타났다. 그러나 아가미에서는 새로운 영동대가 나타나지 않았다. 2. LDH활성은 정상 붕어의 아가미, 간, 및 근육 중 아가미에서 가장 낯았고 근육에서 가장 높았으며, 아가미를 제외한 간과 근육에서는 1일부터 10일간의 동처리에 따라 점차적으로 감소되었다. 3. 동을 처리한 붕어의 간과 근육의 LDH활성 감소는 주로 체내 M-LDH에 대한 동의 억제에 기인된다. 4. 정상 붕어의 아가미, 간, 근육, 혈액, 뇌, 및 신장의 에스테라아제 아이소자임 영동대 수는 각각 3,6,2,2,2 및 2개 였고 이들은 동을 처리한 경우에서도 같았다. 동처리군의 아가미, 간, 혈액 그리고 신장의 에스테라아제 영동대의 상대이동도는 대조군의 그것들과 상이하였다. 5. 정상 붕어의 혈색소 영동대는 양극에 1개 있었다. 동을 처리한 붕어의 혈색소 영동대의 이동도는 정상 붕어의 그 것보다 약간 빠른 것으로 보였다. 6. 동(20ppm)에 5일간 처리한 붕어의 조직학적 연구는 다음과 같았다. 1) 아가미에서는 처음에 표피층이 분리되었다가 분해된 후 완전히 파괴되었다. 2) 간에서는 많은 지방립이 나타났다. 3) 정상 붕어와 동에 처리된 붕어의 근육 사이에서는 조직학적 차이가 없었다. 4) 신장족직은 기부요세관에 손상을 받았다. 요세관세포의 높이가 작아진 후 요세관의 내강이 확대되었다. 많은 기부요세관이 분홍빛의 과립성 형태와 여러 단계의 변성을 나타내었다.

• 약학회지
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• 제33권3호
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• pp.183-190
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• 1989

Angiotensin II, adminstered (infused or injected) intravenously, elicited the antidiuretic action with the decreased parameters of renal function at a small dose ($0.01\;{\mu}g/kg/min$), whereas, at a large dose (0.03, $0.1\;{\mu}g/kg/min$ and $5.0\;{\mu}g/kg$), it produced the diuretic action accompanied the increased amounts of sodium and potassium excreted in urine ($E_{Na}\;and\;R_K$). At this time, glomerular filtration rates (GFR) were weakened slightly and renal plasma flows (RPF) were reduced markedly, and then filtration fractions (FF) were increased. Angiotensin II, infused into a renal artery, exhibited antidiuretic action at a small dose ($0.003\;{\mu}g/kg/min$), and diuretic action at a large dose ($0.01\;{\mu}g/kg/min$), only in infused (experimental) kidney. The mechanism of the action was similar to the cases of the intravenous angiotensin II. The above results suggest that angiotensin II of a large dose produced diuretic action due to mechanism inhibiting reabsorption of electrolytes in renal tubules, mainly in proximal tubule in dog.

• 한국환경보건학회지
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• 제22권4호
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• pp.91-101
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• 1996

Exposure indices are important tools which enable scientists to reliably predict and detect exposures to xenobiotics and resultant cell injury. Since the de novo synthesis of stress proteins can be detected early after exposure to some agents, analysis of toxicant-induced changes in gene expression, i.e. alterations in patterns of protein synthesis, may be useful to develop as biomarkers of exposure and toxicity. The acute and chronic effects of cadmium(Cd, $CdCl_2$ 20 mg/kg) on Wistar male rats were evaluated concerning cadmium contents, tissues enzyme activity, HSP expression. The results of the study were as follows: 1. Less cadmium was absorbed through the digestive tracts, but the ratio of contents in renal to hepatic cadmium was higher at 8 weeks after treatment. 2. ALT(alanine aminotransferase), AST(aspartate aminotransferase), glucose, BUN(blood urea nitrogen), creatinine, the key indices of the clinical changes in hepatic and renal function were significantly changed by the cadmium treatment after 1 week in liver, after 4 weeks in kidney. 3. Enhanced synthesis of 70 KDa relative molecular mass proteins were detected in 2 hours after cadmium exposure, with maximum activity occurring at 8~48 hours. Induction of $HSP_{70}$ was evident at proximal tubules and glomeruli in kidney. Testicular cells produced enough HSP to be detected normally. From the above results, it could be concluded that $HSP_{70}$ induction by the cadmium treatment was a rapid reaction to indicate the exposure of xenobiotics.

• 약학회지
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• 제32권4호
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• pp.258-273
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• 1988

In this study attempts were made to observe the effects of guanabenz on renal function in dog, which manifests the antihypertensive action by inhibition of sympathetic tone through stimulating the presynaptic adrenoceptor (${\alpha}_2-adrenoceptor$). Guanabenz, when injected at a dose of $30.0{\mu}g/kg$, or infused at a dose of $3.0{\mu}g/kg/min$ intravenously, produced diuretic action with increased amounts of $Na^+\;and\;K^+$ in urine, and with decreased reabsorption rates of $Na^+\;and\;K^+$ in renal tubules. It was also observed that the rates of osmolar and free water clearances were increased, but the glomerular filtration rate and renal plasma flow were not changed. Guanabenz injected at a dose of $3.0{\mu}g/kg$ into a carotid artery or infused intravenously at a dose of $3.0{\mu}g/kg/min$ in a state of water diuresis elicited the diuretic action of the similar aspect as a case of guanabenz given intravenously. The diuretic action produced by guanabenz was completly blocked by pretreatment of i.v. prazosin, ${\alpha}_1-adrenoblocking$ agent, or of i.v. yohimbine, ${\alpha}_2-adrenergic$ blocking agent. Prazosin, when given into a renal artery, inhibited the diuretic action by i.v. guanabenz in only injected kidney, whereas in case of yohimbine the action was inhibited in both kidney. Guanabenz infused at a dose of $1.0{\mu}g/kg/min$ into a renal artery exhibited no significant changes of renal function in both kidney. In denervation experiments, guanabenz given intravenously produced typical diuretic action in innervated kidney, whereas in denervated kidney, it did not affect the action at initial period but exhibited the action with increase of only free water clearance at later period. These results suggest that guanabenz produced diuretic action in dog by inhibition of electrolyte reabsorption rates in renal tabules, mainly proximal tubule and of ADH release, which is mediated by stimulating of central sympathetic ${\alpha}_2-receptor$.

• 한국식품영양과학회지
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• 제34권7호
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• pp.968-972
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• 2005

기능성 식품소재로서 이미 많이 알려진 키토산이 신장과 관련하여 식품이나 의료용 소재로서 활용이 가능한 지를 알아보기 위하여 신장 기능과 민감하게 관련이 있는 효소인 RDPase, Udpase의 활성을 체내$\cdot$체외 실험을 통하여 관찰하였다. 체외 실험에서 글리세롤에 의해 유도된 RDPase의 유리$\cdot$활성 감소를 다시 회복시키는 것을 관찰하였다. 체내실험에서 글리세롤 투여에 의하여 손상된 신장의 근위세뇨관에서 급격히 증가한 RDPase의 활성을 키토산이 확실하게 감소시키는 것을 관찰할 수 있었다. 키토산을 공급한 쥐의 소변에서의 Udpase의 활성이 증가하는 것을 관찰하였다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.71-71
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• 1993

Carboxylesterase is widely distributed in the tissues of vertebrates, insects, plants and mycobacteria. Among various tissues of animals and humans, the highest esterase activity with various substrates is found in the liver. Kidney has moderate carboxylesterase activity in the proximal tubules. Considerable esterase activity is also found in the small intestine epithet elial cells and serum of mammals. Besides these tissues, carboxylesterase has been found in the lung, testis, adipose tissue, nasal mucosa and even in the central nervous system. Hepatic microsomal carboxylesterase catalyzes the hydrolysis of a wide variety of endogenous and exogenous compounds such as carboxylester, thioester and aromatic amide. Since carboxylesterases are important for metabolic activation of prodrugs and detoxification of xenobiotics, differences in substrate specificity and immunological properties of this enzyme are important in connection with choosing a suitable laboratory animal for the evaluation of biotransformation and toxicity of drugs. On the other hand, liver, kidney, intestine and serum were found to contain multiple forms of carboxylesterases in animal species and humans. In fact, we have purified more than fifteen isoforms of carboxylesterases from microsomes of liver, kidney and intestinal mucosa of nine animal species and humans. and characteristics of these isoforms were compared each other in terms of their physical and immunochemical properties. On the other hand, we have reported that hepatic microsomal carboxylesterases are induced by many exogenous compounds such as phenobarbital, polycyclic aromatic hydrocarbons, Aroclor 1254, aminopyrine and clofibrate. Later, we showed that some isoforms of hepatic carboxylesterase were induced by glucocorticoids such as dexamethasone and 16 ${\alpha}$-carbonitrile, but other isoforms were rather inhibited by these compounds. These findings indicate that involvement of carboxylesterases in the metabolism and toxicity of drugs should be explained by the isoforms involved. Since 1991, we have carried out detailed research investigating the types of carboxylesterases involved in the metabolic activation of CPT-11, a derivative of camptothecin, to the active metabolite, SN-38. The results obtained strongly suggest that some isoforms of carboxylesterase of liver microsomes and intestinal mucosal membrane are exclusively involved in CPT-11 metabolism. In this symposium, the properties of carboxylesterase isoforms purified from liver, kidney and intestine of animal species and humans are outlined. In addition, metabolism of CPT-11, a novel antitumor agent, by carboxylesterases in relation to the effectiveness will also be discussed.