• 제목/요약/키워드: renal toxicity

검색결과 227건 처리시간 0.021초

Effects of Insamsansa-eum (Renshenshanzha-yin) on Hypercholesterolemia and Analysis of Its Effects according to the Pattern Identification

  • Park Seong-Uk;Jung Woo-Sang;Moon Sang-Kwan;Cho Ki-Ho;Kim Young-Suk;Bae Hyung-Sup;Ko Chang-Nam
    • 대한한의학회지
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    • 제27권2호
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    • pp.253-261
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    • 2006
  • Backgrounds : Hyperlipidemia is a major cause of cardiovascular disease (CVD). Lowering serum cholesterol levels could reduce the risk of CVD. Insamsansa-eum (Renshenshanzha-yin, ISE), composed of Ginseng Radix and Crataegii Fructus, is a new medicine developed to treat hyperlipidemia and CVD. Objectives : In this study, we intended to explore the clinical effects of ISE on patients with hypercholesterolemia, and moreover we also compared its effects according to the pattern identification. Methods : Subjects were administered ISE with the dose of 600 mg three times a day for 4 weeks. Patterns of subjects were identified with diagnostic scoring system for Yin-Yang and the condition of Excess-Deficiency before treatment. Serum lipids were measured at baseline and after 4 weeks of medication. Results : ISE lowered total cholesterol(TC), triglyceride(TG), total lipid(TL), phospholipid(PL) and low density lipoprotein cholesterol(LDL) significantly. Compared with the data of our previous study, it was less effective than Atorvastatin but showed equal lipids-lowering effect to Chunghyul-dan (Qingxue-dan, CHD). In Yang pattern group, ISE was less effective in lowering TG and LDL than it was in not-Yang-not-Yinpattern group. On safety assessment, there was no adverse effect, hepatic or renal toxicity. Conclusions : We suggest that ISE is a safe and useful herbal medicine for hypercholesterolemia, and moreover it could be more useful when it is used for patients with not Yang pattern.

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Physiological, Pharmacological and Toxicological Implications of Heterodimeric Amino Acid Transporters

  • Kanai, Yoshikatsu;Endou, Hitoshi
    • The Korean Journal of Physiology and Pharmacology
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    • 제8권3호
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    • pp.117-127
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    • 2004
  • The heterodimeric amino acid transporter family is a subfamily of SLC7 solute transporter family which includes 14-transmembrane cationic amino acid transporters and 12-transmembrane heterodimeric amino acid transporters. The members of heterodimeric amino acid transporter family are linked via a disulfide bond to single membrane spanning glycoproteins such as 4F2hc (4F2 heavy chain) and rBAT $(related\;to\;b^0,\;^+-amino\;acid\;transporter)$. Six members are associated with 4F2hc and one is linked to rBAT. Two additional members were identified as ones associated with unknown heavy chains. The members of heterodimeric amino acid transporter family exhibit diverse substrate selectivity and are expressed in variety of tissues. They play variety of physiological roles including epithelial transport of amino acids as well as the roles to provide cells in general with amino acids for cellular nutrition. The dysfunction or hyperfunction of the members of the heterodimeric amino acid transporter family are involved in some diseases and pathologic conditions. The genetic defects of the renal and intestinal transporters $b^{0,+}AT/BAT1\;(b^{0,+}-type\;amino\;acid\;transporter/b^{0,+}-type\;amino\;acid\;transporter\;1)$ and $y^+LAT1\;(y^+L-type\;amino\;acid\;transporter\;1)$ result in the amino aciduria with sever clinical symptoms such as cystinuria and lysin uric protein intolerance, respectively. LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x-C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after brain ischemia. Because of broad substrate selectivity, system L transporters such as LAT1 transport amino acid-related compounds including L-Dopa and function as a drug transporter. System L also interacts with some environmental toxins with amino acid-related structure such as cysteine-conjugated methylmercury. Therefore, these transporter would be candidates for drug targets based on new therapeutic strategies.

홍화씨분말이 카드뮴 중독에 미치는 병리조직학적 관찰 (Histopathological Studies on the Effect of Korean Safflower (Carthamus tinctorious L.) Seed Powder on Cadmium Poisoning in Mice)

  • 장종식;권오덕
    • 한국임상수의학회지
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    • 제18권2호
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    • pp.116-123
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    • 2001
  • This study was undertaken to find out the effect of Korean safflower seed powder on histopathological changes of cadmium toxicity in mice. Fifty BALB/c mice were divided into a control group(A) and four experimental groups(B, C, D, E) : group A received tap water and basal diet, group B received tap water and diet supplemented with 3% Korean safflower seed powder alone, group C received basal diet and 300 $\mu\textrm{g}$/g of cadmium, group D and E received basal diet supplemented with 3% and 10% Korean safflower seed powder and 300$\mu\textrm{g}$/g of cadmium respectively. Cadmium dissolved in tap water was used, and the Korean safflower seed powder were mixed with feed. All mice were dissected on the 56th day. Histopathological changes in liver, kidney, lung, cortical osseous tissue of femoral shaft, bone trabecular of femur, and epiphyseal cartilage plate of femur were observed. Group B showed no significant changes compared with the control group. But group C showed the unclearness of specific cells in liver, the loss of architecture and focal necrosis of hepatocyte, the glomerular swelling, degeneration and necrosis of convoluted tubules, desquamation and vacuolization of the greater part of the renal tubular epithelium, the marked congestion and thickness of the wall of alveolus in lung, slightly thinning of the cortical osseous tissue in femoral shaft, reduction of cancellous bone volume and marked narrowness of bone trabecular, marked thinning of epiphyseal cartilage plate and irregular arrangement of columnar structure of cartilage cells. On the other hand, Korean safflower seed powder-treated group showed a little convalescent changes and maintained their normal architectures in liner, kidney, lung, cortical osseous tissue of femoral shaft, bone trabecular of femur and epiphyseal cartilage plate of femur.

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급성 엔도설판 중독의 임상적 고찰 (Clinical Analysis of Acute Endosulfan Poisoning: Single Center Experience)

  • 김소은;김수익;이재백;진영호;정태오;조시온;윤재철
    • 대한임상독성학회지
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    • 제13권2호
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    • pp.71-77
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    • 2015
  • Purpose: Acute endosulfan poisoning is rare but causes significant morbidity and mortality. The aim of our study is to describe complications and features of seizure and determine factors associated with mortality in acute endosulfan poisoning. Methods: Twenty-eight adult patients with acute endosulfan poisoning admitted to our emergency department during a 15-year period were studied retrospectively. The clinical features of seizure, use of antiepileptic drugs during seizure, and hospital courses were evaluated. Clinical factors between survived group and non-survived group were compared for identification of factors associated with mortality. Results: Of the 28 patients with endosulfan poisoning, 4 patients (14.3%) died and 15 (53.6%) patients developed generalized tonic-clonic seizure. Thirteen patients (46.4%) and 5 patients (17.9%) progressed to status epilepticus (SE) and refractory status epilepticus (RSE), respectively. SE and RSE were associated with mortality. Almost all significant complications including shock, acute renal failure, hepatic toxicity, rhabdomyolysis, and cardiac injury developed in SE and RSE patients. Conclusion: SE and RSE were important contributors to death in endosulfan poisoning. Emergency physicians treating endosulfan poisoning should make an effort not to progress seizure following endosulfan poisoning to SE and RSE using a rapid and aggressive antiepileptic drug.

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급성 빙초산 음독의 임상 양상 및 예후 (The Clinical Characteristics and Prognosis after Acute Ingestion of Glacial Acetic Acid)

  • 최갑용;민영기;정윤석;조준필;최상천
    • 대한임상독성학회지
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    • 제10권2호
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    • pp.91-96
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    • 2012
  • Purpose: A retrospective study with a literature review was conducted to identify the clinical characteristics and prognosis after the acute ingestion of glacial acetic acid. Methods: The medical records of 20 patients,who had presented to the emergency department of Ajou University Hospital complaining of the acute ingestion of glacial acetic acid between January 2006 and December 2011, were examined retrospectively. Results: Among the 172 patients admitted for caustics injury, 20 patients ingested glacial acetic acid. The mean age of the patients was $55{\pm}23.5$, and the mean volume of the acid was $84.5{\pm}71.3$ ml. The clinical features included 1) oral ulcers in 12 patients (63.2%), 2) respiratory difficulties in 11 patients (57.9%), 3) oliguria in 8 patients (42.1%), 4) renal toxicity in 7 patients (36.8%), 5) hepatic failure in 7 patients (36.8%), 6) disseminated intravascular boagulopathyin 7 patients (36.8%), 7) low blood pressure in 8 patients (42.1%), and 8) mental changes in 9 patients (47.4%). Ten patients required endotracheal intubation. Nine patients were admitted to the intensive care unit, and 5 patients expired. Conclusion: The ingestion of glacial acetic acid can cause severe symptoms, such as metabolic acidosis, multiple organ failure and upper airway swelling frequently and has a high mortality rate. Therefore, aggressive treatment, including endotracheal intubation, should be considered at the early stages.

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db/db mouse에서 인진(茵蔯), 울금(鬱金), 산사(山査) 복합추출물의 항고지혈 및 항산화 효과 (The Effects of an Extract of Artemisiae Capillaris, Curcumae Longae, and Crataegi Fructus (IUS) on Anti-hyperlipidemia and Anti-oxidation in db/db Mouse Model)

  • 김현태;김윤식;설인찬;유호룡
    • 대한한방내과학회지
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    • 제37권3호
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    • pp.467-483
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    • 2016
  • Objective: This study was performed to investigate the effect of IUS (Inulsan, an extract of Artemisiae capillaris (茵蔯), Curcumae longae (鬱金), and Crataegi fructus (山査)) on anti-hyperlipidemia, anti-oxidation, and anti-inflammation.Method: We administered water extracts of Artemisiae capillaris, Curcumae longae, and Crataegi fructus for three weeks to db/db mice (C57BL/Ks), animal models induced with type 2 diabetes mellitus. Mice were divided into three groups: normal (C57BL/6J mice group), control group (db/db mice without administration of IUS) and IUS group (db/db mice treated with IUS). Then we measured total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride in the serum after the oral administration of IUS.Results: 1. IUS did not show any cytotoxicity in RAW 264.7 cells. 2. IUS decreased AST, ALP, and creatinine levelsand did not show any liver or renal toxicity in the db/db mice. 3. IUS increased DPPH and ABTS radical scavenging activity and decreased ROS production in RAW 264.7 cells. 4. IUS significantly decreased IL-1β, IL-6, and TNF-α production in RAW 264.7 cells. 5. IUS increased HDL cholesterol and significantly decreased total cholesterol and triglyceride in db/db mice. 6. IUS significantly decreased the atherogenic index and cardiac risk factor. 7. In contrast with the control group, fat infiltration in the liver and aorta decreased in IUS treated mice. The cell nucleus was located in the central area in H&E staining of liver. And endomembranes also were more thinner than the control group in H&E staining of aorta.Conclusions: These results suggest that IUS might be effective in the prevention and treatment of dyslipidemia.

Differential Alterations of Endotoxin-induced Cytokine Expression and Mitogen-activated Protein Kinase Activation by Mercury in Mouse Kidney

  • Kim, Sang-Hyun;Kim, Dae-Keun;Shin, Tae-Yong;Choi, Cheol-Hee
    • Toxicological Research
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    • 제20권3호
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    • pp.233-239
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    • 2004
  • The present study was designed to determine the impact of mercury on endotoxin-induced inflammatory cytokine expression and corresponding signal transduction in mouse kidney. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercury in drink-ing water for 14 days and at the end of the treatment period, lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 h prior to euthanasia. The doses of mercury and LPS did not cause hepatotoxicity or renal toxicity as indicated by unaltered plasma alanine aminotransferase and aspartate aminotransferase levels, and terminal UTP nucleotide end-labeling assay from kidney, respectively. Mercury decreased kidney glutathione (GSH) and with LPS, it additively decreased GSH. Mercury activated p38 mitogen-activated protein kinase (MAPK) and additively increased LPS-induced p38 MAPK phosphorylation. In contrast, mercury inhibited LPS-induced activation of extra-cellular signal-regulated kinase (ERK) but had no effect alone. Mercury increased the gene expression of tumor necrosis factor $\alpha$ (TN F$\alpha$) and potentiated LPS-induced TNF$\alpha$ expression. Mercury did not affect LPS-induced interleukin-1$\beta$ (IL-1$\beta$) expression but decreased LPS-induced IL-6 expression. These results suggest that low levels of mercury might augment LPS-induced TNF$\alpha$ expression by altering GSH and p38 MAPK. Mercury modulates LPS-induced p38 and ERK activation, and downstream TNF$\alpha$ and IL-6 expression in kidney, respectively.

Clinical Study on Lobaplatin Combined with 5-Fu and Concurrent Radiotherapy in Treating Patients with Inoperable Esophageal Cancer

  • Jia, Xiao-Jing;Huang, Jing-Zi
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권15호
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    • pp.6595-6597
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    • 2015
  • Objective: To investigate short- and long-term treatment effects and side reactions of lobaplatin plus 5-Fu combined and concurrent radiotherapy in treating patients with inoperable middle-advanced stage esophageal cancer. Methods: Sixty patients with middle-advanced stage esophageal squamous cell cancer were retrospectively analyzed. All patients were administered lobaplatin (50 mg intravenously) for 2 h on day 1, and 5-Fu ($500mg/m^2$) injected intravenously from day 1 to 5 for 1 cycle, in an interval of 21 days for totally 4 cycles. At the same time, late-course accelerated hyperfractionated three-dimensional conformal radiotherapy was performed. Patients were firstly treated with conventional fractionated irradiation (1.8 Gy/d, 5 times/week, a total of 23 treatments, and DT41.4 Gy), and then treated with accelerated hyperfractionated irradiation (1.5 Gy, 2 times/d, a total of 27 Gy in 9 days, an entire course of 6-7 weeks, and DT 68.4Gy). Results: All patients completed treatment, including 10 complete response (CR), 41 partial response (PR), 7 stable disease (SD), and 2 progressive disease (PD). The total effective rate was 85.0% (51/60). Thirty-nine patients had an increased KPS score. One-, 2-, and 3-year survival rates were 85.3%, 57.5%, and 41.7%, respectively. The median survival time was 27 months. The adverse reactions included myelosuppression, which was mainly degree I and II. The occurrence rate of radiation esophagitis was 17.5%. No significant hepatic or renal toxicity was observed. Conclusion: Lobaplatin plus 5-Fu combined with concurrent radiotherapy is safe and effective in treating patients with middle-advanced stage esophageal cancer. However, this result warrants further evaluation by randomized clinical studies.

넙치(Paralichthys olivaceus)의 기관계 구조에 미치는 bis(tri-n-butyltin)oxide (TBTO) 독성 (Toxicity of Bis(tri-n-butyltin)oxide (TBTO) on the Organ Structure of the Flounder, Paralichthys olivaceus)

  • 이정식;강주찬;신윤경;진영국;박정준
    • 환경생물
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    • 제22권1호
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    • pp.133-140
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    • 2004
  • 유기주석화합물이 넙치의 기관계 구조에 미치는 독성을 알아보기 위하여 넙치를 대조구와 TBTO를 첨가한 6개 농도구(0.17, 0.36, 0.60, 3.20, 6.30, 12.50 ${\mu}g \;L^{-1}$)에서 42일 동안 노출 실험을 하였다. 조직상의 변화 정도는 노출 시간과 TBTO농도의 증가에 따라 심하게 나타났다. 저농도의 TBTO 노출구에서 관찰된 초기 조직학적 변화로는 아가미에서는 점액세포와 염세포의 활성, 새판 모세혈관의 충혈, 상피층의 비후, 간췌장에서는 간세포의 활성화와 췌장 효소원과립의 감소, 담관의 변성이 확인되었으며, 신장에서는 모세혈관의 충혈, 호산성세포와 혹색 대식세포군의 출현이 관찰되었다. 고농도의 TBTO 노출구에서 관찰된 조직학적 변화로는 아가미에서는 새판 상피층의 박리와 새판의 붕괴, 간췌장에서는 간세포의 핵응축, 세포질의 혼탁 및 과립변성, 신장에서는 조혈세포의 핵응축, 사구체와 세뇨관의 붕괴 등 정상적인 기능 수행이 어려울 것으로 판단되는 조직상들이 관찰되었다. 이와 같은 결과는 TBTO는 다른 수중오염원과 마찬가지로 어류 기관계의 조직병리학적 변화를 유도한다는 것을 나타낸다.

류마티스 관절염을 가진 만성신질환 환자에서 저용량 methotrexate 투여 후 발생한 중증 범혈구 감소증 2예 (Two Cases of Severe Pancytopenia Associated with Low-Dose Methotrexate Therapy in Patients with Chronic Kidney Disease and Rheumatoid Arthritis)

  • 김홍익;이우현;오장석;홍효림;이인희
    • Journal of Yeungnam Medical Science
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    • 제28권1호
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    • pp.60-69
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    • 2011
  • Due to its efficacy and tolerability, low dose oral methotrexate (MTX) therapy has been widely used for treatment of rheumatoid arthritis (RA). However, it can rarely cause serious, life-threatening hematologic toxicities, such as pancytopenia. We report here on two patients with chronic kidney disease (CKD), who developed severe pancytopenia after 5 years (cumulative dose 1,240 mg) and 4 years (cumulative dose 1,320 mg) of low dose MTX therapy for treatment of RA, respectively. Both patients presented with renal insufficiency, hypoalbuminemia, concurrent use of nonsteroidal anti-inflammatory drugs, and elevated mean corpuscular volume of red blood cells (RECs), all of which are known as risk factors of MTX-induced pancytopenia. Despite receiving treatment, which included REC and platelet transfusions, antibiotic therapy, granulocyte colony stimulating factor, and leucovorin rescue, one patient died of sepsis. Based on our case study, prompt investigation of risk factors associated with MTX toxicity is required for all patients receiving MTX therapy. MTX treatment, even at a low dose, should be discontinued in patients with advanced CKD.

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