• Title/Summary/Keyword: Rat kidney

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Acute oral toxicity and bioavailability of uranium and thorium in contaminated soil

  • Nur Shahidah Abdul Rashid;Wooyong Um ;Ibrahim Ijang ;Kok Siong Khoo ;Bhupendra Kumar Singh;Nurul Syiffa Mahzan ;Syazwani Mohd Fadzil ;Nur Syamimi Diyana Rodzi ;Aina Shafinas Mohamad Nasir
    • Nuclear Engineering and Technology
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    • v.55 no.4
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    • pp.1460-1467
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    • 2023
  • A robust approach was conducted to determining the absolute oral bioavailable (fab) fractions of 238U and 232Th in rats exposed to contaminated soil along with their hematotoxicity and nephrotoxicity. The soil sample is the International Atomic Energy Agency-312 (IAEA-312) certified reference material, whereas blood, bones, and kidneys of in vivo female Sprague-Dawley (SD) rats estimate 238U- and 232Th-fab fractions post-exposure. We predict the bioavailable concentration (Cab) and fab values of 238U and 232Th after acute soil ingestion. The blood 238U (0.750%) and 232Th (0.028%) reach their maximum fab values after 48 h. The 238U (fab: 0.169-0.652%) accumulates mostly in the kidney, whereas the 232Th (fab: 0.004-0.021%) accumulates primarily in the bone. Additionally, 238U is more bioavailable than 232Th. Post 48 h acute ingestion demonstrates noticeable histopathological and hematological alterations, implying that intake of 238U in co-contaminated soil can lead to erythrocytes and proximal tubules damage, whereas, 232Th intake can harm erythrocytes. Our study provides new directions for future research into the health implications of acute oral exposures to 238U and 232Th in co-contaminated soils. The findings offer significant insight into the utilization of in vivo SD rat testing to estimate 238U and 232Th bioavailability and toxicity in exposure assessment.

Effect of Rehmanniae Radix Preparata on Memory in Rats (숙지황이 기억과 망각 속도에 미치는 영향에 대한 실험적 연구)

  • Park Seung Won;Lee Jin Woo;Bae Hyun Su;Shin Min Kyu;Hong Moo Chang
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.57-63
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    • 2003
  • Background: Rehmanniae radix preparata is a medicinal herb widely used in Asian countries, to replenish Yin and Vital Essence through strengthen the kidney function. In Oriental Medicine the brain has physiological relationship with the Vital Essence. And central nerve system (CNS) is also refered to as 'Sea of the Vital Essence'. So if the Vital Essence is strong it will nourish the brain and memory will all be keen. The purpose of this study was to investigate the effect of 7 to 14 days treatment with Rehmanniae radix preparata (3.4 g /100 g, per os) on retention performance of rats in a passive avoidance situation. Methods: Male Sprague-Dawley rats were trained on a one-trial passive avoidance task using a two-way shuttle box by giving a foot shock. They were tested for retention of 6h, 24h, 72h, 168h, and 336h after training. Results: Rehmanniae radix preparata treated rats showed a increased performance in retention test as compared to saline at 6hr (P<0.05) and 24hr (P<0.05). Conclusion: These data suggest that Rehmanniae radix preparata treatment can improve memory in the rat.

Two -week Oral Toxicity Study of 1- (4-methylpiperazinyl) -3- phenylisoquinoline (CWJ-a-5) in sprague-Dawley (SD) Rats (1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5)의 Sprague-Dawley(SD) 랫드를 이용한 2주간 반복 경구투여 독성시험)

  • 강부현;조원제;김대덕;김용범;차신우;장순재
    • Toxicological Research
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    • v.18 no.1
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    • pp.47-57
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    • 2002
  • The subacute oral toxicity of 1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5) was investigated in Sprague-Dawley (SD) rats. Five groups of 5 males and 5 females were orally administered at doses of 0, 37.5, 75, 150 and 200 mg/kg with CWJ-a-5 for 2 weeks. In clinical signs, Salivation was observed in the 75, 150 and 500 mg/kg male and female groups. Loss of fur was observed in the 500 mg/kg male and female group. Body weight were significantly decreased in the 150 and 500 mg/kg male groups and in the 500 mg/kg female group. Food consumption was significantly decreased in the 300 mg/kg male group. In serum biochemistry, total cholesterol and phospholipid were significantly increased in 500 mg/kg male and female group. Aspartate aminotransferase was significantly increased in the 500 mg/kg female group. In histopathological examination, vacuolar degeneration of renal tubules in the kidney, vacuolar degeneration of hepatocytes in the liver vacuolar degeneration of myocytes in the heart, vacuolar degeneration of histiocytes in the spleen and thymus, atrophy of seminiferous tubule and degeneration of germinal epithelium in the testis, vacuolar degeneration of corpus luteum, granulosa cell and theca cell in the ovary were observed in the 150 and 500 mg/kg male and female groups. Based on these results, the no observed adverse effect level (NOAEL) with CWJ-a-5 was considered to be 75 mg/kg and the absolute toxic dose was considered to be 150 mg/kg in this study

Pharmacokinetic profile and tissue distribution of sulfamethazine in pigs and rats (돼지와 랫트에서 sulfamethazine의 약물동태학 및 조직분포)

  • Yun, Hyo-in;Park, Seung-chun;Oh, Tae-kwang;Cho, Joon-hyoung;Park, Jong-myeong
    • Korean Journal of Veterinary Research
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    • v.37 no.2
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    • pp.291-299
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    • 1997
  • In order to establish optimal dosage schedules and withdrawal times for sulfamethazine(SMZ) in pigs, pharmacokinetic and tissue distribution experiments were conducted in pigs. For comparative purposes, tissue depletion kinetics are also studied in rats. From three pigs administered with SMZ i.v., the pharmacokinetic profile of SMZ in two pigs was adequately described by a one-compartment open model whereas that in one pig was patterned after a two-compartment open model. Volume of distribution(Vd) was 0.48~0.57 L/kg and biological half-life($t_{1/2}$) was 11.8-16.8 h. From three pigs dosed with SMZ p.o., pharmacokinetic profile was explainable with a one-compartment open model. Time to reach maximum SMZ concentration in serum (Tmax) was 2.8 h, 3.2 h and 7.5 h. Elimination half-life was 2.8-7.5 h. The descending order in concentration of SMZ was plsama > kidney > liver > lung > heart > pancreas > spleen > duodenum > ileum > brain > adipsoe tissue from three pigs sacrificed at 5h, 29h and 54h after the administration of SMZ, p.o.. The protein binding of SMZ in pigs was 55.2%($2.5{\mu}g/ml$), 71.5% ($5{\mu}g/kg$) and 71.5%($10{\mu}g/ml$). The mean systemic bioavailability (F) of SMZ p.o. was 49.1 %. Meanwhile the pharmacokinetic profile of SMZ in rats was adequately described by a one-compartment open model. Absorption of SMZ p.o. in the rat was very rapid. In conclusion, the oral optimal dosage regimen of SMZ for pigs was the initial dose of 45.7 mg/kg followed by the maintenance dose of 30.2 mg/kg for high specific pathogens to SMZ. The time to reach below the stipulated residual allowable concentration (0.1 ppm) was calculated 93 h after oral administration of 200 mg/kg recommended by manufactureres.

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Production of Biological Active Single Chain Bovine LH and FSH

  • Min, K.S.;Kang, M.H.;Yoon, J.T.;Jin, H.J.;Seong, H.H.;Chang, Y.M.;Chung, H.J.;Oh, S.J.;Yun, S.G.;Chang, W.K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.16 no.4
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    • pp.498-503
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    • 2003
  • Luteinizing hormone as other glycoprotein hormones is characterized by a heterodimeric structure composed a common $\alpha$-subunit noncovalently linked to a specific $\beta$-subunit. The correct conformation of the heterodimer is important for efficient secretion, hormonal-specific post-translational modifications, receptor binding and signal transduction. To determine whether $\alpha$- and $\beta$- subunits can be synthesized as a single polypeptide chain (tethered-bLH and -bFSH) and also display biological activities, the tetheredbLH and -bFSH molecules were constructed and transfected into chinese hamster ovary (CHO-K1) cells. LH and FSH activities were assayed by using the human embryonic kidney (HEK) 293 cells expressing rat LH and FSH receptor genes. The tethered-bLH and - bFSH proteins were efficiently secreted and showed a similar activity to the dimeric bovine LH and FSH $\alpha$/$\beta$ wild type and native purified from bovine pituitary. The tethered-molecules can be permit development of potent new analogues that stimulate ovarian development. Taken together, a single-chain analog can also be constructed to include additional hormone-specific bioactive generating potentially efficacious compounds. These data indicate the potentiality of the single chain approach to further investigate structurefunction relationships of LH and FSH.

Molecular Characterization and Expression Analysis of Equine Vascular Endothelial Growth Factor Alpha (VEGFα) Gene in Horse (Equus caballus)

  • Song, Ki-Duk;Cho, Hyun-Woo;Lee, Hak-Kyo;Cho, Byung Wook
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.5
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    • pp.743-748
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    • 2014
  • The objective of this study was to determine the molecular characteristics of the horse vascular endothelial growth factor alpha gene ($VEGF{\alpha}$) by constructing a phylogenetic tree, and to investigate gene expression profiles in tissues and blood leukocytes after exercise for development of suitable biomarkers. Using published amino acid sequences of other vertebrate species (human, chimpanzee, mouse, rat, cow, pig, chicken and dog), we constructed a phylogenetic tree which showed that equine $VEGF{\alpha}$ belonged to the same clade of the pig $VEGF{\alpha}$. Analysis for synonymous (Ks) and non-synonymous substitution ratios (Ka) revealed that the horse $VEGF{\alpha}$ underwent positive selection. RNA was extracted from blood samples before and after exercise and different tissue samples of three horses. Expression analyses using reverse transcription-polymerase chain reaction (RT-PCR) and quantitative-polymerase chain reaction (qPCR) showed ubiquitous expression of $VEGF{\alpha}$ mRNA in skeletal muscle, kidney, thyroid, lung, appendix, colon, spinal cord, and heart tissues. Analysis of differential expression of $VEGF{\alpha}$ gene in blood leukocytes after exercise indicated a unimodal pattern. These results will be useful in developing biomarkers that can predict the recovery capacity of racing horses.

DNA Microarrays Analysis of Gene Expression Profiles in Diabetes-related genes using Immunosuppressant (면역억제제에 의한 당뇨 관련 유전자의 DNA microarray 분석)

  • Kim, Kyoung-Shin;Kim, Byoung-Soo
    • Journal of Haehwa Medicine
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    • v.21 no.1
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    • pp.11-21
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    • 2012
  • New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. The purpose of this study is to develop novel immune suppressants for PTDM using of action mechanism of them. The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to ${\beta}$-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of ${\beta}$-cells to therapeutical levels of tacrolimus (FK506) or cyclosporin A(CsA). The immunosuppressive drug cyclosporine(CsA) is a potent agent widely used after organ transplantations and various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity. The renal or vascular toxicity is influenced by the degree of the endothelial damage. FK506(tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of Immunosuppressant. In this study, we investigated gene expression patterns induced by Immunosuppressant in RIN-m5F of rat insulinoma cell line. Gene expressions evaluated using cDNA microarry in two clusters were increased or decreased. this study provides comprehensive comparison of the patterns of gene expression changes induced by CsA and FK506 in ${\beta}$-cells. This study could establish that the mode of action mechanism by which currently used insulin inhibitors inducing PTDM could be elucidated at least in part, which raises the possibility that novel immune suppressive PTDM can be developed. The molecular biological study on PTDM will also contribute the progress in diabetes research field as well as in that of PTDM.

Effect of Prior Gastrodia elata Blume diet on Diabetic Mellitus Induced Rats at Antioxidant Effect and Pathophysiology factor (선행된 천마식이가 당뇨유발백서의 항산화효과 및 병태생리학적 인자에 미치는 영향)

  • Sim, Ki-Cheol;Kim, Eun-Jung;Chung, Hun-Woo;Kim, Gi-Do;Kim, Kyoung-Yoon;Kim, Gye-Yeop
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.6
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    • pp.1537-1543
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    • 2008
  • The purpose of this study was investigation to examine the prevention diabetic mellitus and treatment effect on Gastrodia Elata Blume(GEB) dieted at prior and after induced diabetic application. Prior induced diabetic 3 weeks ago application GEB dieted. It is to analysis changes in body weight, blood glucose, SOD, CAT and histopathological findings. For the fingding significantly concentration diabetic rats were divided into 3 different experimental groups and each groups were induced diabetic. Experimental group Ⅰ (STZ-induced diabetic rats; n=10), experimental group Ⅱ (after induced DM and GEB dieted rats; n=10), experimental group Ⅲ (Prior GEB dieted thereafter DM induced; n=10). Prior and After GEB dieted application was that body weight, blood glucose were increase in experimental group Ⅱ, Ⅲ. Specially, group Ⅲ was significantly change than group Ⅱ at 1st weeks. and the level of CAT were significantly decrease in experimental group Ⅱ, Ⅲ than group Ⅰ. but SOD level was increase in experimental group Ⅱ, Ⅲ than group Ⅰ. In histological observation; group Ⅰ showed decrease in the intensity and incidence of vacuolations, cellular infiltration and hypertrophy of in liver and kidney. The Gomori's stain result, group Ⅰ showed disruption ${\beta}$-cell in pancrease.

Comparisons of Renoprotective Activities between White Ginseng Radix and Rootlet in Spontaneously Hypertensive Rats with Diabetes

  • Chung, Sung-Hyun;Ko, Sung-Kwon;Park, Se-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.1
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    • pp.57-61
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    • 2002
  • The renoprotective activities of white ginseng radix and rootlet were compared in spontaneously hypertensive rat (SHR) with diabetes. During oral administration of white ginseng radix (Ginseng Radix Alba, GRA) and white ginseng rootlet (Ginseng Radix Palva, GRP) for four weeks, arterial blood pressure and blood glucose levels were determined at every 10 days. In both GRA- and GRP-treatment groups, arterial blood pressures started to go down after 10 days of administration and maintained throughout the study period. After four weeks administrations of GRA and GRP, diastolic blood pressures were significantly decreased with 17% and 9%, respectively. GRA treatment also decreased blood glucose levels after 10 days of administration when compared with diabetic SHR group. At the end of the experiment, serum creatinine (Scr) and blood urea nitrogen (BUN) were not significantly different between the groups, except 62% higher value of BUN in diabetic SHR group when compared with SHR group. In the diabetic SHR group, the excretion of urinary albumin was increased significantly when compared with SHR. The level of urinary albumin in GRA treated group was markedly reduced when compared with diabetic SHR group $(67.8{\pm}4.7\;vs.\;131.3{\pm}13.5\;mg/24\;h).$ To examine the effects of ginseng radices on an overt diabetic nephropathy, index of kidney hypertrophy and transforming growth $factor-{\beta}1\;(TGF-{\beta}1)$ protein levels were evaluated. The glomerular and tubular cells stained positive for $TGF-{\beta}1$ seemed to be more abundant in diabetic SHR than in those with SHR, and GRA treated rats showed somewhat less $TGF-{\beta}1$ protein in glomerular and tubular cells when compared with diabetic SHR. Our results suggest that GRA might be a useful antihypertensive and antidiabetic agent with renoprotective effect.

Effects of Hwangryungeehwang-tang Aqueous Extracts on Streptozotocin-induced Diabetic Rat (황련지황탕(黃連地黃湯)이 Streptozotocin으로 유발(誘發)된 당뇨병(糖尿病)에 미치는 영향)

  • Yu, Dong-Jo;Yoon, Gyeong-Min;Kang, Seok-Bong
    • The Journal of Internal Korean Medicine
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    • v.32 no.2
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    • pp.288-300
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    • 2011
  • Objectives : The object of this study was to observe the effects of Hwangryungeehwang-tang (HRGHT), which has traditionally been used in Korean medicine for treating diabetes, by administering aqueous extracts to streptozotocin-induced diabetic rats. Methods : Three different dosages of HRGHT extracts were orally administered once a day for 28 days from 3 weeks after streptozotocin treatment (60 mg/kg, single intraperitoneally administered). 6 groups, of 8 rats per group were used in the present study, selected 3 weeks after streptozotocin treatment based on blood glucose levels and body weights. Changes to the body weights, blood glucose levels, serum low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride and total cholesterol levels were observed, as well as changes on the pancreatic, hepatic and kidney malondialdehyde (MDA) contents for lipid peroxidation and glutathione contents for antioxidant effects. The results were compared with a potent antioxidant silymarin 100 mg/kg, of which the effects on streptozotocin-induced diabetes and related complications are already confirmed. Results : Significant decrease of blood glucose levels, serum LDL, total cholesterol, triglyceride levels, pancreatic, hepatic and renal MDA contents and significant increase of body weights, serum HDL levels, pancreatic, hepatic and renal GSH contents were detected in HRGHT extracts 100 and 200 mg/kg administered groups as compared to the streptozotocin control group. The lowest dosage of HRGHT treated group, 50 mg/kg, did not show any favorable effects as compared with the streptozotocin control. Conclusions : HRGHT has favorable effects on diabetes and related hyperlipidemia. Therefore, more detailed mechanism studies should be conduced in future with efficacy tests of individual herbal compositions of HRGHT and screening of the biological active compounds in the herbs.