• Title/Summary/Keyword: renal toxicity

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Effect of Glycyrrhizae Radix Extract on Ischemia-Induced Acute Renal Failure in Rabbits (감초(甘草) 추출물이 허혈에 의한 토끼의 급성 신부전에 미치는 영향)

  • Kim Gyung-Ho;Jeong Hyun-Woo;Park Jin-Young;Lee Young-Joon;Cho Su-In
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.1
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    • pp.98-102
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    • 2006
  • The present stuby was carried out to determine if Radix Glycyrrhizae extract exerts beneficial effect against the ischemia-induced acute renal failure in rabbits. Radix Glycyrrhizae was known to reinforce the function of the spleen and replenish Qi, remove heat and counteract toxicity, dispel phlegm and relieve cough, alleviate spasmodic pain, and to moderate drug actions. It's indications are weakness of the spleen and the stomach marked by lassitude and weakness; cardiac palpitation and shortness of breath; cough with much phlegm; spasmodic pain in the epigastrium, abdomen and limbs; carbuncles and sores. It is often used for reducing the toxic or drastic actions of other drugs. Rabbits were treated with Radix Glycyrrhizae extract via i.v., followed by renal ischemia/reperfusion. Fractional excretion of glucose and phosphate, lipid peroxidation and light microscopy were done to evaluate the beneficial effect of Radix Glycyrrhizae extract on ischemia/reperfusion induced acute renal failure. Renal ischemia/reperfusion caused increase of fractional excretion of glucose and phosphate increased in ischemia-induced animals, which was partially prevented by Radix Glycyrrhizae extract treatment. Ischemia/reperfusion increased lipid peroxidation, which was prevented by Radix Glycyrrhizae extract administration. And the beneficial effect of Radix Glycyrrhizae extract on ischemia/reperfusion induced kidney injury was shown through the light micrographic observation. These results indicate that lipid peroxidation plays a critical role in ischemia-induced acute renal failure. Radix Glycyrrhizae extract exerts the protective effect against acute renal failure induced by renal ischemia/reperfusion.

Acute Hepatic Failure Induced by Xylitol Toxicosis in Two Dogs

  • Lim, Chae-Young;Yoo, Jong-Hyun;Kim, Chun-Geun;Park, Chul;Park, Hee-Myung
    • Journal of Veterinary Clinics
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    • v.25 no.6
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    • pp.510-513
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    • 2008
  • Two dogs were referred due to vomiting, depression and anorexia after ingestion of xylitol gum. Both dogs were presented with hepatic failure and one dog had concurrent renal failure. Aggressive supportive treatment was performed, but these dogs died. Necropsy of one dog revealed acute hepatic necrosis, severe renal damages, and hemoperitoneum. This case report demonstrates potential hazard of xylitol toxicity for dogs with clinicopathological and pathological findings.

Thirteen-week repeated-dose oral toxicity study of the Modified Wenpitang-Hab-Wulingsan (WHW$^{(R)}$) in Sprague-Dawley rats (WHW$^{(R)}$의 랫드에서의 반복경구투여 독성에 관한 연구)

  • Oh, Tae-Woo;Sang, Bae-Hyo;Yoon, Cheol-Ho;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.25 no.3
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    • pp.43-51
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    • 2010
  • Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 mg/kg/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity.

Renal protective effects of zingerone in a mouse model of sepsis

  • Lee, Bong-Seon;Lee, Changhun;Yang, Sumin;Ku, Sae-Kwang;Bae, Jong-Sup
    • BMB Reports
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    • v.52 no.4
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    • pp.271-276
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    • 2019
  • Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to possess pharmacological activities such as anti-inflammatory and anti-apoptotic effects. This study was initiated to determine whether ZGR could modulate renal functional damage in a mouse model of sepsis and to elucidate the underlying mechanisms. The potential of ZGR treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with ZGR resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. Moreover, ZGR inhibited nuclear $factor-{\kappa}B$ activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. ZGR treatment also reduced the plasma levels of interleukin-6 and tumor necrosis $factor-{\alpha}$, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. Our study showed renal suppressive effects of zingerone in a mouse model of sepsis, suggesting that ZGR protects mice against sepsis-triggered renal injury.

Experimental Intervention to Reverse Inhibition of Nitric Oxide Production by Cyclosporin A in Rat Aortic Smooth Muscle Cells (혈관평활근세포에서 Cyclosporin A에 의한 Nitric Oxide 생성억제를 길항하는 실험적 중재법)

  • Kim, In-Kyeom
    • The Korean Journal of Pharmacology
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    • v.32 no.2
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    • pp.211-219
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    • 1996
  • The inhibitory effect of cyclosporin A (CsA) on nitric oxide production is not related to the immunosuppressive action of the drug, but to the renal toxicity and arterial hyper-tension. In this study the experimental interventions to reverse the inhibition of nitric oxide production by cyclosporin A in rat aortic smooth muscle cells were examined. CsA inhibited the accumulation of nitrite, the stable end product of nitric oxide, in culture media in a concentration $(0.1{\sim}100{\mu}g/ml)-dependent$ manner. The inhibitory effect of CsA on nitrite accumulation were not antagonized by arginine (10 mM), a substrate of nitric oxide synthase, nor by calcium ionophore A23187 $(7{\mu}M)$. Forskolin, an activator of adenylate cyclase, which enhanced iNOS induction at transcriptional level, completely reversed the inhibitory action of CsA on nitrite accumulation. However, PMA (2 nM) and PDB (50 nM), PKC activators, increased the inhibitory action of CsA on nitrite accumulalion. From these results, it is suggested that cyclic AMP-elevating agents may be candidates of therapeutic agents in prevention and treatment of renal toxicity and arterial hypertension induced by CsA. Among conventional antihypertensive drugs, calcium channel blockers and ${\alpha}-blockers$ are preferred to ${\beta}-blockers$.

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Comparison of In Vivo Nephrotoxicity in the Rabbit by a Pyrrolidinyl-Thio Carbapenem CW-270031

  • Kim, Jong-Myung;Ha, Jong-Ryul;Oh, Se-Woong;Kim, Hong-Gi;Lee, Jin-Man;Kim, Byung-Oh;Lee, Dong-Gun;Lee, Sang-Han;Kim, Jong-Guk
    • Journal of Microbiology and Biotechnology
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    • v.18 no.11
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    • pp.1768-1772
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    • 2008
  • CW-270031 is a novel synthesized carbapenem antibiotic with a broad antimicrobial activity. Carbapenem antibiotics are well known for their nephrotoxicity. In this study, we evaluated the nephrotoxicity potential of this compound in rabbits, which are known for being more sensitive than other animals to renal insult. CW-270031 was administered to NZW male rabbits via an ear vein (200 mg/kg, single injection). Blood samples were collected on 2, 3, and 4 days after treatment. Urea nitrogen and creatinine in plasma were quantified. Four days after the treatment, all animals were autopsied and histopathological examinations were performed on their kidneys, revealing that cephaloridine and imipenem were highly nephrotoxic, and cefazolin had mild renal toxicity, whereas CW-270031 as well as meropenem and tienam had no toxicity to the kidney. The present findings suggest that CW-270031 is a potential carbapenem antibiotic with no nephrotoxicity.

Effects of Cadmium on Heat Shock Protein Induction and on Clinical Indices in Rats (카드뮴이 랫드의 Heat Shock Protein 발현에 미치는 영향과 독성학적 변화에 관한 연구)

  • 김판기
    • Journal of Environmental Health Sciences
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    • v.22 no.4
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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.

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Effects of Squalene on Renal Toxicity Induced by Lead Acetate in Proximal Tubules of the Mice (생쥐 근위세뇨관에서 납에 의한 신장 독성에 대한 스쿠알렌의 효과)

  • Kim, Jong-Se;Lee, Yu-Hyun;Lee, Jun-Heung
    • Applied Microscopy
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    • v.34 no.3
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    • pp.185-197
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    • 2004
  • To investigate the effect of the squalene against the lead toxicity and recovery of renal failure. Healthy male ICR mice were used for experiment. The activity of nitric oxide (NO) was observed after the intraperitoneal injection in mice. The ultrastructural changes of the kidney were observed after the intraperitoneal injection of lead acetate in mice. The experimental groups were divided into three groups. Group 1 was normal mouse. Group 2 was not treatment with squalene after intraperitoneal contamination of lead acetate (30 mg/kg). And, Group 3 was injected squalene (180 mg/kg) after intraperitoneal contamination of lead acetate. All groups were used to 10 mice. The results were as follow: In the case of the group 2, swelling of the outer membrane and destruction of the inner membrane (cristae) of the mitochondria, dripping of the ribosomes from the rough endoplasmic reticulum were happened at 24 hours and 48 hour. These were gradually reparied after 72 hours. In the case of the group 3, damages of the mitochondria and the rough endoplasmic reticulum were showed less than the group 2 at 24 hours. Especially, after 48 hours, these were almost same as the group 1. In the case of group 2, the level of NO was decreased. However, In the case of group 3, the level of NO was increased more than normal as well as repaired the decreased NO level by Pb (P<0.05). It was concluded that the squalene was the protective and recovery effects for the toxicity of the lead in the renal proximal tubules.

Bromate Formation by Ozonation Process and It′s Effect on Renal Toxicity in rat (오존처리에 의한 Bromate의 생성 및 흰쥐의 신장독성에 미치는 영향)

  • 정운용;이무강;최종원
    • Journal of Life Science
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    • v.12 no.4
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    • pp.442-451
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    • 2002
  • In oder to investigate the effects of pH and temperature on the formation of bromate ion, which is ozonation by-products of bromine containing natural water. At the same intial pH condition, the increase of pH shown similar trends even if the reaction variables such as temperature and reaction time of ozonation were changed. As pH and temperature were increasing, the bromate concentration was increased but bromine components (HOBr/OBr-) were decreased with increasing pH from 3 to 10. Lipid peroxide content in the kidney was increased by bromate which was ingestion with 0.4g/L for 24 weeks in drinking water. Renal cytosolic enzyme system (XO, AO) of bromate group were significantly increased in comparison with those of normal group. But microsomal enzyme system were not affected. BUN level and urinary ${\gamma}$-glutamyltransferase activity were significantly increased in comparison with those of the normal. But, urinary lactate dehydrogenase activity was not affected. Renal glutathione content of rat was significantly decreased in comparison with those of normal rat given bromate. Renal glutathione S-transferase and ${\gamma}$-glutamylcysteine synthetase activities were significantly decreased in bromate-treated group, but change in renal glutathione reductase activity was not significantly different from any other experimental group.

Application of Pediatric Hemodialysis System to Experimental Renal Failure in Dogs (실험적으로 유발한 신부전 개에서 소아용 혈액투석기의 적용에 관한 연구)

  • 신현호;김완희;이충호;남치주;권오경
    • Journal of Veterinary Clinics
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    • v.17 no.2
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    • pp.340-345
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    • 2000
  • The purpose of the present study was to evaluate the possibility of application of pediatric hemodialysis system to dogs weighing less than 6 kg. Six healthy dogs (B .W, 3-6 kg) were used_ Experimental end-stage renal failure was induced by bilateral nephrectomy or bilateral ligation of ure-ters. Hemodialysis was performed when blood urea nitrogen (BUN) value increased over 90 mg/dl and every other day thereafter. Daily investigated parameters included clinical clinical signs such as vomiting, fecal appearance and activity and laboratory data such as PCV, WBC, RBC, BUN, creatinine, Ca, P, $Na^+ Cl^-and K^+$During hemodialysis treatment, BUN and creatinine values were measured hourly. Severe vomiting and inappetence were shown 2 days after infliction of kidney disorder and melena and mucous faces were observed 3 days. The signs were not corrected by hemodialysis treatment. Avel- age hemodialysis treatment time was $5.5 {\times} 0.7$,/TEX> hours until BUN value decreased to normal range. Abnor- mal hematological and electrolytes values were reduced within normal levels after hemodialysis treatments. The complications oft hemodialysis included vomiting, nausea, obstruction of intravascular catheter, tremor, seizure, temporary visual loss and continued decrease in PCV It is suggested that pediatric hemedialysis system can be applied to acute renal failure and acute toxicity. Further works on improvements in maintaining patency of catheter and in managing the complications of hemo- dialysis should be conducted.

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