• Title/Summary/Keyword: renal toxicity

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A Study on the Reduction of Heavy Metal Biotoxicity by Aloe (중금속의 생체독성에 대한 알로에의 저감 연구)

  • 하배진
    • Journal of Environmental Science International
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    • v.7 no.1
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    • pp.46-51
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    • 1998
  • The effects of aloe on the MDA(malondialdehyde) and the blood biochemical components of heavy metal poisoning in SD rat were examined and the following results were obtained. In rat liver homogenate intoxicated with $CdCl_2$, lipidperoxide was increased each 2.37times(24h), 3.31times(72h) but lipidperoxide In aloe administration groups was lower each 47% , 64% than in heavy metal group. In rat kidney homo- genate intoxicated with $CdCl_2$, lipidperoxide was increased 1.85times(24h), 1.33times(72h) but lipidperoxide in groups was almost the same as that of normal group. Lipidperoxide of kidney homogenate was slightly decreased as time passed. Also heavy metal poisoning rats showed high levels(1.38-2.50times) of serum AST, ALT and BUN. However. the administration of aloe significantly inhibited the reduction of them. These results suggest that Cd-induced hepatic and renal injury, via increase llpidpero)Ode and release of AST, ALT and BUN. Aloe may be used to inhibit or prevent the hepatic and renal toxicity which results from the heavy metal.

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Development of the 3rd Generation Anticancer Platinum Complex as New Drug

  • Cho, Yong-Baik;Ph. D.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2002.07a
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    • pp.97-102
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    • 2002
  • Life Science Research Center of SK Chemicals has developed a 3rd-generation anticancer platinum drug for the first time in the nation′s 100-year-old pharmaceutical industry. The Korea Food and Drug Administration (KFDA) approved the sale of "Sunpla" (code name SKI 2053R, general name : Heptaplatin) on July 14, 1999 for the treatment of advance, metastatic gastric cancer. Cisplatin, the 1 st-generation anticancer drug, which was developed by Bristol-Myers of the United States in 1976, is one of the most potent anticancer drugs and is a major component of combination chemotherapy for a variety of human cancers. However its clinical usefulness has frequently been limited not only by undesirable side effects such as severe renal toxicity, nausea, vomiting, ototoxicity, and neurotoxicity but also by the development of resistance. Carboplatin, the 2nd-generation anticancer platinum drug, which was also developed by Bristol-Myers in 1986, has modified the problems of the renal and gastrointestinal toxicities of cisplatin. Carboplatin, however, has no enhanced therapeutic efficacy over cisplatin and does not possess the property to overcome cross-resistance to cisplatin.

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Different Regulation of p53 Expression by Cadmium Exposure in Kidney, Liver, Intestine, Vasculature, and Brain Astrocytes

  • Lee, Jin-Yong;Tokumoto, Maki;Hattori, Yuta;Fujiwara, Yasuyuki;Shimada, Akinori;Satoh, Masahiko
    • Toxicological Research
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    • v.32 no.1
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    • pp.73-80
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    • 2016
  • Chronic exposure to cadmium (Cd) is known to adversely affect renal function. Our previous studies indicated that Cd induces p53-dependent apoptosis by inhibiting gene expression of the ubiquitin-conjugating enzyme (Ube) 2d family in both human and rat proximal tubular cells. In this study, the effects of Cd on protein expression of p53 and apoptotic signals in the kidney and liver of mice exposed to Cd for 12 months were examined, as well as the effects of Cd on p53 protein levels and gene expression of the Ube2d family in various cell lines. Results showed that in the kidney of mice exposed to 300 ppm Cd for 12 months, there was overaccumulation of p53 proteins in addition to the induction of apoptosis, which was triggered specifically in the proximal tubules. Interestingly, the site of apoptosis was the same as that of p53 accumulation in the proximal tubules. In the liver of mice chronically exposed to Cd, gene expression of the Ube2d family tended to be slightly decreased, together with slight apoptosis without the accumulation of p53 protein. In rat small intestine epithelial (IEC-6) cells, Cd decreased not only the p53 protein level but also gene expression of Ube2d1, Ube2d2 and Ube2d4. In human brain microvascular endothelial cells (HBMECs), Cd did not suppress gene expression of the Ube2d family, but increased the p53 protein level. In human brain astrocytes (HBASTs), Cd only increased gene expression of UBE2D3. These results suggest that Cd-induced apoptosis through p53 protein is associated with renal toxicity but not hepatic toxicity, and the modification of p53 protein by Cd may vary depending on cell type.

Single and 4-Week Repeated Dose Toxicity Studies of DA-3585, a Recombinant Human Erythropoietin, in Rabbits (사람 적혈구 조혈인자 DA-3585의 토끼에 대한 단회 및 4주 반복투여 독성시험)

  • Cho, Hyeon;Kim, Dong-Hwan;Kang, Kyung-Koo;Baik, Nam-Gi;Kim, Won-Bae
    • Biomolecules & Therapeutics
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    • v.6 no.2
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    • pp.171-181
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    • 1998
  • DA-3585, a biosynthetic recombinant human erythropoietin has been developed as a treatment for anemia associated with chronic renal failure in Dong-A pharmaceutical Co. Ltd. This study was carried out to assess its acute and subacute toxicities in rabbits. DA-3585 was intravenously administered to rabbits at dose levels of 6250, 12500 or 25000 lU/kg for single dose toxicity study and at dose levels of 100, 500 or 2500 lU/kg/day for 4-week repeated dose toxicity study. In the acute toxicity study, dose up to 25000 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal gross lesions related to DA-3585. In the subacute toxicity study, all animals survived until termination of treatment. DA-3585 had no influence on clinical signs, food and water intake or on body weight changes. Hematological examination showed increases in the number of RBC, hemoglobin contents and hematocrit values with a dose dependent manner in the animals treated with DA-3585. Histopathological examination revealed erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the liver. The changes detected in the hematological and histopathological examination presumably represent exaggerated pharmacological effects of erythropoietin. The NOAEL (no-observed-adverse-effect-level) of DA-3585 was estimated to be 100 lU/kg/ day under this study condition.

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Protective Effect of Korean Red Ginseng Against Dichromate Toxicity

  • Kim, Eun;Hyun, Hak-Chul;Na, Ki-jung
    • Proceedings of the Ginseng society Conference
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    • 1990.06a
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    • pp.132-136
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    • 1990
  • The metabolic disturbance and nephrotoxicity induced by sodium dichromate (20 mg/kg, SC) have been diminished by the administration of Korean red ginseng extract (100 mg/kg, PO). Red ginseng has a powerful potency on the blood urea nitrogen (BUN) increment shown in the early 2h after dichromate intoxication. It normalized the dichromate induced hepatic glycogenolysis. The effect of red ginseng on dichromate induced nephrotoxicity was investigated by hematological analysis, and urinalysis. Ginseng treatment significantly reduced the increases in the urinary excretion of protein and glucose. These effects were dose dependent. Ginseng protected the accumulation of BUN and cretonne in the blood, caused by dichromate intoxication. Unlike CaEDTA, ginseng did not change the urinary excretion chromium. And it could not convert htxavalent chromium to trivalent chromium. These results suggest that ginseng treatment is effective in decreasing the metabolic disturbance, one of the earliest signs of dichromate toxicity, resulting in the protective effect of dichromate induced renal damage.

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Protective Effect of Korean Red Ginseng Against Dichromate Toxicity (중크롬산 독성에 대한 고려홍삼의 방어효과)

  • Kim, Eun;Hyun, Hak-Chul;Na, Ki-Jung
    • Journal of Ginseng Research
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    • v.14 no.2
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    • pp.274-278
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    • 1990
  • The metabolic disturbance and nephrotoxicity induced by sodium dichromate (20 mg/kg, SC) have been diminished by the administration of Korean red ginseng extract (100 mg/kg, PO). Red ginseng has a powerful potency on the blood urea nitrogen (BUN) increment shown in the early 2h after dichromate intoxication. It normalized the dichromate induced hepatic glycogenolysis. The effect of red ginseng on dichroamte induced nephrotoxicity was investigated by hematological analysis, and urinalysis. Ginseng treatment significantly reduced the increases in the urinary excretion of protein and glucose. These effects were dose dependent. Ginseng protected the accumulation of BUN and creatinine in the blood, caused by dichromate intoxication. Unlike CaEDTA, ginseng did not change the urinary excretion of chromiilm and it could not convert hexavalent chronlium to trialvalent chromium. These results suggest that ginseng treatment is effective in decreasing the metabolic disturbance, one of the earliest signs of dichromate toxicity, resulting in the protective effect of dichromate induced renal damage.

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A Case of Central Nervous System Toxicity Associated with Cyclosporine (Cyclosporine에 의한 중추신경계 독성 1례)

  • Lee Do-Yoon;NamGoong Mee-Kyung;Kim Hwang-Min;Lim Baek-Keun
    • Childhood Kidney Diseases
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    • v.1 no.2
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    • pp.179-182
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    • 1997
  • Cyclosporine is an immunosuppressant usually used to prevent renal transplantation rejection. Nephrotoxicity and hypertension are considered as the most frequent side effects of cyclosporine treatment. The neurotoxic effects of cyclosporine such as agitation, anxiety, delirium, depression and psychosis have recently been found. Methylprednisolone may increase as well plasma concentration of cyclosporine, which leads to side effects. Here we report a $Henoch-Sch\"{o}nlein$ nephritis patient treated with cyclosporine and methylprednisolone who has experienced psychosis including visual and auditory hallucination and convulsion.

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Molecular Mechanism for Methylmercury-induced Toxicity in Kidney and Brain Cells

  • Kim, Dae-Kyong;Kang, Mi-Sun;Jeong, Ju-Yeon;Jung, Sung-Yun;Seo, Ji-Heui;Joseph V.Bonventre
    • Proceedings of the PSK Conference
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    • 2003.10a
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    • pp.74-74
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    • 2003
  • Methylmercury (MeHg) is a ubiquitous environmental toxicant that can be exposed to humans by ingestion of contaminated food including fish and bread. MeHg has been suggested to exert its toxicity through its high reactivity to thiols, generation of arachidonic acid and reactive oxygen species (ROS), and elevation of intracellular $Ca^{2+}$ levels ([$Ca^{2+}$]i). However, the precise mechanism has not been fully defined. (omitted)

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Evidence Based Analysis of Cisplatin for Treating Patients with Cutaneous Squamous Cell Carcinoma

  • Shao, Xiao-Hong;Xu, Yun-Sheng;Zhang, Xue-Qi;Li, Wen-Feng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9813-9815
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    • 2014
  • Background: This analysis was conducted to evaluate the efficacy and safety of cisplatin based chemotherapy for treating patients with cutaneous squamous cell carcinoma. Methods: Clinical studies evaluating the efficacy and safety of cisplatin based regimens on response and safety for patients with cutaneous squamous cell carcinoma were identified using a predefined search strategy. Pooled response rates (RR) of treatment were calculated. Results: In cisplatin based regimens, 4 clinical studies which including 50 patients with advanced cutaneous squamous cell carcinoma were considered eligible for inclusion. Regimens included cisplatin, doxorubicin, or vindesine. Pooled analysis suggested that, in all patients, the pooled RR was 60% (30/50) in cisplatin based regimens. Nausea and vomiting were the main side effects. No grade III or IV renal or liver toxicity were observed. No treatment related death occurred with the cisplatin based treatments. Conclusion: Evidence based analysis suggests that cisplatin based regimens are associated with a good response rate and acceptable toxicity for treating patients with cutaneous squamous cell carcinoma.

Subcutaneous Toxicity Evaluation of a Combination Vaccine against Hantaan and Puumala Viruses in Rats for 4 Weeks

  • Lee, Su-Hae;Jung, Eun-Yong;No, Kyong-Ok;Sin, Ji-Soon;Ahn, Chang-Nam;Kim, Dae-Joong;Nam, Sang-Yoon;Kang, Jong-Koo
    • Toxicological Research
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    • v.18 no.2
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    • pp.139-147
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    • 2002
  • Hantaan (HTNV) and Puumala (PUUV) viruses cause hemorrhagic fever with renal syndrome in human. In the present study, the repeated dose toxicity of the HTNV-PUUV combination vaccine was evaluated in Sprague-Dawley rats. Animals were injected subcutaneously for 28 days with dosages of 0, 0.017, 0.17 and 1.7 dose/kg body weight per day, respectively. No any significant changes of body weight, food and water consumptions were shown. There were no death and clinical findings during the experimental period. In both male and female rats, there were not significant changes in hematological and serum biochemical analysis, urinalysis, and ophthalmoscopic and histopathological examination. These results indicate that the HTNV-PUUV combination vaccine may have no toxic effects and no observed adverse effect level (NOAEL) may be over 1.7 dose/kg/day at subcutaneous route in rats.