• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.38-44
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• 2011

Cisplatin is widely used for various types of cancers. However, its side effects, most notably, renal toxicity often limit its clinical utility. Although previous metabolomic studies reported possible toxicity markers, they used small number of animals and statistical approaches that may not perform best in the presence of intra-group variation. Here, we identified urinary biomarkers associated with renal toxicity induced by cisplatin using NMR-based metabolomics combined with Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA). Male Sprague-Dawley rats (n=22) were treated with cisplatin (10 mg/kg single dose), and the urines obtained before and after treatment were analyzed by NMR. Multivariable analysis of NMR data presented clear separation between non-treated and treated groups. The OPLS-DA statistical results revealed that 1,3-dimethylurate, taurine, glucose, glycine and branched-chain amino acid (isoleucine, leucine and valine) were significantly elevated in the treated group and that phenylacetylglycine and sarcosine levels were decreased in the treated group. To test the robustness of the approach, we built a prediction model for the toxicity and were able to predict all the unknown samples (n=14) correctly. We believe the proposed NMR-based metabolomics with OPLS-DA approach and the resulting urine markers can be used to augment the currently available blood markers.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.300-305
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• 2004

Background : Due to increased interest in herbal medicines is recent years, medical circles have made studies of toxicity and side effects of herbal medicines. Particularly the kidney is sensitive to toxicity. A few reports concerning the side effects and toxicity of herbal medicine have been presented recently. This has bought on some distrust in herbal medicines among patients and western doctors. Objectives : The purpose of this study is to determine what effects long-term prescription of one herbal medicine may have on renal function. Methods : Nineteen patients took herbal medicine for eight weeks. Tests of their Blood Urea Nitrogen(BUN), Creatinine of blood plasma, and urine (chemical and microscopic) were taken before taking medicine and at the 2nd, 4th, 8th weeks. Results : After taking a herbal medicine, BUN and Creatinine decreased significantly or remained the same in comparison with the prior interval. Chemical and microscopic examination of urine showed no changes. Conclusions : The results suggest that taking this herbal medicine for a long time does not induce nephrotixicity. Further study is needed for investigating safety and toxicity of herbal medicines.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.358.2-358.2
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• 2002

Platinum(II) coordination complex(cisplatin) has been currently used as one of the most effective compounds in the treatment of various solid tumors. However. its use has been limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program has been aimed at developing drugs capable of diminishing toxicity and improving selective cytotoxicity. (omitted)

• Archives of Pharmacal Research
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• v.29 no.12
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• pp.1164-1170
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• 2006

A triptolide-lysozyme (TP-LZM) conjugate was synthesized to achieve renal specific delivery and to reduce the side effects of triptolide. Triptolide was coupled to lysozyme through succinic via an ester bond with an average coupling degree of 1 mol triptolide per 1 mol lysozyme. The lysozyme can specifically accumulate in the proximal tubular cells of the kidney, making it a potential carrier for targeting drugs to the kidney. The structure of triptolide succinate (TPS) was confirmed by IR, $^{1}H-NMR$, MS and UV. The concentrations of triptolide in various samples were determined by reversed-phase high-performance liquid chromatography (HPLC). In this study, the physicochemical and stability profiles of TP-LZM under various conditions were investgated the stability and releasing profiles of triptolide-lysozyme (TP-LZM) under various conditions. In vitro release trails showed triptolide-lysozyme was relatively stable in plasma (less than 30% of free triptolide released) and could release triptolide quickly in lysosome (more than 80% of free triptolide released) at $37^{\circ}C$ for 24 h. In addition, the biological activities of the conjugate on normal rat kidney proximal tubular cells (NRK52E) were also tested. The conjugate can effectively reduce NO production in the medium of NRK52E induced by lipopolysaccharide (LPS) but with much lower toxicity. These studies suggest the possibility to promote curative effect and reduce its extra-renal toxicity of triptolide by TP-LZM conjugate.

• Nutrition Research and Practice
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• v.12 no.6
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• pp.535-540
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• 2018

BACKGROUND/OBJECTIVES: Propolis has a rich source of bioactive compounds and has renal and hepatic protective properties. The purpose of this study was to investigate the beneficial effect of hydro-ethanolic extract of propolis against paracetamol-induced liver damage and impairment of kidney function, as well as hematological changes in rats. MATERIALS/METHODS: Six groups of rats were used; the first group was served as a control; the second and third groups were treated by propolis extract at a dose of 50 and 100 mg/kg.B.WT. respectively; the fourth group was treated by paracetamol (200 mg/kg.B.WT.); the fifth group was treated by propolis (50 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days; and the sixth group was treated with propolis (100 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days. All the animals were treated for a period of 15 days. At the end of the experimental period, blood samples were collected for measurement of the liver enzymes, serum albumin, protein and creatinine, blood urea nitrogen, hematological parameters, and urine volume, protein and albumin. RESULTS: Paracetamol over dose significantly lowered hemoglobin, serum total protein, albumin, and uric acid, while it significantly increased blood creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, white blood cells, and platelet count as compared to the control. However, these alterations were significantly attenuated by the use of propolis extract and the effect was dose dependent. Interestingly, propolis prevented paracetamol induced proteinuria, low hemoglobin and body weight loss. CONCLUSIONS: Propolis significantly prevented paracetamol induced renal, hepatic and hematological toxicity and might be useful in the management of liver and renal diseases particularly proteinuria.

• Korean Journal of Veterinary Research
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• v.49 no.3
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• pp.253-256
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• 2009

The aim of the present study was to determine the acute and subacute potential of trichlorfon in guppies (Poecilia reticulatus). We first defined the 24 h median tolerance limit ($TLm_{24h}$) of the fish to trichlorfon. Guppies were then treated with $TLm_{24h}$ and 1/10 $TLm_{24h}$ trichlorfon concentrations to evaluate if any histological alterations occurred. The $TLm_{24h}$ value of trichlorfon was 11 ppm. This concentration resulted in acute toxicity to the gills and kidneys with edema, hyperplasia of the gill lamellae, and vacuolated degeneration and necrosis of renal tubular cells. In the case of subacute toxicity using a 10-fold dilution of the $TLm_{24h}$ value (1.1 ppm), no behavioral changes, external lesions or histopathological changes were observed. Therefore, safe concentration of trichlorfon might be 1.1 ppm in guppy for controlling parasitic infections.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8405-8408
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• 2014

Background: This analysis was conducted to evaluate the efficacy and safety of temozolomide based chemotherapy in treating patients with glioma. Methods: Clinical studies evaluating the efficacy and safety of temozolomide based regimens for patients with glioma were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. Results: In temozolomide based regimens, 5 clinical studies including 152 patients with advanced glioma were considered eligible for inclusion. Four clinical studies included temozolomide. Systematic analysis suggested that, in all patients, pooled CR was 21% (32/152), and PR was 21% (32/152). Grade 3/4 toxicity included neutropenia, thrombocytopenia, and anemia. No grade 3 or 4 renal or liver toxicity was observed. No treatment related death occurred with temozolomide based treatment. Conclusion: This systematic analysis suggests that temozolomide based regimens are associated with mild response rate and acceptable toxicity for treatment of glioma patients.

• Mycobiology
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• v.42 no.3
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• pp.215-220
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• 2014

Mushrooms are a recognized component of the human diet, with versatile medicinal properties. Some mushrooms are popular worldwide for their nutritional and therapeutic properties. However, some species are dangerous because they cause toxicity. There are many reports explaining the medicinal and/or toxic effects of these fungal species. Cases of serious human poisoning generally caused by the improper identification of toxic mushroom species are reported every year. Different substances responsible for the fatal signs and symptoms of mushroom toxicity have been identified from various poisonous mushrooms. Toxicity studies of mushroom species have demonstrated that mushroom poisoning can cause adverse effects such as liver failure, bradycardia, chest pain, seizures, gastroenteritis, intestinal fibrosis, renal failure, erythromelalgia, and rhabdomyolysis. Correct categorization and better understanding are essential for the safe and healthy consumption of mushrooms as functional foods as well as for their medicinal use.

• Korean Journal of Veterinary Service
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• v.34 no.1
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• pp.75-79
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• 2011

The recent outbreak of renal failure in infants in China and in animals in USA and Europe has been determined to be caused by melamine adulterated in the food. In the course of the investigation, cyanuric acid was identified in addition to melamine in the offending food. Fish feeds were also recently found to be contaminated with melamine. The purpose of this study was to characterize the histopathological effect and toxicity potential of different concentrations of melamine and cyanuric acid in the kidney of Japanese catfish (Silurus asotus). The fish were administered melamine and cyanuric acid in combination at the concentrations of 12.5, 25, 50, 100 and 200 mg/kg/day for 3 days by single oral administration dissolved in carboxymethyl cellulose. The results showed that renal crystals were observed in renal tubules and collecting ducts at the concentration over 25 mg/kg dose group and the number of crystals in kidney were in proportion to the concentrations of melamine and cyanuric acid.

• The Korea Journal of Herbology
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• v.20 no.3
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• pp.43-49
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• 2005

Objectives : The present study was carried out to determine if Glycyrrhizae Radix extract exerts beneficial effect against the ischemia-induced acute renal failure in rabbits. Glycyrrhizae Radix 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. Methods : Antioxidative effect of 3% concentration of Glycyrrhizae Radix extract was measured. Rabbits were treated with Glycyrrhizae Radix extract via i.v., followed by renal ischemia/reperfusion, and the changes of urine volume, serum creatinine levels, glomerular filtration rate(GFR), fractional Na+ excretion$(FE\;Na^+)\;and\;K^+\;excretion(FE\;K^+)$ in ischemia/reperfusion induced acute renal failure were measured. Results : Renal ischemia/reperfusion caused increase of serum creatinine level, which was accompanied by a reduction in glomerular filtration rate(GFR). The fractional excretion of $Na^+\;and\;K^+$ increased in ischemia-induced animals, which was partially prevented by Glycyrrhizae Radix extract treatment. Conclusions : These results indicate that lipid peroxidation plays a critical role in ischemia-induced acute renal failure. Glycyrrhizae Radix extract exerts the protective effect against acute renal failure induced by renal ischemia/reperfusion, and its effect may be attributed to an antioxidant action.