• BMB Reports
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• 제40권6호
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• pp.1039-1049
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• 2007

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.

• 셀메드
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• 제13권6호
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• pp.5.1-5.8
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• 2023

Objectives: Cassia occidentalis L. is a weed belonging to the Caesalpiniaceae family. The root of this medicinal plant is used for the treatment of various ailments, including kidney diseases. The present study was aimed at evaluating the nephroprotective effects of HAE of the roots of Cassia occidentalis L. against gentamicininduced renal toxicity in albino Wistar rats. Methods: The renal toxicity was induced by subcutaneous administration of gentamicin at 100 mg/kg in the rats belonging to the disease control and treatment groups from the 4^th to the 8^th day. The rats in the treatment group received HAE of the roots of Cassia occidentalis L. at 67 mg/kg b. w. orally for 8 days, while no treatment was given to the rats in the disease control and plain control groups. At the end of the experiment, renal biomarkers viz; s. creatinine, b. urea, and s. uric acid, were investigated. The histopathological examination of the kidney specimens was also carried out. Results: The results of the present study revealed that renal function biomarkers such as s. creatinine, b. urea, and s. uric acid were significantly reduced in the rats of the treatment group as compared to those of the disease control group. Moreover, the histoarchitecture reports of the treatment group's kidney specimens showed significant improvements. Conclusion: The results suggested that the HAE of Cassia occidentalis L. roots promisingly prevented kidney injury in gentamicin-induced nephrotoxic rats. This effect might be due to improved clearance of gentamicin from the renal tubule and decreased generation of reactive oxygen species (ROS).

• 생약학회지
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• 제25권2호
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• pp.140-143
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• 1994

During the serial attempts to identify the chemical and biological characteristics of Ailanthi Cortex Radicis, the root bark of Ailanthus altissima (Simaroubaceae), we find out the serious toxic effect on kidney by chloroform fraction of the methanolic extract of the herb drug. The toxicities were revealed as the increase of urea nitrogen amount in blood and lactate dehydrogenase and ${\gamma}-glutamyltransferase$ activities in urine and the decrease of the concentration of glutathione and both of protein bound and non-protein bound -SH in kidney tissue.

• 대한전해질대사연구회지
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• 제16권2호
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• pp.19-22
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• 2018

Renal Fanconi syndrome (RFS) is caused by generalized proximal tubular dysfunction and can be divided into hereditary and acquired form. Adult-onset RFS is usually associated with drug toxicity or systemic disorders, and modern molecular genetics may explain the etiology of previous idiopathic cases of RFS. Here, we report the case of a 52-year-old woman with RFS whose etiology could not be identified. She presented with features of phosphaturia, renal glucosuria, aminoaciduria, tubular proteinuria, and proximal renal tubular acidosis. Her family history was unremarkable, and previous medications were nonspecific. Her bone mineral density was compatible with osteoporosis, serum intact parathyroid hormone level was mildly elevated, and 25(OH) vitamin D level was insufficient. Her blood urea nitrogen and serum creatinine levels were 8.4 and 1.19 mg/dL, respectively (estimated glomerular filtration rate, $53mL/min/1.73m^2$). Percutaneous renal biopsy was performed but revealed no specific renal pathology, including mitochondrial morphology. No mutation was detected in EHHADH gene. We propose the possibility of involvement of other genes or molecules in this case of adult RFS.

• Environmental Analysis Health and Toxicology
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• 제13권3_4호
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• pp.87-94
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• 1998

The use of cisplatin is limited by severe side effects such as renal toxicity. Our platinum-base drug discovery is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (II) complex analogue [Pt (cis-DACH)(DPPP)]. 2NO$_3$ (PC) containing cis-1,2-diaminocyclohexane as a carrier ligand and 1,3-bis(diphenylphosphino) propane as a leaving group. Furthermore, nitrate was added to improved the solubility. In this study, its structure was determined and its antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma, and in vitro cytotoxicity was determined against primary cultured rabbit kidney proximal tubular and renal cortical cells of human kidney using colorimetric MTT assay. PC demonstrated acceptable antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma and significant activity as compared with that of cisplatin. The toxicity of PC was found quite less than that of cisplatin using MTT and $^3$H-thymidine uptake tests in rabbit proximal tubular cells and human kidney cortical cells. PC was used for human cortical tissue in 7 weeks hitoculture by the glucose-consumption tests. We determined that the new platinum drug has lower nephrotoxicity than cisplatin. Based on these results, this novel platinum (II) complex compound (PC) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• 대한한의학회지
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• 제21권4호
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• pp.276-285
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• 2000

Paraquat is a very potent herbicide which causes fatal toxicity when ingested, and there is no specific antidote against it. Human ingestion induces acute renal failure, hepatic dysfunction and progressive respiratory failure with high mortality rate. Clinical investigation and medical treatment were done on two cases of acute renal failure caused by paraquat poisoning admitted to the Department of Internal Medicine, Wonkwang University Oriental Chonju Medical Hospital. We report two cases of patients who survived after acute paraquat intoxication, by means of oriental medicine such as Gamdutang, a typical antidote of toxins, chinese ink as an absorbent and burned powder of Rhei Radix et Rhizoma for laxative and so on, western medicine such as gastric lavage, diuretics and fluid therapy. We suggest more experiments and studies related to such treatment for paraquat poisoning be conducted.

• 대한수의학회지
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• 제35권4호
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• pp.809-814
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• 1995

The acute and subacute toxicity of fumomsin $B_1$ was evaluted in fingerlings of common carp, Cyprinus carpio. Dipping of fish for acute toxicity was performed for a period of 48 hours, and the $TLm_{48h}$ value(median tolerance limit) was more than 1000 ppm in common carp. Severe damages were observed in various organs and among them, clubbing of gill lamella, lytic degeneration and vacuolation of liver cells, and epithelial edema of renal tubules were relatively prominent. The most significant changes were hyperbasophilic foci of liver cells in subacute toxicity test and these can imply the possibility of hepatocarcinogenecity of fumonisin $B_1$.

• 대한수의학회지
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• 제34권2호
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• pp.369-374
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• 1994

The acute and subacute toxicity of fungicide folpet was evaluated in fingerings of common carp, Cyprinus carpio and goldfish, Carrassius auratus. Dipping of fishes for acute toxicity was performed for a period of 24h, and the TLm value(median tolerance limit) was 1.52 ppm in common carp and 1.45 ppm in goldfish. Severe damages were observed in various organs and among them, clubbing of gill lamella, lytic degeneration and vacuolation of liver cells, and epithelial edema of renal tubules were relatively prominent. The most significant changes were hyperbasophilic foci of liver cells in subacute toxicity test and these can imply the possibility of hepatocarcinogenecity of folpet.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.200-200
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• 2002

Cadmium (Cd) is an environmental pollutant and categorized as a human carcinogen, which has a tendency to accumulate in the human body. The level of Cd in renal cortex and liver are good indicators as an index of Cd exposure in general population. Geometric mean concentration of Cd is 27.4 and 3.1 /g wet weight in renal cortex and liver, respectively, in Korean. Cd is toxic to a number of tissues, notably the liver, kidney, testis, lung, lymphoid tissue and lung. (omitted)

• Biomolecules & Therapeutics
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• 제19권1호
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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.