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Cytoprotectant and Anti-Oxidant Effects of Olive Oil on Cadmium Induced nephrotoxicity in Mice

Open Journal of Pathology 2018年第1期8卷 31-46页

作者： Farooq Ahmed Wani Mahrous AbdelBasset Ibrahim Medhat M. Abdel Moneim Abdul Rahman Hamdan A. Almaeen Pathology Department Faculty of Medicine College of Medicine Aljouf University Aljouf KSA Forensic Medicine and Clinical Toxicology Department College of Medicine Aljouf University Aljouf KSA Faculty of Medicine Suez Canal University Ismailia Egypt Department of Medical Biochemistry & Molecular Biology Faculty of Medicine Benha University Benha Egypt Department of Pathology College of Medicine Aljouf University Aljouf KSA

Background: Cadmium is a heavy metal having toxic effects on most organ systems of the body. Objectives: We aim to investigate the postulated protective properties of olive oil in Cadmium-induced renal toxicity in mice by utilizing standard biomarkers of renal toxicity, oxidative stress and histopathological characterization. Materials and Methods: Forty mice were randomly divided into four groups of 10 mice each. Group 1 served as control group, group 2 was given Extra-virgin olive oil orally, group 3 was given Cadmium chloride and group 4 was given Cadmium chloride with Extra-virgin olive oil. At the end of the experimental period, biochemical analysis histopathology of kidney was done. Results: The present study depicted that blood urea, serum creatinine and the antioxidant markers (Superoxide dismutase, Glutathione peroxidase and Catalase) levels were significantly increased in group 3 compared to group 1 and 2. After administration of Extra-virgin olive oil with Cadmium in group 4, the levels of those markers significantly improved. Histopathology of the renal tissue showed severe damage of glomeruli, severely congested blood vessels and marked dilatation of Bowman’s capsule in group 3 with improvements of these changes in group 4. Conclusion: This study suggests that Extra-virgin olive oil can be used as a cost effective safe anti-oxidative agent in the prevention of Cadmium toxicity.

关键词： Reactive Oxygen Species Cadmium EVOO nephrotoxicity Oxidative Stress

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Decursin Mediated Protection on Cisplatin-induced nephrotoxicity in SD Rats and BDF1 Mice

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Journal of Northeast Agricultural University(English Edition) 2012年第1期19卷 50-56页

作者： Jiang Cheng-zhe Han Ilhyun Choung Seyoung Department of Veterinary Medicine College of Agriculture Yanbian University Yanji 133000 Jilin China Department of Hygienic Chemistry College of Pharmacy Kyung Hee University Scoul 130-701 Korea

Tisplatin is one of the valuable icancer agents against several types of neoplasm. However, nephrotoxicity is the major adverse effect representing in cisplatin therapy. In this study, the animal tests detecting protective effects of a natural compound, Decursin, on cisplatin-induced nephrotoxicity were examined by using in vivo model. Pretreatment Decursin 10, 20 and 40 mg · kg^-1 at 48, 24 and 6 h, and administration of a single dose of Cisplatin 5.2 mg · kg^-1. nephrotoxicity was evaluated by serum BUN and creatinine examination. There was significant difference in body weights, serum BUN and creatinine levels of the normal group. Based on the new understanding of the protective mechanisms of cisplatin-induced nephrotocivity, new strategies can be developed to prevent renal injury or to enhance recovery after cisplatin treatment.

关键词： cisplatin Decursin nephrotoxicity rat mice

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Novel genomic biomarkers for acute gentamicin nephrotoxicity in dog

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Open Journal of Molecular and Integrative Physiology 2013年第3期3卷 125-133页

作者： James Eric McDuffie Jingjin Gao Jingying Ma David La Anton Bittner Manisha Sonee Matthew Wagoner Sandra Snook CREATe-Genomic Technologies Janssen Pharmaceutical Research & Development LLC San Diego USA Drug Safety Sciences Janssen Pharmaceutical Research & Development LLC San Diego USA Drug Safety Sciences Janssen Pharmaceutical Research & Development LLC Spring House USA Safety Assessment AstraZeneca Pharmaceuticals Watham USA

Objectives: Novel biomarkers indicative of drug-induced kidney injury (DIKI) in dogs would have significant application in preclinical drug development. We conducted a feasibility study to identify genomic expression profiles for monitoring progressive, acute DIKI in dogs. Materials and Methods: Animals were intramuscularly administered either 0.9% physiological saline or gentamicin (40 mg/kg/day) for 10 consecutive days and euthanized on day 11. Serum and urine samples were collected at various time points and kidney samples were collected at necropsy for biomarker measurements. Results: Acute gentamicin-induced renal histopathology changes were localized to the proximal convoluted tubules and characterized as slight-to-marked, diffuse cortical-medullary tubular epithelial degeneration/necrosis. Serum creatinine (sCr) and blood urea nitrogen (BUN) elevations suggestive of mild renal dysfunction were first observed on days 7 to 8. Gentamicin-induced increased urinary kidney injury molecule-1 (KIM-1) mRNA was observed on day 6 preceding detectable elevations of sCr and/or BUN. Increased urinary KIM-1 mRNA correlated with multifocal KIM-1 immunostaining in the corticomedullary tubular epithelial cells. Microarray analysis revealed changes in additional mRNA expression products detected in urine and/or kidney that should be further investigated for use as potential biomarkers for acute gentamicin related nephrotoxicity in dogs. Conclusion: These findings suggested the utility of non-invasive urinary genomic parameters for monitoring acute DIKI in dogs.

关键词： Biomarker Gentamicin nephrotoxicity Dog

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Inhibition of calcium oxalate nephrotoxicity with Zamzam water

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Open Journal of Preventive Medicine 2012年第1期2卷 67-71页

作者： Saeed S. Al-Ghamdi Department of Pharmacology and Toxicology Faculty of Medicine Umm Al-Qura University Makkah Kingdom of Saudi Arabia

Zamzam water is well known of its high conductivity. For this fact urologist and nephrologists recommend their patients who are suffering from kidney stones not to drink this water because it could worse their health status. This study was conducted to investigate the effect of Zamzam water on calcium oxalate nephrotoxicity in experimentally induced kidney stones in male Wistar albino rats. Calcium oxalate crystals were induced by orally administration of 200 mg of glycolic acid dissolved in the drinking water. The rats were divided into three groups;six rats each. These include positive control group (given glycolic acid), test group (given glycolic acid plus Zamzam water) and negative group (given drinking water only). After two weeks of treatment, blood analysis of blood urea nitrogen (BUN) and creatinine showed significant differences in positive control group compared to the negative control group, whereas no significant differences were noticed in the level of BUN and creatinine between both the negative control and the test group. Moreover, urine analysis showed a high density of calcium oxalate crystals in the positive control group, whereas no crystals were detected in the negative control and the test groups. Histopathological investigations showed damaging in kidneys of the positive control group with no tissue abnormalities in the negative control and the test group. I concluded from this study that Zamzam water prevents the formation calcium oxalate stone, which probably mean that it has no negative effect on patients suffering from kidney disorders due to crystals formation.

关键词： Zamzam Water Calcium Oxalate nephrotoxicity

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Ethambutol Induced Optic Neuritis Associated with Tenofovir nephrotoxicity

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World Journal of AIDS 2012年第2期2卷 43-47页

作者： Sonia Vibhakar Diana Yu Romina Kee Blake Max Children’s Mercy Hospitals and Clinics Kansas City USA Collaborative Research Unit (CRU) Department of Medicine Cook County Health and Hospitals Sys- tem Chicago USA The Ruth M. Rothstein CORE Center Cook County Health and Hospitals System Chicago USA The Ruth M. Rothstein CORE Center Cook County Health and Hospitals System Chicago USA University of Illinois at Chicago College of Pharmacy Chicago USA

Morbidity and mortality associated with human immunodeficiency virus (HIV) has decreased with highly active anti-retroviral therapy (HAART). Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI) that is preferred by the Department of Health and Human Services (DHHS) HIV treatment guidelines and is widely used for the initial treatment of HIV. Although tenofovir is generally well-tolerated, it has been associated with rare cases of acute nephrotoxicity. HIV-infected patients frequently have co-morbidities that require treatment, thus adding another level of complexity due to drug interactions and medication adverse effects with antiretrovirals. We present a patient who suffered an acute deterioration in renal function from tenofovir, leading to an accumulation of co-administered ethambutol, thus resulting in optic neuritis.

关键词： Tenofovir nephrotoxicity Ethambutol Optic Neuritis Human Immunodeficiency Virus (HIV)

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Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity

Renal inhibition of miR-181a ameliorates 5-fluorouracil-indu...

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首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Xiao-Yun Liu Fei-Ran Zhang Jin-Yan Shang Xiao-Fei Lv Xiao-Chun Lin Xiu Liu Jia-Guo Zhou Si-Jia Liang Department of Pharmacology Cardiac and Cerebral Vascular Research CenterZhongshan School of MedicineSun Yat-Sen University

The development of nephrotoxicity largely limits the clinical use of *** are able to target various genes and involved in the regulation of diverse cellular processes,including cell apoptosis and *** study showed that miR-181 a expression was significantly increased after 5-fluorouracil(5-FU) treatment in renal mesangial cells and kidney tissue,which was associated with decreased baculoviral inhibition of apoptosis protein repeat containing 6(BIRC6) expression and increased apoptotic *** miR-181 a expression enhanced 5-FU-induced p53-dependent mitochondrial apoptosis,including declined Bcl-2/Bax ratio,loss of mitochondrial membrane potential,cytochrome c release,and caspase-9 and caspase-3 ***,inhibition of miR-181 a was associated with reduced p53-mediated mitochondrial apoptosis induced by ***,miR-181 a increased BIRC6 downstream gene p53 protein expression and transcriptional activity by reducing ubiquitin-mediated protein *** found that miR-181 a directly targeted 3'-UTR of BIRC6 mRNA and negatively regulated BIRC6 *** vivo study,knockdown of miR-181 a with adeno-associated virus harboring miR-181 a-tough decoy attenuated 5-FU-induced renal cell apoptosis,inflammation and kidney *** conclusion,these results demonstrate that miR-181 a increases p53 protein expression and transcriptional activity by targeting BIRC6 and promotes5-FU-induced apoptosis in mesangial *** of miR-181 a ameliorates5-FU-induced nephrotoxicity,suggesting that miR-181 a may be a novel therapeutic target for nephrotoxicity treatment during chemotherapy.

关键词： BIRC6 p53 mesangial cells apoptosis nephrotoxicity 5-fluorouracil miR-181a

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Quercetin-borate acid ester crosslinked micelles combined with doxorubicin to overcome cardiotoxicity, nephrotoxicity

Quercetin-borate acid ester crosslinked micelles combined wi...

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2018年第十二届中国药物制剂大会

作者：张明花 Zhanweizhou YadongLiu Jiachengpan Chenggen Qian Minjie Sun Key Department of Pharmaceutics State Key Laboratory of Natural Medicines China Pharmaceutical University

The clinical application of doxorubicin(DOX), an effective anti-cancer drug, has been limited by side effects, especially cardiotoxicity and nephrotoxicity which might be caused by reactive oxygen species(ROS) generated by DOX. To address the above limitations, co-loading DOX with ROS scavenger, like quercetin(Qu), is a smart strategy. In this investigation, quercetin-pending micelles based on boronic-ester coupling co-loaded DOX with Qu were made based on phenylboronic acid-catechol pending between dextrinethylenediamine-phenylboronic acid(Dex-(eda)-PBA) and Qu. DOX was encapsulated in the hydrophobic core of micelles via hydrophobic force. The ATP-responsive boronic-ester could not only enhance the stability of micelle under physiological condition, but also explosively release drug at tumor cells with high concentration of ATP(1-10 mM). More importantly, due to the antioxidant and antiradical properties of Qu, DOX-induced cardiotoxicity and nephrotoxicity were overcome for combination therapy strategy. Meanwhile, Qu could help DOX kill cancer cells owing to causing cell cycle arrest in cancer cell lines at the G0/G1 phase. These results demonstrated that quercetin-pending micelles via ATP-responsive boronic-ester coupling could efficaciously overcome DOX-induced cardiotoxicity and nephrotoxicity as well as promote the anti-cancer effect of DOX.

关键词： ATP-responsive phenylboronic acid cardiotoxicity nephrotoxicity cancer therapy

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Evaluation of Two Biomarkers as Early Indicators for Assessment of Gentamycin-induced nephrotoxicity in Vivo and in Vitro

Evaluation of Two Biomarkers as Early Indicators for Assessm...

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中国畜牧兽医学会动物解剖及组织胚胎学分会第十八次学术研讨会

作者： Chen Meng-Lu Luo Qi-Hui Sun Feng-Jiao Chen Zheng-li Li Ming-yang Zeng Wen Gong Li Cheng Ari-chun Peng Xi Fang Jing Tang Li Geng Yi Key Laboratory of Animal Disease and Human Health of Sichuan Province College of Veterinary MedicineSichuan Agricultural University Sichuan Industrial Institute of Antibiotics in China National Pharmaceutical Group

The aminolycoside Gentamicin is a widely used antibiotic,applied in equine *** its clinical use,concerns remain regarding the potential toxic side-effects,such as *** detection of renal damage is critical in preclinical drug *** study was aimed to determine whether kidney injury molecule-1(KIM-1) and neutrophil gelatinase-associated lipocalin(NGAL) may be early indicators in the assessment of Gentamycin-induced *** our study,a model of Gentamicin-induced nephrotoxicity in male Sprague Dawley rats treated for up to 7 days at 50 or 100mg/kg/day was used to monitor the expressions of novel biomarkers of renal toxicity during the progression of acute kidney injury(AKI).Additionally,biomarkers were assessed in human kidney proximal epithelial cells(HK-2)treated with Gentamicin for 2,6,12,24,36 or 48 h in *** administration of Gentamicin to rats for 1,3,or 7 days resulted in a dose-and time-dependent increase in the expression of KIM-1 and *** expressions of the two biomarkers changed prior to proximal tubule damage and increases in serum creatinine(SCr)and blood urea nitrogen(BUN)levels,suggesting their usefulness for predicting Gentamicin-induced acute kidney injury(AKI)in *** contrast,no significant increase in the expression of the biomarker genes and proteins were evident in HK-2 cells after treated by Gentamycin for up to 48 h,suggesting that they may not be suitable endpoints for sensitive detection of nephrotoxic effects in vitro.

关键词： Gentamycin nephrotoxicity KIM-1 NGAL HK-2 cells

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Pre-treatment serum C-reactive protein level is an independent risk factor for development of nephrotoxicity in patients receiving high-dose vancomycin

Pre-treatment serum C-reactive protein level is an independe...

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中国药学会第十三届青年药学科研成果交流会

作者： He Juan Mao En-Qiang Jing Feng Jiang Hui-Ting Yang Wan-Hua Chen Er-Zhen Department of Pharmacy Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine EICU of Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine

High-dose vancomycin treatment increases the likelihood of vancomycin-related nephrotoxicity.C-reactive protein（CRP） is a sensitive marker of systemic *** the present study,we evaluated the pre-treatment serum CRP level as a risk factor of the development of nephrotoxicity in patients receiving total daily doses of ≥4g of *** extracted from medical records for 174 patients who received total daily doses of ≥4g of intravenous vancomycin for a minimum of 48 hours and had their serum CRP level and erythrocyte sedimentation rate（ESR） tested within 24 hours before vancomycin treatment were subject to final *** analyses showed that patients who developed nephrotoxicity during vancomycin treatment had significantly higher median vancomycin serum concentration,duration of vancomycin treatment,and the serum CRP level within 24 hours before vancomycin treatment than the non-nephrotoxicity *** logistic regression analysis showed that after adjusting for potential confounders including age,sex,body mass index,median vancomycin serum concentration,average vancomycin daily dose,duration of vancomycin treatment,ICU admission status,administration of intravenous contrast or nephrotoxic agents,administration of vasopressors,serum CRP level and ESR within 24 hours before vancomycin treatment,and co-morbidities,median vancomycin serum concentration,duration of treatment,serum CRP level within24 hours before vancomycin treatment,and nephrotoxic medication were found significantly associated with the development of *** was confirmed by multivariate hazard ratio analysis after adjusting for the above potential *** conclusion,this study provides the first evidence supporting that the serum CRP level within24 hours before vancomycin treatment is an independent risk factor for the development of nephrotoxicity in patients receiving total daily doses of ＞4g of ***,the serum CRP level within 24

关键词： vancomycin nephrotoxicity C-reactive protein risk biomarker

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An area under curve-based nomogram to predict vancomycin-associated nephrotoxicity in critically ill patients:a retrospective cohort study

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China Medical Abstracts(Internal Medicine) 2022年第2期39卷 116-116页

作者： WANG Jinlong Dept Critical Care Med Zhongda HospMed SchSoutheast UnivNanjing 210009

Objective To develop an area under curve (AUC)-based nomogram to predict vancomycin-associated nephrotoxicity in critically ill *** This retrospective cohort study included adult patients treated with vancomycin in the intensive care unit at a tertiary teaching hospital from January 2015 to December 2017. Baseline clinical characteristics before vancomycin treatment and pharmacokinetic parameters were collected to establish a prediction model of nephrotoxicity.

关键词： critically nephrotoxicity patients

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