scholarly journals Brodifacoum Induces Early Hemoglobinuria and Late Hematuria in Rats: Novel Rapid Biomarkers of Poisoning

2015 ◽  
Vol 41 (4-5) ◽  
pp. 392-399 ◽  
Author(s):  
Kyle M. Ware ◽  
Douglas L. Feinstein ◽  
Israel Rubinstein ◽  
Guy Weinberg ◽  
Brad H. Rovin ◽  
...  
Keyword(s):  
Blood Cells ◽  
Kidney Injury ◽  
Mass Casualty ◽  
Sprague Dawley ◽  
Free Hemoglobin ◽  
Oral Gavage ◽  
Sprague Dawley Rats ◽  
Novel Biomarkers ◽  
Dose Dependent ◽  
Severe Coagulopathy

Introduction: Brodifacoum (BDF) is a superwarfarin that is used primarily as a rodenticide. There have been increasing numbers of reports of human cases of accidental or intentional BDF ingestion with high mortality rate. Its broad availability and high lethality suggest that BDF should be considered a potential chemical threat. Currently, there is no biomarker for early detection of BDF ingestion in humans; patients typically present with severe coagulopathy. Since we demonstrated earlier that warfarin can induce acute kidney injury with hematuria, we tested whether BDF would also lead to change in urinary biomarkers. Material and Methods: BDF was administered to Sprague Dawley rats via oral gavage. N-acetylcysteine (NAC) was given per os in drinking water 24 h prior to BDF. Urinalysis was performed at different times after BDF administration. Anticoagulation and serum creatinine levels were analyzed in the blood. Results: We observed that within a few hours the animals developed BDF-dose-dependent transient hemoglobinuria, which ceased within 24 h. This was accompanied by a transient decrease in hematocrit, gross hemolysis and an increase in free hemoglobin in the serum. At later times, animals developed true hematuria with red blood cells in the urine, which was associated with BDF anticoagulation. NAC prevented early hemoglobinuria, but not late hematuria associated with BDF. Conclusions: We propose that transient early hemoglobinuria (associated with oxidative stress) with consecutive late hematuria (associated with anticoagulation) are novel biomarkers of BDF poisoning, and they can be used in clinical setting or in mass casualty with BDF to identify poisoned patients.

scholarly journals Hydrochloride pioglitazone protects diabetic rats against podocyte injury through preserving glomerular podocalyxin expression

2014 ◽  
Vol 58 (6) ◽  
pp. 630-639 ◽  
Author(s):  
Yan Xing ◽  
Shandong Ye ◽  
Yumi Chen ◽  
Wen Hu ◽  
Yan Chen
Keyword(s):  
Normal Control ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Urinary Sediment ◽  
Injury Index ◽  
Sprague Dawley Rats ◽  
Dose Dependent

Objective: We sought to test the effect of different dosages of pioglitazone (PIO) on the glomerular expression of podocalyxin and urinary sediment podocalyxin excretion and to explore the potential renoprotective mechanism. Materials and methods: Type 1 diabetes induced with streptozotocin (65 mg/kg) in 36 male Sprague-Dawley rats were randomly allocated to be treated with vehicle or 10, 20, 30 mg/kg/d PIO respectively for 8 weeks. Eight rats were enrolled in the normal control group. Results: At 8th week, rats were sacrificed for the observation of kidney injury through electron microscope. Glomerular podocalyxin production including mRNA and protein were determined by RT-PCR and immunohistochemistry respectively. Levels of urinary albumin excretion and urinary sediment podocalyxin, kidney injury index were all significantly increased, whereas expression of glomerular podocalyxin protein and mRNA were decreased significantly in diabetic rats compared to normal control. Dosages-dependent analysis revealed that protective effect of PIO ameliorated the physiopathological changes and reached a peak at dosage of 20 mg/kg/d. Conclusion: PIO could alleviate diabetic kidney injury in a dose-dependent pattern and the role may be associated with restraining urinary sediment podocalyxin excretion and preserving the glomerular podocalyxin expression.

A pan-NADPH Oxidase Inhibitor Ameliorates Kidney Injury in Type 1 Diabetic Rats

Pharmacology ◽  
2018 ◽  
Vol 102 (3-4) ◽  
pp. 180-189 ◽  
Author(s):  
Debra Dorotea ◽  
Guideock Kwon ◽  
Jung Hwa Lee ◽  
Erika Saunders ◽  
Yun Soo Bae ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Oxidase Inhibitor ◽  
Dependent Manner ◽  
Diabetic Mice ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Dose Dependent

Background: NADPH oxidases (Nox) is a major enzyme system contributing to oxidative stress, which plays an important role in the pathogenesis of diabetic kidney disease (DKD). We have shown an elevation of renal Nox1, Nox2, and Nox4 in diabetic mice. APX-115, a pan-Nox inhibitor, attenuated the progression of DKD in mice. As the standard diabetic mice cannot fully mimic human DKD, the present study was aimed to show the dose-dependent effect and to provide a confirmatory evidence of APX-115 in attenuating DKD in diabetic rats. Method: Type 1 diabetes was induced by a single 60 mg/kg intraperitoneal injection of streptozotocin in Sprague-Dawley rats. 0.5, 5, or 30 mg APX-115/kg/day or losartan 1 mg/kg/day were administered orally to diabetic rats for 8 weeks. Results: APX-115 treatment showed an improvement in kidney function and tubular and podocyte ­injury, as well as attenuation of inflammation, fibrosis, and oxidative stress as much as losartan, a comparative drug and mainstay treatment in DKD. Therapeutic effect of APX-115 was exhibited in a dose-dependent manner; a dose of 30 mg/kg displayed a superior efficacy. Conclusion: This finding verified the pre-clinical data of APX-115 in protecting against DKD, which is important to bring APX-115 toward the next stage of drug development.

Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

2021 ◽  
Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  
Keyword(s):  
Human Lung ◽  
Inhalation Exposure ◽  
Systemic Exposure ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sd Rats ◽  
New Information ◽  
Sprague Dawley Rats ◽  
Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

scholarly journals Enteral Baicalin, a Flavone Glycoside, Reduces Indicators of Cardiac Surgery-Associated Acute Kidney Injury in Rats

2018 ◽  
Vol 9 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Jing Shi ◽  
Guofeng Wu ◽  
Xiaohua Zou ◽  
Ke Jiang
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Injury Index ◽  
Sprague Dawley Rats

Background/Aims: Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common postoperative complications in intensive care medicine. Baicalin has been shown to have anti-inflammatory and antioxidant roles in various disorders. We aimed to test the protective effects of baicalin on CSA-AKI using a rat model. Methods: Sprague-Dawley rats underwent 75 min of cardiopulmonary bypass (CPB) with 45 min of cardioplegic arrest (CA) to establish the AKI model. Baicalin was administered at different doses intragastrically 1 h before CPB. The control and treated rats were subjected to the evaluation of different kidney injury index and inflammation biomarkers. Results: Baicalin significantly attenuated CPB/CA-induced AKI in rats, as evidenced by the lower levels of serum creatinine, serum NGAL, and Kim1. Baicalin remarkably inhibited oxidative stress, reflected in the decreased malondialdehyde and myeloperoxidase activity, and enhanced superoxide dismutase activity and glutathione in renal tissue. Baicalin suppressed the expression of IL-18 and iNOS, and activated the Nrf2/HO-1 pathway. Conclusion: Our data indicated that baicalin mediated CPB/CA-induced AKI by decreasing the oxidative stress and inflammation in the renal tissues, and that baicalin possesses the potential to be developed as a therapeutic tool in clinical use for CSA-AKI.

scholarly journals Comparative study of allogenic and xenogeneic mesenchymal stem cells on cisplatin-induced acute kidney injury in Sprague-Dawley rats

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Rehab H. Ashour ◽  
Mohamed-Ahdy Saad ◽  
Mohamed-Ahmed Sobh ◽  
Fatma Al-Husseiny ◽  
Mohamed Abouelkheir ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Comparative Study ◽  
Kidney Injury ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS OF CURCUMIN CONTRIBUTE INTO ATTENUATION OF ACUTE GENTAMICIN-INDUCED NEPHROTOXICITY IN RATS

2019 ◽  
pp. 466-468 ◽  
Author(s):  
HAYDER M AL-KURAISHY ◽  
ALI I AL-GAREEB ◽  
HUDA ABDULBAKI RASHEED
Keyword(s):  
Oxidative Stress ◽  
Serum Creatinine ◽  
Cystatin C ◽  
Kidney Injury ◽  
Specific Situation ◽  
Distilled Water ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Group 2 ◽  
Nephroprotective Effect

Objectives: Nephrotoxicity is a renal-specific situation in which the excretion of toxic metabolites is reduced due to toxic agents and drugs. Gentamicin is an antibiotic belongs to aminoglycoside group which may induce nephrotoxicity due to induction of oxidative stress. Curcumin is a component of traditional medicine with significant nephroprotective effect. Therefore, the objective of the present study was to evaluate the nephroprotective effect of curcumin on gentamicin-induced nephrotoxicity. Methods: A total of 30 male Sprague-Dawley rats were used which divided into Group 1 (n=10): Rats treated with distilled water 5 ml/kg plus normal saline 5 ml/kg for 12 days, Group 2 (n=10): Rats treated with distilled water 5 ml/kg plus gentamicin 100 mg/kg for 12 days, and Group 3 (n=10): Rats treated with curcumin 100 mg/kg plus gentamicin 100 mg/kg for 12 days. Blood urea, serum creatinine, malondialdehyde (MDA), kidney injury molecule (KIM-1), and cystatin-C were measured in both control and experimental groups. Results: Rats treated with gentamicin showed nephrotoxicity as evident by significant elevation in blood urea, serum creatinine, KIM-1, MDA, and cystatin-C sera levels. Curcumin leads to significant reduction of blood urea and serum creatinine compared to gentamicin group, p<0.05. Curcumin also reduced MDA, KIM-1, and cystatin-C sera levels significantly compared to gentamicin group, p<0.01. Conclusion: Curcumin produced significant nephroprotective effect on gentamicin-induced nephrotoxicity through modulation of oxidative stress and inflammatory biomarkers.

Glutamine promotes triglyceride absorption in a dose-dependent manner

2002 ◽  
Vol 282 (2) ◽  
pp. G317-G323 ◽  
Author(s):  
Jeffrey B. Schwimmer ◽  
Looi Ee ◽  
Shuqin Zheng ◽  
Patrick Tso
Keyword(s):  
Amino Acid ◽  
Amino Acid Mixture ◽  
Lipid Absorption ◽  
Acid Mixture ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Feeding Tubes ◽  
Mesenteric Lymph ◽  
Sprague Dawley Rats ◽  
Dose Dependent

Dietary proteins may play a role in lipid absorption. Whether amino acids are specifically involved is unknown. We hypothesized that enterally administered l-glutamine (l-Gln) given with a lipid meal increases triglyceride (TG) absorption in rats. Mesenteric lymph fistulae and gastroduodenal feeding tubes were placed in adult male Sprague-Dawley rats. The animals received an enteral bolus of Intralipid (5 ml) followed by enteral infusion of increasing concentrations of l-Gln in saline (0, 85, 170, or 340 mM) or equimolar concentrations of the inactive isomer d-Gln or an essential amino acid mixture without Gln. Lymph was collected continuously for 6 h and analyzed for TG content. Animals infused with 85 mM l-Gln had a 64% increase in total TG output vs. controls ( P < 0.05) despite no difference in lymph flow rate. Total TG output for animals infused with 340 mMl-Gln declined by 43% vs. controls ( P < 0.05). The effect of Gln in promoting lymphatic fat transport is specific to l-Gln and not shared by d-Gln or an equivalent amino acid mixture. l-Gln is capable of either promoting or impairing lymphatic TG transport in a dose-dependent manner.

Cinnamomum cassia ameliorates Ni-NPs-induced liver and kidney damage in male Sprague Dawley rats

2020 ◽  
Vol 39 (11) ◽  
pp. 1565-1581
Author(s):  
S Iqbal ◽  
F Jabeen ◽  
C Peng ◽  
MU Ijaz ◽  
AS Chaudhry
Keyword(s):  
Dependent Manner ◽  
Sprague Dawley ◽  
Cinnamomum Cassia ◽  
Preliminary Information ◽  
Sprague Dawley Rats ◽  
Liver And Kidney ◽  
Altered Blood ◽  
Biochemical Analyses ◽  
Dose Dependent ◽  
Different Doses

Nickel nanoparticles (Ni-NPs) have been widely used in various industries related to electronics, ceramics, textiles, and nanomedicine. Ambient and occupational exposure to Ni-NPs may bring about potential detrimental effects on animals and humans. Thus, there is a growing effort to identify compounds that can ameliorate NPs-associated pathophysiologies. The present study examined Cinnamomum cassia ( C. cassia) bark extracts (CMBE) for its ameliorative activity against Ni-NPs-induced pathophysiological and histopathological alterations in male Sprague Dawley rats. The biochemical analyses revealed that dosing rats with Ni-NPs at 10 mg/kg/body weight (b.w.) significantly altered the normal structural and biochemical adaptations in the liver and kidney. Conversely, supplementations with CMBE at different doses (225, 200, and 175 mg/kg/b.w. of rat) ameliorated the altered blood biochemistry and reduced the biomarkers of liver and kidney function considerably ( p < 0.05) in a dose-dependent manner. However, the best results were at 225 mg/kg/b.w. of rat. The study provided preliminary information about the protective effect of C. cassia against Ni-NPs indicated liver and kidney damages. Future investigations are needed to explore C. cassia mechanism of action and isolation of single constituents of C. cassia to assess their pharmaceutical importance accordingly.

scholarly journals Effects of Xuesaitong on the Pharmacokinetics of Losartan: An In Vivo UPLC-MS/MS Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Weina Ma ◽  
Lei Lv ◽  
Jungang Guo ◽  
Yongjun Meng ◽  
Yinghua Wang ◽  
...  
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Multiple Blood ◽  
Apparent Volume Of Distribution ◽  
Noncompartmental Model

The aim of this study was to examine whether Xuesaitong, a multiherbal formulation for coronary heart disease, alters the pharmacokinetics of losartan. Adult male Sprague Dawley rats randomly received losartan (10 mg/kg) or losartan plus Xuesaitong (10 mg/kg) through an oral gavage (n = 6). Multiple blood samples were obtained for up to 36 h to determine the concentrations of losartan and its active metabolite, EXP3174, through ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetics were estimated using a noncompartmental model. The half-life (t1/2) of losartan was decreased by Xuesaitong (4.26 ± 1.51 vs. 6.35 ± 2.10 h; P<0.05). The apparent volume of distribution (Vd) of losartan was also decreased by the combination of losartan and Xuesaitong (4.41 ± 1.61 vs. 7.20 ± 2.41 mL; P<0.05). The time to maximum concentration (Tmax) of losartan was increased by Xuesaitong (1.06 ± 1.04 vs. 0.13 ± 0.05 h; P<0.05). Xuesaitong also decreased the t1/2 of EXP3174 (8.22 ± 1.41 vs. 6.29 ± 1.38 h; P<0.05). These results suggest that there is a complex interaction between losartan and Xuesaitong. In addition to enhanced elimination of losartan and EXP3174, Xuesaitong may also decrease the absorption rate and Vd of losartan.

Hesperidin Shows Protective Effects on Renal Function in Ischemia-induced Acute Kidney Injury (Sprague-Dawley Rats)

2019 ◽  
Vol 51 (8) ◽  
pp. 2838-2841
Author(s):  
Won Seo Park ◽  
Min Su Park ◽  
Sang Wook Kang ◽  
Seul A. Jin ◽  
Youngchul Jeon ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Injury ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats
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