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.

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.

Biochemical changes and oxidative stress induced by zearalenone in the liver of pregnant rats

2014 ◽  
Vol 34 (1) ◽  
pp. 65-73 ◽  
Author(s):  
C Zhou ◽  
Y Zhang ◽  
S Yin ◽  
Z Jia ◽  
A Shan
Keyword(s):  
Oxidative Stress ◽  
Messenger Rna ◽  
Experimental Period ◽  
Normal Diet ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Sprague Dawley Rats ◽  
Albumin Content ◽  
Dose Dependent

The aim of the present research was to examine the toxic influence of different doses of zearalenone (ZEN) on the liver, especially oxidative stress induced by ZEN on the liver. A total of 48 pregnant Sprague-Dawley rats were randomly assigned into 4 treatments groups with 12 animals in each. The rats were fed with a normal diet treated with 0 mg/kg (control), 50 mg/kg (treatment 1), 100 mg/kg (treatment 2), or 150 mg/kg (treatment 3) ZEN in feed on gestation days (GDs) 0–7 and then all the rats were fed with a normal diet on GDs 8–20. The experimental period lasted 21 days. The results showed that exposure to ZEN induced increase in aspartate amino transferase, alanine aminotransferase, and alkaline phosphatase activities and decrease in total protein and albumin content in a dose-dependent manner and also induce decrease in superoxide dismutase and glutathione peroxidase activities and increase in malondialdehyde content in a dose-dependent manner in the serum and the liver. The increased transcription of cytochrome P450 2E1 (CYP2E1) was detected in the liver after exposure to ZEN. These results suggested that ZEN not only caused damage in the liver of pregnant rats in a dose-dependent manner but also induced the messenger RNA expression of CYP2E1 in the liver.

Combination of Naringenin and Lisinopril Ameliorates Nephropathy in Type-1 Diabetic Rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Yogesh A. Kulkarni ◽  
Sachin V. Suryavanshi
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Renal Damage ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Glycation End Products ◽  
Histopathological Studies ◽  
Diabetes Induction

Background: Diabetes is a metabolic disorder affecting large percentage of population worldwide. Chronic hyperglycemic condition leads to generation of advanced glycation end products, reactive oxygen species and inflammatory cytokines, which worsen functioning of kidney. Clinical management of diabetic nephropathy is difficult as it requires multifocused approach. Hence, Combination of lisinopril a drug used in clinical practice for nephropathy and naringenin, a flavonoid reported to have significant effect in nephropathy may show additive of synergistic effect with less side effects. Objective: The objective of present study was to evaluate the effect of combination of lisinopril with naringenin in diabetic nephropathy. Methods: Diabetes was induced in male Sprague Dawley rats by streptozotocin (55 mg/kg, i.p.). After four weeks of diabetes induction animals were treated with naringenin alone and combination of Lisinopril and naringenin for next four weeks. At the end of study, various urine and biochemical parameters were evaluated. Oxidative stress parameters like malondialdehyde, reduced glutathione; catalase and superoxide dismutase for kidney tissues were estimated and histopathology studies of kidney were carried out. Results: Combination of lisinopril (10 mg/kg) and naringenin (25 and 50 mg/kg) treatment showed significant improvement in the biochemical and urine parameters. Combination treatment also attenuated renal oxidative stress and renal damage as observed in histopathological studies. Conclusion: Treatment with combination of lisinopril and naringenin showed promising effect in diabetic nephropathy in rats.

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 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 Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the Akt/GSK-3β/Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 5/6 Nephrectomized Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Hong-feng Zhang ◽  
Jia-hong Wang ◽  
Yan-li Wang ◽  
Cheng Gao ◽  
Yan-ting Gu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Dependent Manner ◽  
Salvianolic Acid ◽  
Nrf2 Signaling Pathway ◽  
Antioxidative Effects ◽  
Dose Dependent

Salvianolic acid A (SAA) is a bioactive polyphenol extracted from Salviae miltiorrhizae Bunge, which possesses a variety of pharmacological activities. In our previous study, we have demonstrated that SAA effectively attenuates kidney injury and inflammation in an established animal model of 5/6 nephrectomized (5/6Nx) rats. However, there has been limited research regarding the antioxidative effects of SAA on chronic kidney disease (CKD). Here, we examined the antioxidative effects and underlying mechanisms of SAA in 5/6Nx rats. The rats were injected with SAA (2.5, 5, and 10 mg·kg-1·d-1, ip) for 28 days. Biochemical, flow cytometry, and Western blot analyses showed that SAA significantly increased the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GPx), and catalase (CAT) and lowered the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and NADPH oxidase 4 (NOX-4) in a dose-dependent manner in 5/6Nx rats and in H2O2-induced HK-2 cells in vitro. Moreover, SAA enhanced the activation of the protein kinase B/glycogen synthase kinase-3β/nuclear factor-erythroid-2-related factor 2 (Akt/GSK-3β/Nrf2) signaling pathway in a dose-dependent manner and subsequently increased the expression of heme oxygenase-1 (HO-1) in the kidney of 5/6Nx rats, which were consistent with those obtained in H2O2-induced HK-2 cells in vitro shown by Western blot analysis. Furthermore, SAA significantly increased the expression of intranuclear Nrf2 and HO-1 proteins compared to HK-2 cells stimulated by LPS on the one hand, which can be enhanced by QNZ to some extent; on the other hand, SAA significantly lowered the expression of p-NF-κB p65 and ICAM-1 proteins compared to HK-2 cells stimulated by H2O2, which can be abrogated by ML385 to some extent. In conclusion, our results demonstrated that SAA effectively protects the kidney against oxidative stress in 5/6Nx rats. One of the pivotal mechanisms for the protective effects of SAA on kidney injury was mainly related with its antioxidative roles by activating the Akt/GSK-3β/Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway.

scholarly journals Collagen-Induced Reduction in Rat Circulating Platelet Count: Influence of Platelet Function Inhibitors

1977 ◽  
Author(s):  
I.B. Holmes
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Test System ◽  
Collagen Fibrils ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Dose Dependent ◽  
Double Lumen Cannula ◽  
Antiinflammatory Compound

The effect on circulating platelet count of repeated intravenous infusions of collagen fibrils was measured in male OFA Sprague-Dawley rats (400-550 g). Citrated blood was pumped from the left carotid artery of anaesthetized animals, via a siliconized double-lumen cannula, into the manifold of a Technicon Autocounter, for continuous registration of platelet count. Native collagen fibrils (Collagenreagent ‘Horm’) were infused intravenously for 1 min at 15 min intervals. Successive increasing collagen doses (20-320 pg/kg) induced dose-dependent reduction in platelet count, measured as absolute platelet number disappearing from the circulation. Repeated infusion of collagen 160 pg/kg produced constant, partially reversible, reduction in platelet count. Several known inhibitors of platelet aggregation were investigated in the described test system. Collagen effects were inhibited in a dose-dependent manner to a maximum of 50-60 %, and drug activity was thus quantitated on the basis of dose producing 30 % inhibition (ID30): prostaglandin E1 (1.6 pg/kg/min i.v. infusion), SH-869 (1.1 mg/kg i.v.), aspirin (33.1 mg/kg p.o.), proquazone, a new non-steroidal antiinflammatory compound (5.0 mg/kg p.o.). That part of the collagen response not inhibited might be attributed to the initial phase of platelet adhesion to collagen, known to be relatively refractive to platelet function inhibitors.

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