scholarly journals Salvia miltiorrhizaInjection Ameliorates Renal Damage Induced by Lead Exposure in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Lei Li ◽  
Yuanyuan Zhang ◽  
Juanjuan Ma ◽  
Weichong Dong ◽  
Qiongtao Song ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Salvia Miltiorrhiza ◽  
Kidney Injury ◽  
Serum Levels ◽  
Organ Injury ◽  
Therapeutic Drug ◽  
High Dose ◽  
Protective Effects ◽  
Pb Accumulation ◽  
And Function

Exposure to lead (Pb) can induce kidney injury and our recent studies have found thatSalvia miltiorrhiza(SM) injection, a traditional Chinese medicine, could protect against the organ injury induced by iron overload. This study was designed to investigate the protective effects of SM injection on nephrotoxicity induced by Pb acetate in mice and to elucidate the potential mechanism(s). Healthy male mice were randomly divided into four groups: control, Pb, low-doseSalvia miltiorrhiza(L-SM), and high-doseSalvia miltiorrhiza(H-SM). SM injection dose dependently reduced the Pb accumulation in the kidney, decreased kidney coefficients, and ameliorated renal structure and function from the morphology analysis. Meanwhile, SM administration downregulated serum levels of blood urea nitrogen (BUN) and creatinine (CR), decreased malondialdehyde (MAD) content, and increased activities of super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the kidney homogenate. Moreover, SM injection reduced the level of renal apoptosis by immunohistochemical staining analysis. Our findings implicate the therapeutic potential of SM injection for Pb-induced nephrotoxicity, which were at least partly due to the decrease of Pb accumulation, inhibition of lipid peroxidation, and suppression of renal apoptosis. These results provided preliminary experimental support for Danshen as a therapeutic drug for Pb poisoning diseases.

The Role of the CX3CL1-CX3CR1 Axis in Renal Disease

2021 ◽  
Author(s):  
Diana Hamdan ◽  
Lisa A. Robinson
Keyword(s):  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Transmembrane Protein ◽  
Soluble Form ◽  
Protective Effects ◽  
Chronic Kidney Diseases ◽  
The Family ◽  
Soluble Species ◽  
And Function

Excessive infiltration of immune cells into the kidney is a key feature of acute and chronic kidney diseases. The family of chemokines are key drivers of this process. CX3CL1 (fractalkine) is one of two unique chemokines synthesized as a transmembrane protein which undergoes proteolytic cleavage to generate a soluble species. Through interacting with its cognate receptor, CX3CR1, CX3CL1 was originally shown to act as a conventional chemoattractant in the soluble form, and as an adhesion molecule in the transmembrane form. Since then, other functions of CX3CL1 beyond leukocyte recruitment have been described, including cell survival, immunosurveillance, and cell-mediated cytotoxicity. This review summarizes diverse roles of CX3CL1 in kidney disease and potential uses as a therapeutic target and novel biomarker. As the CX3CL1-CX3CR1 axis has been shown to contribute to both detrimental and protective effects in various kidney diseases, a thorough understanding of how the expression and function of CX3CL1 are regulated is needed to unlock its therapeutic potential.

scholarly journals Dexrazoxane preferentially mitigates doxorubicin cardiotoxicity in female children with sarcoma

Open Heart ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. e001025 ◽  
Author(s):  
Hari K Narayan ◽  
Mary E Putt ◽  
Nikitha Kosaraju ◽  
Alejandro Paz ◽  
Shivani Bhatt ◽  
...  
Keyword(s):  
Circumferential Strain ◽  
Wall Stress ◽  
Left Ventricular ◽  
High Dose ◽  
Protective Effects ◽  
Cavity Size ◽  
Linear Regression Models ◽  
Cardioprotective Effects ◽  
And Function

ObjectiveWe sought to determine how sex and dexrazoxane therapy influence cardiac remodelling in children with sarcoma receiving high-dose doxorubicin.MethodsIn a retrospective cohort of 85 children with sarcoma receiving high-dose doxorubicin, echocardiography measures prior to, early after (within 6 months of doxorubicin completion) and 1 – 2 years after doxorubicin completion were quantified. At each follow-up visit, multivariable, propensity-adjusted linear regression models evaluated dexrazoxane’s effects on changes in left ventricular (LV) shortening fraction (SF), structure, strain and wall stress for subgroups divided by sex. Likelihood ratio tests assessed the interaction between sex and dexrazoxane in determining these changes.ResultsEarly after doxorubicin completion, males not treated with dexrazoxane (n = 15) developed increased cavity size and diminished circumferential strain; females (n = 8) developed diminished SF and strain indices, and increased cavity size and wall stress. With dexrazoxane, males (n = 33) demonstrated less deterioration in circumferential strain by 3.4% (95% CI 0.01 to 6.8), and females (n = 29) demonstrated less reduction in SF by 5.7% (95% CI 2.1 to 9.3), and had mitigation of increases in cavity size and wall stress. In interaction analyses, females had greater protection with dexrazoxane with regard to SF (p = 0.019) and cavity size in diastole (p = 0.002) and systole (p ≤ 0.001). These findings largely persisted 1 – 2 years after doxorubicin therapy.ConclusionsEarly, sustained alterations in LV structure and function occur in children with sarcoma after high-dose doxorubicin, with adverse changes and protective effects of dexrazoxane more pronounced in females as compared with males. Dexrazoxane may have sex-specific cardioprotective effects.

scholarly journals Effect of continuous furosemide infusion on outcome of acute kidney injury

2019 ◽  
Vol 35 (3) ◽  
Author(s):  
Jie Ni ◽  
Hui Jiang ◽  
Fang Wang ◽  
Long Zhang ◽  
Dujuan Sha ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Intravenous Infusion ◽  
Urine Output ◽  
Kidney Injury ◽  
Oxygenation Index ◽  
Serum Levels ◽  
High Dose ◽  
Clinical Effects ◽  
Continuous Intravenous Infusion ◽  
Urea Nitrogen

Objective: To evaluate the clinical effects of continuous intravenous infusion with high-dose furosemide on early acute kidney injury (AKI) complicated with acute lung edema. Methods: Ninety patients who had been treated by furosemide at routine dose for 12 hour but with unsatisfactory outcomes were selected and subjected to continuous intravenous infusion with high-dose furosemide. The dose was adjusted according to hourly urine output. Serum levels of urea nitrogen, creatinine and potassium, pH, oxygenation index and mechanical ventilation time before and 6, 12, 24, 48 and 72 hour after treatment were compared. Results: The urine outputs before and 6, 12, 24, 48 and 72 hour after treatment were (10.71±1.81), (164.52±21.42), (189.71±29.61), (181.33±23.52), (176.82±24.80) and (164.52±18.91) ml/h respectively. Compared with data before treatment, the serum levels of urea nitrogen, creatinine and potassium significantly decreased while pH and oxygenation index significantly increased after six hour of treatment (P<0.05). After treatment, the kidney functions of 80 patients (88.9%) were completely recovered, without obvious adverse reactions. Conclusion: For patients with early AKI complicated with acute pulmonary edema who cannot be cured by diuretic agent at routine dose, high-dose furosemide increases urine output and improves success rate. doi: https://doi.org/10.12669/pjms.35.3.1012 How to cite this:Ni J, Jiang H, Wang F, Zhang L, Sha D, Wang J. Effect of continuous furosemide infusion on outcome of acute kidney injury. Pak J Med Sci. 2019;35(3):---------. doi: https://doi.org/10.12669/pjms.35.3.1012 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Dexmedetomidine Pretreatment Attenuates Kidney Injury and Oxidative Stress during Orthotopic Autologous Liver Transplantation in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaofang Yu ◽  
Xinjin Chi ◽  
Shan Wu ◽  
Yi Jin ◽  
Hui Yao ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Kidney Injury ◽  
Receptor Blocker ◽  
High Dose ◽  
Related Factor ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
S Model ◽  
Autologous Liver

This paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective effects during orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group D1), high dose Dex (group D2), atipamezole (a nonspecificα2receptor blocker) + high dose Dex (group B1), ARC239 (a specificα2B/creceptor blocker) + high dose Dex (group B2), and BRL-44408 (a specificα2Areceptor blocker) + high dose Dex (group B3). Then histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and oxidants and antioxidants were performed 8 hours after OALT. We found that pretreatment with Dex activated Nrf2 in glomerular cells and upregulated antioxidants but reduced oxidants (allP<0.01, group D2 versus group M). Atipamezole and BRL-44408, but not ARC239, reversed these protective effects. In conclusion, pretreatment with Dex activates Nrf2 throughα2Areceptor, increases the antioxidant levels, and attenuates renal injury during OALT.

scholarly journals Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model

2019 ◽  
Vol 317 (2) ◽  
pp. F264-F274 ◽  
Author(s):  
Satoshi Tanimura ◽  
Katsuyuki Tanabe ◽  
Hiromasa Miyake ◽  
Kana Masuda ◽  
Keigo Tsushida ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Endothelial Cells ◽  
Kidney Injury ◽  
Protective Effects ◽  
Tubular Injury ◽  
Injury Model ◽  
Peritubular Capillaries ◽  
Renal Tubular ◽  
And Function ◽  
Hospital Acquired

Acute kidney injury (AKI) is frequently encountered in clinical practice, particularly secondarily to cardiovascular surgery and administration of nephrotoxic agents, and is increasingly recognized for initiating a transition to chronic kidney disease. Clarifying the pathogenesis of AKI could facilitate the development of novel preventive strategies, because the occurrence of hospital-acquired AKI is often anticipated. Vasohibin-1 (VASH1) was initially identified as an antiangiogenic factor derived from endothelial cells. VASH1 expression in endothelial cells has subsequently been reported to enhance cellular stress tolerance. Considering the importance of maintaining peritubular capillaries in preventing the progression of AKI, the present study aimed to examine whether VASH1 deletion is involved in the pathogenesis of cisplatin-induced AKI. For this, we injected male C57BL/6J wild-type (WT) and VASH1 heterozygous knockout (VASH1+/−) mice intraperitoneally with either 20 mg/kg cisplatin or vehicle solution. Seventy-two hours after cisplatin injection, increased serum creatinine concentrations and renal tubular injury accompanied by apoptosis and oxidative stress were more prominent in VASH1+/− mice than in WT mice. Cisplatin-induced peritubular capillary loss was also accelerated by VASH1 deficiency. Moreover, the increased expression of ICAM-1 in the peritubular capillaries of cisplatin-treated VASH1+/− mice was associated with a more marked infiltration of macrophages into the kidney. Taken together, VASH1 expression could have protective effects on cisplatin-induced AKI probably by maintaining the number and function of peritubular capillaries.

scholarly journals Mitochondrial Protection by PARP Inhibition

2020 ◽  
Vol 21 (8) ◽  
pp. 2767 ◽  
Author(s):  
Ferenc Gallyas Jr ◽  
Balazs Sumegi
Keyword(s):  
Oxidative Stress ◽  
Nuclear Dna ◽  
Therapeutic Potential ◽  
Parp Inhibitors ◽  
Parp Inhibition ◽  
Protective Effects ◽  
Parp Activation ◽  
Oncological Diseases ◽  
Basic Features ◽  
And Function

Inhibitors of the nuclear DNA damage sensor and signalling enzyme poly(ADP-ribose) polymerase (PARP) have recently been introduced in the therapy of cancers deficient in double-strand DNA break repair systems, and ongoing clinical trials aim to extend their use from other forms of cancer non-responsive to conventional treatments. Additionally, PARP inhibitors were suggested to be repurposed for oxidative stress-associated non-oncological diseases resulting in a devastating outcome, or requiring acute treatment. Their well-documented mitochondria- and cytoprotective effects form the basis of PARP inhibitors’ therapeutic use for non-oncological diseases, yet can limit their efficacy in the treatment of cancers. A better understanding of the processes involved in their protective effects may improve the PARP inhibitors’ therapeutic potential in the non-oncological indications. To this end, we endeavoured to summarise the basic features regarding mitochondrial structure and function, review the major PARP activation-induced cellular processes leading to mitochondrial damage, and discuss the role of PARP inhibition-mediated mitochondrial protection in several oxidative stress-associated diseases.

Cardioprotective and antihypertensive effects of Enicostemma littorale Blume extract in fructose-fed rats

2012 ◽  
Vol 90 (8) ◽  
pp. 1065-1073 ◽  
Author(s):  
Niraj M. Bhatt ◽  
Meenal Chavda ◽  
Dipali Desai ◽  
Rishit Zalawadia ◽  
Vaibhav B. Patel ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vascular Reactivity ◽  
Therapeutic Potential ◽  
Serum Levels ◽  
Cardiovascular Complications ◽  
Oral Glucose ◽  
Protective Effects ◽  
High Fructose ◽  
Enicostemma Littorale ◽  
High Level

We investigated the protective effects of Enicostemma littorale Blume (EL) extract on hypertension and insulin resistance along with its associated cardiovascular complications in high fructose (HF) fed rats. For this, rats were divided among 4 groups: (i) control, fed laboratory chow; (ii) fed with a high level of fructose; (iii) fed with a high level of fructose plus E. littorale extract; and (iv) fed with a high level of fructose plus rosiglitazone (Rg). EL and Rg treatments were given simultaneously with HF diet. The results show that untreated HF-fed rats showed altered oral glucose tolerance, increased fasting insulin, and increased fasting glucose. These rats also exhibited hypertriglyceridemia, moderate hypertension, platelet hyperaggregability, decreased prothrombin time, activated partial thromboplastin time, altered vascular reactivity, and increased serum levels of enzymes (creatine kinase, type muscle–brain (CK-MB), aspartate aminotransferase (SGOT), lactate dehydrogenase (LDH), and alanine aminotransferase (SGPT). This is the first demonstration of platelet hyperaggregation and prothrombotic alteration in HF-fed rats. HF-fed rats treated with EL showed improved insulin resistance, along with reduced hypertriglyceridemia, hypertension, platelet aggregability, blood coagulation, serum enzymes (CK-MB, SGOT, LDH and SGPT), and vascular reactivity. These effects of EL in HF-induced hypertensive rats might be associated with the suppression of hyperinsulinemia and hypertriglyceridemia, along with its antiatherogenic and antithrombogenic potential. These data indicate that the aqueous extract of EL has great therapeutic potential for the prevention and (or) management of insulin resistance and the associated hypertension.

scholarly journals Therapeutic Potential of Inorganic Nanoparticles for the Delivery of Monoclonal Antibodies

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Christopher T. Turner ◽  
Steven J. P. McInnes ◽  
Nicolas H. Voelcker ◽  
Allison J. Cowin
Keyword(s):  
Monoclonal Antibodies ◽  
Side Effects ◽  
Therapeutic Potential ◽  
Release Profile ◽  
Inorganic Nanoparticles ◽  
Therapeutic Drug ◽  
High Dose ◽  
Effector Functions ◽  
Delivery Strategies ◽  
High Degree

Monoclonal antibodies (mAbs), available for a range of diseases, including tumours, leukemia, and multiple sclerosis, are emerging as the fastest growing area of therapeutic drug development. The greatest advantage of therapeutic mAbs is their ability to bind with a high degree of specificity to target proteins involved in disease pathophysiology. In response, effector functions are triggered and these ameliorate the disease cascade. As an alternative to this reliance on effector functions, drugs can be conjugated to mAbs. The ability to target compounds to the site of pathology minimises the nonspecific side effects associated with systemic administration. In both instances, optimising the delivery, absorption, and distribution of the mAbs, whilst minimising potential side effects, remain the key hurdles to improved clinical outcomes. Novel delivery strategies are being investigated with more vigour in recent years, and nanoparticles are being identified as suitable vehicles. In conjunction with permitting a controlled release profile, nanoparticles protect the drug from degradation, reducing both the dose and frequency of administration. Moreover, these particles shield the patient from the immune complications associated with high dose mAb infusions or drug cytotoxicity. This review outlines recent advances in nanoparticle technology and how they may be of benefit as therapeutic mAb delivery/targeting vehicles.

scholarly journals Protective effects of ethanolic extract of Alhagi maurorum roots on renal failure induced by acetaminophen in mice

2021 ◽  
Vol 8 (1) ◽  
pp. 16-22
Author(s):  
Seham I AL-Nafea ◽  
Mohammed O Aljahdali
Keyword(s):  
Oxidative Stress ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Serum Levels ◽  
High Dose ◽  
Root Extract ◽  
Protective Effects ◽  
Oxidative Stress Biomarkers ◽  
Protective Actions ◽  
And Oxidative Stress

The protective actions of ethanol Alhagi maurorum (AM) root ethanol extract on acetaminophen-induced oxidative stress and renal toxicity in mice was evaluated. Forty male SWR strain albino mice aged 8 weeks were grouped into five groups. G1 (n=5): as control. G2 (n=5): administered orally a single dose of acetaminophen (2000mg/kg). G3 (n=10) administrated orally 200 mg/kg of roots ethanol extract for one week then acetaminophen as G2 at 8th day and; G4 (n=10) administrated orally 400 mg/kg of roots ethanol extract for one week then acetaminophen as G2 at 8th day; G5 (n=10) administrated orally 600 mg/kg of roots ethanol extract for one week then acetaminophen as G2 at 8th day. At end of experiments, the mice were killed under anesthesia and blood samples were gathered to preform complete blood test (CBC), serum levels of urea and creatinine and oxidative stress biomarkers as superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) using available Elisa mice kits. Kidneys were removed and histologically examined. Acetaminophen intake significantly elevated WBCs, neutrophils, monocytes, urea and creatinine levels and significantly decreased RBCs, hemoglobin, hematocrit, GSH, SOD and CAT (P <0.05). Treatment with Alhagi maurorum roots extract especially high dose (600 mg/kg) resulted in decreased in WBCs, neutrophils, monocytes, urea and creatinine levels and significantly increased RBCs, hemoglobin, hematocrit, GSH, SOD and CATversusacetaminophen group. Alhagi maurorum root extract treatment similarly decreased renal histological alteration induced by acetaminophen. This study can be utilized as prove of reading that Alhagi maurorum ethanol root extract especially high dose might be administered to prevent renal destruction induced by acetaminophen due to its antioxidant activity

scholarly journals Regulation of Bcl-2 and the NF-kB Signaling Pathway by Succinyl Rotundic Acid in Livers of Rats with Alcoholic Hepatitis

2021 ◽  
Vol 25 (03) ◽  
pp. 730-734
Author(s):  
Yufang He
Keyword(s):  
Alcoholic Hepatitis ◽  
Caspase 3 ◽  
Serum Levels ◽  
Antagonistic Effect ◽  
Signal Pathways ◽  
High Dose ◽  
Protective Effects ◽  
Inflammatory Reactions ◽  
Protein Levels ◽  
Rotundic Acid

In this study, the protective effects of succinyl rotundic acids on alcoholic hepatitis in irradiated rats as well as the effects of Bcl-2-Bax-caspase-3 and the NF-kB signal pathways were studied. SD rats were divided into four groups randomly: normal; model; and succinyl rotundic acid low-, middle-, and high-dose groups. Distilled water, 60% ethanol and 60% ethanol +SRA, respectively, were given for 30 days. ELISA was used to measure serum levels of LDH, AST, ALT, NOS, NO, MDA, GSH and TG. Western blotting was used to measure protein levels of Bcl-2, Bax, caspase-3, NF-kB p 65, IKBA, HO-1, Nrf2 and CYP2E1. Compared with the model group, LDH, AST, ALT, NOS, NO, MDA and TG levels were lower in serum of low-, middle-, and high-dose groups (P < 0.01, P < 0.05 and P < 0.05 in all); GSH content was greater in serum of low-, middle- and high-dose groups (P < 0.05). Levels of Bcl-2, HO-1, and Nrf2 were greater (P < 0.01 in all); those of Bax, caspase-3, NF-kB p65, IKBA, and CYP2E1 were lower (P < 0.01 and P < 0.001 in all). These findings suggest that succinyl rotundic acid reduces inflammatory reactions by reducing levels of NOS and NO, regulating levels of Bcl-2, Bax, caspase-3, NF-kB, and anti-oxidative stress pathways, and has an antagonistic effect on alcoholic liver injury. The agent has potential to treat clinical alcoholic liver disease. © 2021 Friends Science Publishers

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