Protective effect of febuxostat in sepsis-induced liver and kidney injuries after cecal ligation and puncture with the impact of xanthine oxidase, interleukin 1β, and c-Jun N-terminal kinases

2020 ◽  
Vol 39 (7) ◽  
pp. 906-919 ◽  
Author(s):  
YF Ibrahim ◽  
RR Fadl ◽  
SAE Ibrahim ◽  
MF Gayyed ◽  
AMA Bayoumi ◽  
...  
Keyword(s):  
Protective Effect ◽  
Xanthine Oxidase ◽  
Tissue Injury ◽  
Cecal Ligation ◽  
Elevated Serum ◽  
Albino Rats ◽  
Cecal Ligation And Puncture ◽  
Necrosis Factor Alpha ◽  
Liver And Kidney ◽  
The Impact

Sepsis is one of the most common causes of death among hospitalized patients. Activity of xanthine oxidase (XO), a reactive oxygen species-producing enzyme, is known to be elevated in septic patients. Our aim was to investigate the possible protective role of XO inhibitor, febuxostat (FEB), in a rat model of sepsis-induced liver and kidney injures. Adult male albino rats were divided into four groups ( n = 12 each): sham control, sham + FEB, cecal ligation and puncture (CLP), and CLP + FEB groups. FEB (10 mg/kg per os (p.o.)) was given once daily for 2 days and 30 min prior to laparotomy with CLP. CLP was associated with a high mortality rate accompanied by significant liver and kidney injuries indicated by elevated serum alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels and confirmed by histopathological tissue injury. Moreover, there was an increase in neutrophil gelatinase-associated lipocalin, uric acid, malondialdehyde, and nitric oxide levels and with decreased superoxide dismutase activity and total antioxidant capacity. In addition, CLP caused increased expression of the inflammatory markers tumor necrosis factor alpha, interleukin 1beta protein levels, and nuclear factor kappa B immunoexpression. Finally, CLP operated rats exhibited an upregulation in the apoptotic mediators, caspase 3, and P-C-Jun N-terminal kinases (JNK) proteins. FEB treatment of CLP rats caused a significant improvement and normalization in all measured parameters. Moreover, FEB amerliorates degenerative histopathological changes and improves the overall survival rate. In conclusion, FEB exhibited a protective effect in sepsis-induced liver and kidney injuries most probably through its anti-inflammatory, antioxidant, and antiapoptotic properties and attenuating JNK signaling pathway secondary to its XO enzyme inhibitory activity.

scholarly journals The Effects of Montelukast on Antioxidant Enzymes and Proinflammatory Cytokines on the Heart, Liver, Lungs, and Kidneys in a Rat Model of Cecal Ligation and Puncture–Induced Sepsis

2011 ◽  
Vol 11 ◽  
pp. 1341-1356 ◽  
Author(s):  
Ali Kagan Coskun ◽  
Murat Yigiter ◽  
Akgun Oral ◽  
Fehmi Odabasoglu ◽  
Zekai Halici ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Cecal Ligation ◽  
Lipid Peroxide ◽  
Multiple Organ ◽  
Control Group ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Cecal Ligation And Puncture ◽  
Necrosis Factor Alpha ◽  
Liver And Kidney

We investigated the potential protective effects of montelukast (MLK) on cecal ligation and puncture (CLP)–induced tissue injury in vital organs — liver, heart, kidneys, and especially lungs — through inhibition of the proinflammatory cytokine response and the generation of reactive oxygen species (ROS) in rats. The rat groups were (1) a 10-mg/kg MLK-treated CLP group; (2) a 20-mg/kg MLK-treated CLP group; (3) a 20-mg/kg MLK-treated, sham-operated group; (4) a CLP control group; and (5) a sham-operated control group. MLK treatment significantly decreased proinflammatory (tumor necrosis factor-alpha, interleukin-6) cytokine levels following CLP. The lipid peroxide level increased in the lung, heart, liver, and kidney tissues after CLP-induced sepsis, and myeloperoxidase activity increased in the lung, heart, and liver tissues. MLK attenuated this elevation in all tissues except the kidney, dose dependently. The glutathione levels and superoxide dismutase activity were significantly increased in the lung, liver, and kidney tissues after MLK treatment. MLK treatment after CLP also potentially reduced mortality. The lung and kidney tissues were the most protected by MLK under sepsis conditions. We can suggest that MLK reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure.

Platycodin D Ameliorates Acute Kidney Injury in Septic Rats by Regulating Mitogen Activated Protein Kinase Pathway

2020 ◽  
Vol 19 (3) ◽  
pp. 270-276
Author(s):  
Jianying Wang ◽  
Xiaoting Yu
Keyword(s):  
Acute Kidney Injury ◽  
Protein Kinase ◽  
Protective Effect ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
B Cell Lymphoma ◽  
Mitogen Activated Protein Kinase ◽  
Cecal Ligation And Puncture ◽  
Platycodin D ◽  
Mitogen Activated Protein

Acute kidney injury is a severe complication of sepsis. We have shown a protective effect of Platycodin D on sepsis induced acute kidney injury in an animal model that employs cecal ligation and puncture. Cecal ligation and puncture induced a series of degenerative changes in kidney, such as edema, hyperemia, and expansion in glomerular capillary, and inflammatory cells infiltration that were attenuated by Platycodin D. Also, rise in proinflammatory cytokine levels in septic rats was blunted by Platycodin D. Furthermore, Platycodin D administration reduced rise in serum levels of kidney injury markers-blood urea nitrogen and serum creatinine-in septic rats. Moreover, Platycodin D administration also suppressed the cell apoptosis in kidney that was associated with enhanced B-cell lymphoma 2 protein and reduced cleaved cysteine-aspartic protease-3 and BCL2-associated X protein. Lastly, Platycodin D administration attenuated sepsis-induced increase of phospho (p)-extracellular signal-regulated kinase, p-c-Jun NH2-terminal kinase, and p-p38. In conclusion, Platycodin D demonstrated protective effect against sepsis induced acute kidney injury through inactivation of mitogen activated protein kinase pathways, thus providing promising therapeutic strategy for the treatment of sepsis.

l-theanine alleviates liver and kidney dysfunction in septic rats induced by cecal ligation and puncture

Life Sciences ◽  
2020 ◽  
Vol 249 ◽  
pp. 117502 ◽  
Author(s):  
Meltem Malkoç ◽  
Huriye Patan ◽  
Serap Özer Yaman ◽  
Süleyman Türedi ◽  
Gökçen Kerimoğlu ◽  
...  
Keyword(s):  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Kidney Dysfunction ◽  
Liver And Kidney

scholarly journals Microscopic and biochemical changes on liver and kidney of Wistar rats on combination antiretroviral therapy: the impact of naringenin and quercetin

2020 ◽  
Vol 9 (5) ◽  
pp. 601-608
Author(s):  
Edidiong Nnamso Akang ◽  
Olufunke O Dosumu ◽  
Ini-ibehe Essien Okoko ◽  
Oluwatomisin Faniyan ◽  
Ademola A Oremosu ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Wistar Rats ◽  
Combination Antiretroviral Therapy ◽  
Necrosis Factor Alpha ◽  
Immunodeficiency Virus ◽  
Male Wistar Rats ◽  
Liver And Kidney ◽  
Factor Alpha ◽  
Continuous Use ◽  
The Impact

Abstract Combination antiretroviral therapy (cART), which is a lifelong therapy for people living with human immunodeficiency virus, has been associated with nephrotoxicity and hepatotoxicity leading to its discontinuation. This study aimed at investigating the ameliorative potential of naringenin and quercetin on cART-induced hepatotoxicity and nephrotoxicity. Seventy male Wistar rats (225–260 g) were divided into seven groups as control, cART, naringenin, quercetin, dimethyl sulfoxide (DMSO), naringenin/cART (CN) and quercetin/cART (CQ). cART (24 mg/kg), naringenin (50 mg/kg) and quercetin (50 mg/kg) were dissolved in 1% v/v DMSO and administered orally for 56 days. Combination of cART and bioflavonoids had significant increase in superoxide dismutase (P < 0.05), catalase (P < 0.01), reduced glutathione (P < 0.001) and decreased malondialdehyde (P < 0.001) compared to cART only. Tumor necrosis factor Alpha (TNFα) level increased significantly in cART and CQ (P < 0.01) groups, while others showed no significant changes compared to control. TNFα also significantly decreased in CQ level compared to cART (P < 0.001). In addition, significant increase in creatinine level in cART only indicated progressive renal toxicity. Also, progressive pathological changes including congested blood vessels and hepatocellular necrosis were found in the liver, while the kidney had glomerular atrophy, and tubular distortion in cART-only group. Control, naringenin- and quercetin-treated groups showed normal renal and hepatic cytoarchitecture. These findings elucidate that progressive renal and hepatic toxicity is associated with the continuous use of cART; however, a combination of quercetin and naringenin with cART showed possible potential of ameliorating the damages posed by cART.

Protective effect of β-glucan on lung injury after cecal ligation and puncture in rats

2005 ◽  
Vol 31 (6) ◽  
pp. 865-870 ◽  
Author(s):  
Hulya Babayigit ◽  
Can Kucuk ◽  
Erdogan Sozuer ◽  
Cevad Yazici ◽  
Kader Kose ◽  
...  
Keyword(s):  
Lung Injury ◽  
Protective Effect ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture

Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β2-microgloblin knockout mice

2006 ◽  
Vol 290 (2) ◽  
pp. G277-G284 ◽  
Author(s):  
Victor T. Enoh ◽  
Cheng Y. Lin ◽  
Tushar K. Varma ◽  
Edward R. Sherwood
Keyword(s):  
Metabolic Acidosis ◽  
Knockout Mice ◽  
Nk Cell ◽  
Plasma Concentrations ◽  
Cecal Ligation ◽  
Systemic Infection ◽  
Cecal Ligation And Puncture ◽  
Wild Type ◽  
Term Survival ◽  
The Impact

Our previous studies showed that β2-microglobulin knockout mice treated with anti-asialoGM1 (β2MKO/αAsGM1 mice) are resistant to injury caused by cecal ligation and puncture (CLP). However, CLP-induced injury is complex. Potential mechanisms of injury include systemic infection, cecal ischemia, and translocation of bacterial toxins such as endotoxin and superantigens. Currently, it is unclear which of these mechanisms of injury contributes to mortality in wild-type mice and whether β2MKO/αAsGM1 mice are resistant to any particular mechanisms of injury. In the present study, we hypothesized that systemic infection is the major cause of injury after CLP in wild-type mice and that β2MKO/αAsGM1 mice are resistant to infection-induced injury. To test this hypothesis, wild-type and β2MKO/αAsGM1 mice were treated with the broad-spectrum antibiotic imipenem immediately after CLP to decrease the impact of systemic infection in our model. Treatment of wild-type and β2MKO/αAsGM1 mice with imipenem decreased bacterial counts by at least two orders of magnitude. However, all wild-type mice, whether treated with saline or imipenem, died by 42 h after CLP and had significant hypothermia, metabolic acidosis, and high plasma concentrations of the cytokines interleukin-6, macrophage inflammatory protein-2, and keratinocyte-derived chemokine. β2MKO/αAsGM1 mice showed 40% long-term survival, which was increased to 90% by imipenem treatment. β2MKO/αAsGM1 mice had less hypothermia, decreased metabolic acidosis, and lower cytokine concentrations at 18 h after CLP compared with wild-type mice. These results suggest that infection is not the major cause of mortality for wild-type mice in our model of CLP. Other mechanisms of injury such as cecal ischemia or translocation of microbial toxins may be more important. β2MKO/αAsGM1 mice appear resistant to these early, non-infection-related causes of CLP-induced injury but showed delayed mortality associated with bacterial dissemination, which was ablated by treatment with imipenem.

scholarly journals Hepatorenal Effects of Diclofenac and Ciprofloxacin in Rats

2021 ◽  
Vol 3 (2) ◽  
pp. 186-198
Author(s):  
Elkhatim H. Abdelgadir ◽  
Khalid O. Alzaidi ◽  
Mohamed E. Ramady ◽  
Sayed A. M. Amer
Keyword(s):  
Toxic Effect ◽  
Tissue Injury ◽  
Chronic Administration ◽  
Inflammatory Cells ◽  
Albino Rats ◽  
Albino Rat ◽  
Therapeutic Drugs ◽  
Liver And Kidney ◽  
Group A ◽  
High Doses

The toxic effect of diclofenac (DCF) sodium and Ciprofloxacin (CIP) on gene expression of cytochrome P450 oxidase (CYPs) and the histology of liver and kidney of male albino rat has been evaluated in this study. DCF and CIP were chosen since they are inhibitors for specific CYP enzymes. Thirty-five adult male albino rats were divided into 7 groups of 5 animals each (A, B, C, D, E, F and G) and were treated orally with drugs for 21 consecutive days. Group A served as the control while B and C were treated with 5.3, 10.6 mg/kg body weight (bw) DCF sodium and groups D and E were treated with 40 and 80 mg/kg bw CIP, respectively. Groups F and G were treated with a mixture of the low and the high doses of both drugs, respectively. Both drugs significantly downregulated the mRNA expression of CYP1a2, CYP3a4 and CYP2c9. They caused hepatorenal histological changes. In the liver, massive fibrosis, necrosis, inflammatory cell infiltration with hemorrhages and hydrophilic degeneration have been observed. A massive tissue injury with glomerular and tubular damages due to sever necrosis, degeneration of concomitant inflammatory cells and blood vessels congestion have been shown in renal tissues. Although DCF and CIP are still used as therapeutic drugs, their use should be limited as their chronic administration induces a toxic effect on human health.

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