Hyperbaric oxygen treatment ameliorates gentamicin-induced nephrotoxicity and expression of kidney injury molecule 1 in the rat model

2019 ◽  
pp. 125-133
Author(s):  
Özlem Öztopuz ◽  
◽  
Hakan Türkön ◽  
Müşerref Hilal Şehitoğlu ◽  
Başak Büyük ◽  
...  
Keyword(s):  
Hyperbaric Oxygen ◽  
Renal Toxicity ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Total Antioxidant Status ◽  
Potential Method ◽  
Albino Rats ◽  
Serum Samples ◽  
Tissue Samples ◽  
Tnf Α

In recent years, hyperbaric oxygen (HBO2) therapy has been considered as an effective method for the treatment of gentamicin (GM)-induced renal toxicity. However, the findings related to the use of HBO2 for GM toxicity are limited and contradictory. The aim of this study is to investigate the protective role of HBO2 on GM-induced nephrotoxicity. For this purpose, Wistar albino rats (n=28) were randomly divided into four equal groups: C, HBO2, GM and GM+HBO2. GM (100 mg/kg, ip) and HBO2 were applied over seven days. On the eighth day blood and kidney tissue samples were harvested. The albumin, creatinine, and urea levels were determined from serum samples. Superoxide dismutase (SOD), glutathion peroxidase (GSH-Px) activities, malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) values were analyzed spectrophotometrically. The relative expression level of TNF-α, IL-1β and Kim-1 gene were determined by qRT-PCR assays; histopathologic investigation was completed in kidney tissue samples. Serum urea, albumin and creatinine levels significantly increased in the GM group compared to the GM+HBO2 group. For antioxidant parameters the GM+HBO2 group was not statistically different from the C group but was significantly different compared with the GM group. TNF-α, IL-1β and Kim-1 gene expression levels in the GM group were statistically increased compared to the GM+HBO2 group (p=0.015, p=0.024, p=0.004) respectively. Severe tubular necrosis, epithelial desquamation and mild peritubular hemorrhage were observed in the GM-administrated group, while HBO2 exposure ameliorated these alterations. In conclusion, HBO2 exposure may be defined as a potential method for the prevention of GM-induced renal toxicity.

scholarly journals Caspase-1-Inhibitor AC-YVAD-CMK Inhibits Pyroptosis and Ameliorates Acute Kidney Injury in a Model of Sepsis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mei Yang ◽  
Jin-tao Fang ◽  
Ni-shang Zhang ◽  
Long-jiang Qin ◽  
Yang-yang Zhuang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cecal Ligation ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Serum Levels ◽  
Interleukin 18 ◽  
Tissue Samples ◽  
Caspase 1 ◽  
Tnf Α ◽  
Histologic Changes

Objective. To observe the protective effect of AC-YVAD-CMK on sepsis-induced acute kidney injury in mice and to explore its possible mechanisms primarily. Methods. Eighteen male C57BL/6 mice were randomly divided into sham-operated group (Control), cecal ligation and puncture group (CLP), and CLP model treated with AC-YVAD-CMK group (AC-YVAD-CMK) ( n = 6 in each group). Mice were sacrificed at 24 h after operation, and blood and kidney tissue samples were collected for analyses. Histologic changes were determined microscopically following HE staining. The expression of Ly-6B and CD68 was investigated using immunohistochemistry. Serum concentrations of creatinine (sCR) and blood urea nitrogen (BUN) were measured. Serum levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), TNF-α, and interleukin-6 (IL-6) were determined by ELISA. The expressions of Caspas-1, NLRP-1, IL-1β, and IL-18 in renal tissues were investigated using Western blot. Immunofluorescence staining was used to detect the expression of GSDMD protein in renal tissues. Results. AC-YVAD-CMK treatment significantly alleviates sepsis-induced acute kidney injury, with decreased histological injury in renal tissues, suppresses the accumulation of neutrophils and macrophages in renal tissues, and decreased sCR and BUN level ( P < 0.05 ). Attenuation of sepsis-induced acute kidney injury was due to the prohibited production of inflammatory cytokines and decrease expression of Caspas-1, NLRP-1, IL-1β, and IL-18 in renal tissues. In addition, AC-YVAD-CMK treatment significantly reduced the expression of GSDMD in renal tissues compared to those observed in controls ( P < 0.05 ). Conclusions. We demonstrated a marked renoprotective effect of caspase-1-inhibitor AC-YVAD-CMK in a rat model of sepsis by inhibition of pyroptosis.

scholarly journals Nephroprotective effects of eriocitrin via alleviation of oxidative stress and DNA damage against cisplatin-induced renal toxicity

2020 ◽  
Vol 45 (4) ◽  
pp. 381-388
Author(s):  
Yongsheng Jing ◽  
Xiaoqing Wu ◽  
Huili Jiang ◽  
Rong Wang
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Normal Control ◽  
Renal Toxicity ◽  
Kidney Tissue ◽  
Protective Measure ◽  
Control Group ◽  
Tissue Samples ◽  
Tnf Α ◽  
Cytokine Levels

AbstractBackgroundCisplatin, a common anti-neoplastic drug used in the medical industry for cancer treatment has shown adverse nephrotoxic effects. This research targets to demonstrate the protective measure of eriocitrin, a bioactive flavonoid, against cisplatin-induced renal toxicity in rats.Materials and methodsRats of normal control and model groups were treated with saline whereas experimental groups received oral administration of eriocitrin (25 and 50 mg/kg b.w.) for 10 days and a single intraperitoneal (i.p.) injection of cisplatin (8 mg/kg b.w.) was given on the 7th day for all except normal control group. Blood serum, urine, and kidney tissue samples were collected for analysis.ResultsCisplatin-induced rats demonstrated significant renal toxicity and damage. Eriocitrin dose-dependently reversed the effects by decreasing the proteinuria in urine, and urea, creatinine, lipid peroxidation, nitric oxide (NO) and pro-inflammatory cytokine levels (TNF-α, IL-1β) in serum. The tissue levels of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were increased, whereas the levels of tissue DNA fragmentation and serum PARP-1 and Caspase-3 were reduced against model group. Histopathological modulations were supporting the protective effect of eriocitrin.ConclusionEriocitrin has significant nephroprotective effects against cisplatin-induced renal toxicity by alleviating oxidative stress, preventing apoptosis and DNA damage.

scholarly journals MicroRNA Expression and Intestinal Permeability in Children Living in a Slum Area of Bangladesh

2021 ◽  
Vol 8 ◽  
Author(s):  
Humaira Rashid ◽  
Towfida J. Siddiqua ◽  
Biplob Hossain ◽  
Abdullah Siddique ◽  
Mamun Kabir ◽  
...  
Keyword(s):  
Intestinal Permeability ◽  
Mirna Expression ◽  
Fold Change ◽  
Serum Samples ◽  
Tissue Samples ◽  
Expression Levels ◽  
Tnf Α ◽  
Stool Samples ◽  
Ifn Γ ◽  
Taqman Array

Introduction: MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression. Changes in miRNA expression have been reported in a number of intestinal diseases, in both tissue samples and readily accessible specimens like stools. Pathogenic infections, diet, toxins, and other environmental factors are believed to influence miRNA expression. However, modulation of miRNAs in humans is yet to be thoroughly investigated. In this study, we examined the expression levels of two human miRNAs (miRNA-122 and miRNA-21) in stool samples of a group of Bangladeshi children who had an altered/increased intestinal permeability (IIP).Methods: Stool samples were collected from children with IIP (L:M &gt; 0.09) and normal intestinal permeability (NIP) (L:M ≤ 0.09). Quantitative PCR was performed to quantify the levels of miRNA-122 and miR-21 in stools. Commercial ELISA kits were used to measure gut inflammatory markers Calprotectin and REG1B. Serum samples were tested using Human Bio-Plex Pro Assays to quantify IL-1β, IL-2, IL-5, IL-10, IL-13, IFN-γ, and TNF-α. Total nucleic acid extracted from stool specimens were used to determine gut pathogens using TaqMan Array Card (TAC) system real-time polymerase chain reaction.Results: The expression levels of miRNA-122 (fold change 11.6; p &lt; 0.001, 95% CI: 6.14–11.01) and miR-21 (fold change 10; p &lt; 0.001, 95% CI: 5.05–10.78) in stool were upregulated in children with IIP than in children with normal intestinal permeability (NIP). Significant correlations were observed between stool levels of miR-122 and miR-21 and the inflammatory cytokines IL-1β, IL-2, IFN-γ, and TNF-α (p &lt; 0.05). Children with IIP were frequently infected with rotavirus, Campylobacter jejuni, Bacteroides fragilis, adenovirus, norovirus, astrovirus, and various Escherichia coli strains (ETEC_STh, ETEC_STp, EAEC_aaiC, EAEC_aatA) (p &lt; 0.001). miR-122 significantly correlated with the fecal inflammatory biomarkers REG1B (p = 0.015) and Calprotectin (p = 0.030), however miR-21 did not show any correlation with these fecal biomarkers.

The Effect of Thymol on Renal Toxicity Induced by Mercury Chloride in Rats

2021 ◽  
Author(s):  
Hamid Reza Jamshidi ◽  
Faezeh Taheri
Keyword(s):  
Mercuric Chloride ◽  
Renal Toxicity ◽  
Corn Oil ◽  
Kidney Tissue ◽  
Control Group ◽  
Mercury Chloride ◽  
Protective Effects ◽  
Tissue Samples ◽  
Significant Difference ◽  
Anti Oxidant

Background and Aims: Mercuric chloride is highly toxic once absorbed into the bloodstream, especially the kidneys in which it is collected. Mercury chloride increases hydrogen peroxide and enhances the destruction of protective enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPX), leading to oxidative stress. Besides, thymol has anti-oxidant effects and can increase the activity of SOD and GPX. This study aims to evaluate the efficacy of thymol on mercury chloride-induced toxicity. Materials and Methods: In this study, 30 rats, consisting of 6 groups of 5, were used. Control group receiving a single dose of 0.5 mg/kg mercuric chloride for 15 days, third, fourth, and fifth group received intraperitoneal injection of mercuric chloride at a dose of 0.5 mg/kg for 15 days plus thymol at a dose of 10, 30, 50 mg/kg. The sixth group received mercuric chloride at a dose of 0.5 mg/kg for 15 days plus thymol at 30 mg/kg per day for ten days. Results: Results showed a significant difference in the activity of catalase enzyme in kidney tissue samples test. According to the results of SOD, there is a significant difference between the group of corn oil and the group of mercury chloride and between the group of mercury chloride and the group that receives thymol at a dose of 10, 30, 50 mg/kg (p ≤ 0.05). Conclusions: It can be concluded that mercury chloride-induced kidney toxicity and thymol have anti-oxidant protective effects for SOD and GPX.

scholarly journals Ethanolic Extract of Syzygium cumini Causes Toxic Effects on Ethanol-induced Liver and Kidney Damage in Albino Wistar Rats: A Biochemical and Histological Study

2022 ◽  
Vol 16 (1) ◽  
pp. 63-72
Author(s):  
Abba Aji Manu ◽  
◽  
Bello Muhammad Musa ◽  
Martha Orendu Oche Attah ◽  
Helga Ishaya Bedan ◽  
...  
Keyword(s):  
Histological Study ◽  
Kidney Tissue ◽  
Ethanolic Extract ◽  
Albino Rats ◽  
Syzygium Cumini ◽  
Tissue Samples ◽  
Inflammatory Conditions ◽  
Therapeutic Value ◽  
Liver And Kidney ◽  
Wistar Albino Rats

Background: The therapeutic value of Syzygium cumini (S. cumini) has been documented in traditional medicine for the treatment of many diseases and ailments. Various preparations of this plant have been made and used especially for liver inflammatory conditions in livestock. Further, many liver diseases in humans are inflammatory conditions, which are caused by alcohol intake. This study sought to examine the effect of S. cumini on ethanol-induced hepatotoxicity in Wistar albino rats. Methods: Twenty-five rats were divided into five groups of five rats each. The first group was control and the other four were administered ethanol at varying doses to induce liver and kidney damages. Two doses of the S. cumini extract were administered at a concentration of 200 mg/kg or 400 mg/kg. Silymarin was administered to the last group at 10 mg/kg. The liver and kidney tissue samples were collected and preserved for histological analyses and the rat sera were analyzed for the associated biochemical biomarkers. Results: Histopathological analyses revealed pyknotic nuclei and distortion in the arrangement of the hepatocytes in extract-treated groups. The kidney tissue samples showed signs of interstitial bleeding and aggregation of lymphocytes in the peri-glomerular areas. The analyses of the biochemical parameters revealed that there were significant increases in the aspartate aminotransferase (AST), alanine transaminase (ALT), Urea and creatinine in the sera of the groups treated with the extract compared to those of the controls (P<0.05). Conclusion: The S. cumini extract caused elevation of serum hepatic and renal biomarkers at 400 mg/kg and did not have a hepatoprotective effect.

scholarly journals EFFECT OF LYCOPENE IN AMELIORATION OF TESTICULAR AND RENAL TOXICITY INDUCED BY BOLDENONE UNDECYLENATE IN MALE ALBINO RATS

2019 ◽  
Vol 3 (3) ◽  
Author(s):  
Samar S Ibrahim ◽  
Alshaimaa M Said
Keyword(s):  
Dna Fragmentation ◽  
Renal Toxicity ◽  
Histopathological Examination ◽  
Kidney Tissue ◽  
Serum Testosterone ◽  
Control Group ◽  
Albino Rats ◽  
Total Antioxidant ◽  
Factor Α ◽  
Necrosis Factor

Background: The present study was designed to evaluate the relative ameliorating efficacy of lycopene against the deleterious effects of boldenone, an androgenic steroid, on the rat testis and kidney.  Materials and Methods: 40 male albino rats were divided into four groups; control group received intramuscular (i.m) injection of olive oil once a week; lycopene (Lc) group received lycopene (10 mg/kg b.w p.o daily); boldenone (Bol) group received (5 mg/kg b.w i.m once a week); Bol + Lc group received boldenone (5 mg/kg b.w i.m once a week) and lycopene (10 mg/kg b.w p.o daily) all for four weeks. Results: intramuscular injection of boldenone significantly induced lipid peroxidation and DNA fragmentation as well as inhibited total antioxidant capacity (TAC) and catalase (CAT) activity in testis and kidney tissue. Additionally, up-regulation of Bax and down-regulation of Bcl-2 gene expression after Bol injection along with marked increase in serum inflammatory cytokines and decrease in serum testosterone. These alterations were confirmed by the histopathological examination of testis and kidney. On the other hand, lycopene oral administration attenuated the testicular and renal injuries induced by boldenone injection. Conclusion: administration of antioxidants as lycopene effectively ameliorated the adverse effects of boldenone on testis and kidney tissues. Key words: Boldenone undecylenate, lycopene, DNA fragmentation, interleukin-1β, tumor necrosis factor-α, apoptosis.

Protective Effects of Berberine as A Natural Antioxidant and Anti-Inflammatory Agent Against Nephrotoxicity Induced by Cyclophosphamide in Mice

2021 ◽  
Author(s):  
Mohammad Amin Mombeini ◽  
Hadi Kalantar ◽  
Elahe Sadeghi ◽  
Mehdi Goudarzi ◽  
Hamidreza Khalili ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Serum Levels ◽  
Stress Factors ◽  
Control Group ◽  
Protective Effects ◽  
Group I ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Purpose Cyclophosphamide is an alkylating agent with nephrotoxicity that constraints its clinical application. Berberine is an isoquinoline derivative alkaloid with biological functions like antioxidant and anti-inflammatory. The current research intended to examine the nephroprotective impacts of berberine against cyclophosphamide-stimulated nephrotoxicity. Methods Forty animal subjects were randomly separated into five categories of control (Group I). Cyclophosphamide (200 mg/kg, i.p., on 7th day) (Group II), and groups III and IV that received berberine 50 and 100 mg/kg orally for seven days and a single injection of cyclophosphamide on 7th day. Group V as berberine (100 mg/kg, alone). On day 8, blood samples were drawn from the retro-orbital sinus to determine serum levels of blood urea nitrogen (BUN), creatinine (Cr), Neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) as biomarkers for kidney injury. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities as oxidative stress factors, tumor necrosis factor- α (TNF-α) and interleukin 1 beta (IL-1β) levels as inflammatory mediators were assessed in kidney tissue. Results The results of this study demonstrated that berberine was able to protect remarkably the kidney from CP-induced injury through decreasing the level of BUN, Cr, NGAL, KIM-1, NO, MDA TNF-α, IL-1β and increasing the level of GSH, CAT, SOD and GPx activities. Conclusion Berberine may be employed as a natural agent to prevent cyclophosphamide-induced nephrotoxicity through anti-oxidant and anti-inflammatory effects.

scholarly journals Identification of novel metabolomic biomarkers in an experimental model of septic acute kidney injury

2019 ◽  
Vol 316 (1) ◽  
pp. F54-F62 ◽  
Author(s):  
Jose L. Izquierdo-Garcia ◽  
Nicolás Nin ◽  
Pablo Cardinal-Fernandez ◽  
Yenny Rojas ◽  
Marta de Paula ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Blood Flow ◽  
Arterial Pressure ◽  
Experimental Model ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Principal Component ◽  
Renal Tissue ◽  
Serum Samples ◽  
Neutrophil Gelatinase Associated Lipocalin

The aim of this study is the identification of metabolomic biomarkers of sepsis and sepsis-induced acute kidney injury (AKI) in an experimental model. Pigs were anesthetized and monitored to measure mean arterial pressure (MAP), systemic blood flow (QT), mean pulmonary arterial pressure, renal artery blood flow (QRA), renal cortical blood flow (QRC), and urine output (UO). Sepsis was induced at t = 0 min by the administration of live Escherichia coli ( n = 6) or saline ( n = 8). At t = 300 min, animals were killed. Renal tissue, urine, and serum samples were analyzed by nuclear magnetic resonance (NMR) spectroscopy. Principal component analyses were performed on the processed NMR spectra to highlight kidney injury biomarkers. Sepsis was associated with decreased QT and MAP and decreased QRA, QRC, and UO. Creatinine serum concentration and neutrophil gelatinase-associated lipocalin (NGAL) serum and urine concentrations increased. NMR-based metabolomics analysis found metabolic differences between control and septic animals: 1) in kidney tissue, increased lactate and nicotinuric acid and decreased valine, aspartate, glucose, and threonine; 2) in urine, increased isovaleroglycine, aminoadipic acid, N-acetylglutamine, N-acetylaspartate, and ascorbic acid and decreased myoinositol and phenylacetylglycine; and 3) in serum, increased lactate, alanine, pyruvate, and glutamine and decreased valine, glucose, and betaine concentrations. The concentration of several metabolites altered in renal tissue and urine samples from septic animals showed a significant correlation with markers of AKI (i.e., creatinine and NGAL serum concentrations). NMR-based metabolomics is a potentially useful tool for biomarker identification of sepsis-induced AKI.

Nitric Oxide Modulation as a Potential Molecular Mechanism Underlying the Protective Role of NaHS in Liver Ischemia Reperfusion Injury

2021 ◽  
Vol 14 ◽  
Author(s):  
Salwa A. Ibrahim ◽  
Seham A. Abdel-Gaber ◽  
Mohamed A. Ibrahim ◽  
Entesar F. Amin ◽  
Rehab K. Mohammed ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Histopathological Examination ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Albino Rats ◽  
High Morbidity ◽  
Tissue Samples ◽  
Sodium Hydrosulfide ◽  
Tnf Α

Background and aim: Liver IR is a frequent clinical complication with high morbidity and mortality. The present study evaluated the possible protective effect of sodium hydrosulfide (NaHS), a H2S donor, in IR-induced hepatic injury and explored the mechanisms of actions of the investigated drug. Methods: Male albino rats (200-230 g) were divided into the following groups: group 1:Sham-operated non treated rats, group 2: IR non treated rats, group 3: L-NNA + IR rats, group 4: NaHS + IR rats, group 5: L-NNA + NaHS + IR rats. Blood samples were collected for ALT determination. Liver tissue samples were used for the assessment of GPx, catalase, SOD, MDA, total nitrites and TNF-α. Parts from the liver were fixed in 10% formalin solution for histopathological examination and immunohistochemical examination of iNOS, eNOS and caspase-3. Results: NaHS protected the liver against IR. This hepatoprotection was associated with normalization of antioxidant enzyme activity and decrease in hepatic MDA, TNF-α and expression of caspase-3 and iNOS. Conclusion: NaHS is hepatoprotective in IR injury. The hepatoprotective effects of NaHS are associated with antioxidant, anti-inflammatory and antiapoptotic effects. These effects are probably mediated via NO modulation.

scholarly journals FcER1: A Novel Molecule Implicated in the Progression of Human Diabetic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Swastika Sur ◽  
Mark Nguyen ◽  
Patrick Boada ◽  
Tara K. Sigdel ◽  
Hans Sollinger ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Target Genes ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Rational Drug Design ◽  
Transcriptional Analysis ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Diabetic Kidney

Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p &lt; 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p &lt; 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design.

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