scholarly journals Pre-Treatment with Curcumin Ameliorates Cisplatin-Induced Kidney Damage by Suppressing Kidney Inflammation and Apoptosis in Rats

Drug Research ◽  
2018 ◽  
Vol 69 (02) ◽  
pp. 75-82 ◽  
Author(s):  
Vivian Soetikno ◽  
Shinta Sari ◽  
Lulu Ul Maknun ◽  
Nielda Sumbung ◽  
Deliana Rahmi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Histopathological Examination ◽  
Kidney Injury ◽  
Kidney Damage ◽  
Protective Effects ◽  
Protection Effect ◽  
Tnf Α ◽  
Pre Treatment ◽  
Damage Protection

Abstract Objective In addition to oxidative stress, inflammation and apoptosis have an important role in the pathogenesis of cisplatin-induced kidney damage. This study aimed to investigate the molecular mechanisms of protective effects of curcumin against cisplatin-induced kidney inflammation and apoptosis in rats. Materials and Methods Eighteen rats were equally divided into three groups; normal (0.5% CMC-Na), cisplatin (CDPP) (7 mg/kg i.p.), and cisplatin+curcumin (CMN100) groups. Curcumin was given at a dose of 100 mg/kg orally for nine days, starts one week before giving a single dose of cisplatin. Kidney and plasma were taken for analysis. Results Cisplatin challenged rats demonstrated kidney injury as shown by reduced creatinine clearance, increased of plasma BUN, plasma creatinine, and kidney MDA, decreased of kidney GSH levels, and kidney histopathology alterations. Also, cisplatin increased ERK1/2 phosphorylation and NF-κB expression, which subsequently increased mRNA expression of TNF-α, IL-6, KIM-1, NGAL, and Bax/Bcl-2 ratio as well as decreased mRNA expression of IL-10 in kidney tissues. Pre-treatment with curcumin significantly ameliorated inflammation and apoptosis induced by cisplatin. In addition, curcumin downregulated Ctr1 and OCT2 drug transporters as compared to cisplatin group. Histopathological examination furthers confirmed the kidney damage protection effect of curcumin. Conclusions These data indicate that curcumin has nephroprotective properties against cisplatin-induced kidney damage in rats and this effect is associated with its anti-inflammatory and anti-apoptosis profiles, in addition to its antioxidant. Hence, curcumin may be useful for preventing kidney damage against cisplatin administration.

scholarly journals Protective effects of 4, 5-O-dicaffeoylquinic acid against mouse sepsis via down-regulation of TNF-α, IL-6 and IL-8

2020 ◽  
Vol 19 (4) ◽  
pp. 715-720
Author(s):  
XiaoBo Wang ◽  
JianHua Wu ◽  
BuKao Ni
Keyword(s):  
Survival Rate ◽  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Cecal Ligation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Dicaffeoylquinic Acid ◽  
Xanthium Sibiricum ◽  
Tnf Α

Purpose: To investigate the protective effects of 4, 5-O-dicaffeoylquinic acid (DCQA) isolated from Xanthium sibiricum Patr. against mouse sepsis caused by cecal ligation/puncture (CLP) in vivo, as well as the molecular mechanisms of action involved.Methods: DCQA (7.5, 15, and 30 mg/kg/day) were administered to the mice with sepsis and the survival rate was obtained. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 were examined by enzyme-linked immunosorbent assay (ELISA). Subsequently, the lipopolysaccharide (LPS) neutralizing ability of DCQA (2, 4, and 8 μg/mL) was measured using limulus amebocyte lysate (LAL) test in vitro. Furthermore, the effect of DCQA (10, 20, and 40 μg/mL) on mRNA expression of TNF-α, IL-6, and IL-8 in LPS (100 ng/mL)-treated RAW 264.7 cells was assessed using quantitative real time-polymerase chain reaction (RT-qPCR) assay.Results: DCQA significantly improved the survival rate of mice with sepsis caused by CLP (35, 50, and 65 %, respectively vs. 15 % for control, p < 0.05). LPS levels fell on co-incubation with DCQA in vitro. Moreover, ELISA and RT-qPCR results revealed that DCQA treatment lowered tendency in the mRNA expression of TNF-α, IL-6, and IL-8 (p < 0.01).Conclusion: DCQA exhibits protective effects against sepsis in mice mediated by downregulating TNF-α, IL-6, and IL-8. Further studies, in animals and humans are requied to determine the safety and efficacy of DCQA in both animal and clinical management of sepsis. Keywords: Xanthium sibiricum, 4,5-O-Dicaffeoylquinic acid, Sepsis, Cecal ligation and puncture, Lipopolysaccharide, TNF-α, IL-6, IL-8

scholarly journals Interleukin-22 mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury

2020 ◽  
Author(s):  
Wei Chen ◽  
Yilan Shen ◽  
Jiajun Fan ◽  
Xian Zeng ◽  
Xuyao Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Kidney Damage ◽  
Metabolic Reprogramming ◽  
Protective Effects ◽  
Interleukin 22 ◽  
Renal Tubular ◽  
Stage Renal Disease ◽  
End Stage

AbstractKidney damage initiates the deteriorating metabolic states in tubule cells that lead to the development of end-stage renal disease (ESTD). Interleukin 22 (IL-22) is an effective therapeutic antidote for kidney injury via promoting kidney recovery, but little is known about the underlying molecular mechanisms. Here we first provide evidence that IL-22 attenuates kidney injury via metabolic reprogramming of renal tubular epithelial cells (TECs). Specifically, our data suggest that IL-22 regulates mitochondrial function and glycolysis in damaged TECs. Further observations indicate that IL-22 alleviates the accumulation of mitochondrial reactive oxygen species (ROS) and dysfunctional mitochondria via the induction of AMPK/AKT signaling and PFBFK3 activities. In mice, amelioration of kidney injury and necrosis and improvement of kidney functions via regulation of these metabolism relevant signaling and mitochondrial fitness of recombinant IL-22 are certificated in cisplatin induced kidney damage and diabetic nephropathy (DN) animal models. Taken together, our findings unravel new mechanistic insights into protective effects of IL-22 on kidney and highlight the therapeutic opportunities of IL-22 and the involved metabolic regulators in various kidney diseases.

scholarly journals Investigation of the Effects of Artemisinin on Testis and Kidney Injury Induced by Doxorubicin

2019 ◽  
Vol 69 (2) ◽  
pp. 177-191 ◽  
Author(s):  
Hidayet Tutun ◽  
Özlem Özmen ◽  
İbrahim Aktaş ◽  
Alper Yalçin ◽  
Ahmet Türk
Keyword(s):  
Caspase 3 ◽  
Histopathological Examination ◽  
Kidney Injury ◽  
Testicular Toxicity ◽  
Protective Effects ◽  
Oral Gavage ◽  
Immunohistochemical Examination ◽  
Single Intraperitoneal Injection ◽  
Tnf Α ◽  
Structural Abnormalities

Abstract Artemisinin, an antimalarial drug, has anticancer activity and possesses protective effects against several tissue injuries. The aim of the present study was to investigate the effects of artemisinin on doxorubicin-induced renal and testicular toxicity in rats. Doxorubicin was administered to rats at a single dose of 10 mg/kg body weight (b.w.) as a single intraperitoneal injection. Application of artemisinin was by using oral gavage feeding needle for 14 days at different specified doses (7 mg/kg and 35 mg/kg b.w.). At the end of the experiments, kidney and testis samples were collected and used for histopathological and immunohistochemical examinations. At histopathological examination, while hyperemia was the marked finding in kidney and testis of rats treated with doxorubicin only, no evidence of structural abnormalities showed in other groups. Immunohistochemical examination of the testes and kidneys demonstrated significantly increased expression of caspase-3, TNF-α, iNOS and NF-κB in rats treated with doxorubicin only. Artemisinin decreased the doxorubicin-induced overexpression of NF-κB, iNOS, TNFα and caspase-3 in these tissues of rats. Artemisinin can protect the kidney and testis against doxorubicin-induced nephrotoxicity and testotoxicity, probably through a decrease of caspase-3, TNF-α, iNOS and NF-κB expressions. It may be concluded that artemisinin has a potential for clinical use in the treatment of kidney and testis damage induced by doxorubicin. Further researches are required to determine the appropriate combination of artemisinin with doxorubicin.

scholarly journals Alleviation of Oxidative Stress in Dental Pulp Cells Following 4-Hexylresorcinol Administration in a Rat Model

2021 ◽  
Vol 11 (8) ◽  
pp. 3637
Author(s):  
Jun-Ho Chang ◽  
Dae-Won Kim ◽  
Seong-Gon Kim ◽  
Tae-Woo Kim
Keyword(s):  
Oxidative Stress ◽  
Dental Pulp ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Mandibular Incisor ◽  
Tnf Α ◽  
Total Antioxidant ◽  
Pulp Cells ◽  
Pre Treatment

Damaged dental pulp undergoes oxidative stress and 4-hexylresorcinol (4HR) is a well-known antioxidant. In this study, we aimed to evaluate the therapeutic effects of a 4HR ointment on damaged dental pulp. Pulp cells from rat mandibular incisor were cultured and treated with 4HR or resveratrol (1–100 μM). These treatments (10–100 μM) exerted a protective effect during subsequent hydrogen peroxide treatments. The total antioxidant capacity and glutathione peroxidase activity were significantly increased following 4HR or resveratrol treatment (p < 0.05), while the expression levels of TNF-α and IL1β were decreased following the exposure to 4HR pre-treatment in an in vitro model. Additionally, the application of 4HR ointment in an exposed dental pulp model significantly reduced the expression of TNF-α and IL1β (p < 0.05). Conclusively, 4HR exerted protective effects against oxidative stress in dental pulp tissues through downregulating TNF-α and IL1β.

α2-Adrenoceptor agonist dexmedetomidine protects septic acute kidney injury through increasing BMP-7 and inhibiting HDAC2 and HDAC5

2012 ◽  
Vol 303 (10) ◽  
pp. F1443-F1453 ◽  
Author(s):  
Chung-Hsi Hsing ◽  
Chiou-Feng Lin ◽  
Edmund So ◽  
Ding-Ping Sun ◽  
Tai-Chi Chen ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Histone H3 ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Protective Effects ◽  
Tnf Α

Bone morphogenetic protein (BMP)-7 protects sepsis-induced acute kidney injury (AKI). Dexmedetomidine (DEX), an α2-adrenoceptor (α2-AR) agonist, has anti-inflammatory effects. We investigated the protective effects of DEX on sepsis-induced AKI and the expression of BMP-7 and histone deacetylases (HDACs). In vitro , the effects of DEX or trichostatin A (TSA, an HDAC inhibitor) on TNF-α, monocyte chemotactic protein (MCP-1), BMP-7, and HDAC mRNA expression in LPS-stimulated rat renal tubular epithelial NRK52E cells, was determined using real-time PCR. In vivo, mice were intraperitoneally injected with DEX (25 μg/kg) or saline immediately and 12 h after cecal ligation and puncture (CLP) surgery. Twenty-four hours after CLP, we examined kidney injury and renal TNF-α, MCP-1, BMP-7, and HDAC expression. Survival was monitored for 120 h. LPS increased HDAC2, HDAC5, TNF-α, and MCP-1 expression, but decreased BMP-7 expression in NRK52E cells. DEX treatment decreased the HDAC2, HDAC5, TNF-α, and MCP-1 expression, but increased BMP-7 and acetyl histone H3 expression, whose effects were blocked by yohimbine, an α2-AR antagonist. With DEX treatment, the LPS-induced TNF-α expression and cell death were attenuated in scRNAi-NRK52E but not BMP-7 RNAi-NRK52E cells. In CLP mice, DEX treatment increased survival and attenuated AKI. The expression of HDAC2, HDAC5, TNF-α, and MCP-1 mRNA in the kidneys of CLP mice was increased, but BMP-7 was decreased. However, DEX treatment reduced those changes. DEX reduces sepsis-induced AKI by decreasing TNF-α and MCP-1 and increasing BMP-7, which is associated with decreasing HDAC2 and HDAC5, as well as increasing acetyl histone H3.

scholarly journals Protective Effects of Pelargonidin on Lipopolysaccharide-induced Hepatic Failure

2018 ◽  
Vol 13 (1) ◽  
pp. 1934578X1801300 ◽  
Author(s):  
Wonhwa Lee ◽  
Yuri Lee ◽  
Jaehong Kim ◽  
Jong-Sup Bae
Keyword(s):  
Liver Failure ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Serum Levels ◽  
Primary Response ◽  
Protective Effects ◽  
Toll Like Receptor 4 ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Lps Treatment

Pelargonidin (PEL) is a well-known red pigment found in plants and has important biological activities that are potentially beneficial for human health. The aim of this study was to investigate the effect of PEL on lipopolysaccharide (LPS)-induced liver failure in mice, and to elucidate its underlying molecular mechanisms. Liver failure was induced by LPS (15 mg/kg, i.p) in mice, and 12 h later, they were treated intravenously with PEL. Administration of LPS significantly increased mortality, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and inflammatory cytokines, and expression of toll-like receptor 4 (TLR4) protein; PEL treatment effectively countered these effects of LPS. Further, LPS treatment markedly increased the expression of myeloid differentiation primary response gene 88 (MyD88), phosphorylation of p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), and expressions of nuclear proteins, such as nuclear factor (NF)-κB and phosphorylated c-Jun. Additionally, LPS increased the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. All these effects of LPS were attenuated by PEL. In addition, the LPS-mediated increase in the level of serum interferon (IFN)-β expression of the TLR-associated activator of IFN (TRIF) protein, and phosphorylation of IFN regulator factor 3 (IRF3) were reduced by PEL. Our results suggest that PEL attenuates LPS-induced liver damage by inhibition of the TLR-mediated inflammatory pathway and could be used to treat liver diseases.

scholarly journals Effect of Glutathione Depletion on Nrf2/ARE Activation by Deltamethrin in PC12 Cells

2013 ◽  
Vol 64 (1) ◽  
pp. 87-97 ◽  
Author(s):  
Huangyuan Li ◽  
Siying Wu ◽  
Junnian Chen ◽  
Bo Wang ◽  
Nian Shi
Keyword(s):  
Mrna Expression ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Glutathione Depletion ◽  
Nuclear Accumulation ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Cell Protection ◽  
Nrf2 Activation ◽  
Pre Treatment

Transcription factor NF-E2-related factor 2 (Nrf2) is important for cell protection against chemical-induced oxidative stress. Previously, we have reported that in PC12 cells, Nrf2 can be triggered by deltamethrin (DM), a commonly used pyrethroid insecticide. Molecular mechanisms behind Nrf2 activation by DM are still unclear. Here we studied the effects of cell glutathione (GSH) depletion on Nrf2 activation by DM. We found that DM enhanced Nrf2 expression at the mRNA and protein levels and increased nuclear Nrf2 levels. Activation of Nrf2 was associated with activation of its downstream targets, such as heme oxygenase-1 (HO-1) and glutamate cysteine ligase catalytic subunit (GCLC). In contrast, DL-buthionine-[S,R]- sulfoximine (BSO), a known GSH-depleting agent, did not increase Nrf2 protein expression or cause its nuclear accumulation. However, pre-treatment with BSO triggered mRNA expression of HO-1 and GCLC. Furthermore, BSO pre-treatment suppressed DM-induced Nrf2 upregulation and activation and lowered mRNA expression of HO-1 and GCLC upon DM treatment. These data demonstrate that GSH depletion is not necessary for the activation of Nrf2/ARE by DM in PC12 cells, and that GCLC and HO-1 expression can increase through other signalling pathways.

scholarly journals Hyperbaric oxygen enhances neutrophil apoptosis and their clearance by monocyte-derived macrophages

2015 ◽  
Vol 93 (4) ◽  
pp. 405-416 ◽  
Author(s):  
Anwar J. Almzaiel ◽  
Richard Billington ◽  
Gary Smerdon ◽  
A. John Moody
Keyword(s):  
Mrna Expression ◽  
Hyperbaric Oxygen ◽  
Inflammatory Cytokine ◽  
Cytokine Gene Expression ◽  
Neutrophil Apoptosis ◽  
Normobaric Hyperoxia ◽  
Tnf Α ◽  
Pre Treatment ◽  
Bovine Neutrophils ◽  
Anti Inflammatory Cytokine

Neutrophil apoptosis and clearance by macrophages are essential for wound healing. Evidence suggests that hyperbaric oxygen (HBO) exposure may enhance neutrophil apoptosis, but HBO effects leading to neutrophil clearance by macrophages are still unclear. In the current study, bovine neutrophils and monocyte-derived macrophages (MDMΦ) were co-cultured under HBO (97.9% O2, 2.1% CO2 at 2.4 atm absolute (ATA)) (1 atm = 101.325 kPa), hyperbaric normoxia (8.8% O2 at 2.4 ATA), normobaric hyperoxia (95% O2, 5% CO2), normoxia (air), and normobaric hypoxia (5% O2, 5% CO2). Phagocytosis of fresh and 22 h aged neutrophils by MDMΦ was increased after HBO pre-treatment, assessed using flow cytometry and light microscopy. Enhanced clearance of neutrophils was accompanied by an increase in H2O2 levels following HBO pre-treatment with upregulation of IL-10 (anti-inflammatory cytokine) mRNA expression in LPS-stimulated MDMΦ that had ingested aged neutrophils. TNF-α (pro-inflammatory cytokine) gene expression did not change in LPS-stimulated MDMΦ that had ingested fresh or aged neutrophils after HBO, pressure, and hyperoxia. These findings suggest that HBO-activated MDMΦ participate in the clearance of apoptotic cells. Uptake of neutrophils by MDMΦ exposed to HBO may contribute to resolution of inflammation, because HBO induced up-regulation of IL-10 mRNA expression.

Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation, and amyloidogenesis: possible role of brain-derived neurotrophic factor

2017 ◽  
Vol 95 (7) ◽  
pp. 850-860 ◽  
Author(s):  
Waleed A.I. Khallaf ◽  
Basim A.S. Messiha ◽  
Amira M.H. Abo-Youssef ◽  
Nesrine S. El-Sayed
Keyword(s):  
Nitric Oxide ◽  
Cognitive Impairment ◽  
Angiotensin Ii ◽  
Nitrosative Stress ◽  
Histopathological Examination ◽  
Control Group ◽  
Angiotensin Ii Receptor Blocker ◽  
Protective Effects ◽  
Brain Levels ◽  
Tnf Α

Angiotensin II has pro-inflammatory and pro-oxidant potentials. We investigated the possible protective effects of the Angiotensin II receptor blocker telmisartan, compared with the superoxide scavenger tempol, on lipopolysaccharide (LPS)-induced cognitive decline and amyloidogenesis. Briefly, mice were allocated into a normal control group, an LPS control group, a tempol treatment group, and 2 telmisartan treatment groups. A behavioral study was conducted followed by a biochemical study via assessment of brain levels of beta amyloid (Aβ) and brain-derived neurotropic factor (BDNF) as amyloidogenesis and neuroplasticity markers, tumor necrosis factor alpha (TNF-α), nitric oxide end products (NOx), neuronal and inducible nitric oxide synthase (nNOS and iNOS) as inflammatory markers, and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH), and nitrotyrosine (NT) as oxido-nitrosative stress markers. Finally, histopathological examination of cerebral cortex, hippocampus, and cerebellum sections was performed using routine and special Congo red stains. Tempol and telmisartan improved cognition, decreased brain Aβ deposition and BDNF depletion, decreased TNF-α, NOx, nNOS, iNOS, MDA, and NT brain levels, and increased brain SOD and GSH contents, parallel to confirmatory histopathological evidences. In conclusion, tempol and telmisartan are promising drugs in managing cognitive impairment and amyloidogenesis, at least via upregulation of BDNF with inhibition of neuroinflammation and oxido-nitrosative stress.

Ameliorative, Antioxidant and Immunomodulatory Potential of Vitamin D on Aminoglycoside Induced Acute Kidney Injury in Wistar Rats

2021 ◽  
Author(s):  
Neeraj Thakur ◽  
S.K. Shukla ◽  
A.H. Ahmad ◽  
N.S. Jadon ◽  
J.L. Singh ◽  
...  
Keyword(s):  
Vitamin D ◽  
Acute Kidney Injury ◽  
Histopathological Examination ◽  
Kidney Injury ◽  
Serum Biochemistry ◽  
Mean Value ◽  
Tnf Α ◽  
The Mean ◽  
Group B ◽  
Immunomodulatory Potential

Background: Acute kidney injury causes an abrupt decline in renal filtration and affects animals in a similar way to humans. Diagnosis can be made based on urinalysis, serum biochemistry and various biomarkers. The present study was conducted to evaluate the ameliorative, antioxidant and immunomodulatory potential of vitamin D in rats induced with acute kidney injury. Methods: In the present study, group A rats were taken as healthy control, group B rats were given gentamicin @ 100 mg/kg BW intraperitoneally for 8 days and were considered as disease control and group C rats were treated with Vitamin D @ 0.4 µg/kg/day subcutaneously for 8 days along with intraperitoneal gentamicin injection. Reduced glutathione (GSH), lipid peroxide (LPO), catalase and superoxide dismutase (SOD) were estimated in erythrocytes on day 0, 4 and 8. Tumor necrosis factor alpha (TNF α) and interleukin 10 (IL 10) were also estimated along with urine and serum biochemistry on day 0, 4 and 8. Kidney tissue samples were collected on day 8 for histopathological examination. Result: The mean values of GSH, catalase and SOD were significantly (P less than 0.05) higher whereas the mean value of LPO was significantly (P less than 0.05) lower in group C compared to group B on day 4 and 8. On day 4 and 8, the mean value of TNF α was significantly (P less than 0.05) lower, while the mean value of IL-10 was significantly (P less than 0.05) higher in rats treated with vitamin D as compared to disease control. Histopathological examination along with urine and serum biochemistry revealed protective efficacy of vitamin D in acute kidney injury. Based on the findings of the present study, it is concluded that vitamin D is having ameliorative efficacy along with antioxidant and immunomodulatory potential in case of gentamicin induced acute kidney injury in Wistar rats. However, detailed studies are required to explore the therapeutic potential of vitamin D in clinical cases of kidney diseases.

Sign in / Sign up

Export Citation Format

Share Document