scholarly journals Formononetin Upregulates Nrf2/HO-1 Signaling and Prevents Oxidative Stress, Inflammation, and Kidney Injury in Methotrexate-Induced Rats

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 430 ◽  
Author(s):  
Saleem H. Aladaileh ◽  
Omnia E. Hussein ◽  
Mohammad H. Abukhalil ◽  
Sultan A. M. Saghir ◽  
May Bin-Jumah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Caspase 9 ◽  
Tnf Α ◽  
Cox 2 ◽  
Kidney Injury Molecule 1

Acute kidney injury (AKI) is a serious complication of methotrexate (MTX). This study explored the protective effect of the isoflavone formononetin (FN) against MTX nephrotoxicity with an emphasis on oxidative stress, inflammation, and nuclear factor (erythroid-derived 2)-like 2/heme oxygenase 1 (Nrf2/HO-1) signaling. Rats received FN (10, 20, and 40 mg/kg) for 10 days and a single dose of MTX on day 7. MTX induced kidney injury was characterized by increased serum creatinine and urea, kidney injury molecule-1 (Kim-1), and several histological alterations. FN ameliorated kidney function and inhibited the renal tissue injury induced by MTX. Reactive oxygen species (ROS), lipid peroxidation (LPO), nitric oxide, and 8-Oxo-2′-deoxyguanosine were increased, whereas antioxidant defenses were diminished in the kidney of MTX-administered rats. In addition, MTX upregulated renal iNOS, COX-2, TNF-α, IL-1β, Bax, caspase-9, and caspase-3, and decreased Bcl-2, Nrf2, and HO-1. FN suppressed oxidative stress, LPO, DNA damage, iNOS, COX-2, proinflammatory cytokines, and apoptosis, and boosted Bcl-2, antioxidants, and Nrf2/HO-1 signaling in MTX-administered rats. In conclusion, FN prevents MTX-induced AKI by activating Nrf2/HO-1 signaling and attenuates oxidative damage and inflammation. Thus, FN may represent an effective adjuvant that can prevent MTX nephrotoxicity, pending further mechanistic studies.

scholarly journals Curcumin Ameliorates Lead-Induced Hepatotoxicity by Suppressing Oxidative Stress and Inflammation, and Modulating Akt/GSK-3β Signaling Pathway

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 703 ◽  
Author(s):  
Ahlam Alhusaini ◽  
Laila Fadda ◽  
Iman H. Hasan ◽  
Enas Zakaria ◽  
Abeer M. Alenazi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Tissue Injury ◽  
Elevated Serum ◽  
Antioxidant Defenses ◽  
Exact Role ◽  
Toxic Heavy Metal ◽  
Tnf Α ◽  
Gsk 3Β

Lead (Pb) is a toxic heavy metal pollutant with adverse effects on the liver and other body organs. Curcumin (CUR) is the principal curcuminoid of turmeric and possesses strong antioxidant and anti-inflammatory activities. This study explored the protective effect of CUR on Pb hepatotoxicity with an emphasis on oxidative stress, inflammation and Akt/GSK-3β signaling. Rats received lead acetate and CUR and/or ascorbic acid (AA) for seven days and samples were collected for analyses. Pb(II) induced liver injury manifested by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as histopathological alterations, including massive hepatocyte degeneration and increased collagen deposition. Lipid peroxidation, nitric oxide, TNF-α and DNA fragmentation were increased, whereas antioxidant defenses were diminished in the liver of Pb(II)-intoxicated rats. Pb(II) increased hepatic NF-κB and JNK phosphorylation and caspase-3 cleavage, whereas Akt and GSK-3β phosphorylation was decreased. CUR and/or AA ameliorated liver function, prevented tissue injury, and suppressed oxidative stress, DNA damage, NF-κB, JNK and caspase-3. In addition, CUR and/or AA activated Akt and inhibited GSK-3β in Pb(II)-induced rats. In conclusion, CUR prevents Pb(II) hepatotoxicity via attenuation of oxidative injury and inflammation, activation of Akt and inhibition of GSK-3β. However, further studies scrutinizing the exact role of Akt/GSK-3β signaling are recommended.

scholarly journals Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5717 ◽  
Author(s):  
Jung-Yeon Kim ◽  
Jaechan Leem ◽  
Kwan-Kyu Park
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Therapeutic Option ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Kidney Injury ◽  
Heme Oxygenase 1 ◽  
Anti Inflammatory

Sepsis is the major cause of acute kidney injury (AKI) in severely ill patients, but only limited therapeutic options are available. During sepsis, lipopolysaccharide (LPS), an endotoxin derived from bacteria, activates signaling cascades involved in inflammatory responses and tissue injury. Apamin is a component of bee venom and has been shown to exert antioxidative, antiapoptotic, and anti-inflammatory activities. However, the effect of apamin on LPS-induced AKI has not been elucidated. Here, we show that apamin treatment significantly ameliorated renal dysfunction and histological injury, especially tubular injury, in LPS-injected mice. Apamin also suppressed LPS-induced oxidative stress through modulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and heme oxygenase-1. Moreover, tubular cell apoptosis with caspase-3 activation in LPS-injected mice was significantly attenuated by apamin. Apamin also inhibited cytokine production and immune cell accumulation, suppressed toll-like receptor 4 pathway, and downregulated vascular adhesion molecules. Taken together, these results suggest that apamin ameliorates LPS-induced renal injury through inhibiting oxidative stress, apoptosis of tubular epithelial cells, and inflammation. Apamin might be a potential therapeutic option for septic AKI.

scholarly journals Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096399
Author(s):  
Guixiang Liao ◽  
Zhihong Zhao ◽  
Hongli Yang ◽  
Xiaming Li
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Interleukin 1 ◽  
Dependent Manner ◽  
Ht22 Cells ◽  
Tnf Α ◽  
Radiation Induced ◽  
Cox 2

Objective Sirtuin 3 (SIRT3) plays a vital role in regulating oxidative stress in tissue injury. The aim of this study was to evaluate the radioprotective effects of honokiol (HKL) in a zebrafish model of radiation-induced brain injury and in HT22 cells. Methods The levels of reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were evaluated in the zebrafish brain and HT22 cells. The expression levels of SIRT3 and cyclooxygenase-2 (COX-2) were measured using western blot assays and real-time polymerase chain reaction (RT-PCR). Results HKL treatment attenuated the levels of ROS, TNF-α, and IL-1β in both the in vivo and in vitro models of irradiation injury. Furthermore, HKL treatment increased the expression of SIRT3 and decreased the expression of COX-2. The radioprotective effects of HKL were achieved via SIRT3 activation. Conclusions HKL attenuated oxidative stress and pro-inflammatory responses in a SIRT3-dependent manner in radiation-induced brain injury.

scholarly journals Tubulointerstitial Biomarkers for Diabetic Nephropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Bancha Satirapoj
Keyword(s):  
Diabetic Nephropathy ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Cardiovascular Complications ◽  
Renal Tissue ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Potential Applications ◽  
Novel Biomarkers ◽  
Kidney Injury Molecule 1

Patients with diabetic nephropathy have a higher risk of mortality, mostly from cardiovascular complications. Standard biomarkers including serum creatinine, estimated glomerular filtration rate, and albuminuria are imprecise, do not directly measure renal tissue injury, and are relatively insensitive to small changes in renal function. Thus, availability of novel biomarkers that are sensitive, specific, and precise as well as able to detect kidney injury and predict clinically significant outcomes would be widely useful in diabetic nephropathy. Novel biomarkers of the processes that induce tubulointerstitial changes may ultimately prove to better predict renal progression and prognosis in type 2 diabetes. Recently, certain biomarkers, which were initially identified in acute kidney injury, also have been reported to confer value in evaluating patients with chronic kidney disease. Biomarkers such as cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), angiotensinogen, periostin, and monocyte chemoattractant protein-1 (MCP-1) reflect tubular injury. In this article, we focused on the potential applications of these biomarkers in diabetic nephropathy.

scholarly journals Sulforaphane Attenuates Contrast-Induced Nephropathy in Rats via Nrf2/HO-1 Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Zhihong Zhao ◽  
Guixiang Liao ◽  
Qin Zhou ◽  
Daoyuan Lv ◽  
Harry Holthfer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Model ◽  
Renal Tissue ◽  
Antioxidant Defenses ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Contrast Induced Nephropathy ◽  
Hk2 Cells

Background. Oxidative stress plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of this study was to investigate the antioxidant effects of sulforaphane (SFN) in a rat model of CIN and a cell model of oxidative stress in HK2 cells.Methods. Rats were randomized into four groups (n=6per group): control group, Ioversol group (Ioversol-induced CIN), Ioversol + SFN group (CIN rats pretreated with SFN), and SFN group (rats treated with SFN). Renal function tests, malondialdehyde (MDA), and reactive oxygen species (ROS) were measured. Western blot, real-time polymerase chain reaction analysis, and immunohistochemical analysis were performed for nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1) detection.Results. Serum blood urea nitrogen (BUN), creatinine, and renal tissue MDA were increased after contrast exposure. Serum BUN, creatinine, and renal tissue MDA were decreased in the Ioversol + SFN group as compared with those in the Ioversol group. SFN increased the expression of Nrf2 and HO-1 in CIN rats and in Ioversol-induced injury HK2 cells. SFN increased cell viability and attenuated ROS level in vitro.Conclusions. SFN attenuates experimental CIN in vitro and in vivo. This effect is suggested to activate the Nrf2 antioxidant defenses pathway.

Amelioration of Cisplatin-induced renal inflammation by Recombinant Human Golimumab in Mice

2021 ◽  
Vol 22 ◽  
Author(s):  
Vishal Pavitrakar ◽  
Rustom Mody ◽  
Selvan Ravindran
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Significant Rise ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Study Results ◽  
Kidney Injury Molecule 1 ◽  
Tgf Β1

Background: One of the most commonly used anti-cancer agents, Cisplatin (CDDP) often causes nephrotoxicity by eliciting inflammation and oxidative stress. Golimumab, an anti-TNF biologic, is prescribed for the management of numerous inflammatory ailments like psoriatic and rheumatoid arthritis ulcerative colitis, and ankylosing spondylitis. Objective: Current study has explored the effects of anti-TNF biologics golimumab on mice due to cisplatin-induced nephrotoxicity. Method: Renal toxicity was caused by administration of single cisplatin injection at 25 mg/kg by intraperitoneal (i/p) route. Golimumab (24 mg/kg, s.c.) was administered consecutively for 7 days. The parameters such as renal functions, oxidative stress, inflammation, and renal damage were evaluated on the 7th day of experiments. Results: Cisplatin administration caused nephrotoxicity as shown by a significant elevation of various parameters viz; serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), urea nitrogen (BUN), and cystatin C. There was a significant rise in urinary clusterin, kidney injury molecule 1 (KIM-1), and β-N-acetylglucosaminidase (NAG) concentrations in the animals treated with cisplatin-. The markers of oxidative stress (malondialdehyde, reduced glutathione, and catalase), inflammation (IL-6, TNF-α, IL-10, IL-1β, MCP-1, ICAM-1, and TGF-β1), and apoptosis (caspase-3) were also altered in serum and/or kidneys of cisplatin animals. Further, cisplatin-caused histopathological changes in proximal tubular cells as observed in the H&E staining of renal tissue. Golimumab treatment reduced all markers of kidney injury and attenuated cell death. Golimumab significantly reduced inflammatory cytokines TNFα, IL- 6, MCP-1, IL- 1β, ICAM-1, and TGF-β1 and increased anti-inflammatory cytokine IL-10 in cisplatin-intoxicated mice. Conclusion: The study results suggest that golimumab prevented nephrotoxicity induced by cisplatin- through inhibition of oxidative stress, apoptotic cell death inflammatory response, thus improving renal function.

scholarly journals Accelerated receptor shedding inhibits kidney injury molecule-1 (KIM-1)-mediated efferocytosis

2014 ◽  
Vol 307 (2) ◽  
pp. F205-F221 ◽  
Author(s):  
Rushi Gandhi ◽  
James Yi ◽  
Jihyen Ha ◽  
Hang Shi ◽  
Ola Ismail ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Kidney Injury ◽  
Apoptotic Cells ◽  
Cellular Injury ◽  
Dependent Manner ◽  
Extracellular Milieu ◽  
Tnf Α ◽  
Receptor Shedding ◽  
Kidney Injury Molecule 1 ◽  
Dose Dependent

Efficient clearance of apoptotic cells (efferocytosis) prevents inflammation and permits repair following tissue injury. Kidney injury molecule-1 (KIM-1) is a receptor for phosphatidylserine, an “eat-me” signal exposed on the surface of apoptotic cells that marks them for phagocytic clearance. KIM-1 is upregulated on proximal tubule epithelial cells (PTECs) during ischemic acute kidney injury (AKI), enabling efferocytosis by surviving PTECs. KIM-1 is spontaneously cleaved at its ectodomain region to generate a soluble fragment that serves a sensitive and specific biomarker for AKI, but the biological relevance of KIM-1 shedding is unknown. Here, we sought to determine how KIM-1 shedding might regulate efferocytosis. Using cells that endogenously and exogenously express KIM-1, we found that hydrogen peroxide-mediated oxidative injury or PMA treatment accelerated KIM-1 shedding in a dose-dependent manner. KIM-1 shedding was also accelerated when apoptotic cells were added. Accelerated shedding or the presence of excess soluble KIM-1 in the extracellular milieu significantly inhibited efferocytosis. We also identified that TNF-α-converting enzyme (TACE or ADAM17) mediates both the spontaneous and PMA-accelerated shedding of KIM-1. While accelerated shedding inhibited efferocytosis, we found that spontaneous KIM-1 cleavage does not affect the phagocytic efficiency of PTECs. Our results suggest that KIM-1 shedding is accelerated by worsening cellular injury, and excess soluble KIM-1 competitively inhibits efferocytosis. These findings may be important in AKI when there is severe cellular injury.

TLR2 and TLR4 play opposite role in autophagy associated with cisplatin-induced acute kidney injury

2018 ◽  
Vol 132 (16) ◽  
pp. 1725-1739 ◽  
Author(s):  
Magaiver Andrade-Silva ◽  
Marcos Antonio Cenedeze ◽  
Luiz Augusto Perandini ◽  
Raphael José Ferreira Felizardo ◽  
Ingrid Kazue Mizuno Watanabe ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Protective Function ◽  
Autophagy Induction ◽  
Lower Expression

Acute kidney injury (AKI) is considered an inflammatory disease in which toll-like receptors (TLRs) signaling pathways play an important role. The activation of TLRs results in production of several inflammatory cytokines leading to further renal damage. In contrast, TLRs are key players on autophagy induction, which is associated with a protective function on cisplatin-induced AKI. Hence, the present study aimed to evaluate the specific participation of TLR2 and TLR4 molecules on the development of cisplatin-induced AKI. Complementarily, we also investigated the link between TLRs and heme oxygenase-1 (HO-1), a promisor cytoprotective molecule. First, we observed that only the absence of TLR2 but not TLR4 in mice exacerbated the renal dysfunction, tissue injury and mortality rate, even under an immunologically privileged microenvironment. Second, we demonstrated that TLR2 knockout (KO) mice presented lower expression of autophagy-associated markers when compared with TLR4 KO animals. Similar parameter was confirmed in vitro, using tubular epithelial cells derived from both KO mice. To test the cross-talking between HO-1 and TLRs, hemin (an HO-1 internal inducer) was administrated in cisplatin-treated TLR2 and TLR4 KO mice and it was detected an improvement in the global renal tissue parameters. However, this protection was less evident at TLR2 KO mice. In summary, we documented that TLR2 plays a protective role in cisplatin-induced AKI progression, in part, by a mechanism associated with autophagy up-regulation, considering that its interplay with HO-1 can promote renal tissue recover.

Pretreatment with Gallic Acid Mitigates Cyclophosphamide Induced Inflammation and Oxidative Stress in Mice

2021 ◽  
Vol 14 ◽  
Author(s):  
Saeed Baharmi ◽  
Heibatullah Kalantari ◽  
Mojtaba Kalantar ◽  
Mehdi Goudarzi ◽  
Esrafil Mansouri ◽  
...  
Keyword(s):  
Gallic Acid ◽  
Kidney Injury ◽  
Saline Group ◽  
Renal Tissue ◽  
Protective Agent ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Tnf Α ◽  
Group 5 ◽  
Kidney Injury Molecule 1 ◽  
Α Level

Background: Cyclophosphamide (CP) as an alkylating compound has been widely applied to treat cancer and autoimmune diseases. CP is observed to be nephrotoxic in humans and animals because it produces reactive oxygen species. Gallic acid (GA), a polyhydroxy phenolic compound, is reported to exhibit antioxidant and anti-inflammatory effects. Objective: The current research aimed at evaluating the GA effect on CP-related renal toxicity. Methods: In total, 35 male mice were assigned to 5 groups. Group1: receiving normal saline, group 2: CP group, receiving one CP injection (200 mg/kg; i.p.) on day 6. Groups 3 and 4: GA+CP, GA (10 and 30 mg/kg; p.o.; respectively) received through six consecutive days plus CP on the 6th day 2 hr after the last dose of GA, group 5: received GA (30 mg/kg; p.o.) for six consecutive days. Then on day 7, blood samples were collected for determining creatinine (Cr), serum kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and neutrophil gelatinase-associated lipocalin (NGAL) concentrations. Malondialdehyde (MDA), nitric oxide (NO) concentration, catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx) activities, and IL-1β, TNF-α levels were assessed in renal tissue. Results: CP administration significantly increases KIM-1, NGAL, Cr, BUN, MDA, NO, IL-1β, and TNF-α level. It also decreases GSH concentration, SOD, GPx, and CAT function. Pretreatment with GA prevented these changes. Histopathological assessments approved the GA protective effect. Conclusion: Our results showed that GA is possibly effective as a protective agent in cyclophosphamide-associated toxicities.

scholarly journals 15-Deoxy-Δ12,14-prostaglandin J2Exerts Antioxidant Effects While Exacerbating Inflammation in Mice Subjected to Ureteral Obstruction

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Line Nilsson ◽  
Fredrik Palm ◽  
Rikke Nørregaard
Keyword(s):  
Oxidative Stress ◽  
Ureteral Obstruction ◽  
Kidney Injury ◽  
Oxidative Stress Marker ◽  
Obstructive Nephropathy ◽  
Heme Oxygenase 1 ◽  
Downstream Target ◽  
High Concentrations ◽  
Kidney Injury Molecule 1 ◽  
And Oxidative Stress

Urinary obstruction is associated with inflammation and oxidative stress, leading to renal dysfunction. Previous studies have shown that 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2) has both antioxidant and anti-inflammatory effects. Using a unilateral ureteral obstruction (UUO) mouse model, we examined the effects of 15d-PGJ2on oxidative stress and inflammation in the kidney. Mice were subjected to UUO for 3 days and treated with 15d-PGJ2. Protein and RNA expression were examined using immunoblotting and qPCR. 15d-PGJ2increased NF-E2-related nuclear factor erythroid-2 (Nrf2) protein expression in response to UUO, and heme oxygenase 1 (HO-1), a downstream target of Nrf2, was induced by 15d-PGJ2. Additionally, 15d-PGJ2prevented protein carbonylation, a UUO-induced oxidative stress marker. Inflammation, measured by nuclear NF-κB, F4/80, and MCP-1, was increased in response to UUO and further increased by 15d-PGJ2. Renal injury was aggravated by 15d-PGJ2treatment as measured by kidney injury molecule-1 (KIM-1) and cortical caspase 3 content. No effect of 15d-PGJ2was observed on renal function in mice subjected to UUO. This study illustrates differentiated functioning of 15d-PGJ2on inflammation and oxidative stress in response to obstructive nephropathy. High concentrations of 15d-PGJ2protects against oxidative stress during 3-day UUO in mice; however, it aggravates the associated inflammation.

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