scholarly journals Protective Effect of Astaxanthin on Ochratoxin A-Induced Kidney Injury to Mice by Regulating Oxidative Stress-Related NRF2/KEAP1 Pathway

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1386 ◽  
Author(s):  
Lin Li ◽  
Yueli Chen ◽  
Danyang Jiao ◽  
Shuhua Yang ◽  
Lin Li ◽  
...  

The present study aimed to investigate the effects of astaxanthin (ASX) on ochratoxin A (OTA)-induced renal oxidative stress and its mechanism of action. Serum kidney markers, histomorphology, ultrastructural observation, and oxidative stress indicators were assessed. Meanwhile, quantitative real-time reverse transcription PCR and western blotting detection of NRF2 (encoding nuclear factor, erythroid 2 like) and members of the NRF2/KEAP1 signaling pathway (KEAP1 (encoding Kelch-like ECH-associated protein), NQO1 (encoding NAD(P)H quinone dehydrogenase), HO-1 (encoding heme oxygenase 1), γ-GCS (gamma-glutamylcysteine synthetase), and GSH-Px (glutathione peroxidase 1)) were performed. Compared with the control group, the OTA-treated group showed significantly increased levels of serum UA (uric acid) and BUN (blood urea nitrogen), tubular epithelial cells were swollen and degenerated, and the levels of antioxidant enzymes decreased significantly, and the expression of NRF2 (cytoplasm), NQO1, HO-1, γ-GCS, and GSH-Px decreased significantly. More importantly, after ASX pretreatment, compared with the OTA group, serum markers were decreased, epithelial cells appeared normal; the expression of antioxidant enzymes increased significantly, NQO1, HO-1, γ-GCS and GSH-Px levels increased significantly, and ASX promoted the transfer of NRF2 from the cytoplasm to the nucleus. These results highlight the protective ability of ASX in renal injury caused by OTA exposure, and provide theoretical support for ASX’s role in other mycotoxin-induced damage.

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Esmaeel Babaeenezhad ◽  
Forouzan Hadipour Moradi ◽  
Sobhan Rahimi Monfared ◽  
Mohammad Davood Fattahi ◽  
Maryam Nasri ◽  
...  

Clinical application of gentamicin (GM) is well known to be associated with the development of acute kidney injury (AKI). This study was the first to investigate the possible protective effects of D-limonene (D-lim) on AKI following GM administration in rats. 32 rats arranged in four groups ( n = 8 ): (1) the control group received saline intraperitoneally (0.5 ml/day) and orally (0.5 ml/day), (2) the D-lim group received D-lim (100 mg/kg) orally and saline (0.5 ml/day) intraperitoneally, (3) the GM group received GM (100 mg/kg/day) intraperitoneally and saline (0.5 ml/day) orally, and (4) the treated group received intraperitoneal GM (100 mg/kg) and oral D-lim (100 mg/kg). All treatments were performed daily for 12 consecutive days. Results revealed that D-lim ameliorated GM-induced AKI, oxidative stress, mitochondrial apoptosis, and inflammation. D-lim showed nephroprotective effects as reflected by the decrease in serum urea and creatinine and improvement of renal histopathological changes. D-lim alleviated GM-induced oxidative stress by increasing the activities of renal catalase, serum and renal glutathione peroxidase, and renal superoxide dismutase and decreasing renal malondialdehyde and serum nitric oxide levels. Intriguingly, D-lim suppressed mitochondrial apoptosis by considerably downregulating Bax and caspase-3 (Casp-3) mRNA and protein expressions and markedly enhancing Bcl2 mRNA and protein expressions. Furthermore, D-lim significantly decreases GM-induced inflammatory response through downregulation of NF-κB, IL-6, and TNF-α mRNA and/or protein expressions and decrease in renal myeloperoxidase activity. Finally, D-lim remarkably downregulated PCNA protein expression in the treated group compared with the GM group. In brief, this study showed that D-lim alleviated AKI following GM administration in rats, partially through its antioxidant, anti-inflammatory, and antiapoptotic activities as well as downregulation of PCNA expression.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Milan Ivanov ◽  
Zoran Miloradovic ◽  
Nevena Mihailovic-Stanojevic ◽  
Djurdjica Jovovic ◽  
Danijela Karanovic ◽  
...  

Abstract Background and Aims Renal ischemia–reperfusion (RIR) injury is one of the factors in the development of acute kidney injury (AKI). AKI is multifactorially caused, but the mechanism of pathogenesis and development of this disease is still incompletely defined. AKI is characterized by the sudden appearance, rapid progression of disease and very uncertain and often fatal outcome. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the breakdown of heme to biliverdin, carbon monoxide, and iron. HO-1 is now recognized as a protection factor in acute kidney injury. The aim of this study was to determine the effect of preconditioning with hyperbaric oxygen (HBO) on HO-1 expression in kidney tissue and kidney function in spontaneously hypertensive rats (SHR) during kidney ischemia–reperfusion injury. Method An experiment was performed in anesthetized, adult six-month-old male SHR. The right kidney was removed and the renal ischemia was performed by clamping the left renal artery for 40 minutes. SHR were randomly selected in three experimental groups: sham operated group (SHAM; n=7); AKI control group (AKI; n=9); and AKI group with HBO (AKI+HBO; n=9). Treated group were placed into experimental HBO chambers and exposed to pure oxygen, twice a day (in a 12 hour period, 8AM and 8 PM) for two consecutive days in the following manner: 10 minutes slow compression, 2.026 bar for 60 minutes, 10 minutes slow decompression. Mean arterial pressure (MAP) and HO-1 expression in kidney tissue were measured 24h after reperfusion. Clearance of creatinine (CCr), urea (CUr) and phosphate (CPh) were calculated 24h after reperfusion. Results After AKI induction reduction of blood pressure was recorded in both groups with AKI. Preconditioning with HBO significantly improved kidney function in rats with AKI compared to control group. HO-1 expression in kidney tissue was significantly higher in the treated group (p<0,01) compared to SHAM and AKI control group. Conclusion Our results suggest that HBO treatment improves kidney function in the AKI+HBO vs. AKI control group. This implies that increased level of HO-1 due to preconditioning with hyperbaric oxygen may have beneficial effects on kidney function, and potentially protective effect in an ischemic model of AKI with hypertension.


Author(s):  
Chandresh Shyam ◽  
Devinder K Dhawan ◽  
Vijayta D Chadha

 Objectives: The present study was undertaken to investigate the possible protective potential of wheatgrass extract against radiation-induced toxicity in peripheral lymphocytes of rats exposed to a fractionated dose of X-rays.Methods: Effects of the X-irradiation with and without wheatgrass were studied on various parameters in peripheral lymphocytes including antioxidant defense system and apoptosis. Male Sprague-Dawley rats were divided into four different groups: Normal control group, X-ray-irradiated group (21 Gy over a span of 7 days), wheatgrass-treated group (80 mg/100 g bodyweight for 2 weeks), and X-rays-irradiated + wheatgrass-treated group. All the biochemical indices which included lipid peroxidation (LPO), reduced glutathione, reactive oxygen species (ROS), and activities of antioxidant enzymes were investigated in lymphocytes. Terminal deoxynucleotidyl transferase dUTP nick-end labeling assay was carried out to assess the apoptosis in lymphocytes following whole-body X-irradiation.Results: Whole-body X-irradiation to rats resulted in significant increase in LPO with concomitant depression of antioxidant enzymes activities, namely, superoxide dismutase, catalase, and glutathione peroxidise (GPx) in lymphocytes. Further, the present study witnessed a significant increase in the number of apoptotic lymphocytes in the X-irradiated animals. However, wheatgrass supplementation lowered the LPO levels, restored cellular antioxidant status, and provided significant protection against radiation-induced apoptosis.Conclusions: Based on these observations, the present study suggests that wheatgrass extract has the potential to be used as an effective radioprotectant against radiation-induced oxidative stress and apoptosis in peripheral lymphocytes of whole-body X-ray-exposed rats.


2019 ◽  
Vol 6 (1) ◽  
pp. 41-47
Author(s):  
Hala S. Bash ◽  
Ihsan S. Rabeea

Background: Cisplatin is an anticancer drug used in the management of solid tumors, however, dose-related nephrotoxicity is one of its major problems. Agents having antioxidants, antiinflammatory and/or antiapoptotic activities may thus represent potential therapeutic options to avoid cisplatin-induced nephrotoxicity. Among these agents, coenzyme Q10 has several pharmacological properties including antioxidant, anti-inflammatory and/or anti-apoptotic effects. Objective: The current study aimed to examine whether coenzyme Q10 could attenuate cisplatininduced nephrotoxicity or not. Methods: 24 adult rats were randomly separated into three groups (8 rats per group). The first one was the control group, rats receiving vehicle (olive oil) intraperitoneally. The second group was Cisplatin treated group, rats were receiving 13 mg/kg of Cisplatin intraperitoneally as a single dose. The third group (Cisplatin + Coenzyme Q10), rats were receiving 13 mg/kg as a single intraperitoneal dose of Cisplatin and coenzyme Q10 daily for six consecutive days (10 mg/kg intraperitoneally). Results: Cisplatin caused significant increases in serum creatinine and severe histological lesions. Cisplatin treated group also showed a significant elevation in renal malondialdehyde concentration as a marker of oxidative stress; renal tumor necrosis factor-alpha concentration as a marker of inflammation; and Kidney injury molecule -1 concentration. Coenzyme Q10 significantly attenuated cisplatininduced nephrotoxicity through lowering serum creatinine and improving nephrotoxicity histological scores. Coenzyme Q10 also significantly reduced the renal concentration of MDA, TNF-α and KIM-1 relative to cisplatin treated group. Conclusions: Coenzyme Q10 has a potential nephroprotective effect against cisplatin-induced nephrotoxicity that was demonstrated by biochemical and histopathological analysis.


2021 ◽  
pp. 096032712110099
Author(s):  
F Sahindokuyucu-Kocasari ◽  
Y Akyol ◽  
O Ozmen ◽  
SB Erdemli-Kose ◽  
S Garli

Methotrexate (MTX) is a drug used in the treatment of various types of cancer and inflammatory diseases, but its clinical use has been restricted due to its toxicity. Apigenin (API) is an effective flavonoid with antioxidant and anti-inflammatory properties. The aim of this study was to determine the protective effect of API against MTX-induced liver and kidney toxicity. Four groups with 12 male mice each were used. The control and API groups were received 0.9% saline (ip) and API (3 mg/kg ip) for 4 days, respectively. The MTX group were given a single dose of MTX (20 mg/kg ip) on the fourth day. The MTX + API group were administered API for 7 days and then MTX on fourth day. Blood, liver and kidney were collected to evaluate tissue injury markers, oxidative stress biomarkers, and histopathological and immunohistochemical assessments. In MTX-treated group, significant increases in aminotransferases activities, creatinine and malondialdehyde (MDA) levels and significant decreases in catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase1 (SOD1) activities and glutathione (GSH) levels were determined compared to the control group. Furthermore, histopathological changes and significant increases in caspase-3, C-reactive protein (CRP), granulocyte colony-stimulating factor (G-CSF), and inducible nitric oxide synthase (iNOS) expressions were detected in both liver and kidney tissues of MTX-treated mice. Pretreatment with API alleviates liver and kidney toxicity by attenuating oxidative stress and tissue injury markers, histopathological alterations, and apoptosis and inflammation. These results suggest that API has a protective effect against oxidative stress and liver-kidney toxicity induced by MTX.


2020 ◽  
Vol 8 (3) ◽  
pp. 239-254 ◽  
Author(s):  
Reza Mahjub ◽  
Farzane K. Najafabadi ◽  
Narges Dehkhodaei ◽  
Nejat Kheiripour ◽  
Amir N. Ahmadabadi ◽  
...  

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.


2020 ◽  
Vol 70 (2) ◽  
pp. 227-237
Author(s):  
Eda Güneş

Abstract The aim of the this study was to evaluate the effects of fresh, dried and freeze-dried Centaurea depressa M. Bieb. (Asteraceae) on the oxidant and antioxidant status of the model organism D. melanogaster Meigen (Diptera: Drosophilidae) experimentally. The study was carried out from 2016 to 2019, and plant leaf extracts (0-50 mg/l) were added to insect standard artificial diets. The total protein, protein carbonyl content and glutathione-S-transferase, superoxide dismutase and catalase activities were quantified at the insect’s third larval stage. Our data showed that protein carbonyl content varied from 2.70 nmol/mg protein in the control group to 59.11 nmol/mg protein in the group fed with fresh leaf extract signifying induction of oxidative stress. All extracts increased the levels of all antioxidant enzymes and decreased the amounts of total protein. Meanwhile, the group fed with the freeze-dried extract showed no significant difference in the levels of total protein and protein carbonyl content except at the 50 mg/l concentration of the extract. Moreover, this group had superoxide dismutase and catalase activities 4 to 5 times higher than in the control group. In conclusion, induction of oxidative stress indicates that the fresh form of C. depressa leaves may have potential as a natural pesticide, whereas induction of endogenous antioxidant enzymes by the freeze-dried extract suggest its potential as an antioxidant.


Zygote ◽  
2019 ◽  
Vol 27 (6) ◽  
pp. 432-435
Author(s):  
Thais Rose dos Santos Hamilton ◽  
Gabriela Esteves Duarte ◽  
José Antonio Visintin ◽  
Mayra Elena Ortiz D’Ávila Assumpção

SummaryLong-term heat stress (HS) induced by testicular insulation generates oxidative stress (OS) on the testicular environment; consequently activating antioxidant enzymes such as superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx). The aim of this work was to immunolocalize antioxidant enzymes present in different cells within the seminiferous tubule when rams were submitted to HS. Rams were divided into control (n = 6) and treated group (n = 6), comprising rams subjected to testicular insulation for 240 h. After the testicular insulation period, rams were subjected to orchiectomy. Testicular fragments were submitted to immunohistochemistry for staining against SOD, GR and GPx enzymes. We observed immunolocalization of GPx in more cell types of the testis after HS and when compared with other enzymes. In conclusion, GPx is the main antioxidant enzyme identified in testicular cells in an attempt to maintain oxidative balance when HS occurs.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao-lei Wang ◽  
Tuo Zhang ◽  
Liu-hua Hu ◽  
Shi-qun Sun ◽  
Wei-feng Zhang ◽  
...  

Statins are a promising new strategy to prevent contrast-induced acute kidney injury (CI-AKI). In this study we compared the ameliorative effect of different statins in a rat model of CI-AKI. Sprague-Dawley rats were divided into five groups: control group; CI-AKI group; CI-AKI + rosuvastatin group (10 mg/kg/day); CI-AKI + simvastatin group (80 mg/kg/day); and CI-AKI + atorvastatin group (20 mg/kg/day). CI-AKI was induced by dehydration for 72 hours, followed by furosemide intramuscular injection 20 minutes before low-osmolar contrast media (CM) intravenous injection. Statins were administered by oral gavage once daily for 3 consecutive days before CM injection and once 4 hours after CM injection. Rats were sacrificed 24 hours after CM injection, and renal function, kidney histopathology, nitric oxide (NO) metabolites, and markers of oxidative stress, inflammation, and apoptosis were evaluated. The results showed that atorvastatin and rosuvastatin but not simvastatin ameliorated CM-induced serum creatinine elevation and histopathological alterations. Atorvastatin and rosuvastatin showed similar effectiveness against CM-induced oxidative stress, but simvastatin was less effective. Atorvastatin was most effective against NO system dysfunction and cell apoptosis, whereas rosuvastatin was most effective against inflammation. Our findings indicate that statins exhibit differential effects in preventing CI-AKI when given at equivalent lipid-lowering doses.


2010 ◽  
Vol 25 (3) ◽  
pp. 304-310 ◽  
Author(s):  
Cleber Rosito Pinto Kruel ◽  
Luis Felipe Ribeiro Pinto ◽  
Tania Cristina Moita Blanco ◽  
Theresa Christina Barja-Fidalgo ◽  
Levi Lourenzo Melo ◽  
...  

PURPOSE: To study the expression of heme-oxygenase-1 (HO-1), an enzyme induced by oxidative stress, in specimens obtained from an experimental model in rats that evaluated the role of gastric and duodenal reflux in esophageal carcinogenesis. METHODS: Esophageal specimens embedded in paraffin obtained from different experimental groups of rats were used for immunohistochemistry analysis of HO-1 expression. The rats had been divided into the following groups and were killed after 22 weeks: (1) cardioplasty to induce acid reflux; (2) esophagoduodenal anastomosis to induce duodenal reflux; (3) no treatment; (4) cardioplasty + diethylnitrosamine (DEN); (5) esophagoduodenal anastomosis + DEN; and (6) DEN. The study sample comprised 3 specimens from each group with the most severe histopathological lesions found on each study branch. RESULTS: The expression of HO-1 was seen only in rat specimens submitted to esophagoduodenal anastomosis (Groups 2 and 5), and the analysis of mean fluorescence intensity revealed a significant increase of HO-1 expression (4.8 and 4.6 fold, respectively) when compared with the control group (Group 3) (p<0.05). The main target for HO-1 induction was the inflammatory cells inside the tumor or in subepithelial areas. Rats exposed to gastric reflux had no HO-1 expression. CONCLUSION: Reflux esophagitis induced by reflux of duodenal contents, which provoked considerable oxidative stress, may play an important role in esophageal carcinogenesis. Acid reflux did not induce oxidative stress in this experimental model.


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