Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases

Background: Achilles tendinopathy, seen in athletes and manual labor workers, is an inflammatory condition characterized by chronic tendon pain. Owing to the toxicity that develops in various organs attributed to the use of anti–inflammatory drugs, there is a need for new therapeutic agents. Purpose: In the present study, the effects of quercetin (Que), the one that attracted the most attention of researchers studying this group of flavonoids, were investigated against collagenase–induced tendinopathy. Study Design: Controlled laboratory study. Methods: A total of 35 Sprague-Dawley rats were used in the study. Tendinopathy was created by injecting a single dose of collagenase (10 μL; 10 mg/mL) into the tendons of rats. Thirty minutes after the injection, Que was administered at doses of 25 or 50 mg/kg. Que administration was carried out for 7 days. Animals underwent a motility test at the end of the study. In addition, markers of oxidative stress, inflammation, apoptosis, and autophagy, as well as the expression levels of matrix metalloproteinases (MMPs 2, 3, 9, and 13), ICAM-1, and STAT3, were measured in tendon tissues with biochemical, molecular, and Western blot techniques. Results: The results showed that oxidative stress, inflammation, apoptosis, and autophagy were triggered by the injection of collagenase. In addition, MMPs, ICAM-1, and STAT3 were activated to participate in the development of tendinopathy. Que was found to reduce ICAM-1 levels in tendon tissue. Moreover, Que showed antioxidant, anti–inflammatory, antiapoptotic, and antiautophagic effects on tendons against tendinopathy. More important, Que suppressed the expression of MMPs in the tendon tissues. Conclusion: Que has protective properties against collagenase–induced tendon damage in rats. Clinical Relevance: We believe that with further study, Que may be shown to be an alternative treatment option for athletes or others who experience tendon injuries.

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Effect of liposome-encapsulated hemoglobin resuscitation on proteostasis in small intestinal epithelium after hemorrhagic shock

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00157.2016 ◽

2016 ◽

Vol 311 (1) ◽

pp. G180-G191 ◽

Cited By ~ 2

Author(s):

Geeta Rao ◽

Vivek R. Yadav ◽

Shanjana Awasthi ◽

Pamela R. Roberts ◽

Vibhudutta Awasthi

Keyword(s):

Oxidative Stress ◽

Hemorrhagic Shock ◽

Multiorgan Failure ◽

Sprague Dawley ◽

Barrier Dysfunction ◽

Protective Mechanisms ◽

Unfolded Protein ◽

Sprague Dawley Rats ◽

Markers Of Oxidative Stress ◽

Protein Response

Gut barrier dysfunction is the major trigger for multiorgan failure associated with hemorrhagic shock (HS). Although the molecular mediators responsible for this dysfunction are unclear, oxidative stress-induced disruption of proteostasis contributes to the gut pathology in HS. The objective of this study was to investigate whether resuscitation with nanoparticulate liposome-encapsulated hemoglobin (LEH) is able to restore the gut proteostatic mechanisms. Sprague-Dawley rats were recruited in four groups: control, HS, HS+LEH, and HS+saline. HS was induced by withdrawing 45% blood, and isovolemic LEH or saline was administered after 15 min of shock. The rats were euthanized at 6 h to collect plasma and ileum for measurement of the markers of oxidative stress, unfolded protein response (UPR), proteasome function, and autophagy. HS significantly increased the protein and lipid oxidation, trypsin-like proteasome activity, and plasma levels of IFNγ. These effects were prevented by LEH resuscitation. However, saline was not able to reduce protein oxidation and plasma IFNγ in hemorrhaged rats. Saline resuscitation also suppressed the markers of UPR and autophagy below the basal levels; the HS or LEH groups showed no effect on the UPR and autophagy. Histological analysis showed that LEH resuscitation significantly increased the villus height and thickness of the submucosal and muscularis layers compared with the HS and saline groups. Overall, the results showed that LEH resuscitation was effective in normalizing the indicators of proteostasis stress in ileal tissue. On the other hand, saline-resuscitated animals showed a decoupling of oxidative stress and cellular protective mechanisms.

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Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Cellular Physiology and Biochemistry ◽

10.1159/000452575 ◽

2016 ◽

Vol 40 (3-4) ◽

pp. 621-632 ◽

Cited By ~ 11

Author(s):

Qing Zhao ◽

Jianyong Yin ◽

Zeyuan Lu ◽

Yiwei Kong ◽

Guangyuan Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Caspase 3 ◽

Vehicle Group ◽

Control Group ◽

Therapeutic Effects ◽

Protective Effects ◽

Sprague Dawley ◽

Contrast Induced Nephropathy ◽

Sprague Dawley Rats ◽

Hk2 Cells

Background: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. Methods: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured. Results: Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H2O2-induced increases in ROS, apoptosis and caspase-3 levels. Conclusions: Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.

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Treatment with pyrrolidine dithiocarbamate improves proteinuria, oxidative stress, and glomerular hypertension in overload proteinuria

AJP Renal Physiology ◽

10.1152/ajprenal.90201.2008 ◽

2008 ◽

Vol 295 (5) ◽

pp. F1431-F1439 ◽

Cited By ~ 12

Author(s):

Edilia Tapia ◽

Dolores J. Sánchez-González ◽

Omar N. Medina-Campos ◽

Virgilia Soto ◽

Carmen Ávila-Casado ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Enzymes ◽

Inflammatory Cell ◽

Pyrrolidine Dithiocarbamate ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Glomerular Hypertension ◽

Markers Of Oxidative Stress ◽

Glomerular Hemodynamics ◽

Reduced Activity

We evaluated whether the blockade of the proinflammatory transcription factor NF-κB would modify the oxidative stress, inflammation, and structural and hemodynamic alterations found in the kidney as a result of massive proteinuria. Twenty male Sprague-Dawley rats were injected with 2 g of BSA intraperitoneally daily for 2 wk. Ten of them received in addition the inhibitor of NF-κB activation pyrrolidine dithiocarbamate (PDTC; 200 mg·kg−1·day−1 sc) and the rest received vehicle. Seven rats that received intraperitoneal saline were used as controls. Glomerular hemodynamics were studied after 14 days. Markers of oxidative stress (NF-κB subunit p65+ cells, 3-nitrotyrosine, and 4-hydroxynonenal), inflammation (cortical CD68+ cells and NOS-II), and afferent arteriole damage were assessed by immunohistochemistry and morphometry. Activity of antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase was evaluated in renal cortex and medulla. Albumin overload induced massive proteinuria, oxidative stress with reduced activity of antioxidant enzymes, NF-κB activation, inflammatory cell infiltration, a significant presence of proteinaceous casts, systemic and glomerular hypertension, as well as arteriolar remodeling. Treatment with PDTC prevented or improved all of these findings. In this model of nephrotic syndrome, we demonstrate a key role for oxidative stress and inflammation in causing systemic and glomerular hypertension and proteinuria. Oxidative stress and inflammation may have a key role in accelerating renal injury associated with intense proteinuria.

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Methane Saline Ameliorates Traumatic Brain Injury through Anti-Inflammatory, Antiapoptotic, and Antioxidative Effects by Activating the Wnt Signalling Pathway

BioMed Research International ◽

10.1155/2020/3852450 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Meng Li ◽

Weiman Gao ◽

Le Ji ◽

Jia Li ◽

Wanting Jiang ◽

...

Keyword(s):

Oxidative Stress ◽

Wnt Pathway ◽

Wnt Signalling ◽

Signalling Pathway ◽

Sprague Dawley ◽

Wnt Signalling Pathway ◽

Sprague Dawley Rats ◽

Antioxidative Effects ◽

Anti Inflammatory

Objective. Methane saline (MS) can be used to treat many diseases via its anti-inflammatory, antiapoptotic, and antioxidative activities. However, to date, there is no published evidence as to whether MS has any effect on traumatic brain injury (TBI). The Wnt signalling pathway regulates cell proliferation, differentiation, migration, and apoptosis; however, whether the Wnt signalling pathway regulates any effect of MS on TBI is unknown. This study was designed to explore the role of MS in the treatment of TBI and whether the Wnt pathway is involved. Methods. Sprague-Dawley rats were randomly divided into five groups: sham, TBI, TBI+10 ml/kg MS, TBI+20 ml/kg MS, and TBI+30 ml/kg MS. After induction of TBI, MS was injected intraperitoneally once daily for seven consecutive days. Neurological function was evaluated by the Neurological Severity Score (NSS) at 1, 7, and 14 days after TBI. Haematoxylin-eosin (HE) staining, inflammatory factors, neuron-specific enolase (NSE) staining, oxidative stress, and cell apoptosis were measured and compared 14 d after TBI to identify the optimal dose of MS and to investigate the effect of MS on TBI. In the second experiment, Sprague-Dawley rats were randomly divided into four groups: sham, TBI, TBI+20 ml/kg MS, and TBI+20 ml/kg MS+Dickkopf-1 (DKK-1, a specific inhibitor of the Wnt pathway). NSE, caspase-3, superoxide dismutase (SOD), Wnt3a, and β-catenin were detected by real-time PCR and Western blotting. The results from each group were compared 14 d after TBI to determine the regulatory role of the Wnt pathway. Results. Methane saline significantly inhibited inflammation, oxidative stress, and cell apoptosis, thus protecting neurons within 14 days of TBI. The best treatment effect against TBI was obtained with 20 ml/kg MS. When the Wnt pathway was inhibited, the treatment effect of MS was impaired. Conclusion. Methane saline ameliorates TBI through its anti-inflammatory, antiapoptotic, and antioxidative effects via activation of the Wnt signalling pathway, which plays a part but is not the only mechanism underlying the effects of MS. Thus, MS may be a novel strategy for treating TBI.

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Effects of Curcumin on the Renal Toxicity Induced by Ochratoxin A in Rats

Antioxidants ◽

10.3390/antiox9040332 ◽

2020 ◽

Vol 9 (4) ◽

pp. 332 ◽

Cited By ~ 1

Author(s):

Sara Damiano ◽

Emanuela Andretta ◽

Consiglia Longobardi ◽

Francesco Prisco ◽

Orlando Paciello ◽

...

Keyword(s):

Oxidative Stress ◽

Ochratoxin A ◽

Renal Toxicity ◽

Bioactive Compound ◽

Scientific Data ◽

Tubular Damage ◽

Therapeutic Effects ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

And Oxidative Stress

Ochratoxin A (OTA) is a powerful nephrotoxin and the severity of its damage to kidneys depends on both the dose and duration of exposure. According to the scientific data currently available, the mechanism of action still is not completely clarified, but it is supposed that oxidative stress is responsible for OTA-induced nephrotoxicity. Bioactive compound use has emerged as a potential approach to reduce chronic renal failure. Therefore, curcumin (CURC), due to its therapeutic effects, has been chosen for our study to reduce the toxic renal effects induced by OTA. CURC effects are examined in Sprague Dawley rats treated with CURC (100 mg/kg), alone or in combination with OTA (0.5 mg/kg), by gavage daily for 14 days. The end result of the experiment finds rats treated with OTA show alterations in biochemical and oxidative stress parameters in the kidney, related to a decrease in the Glomerular Filtration Rate (GFR). Conversely, the administration of CURC attenuates oxidative stress and prevents glomerular hyperfiltration versus the OTA group. Furthermore, kidney histological tests show a reduction in glomerular and tubular damage, inflammation and tubulointerstitial fibrosis. This study shows that CURC can mitigate OTA–induced oxidative damage in the kidneys of rats.

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The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats

10.21203/rs.2.16758/v3 ◽

2020 ◽

Author(s):

Jie Guo ◽

Xiaolu Cao ◽

Xianmin Hu ◽

Shulan Li ◽

Jun Wang

Keyword(s):

Oxidative Stress ◽

Terminal Deoxynucleotidyl Transferase ◽

Tunel Staining ◽

Apoptotic Cells ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Tnf Α ◽

Anti Inflammatory ◽

Factor Α ◽

Necrosis Factor

Abstract Background: Acrylamide (ACR) formed during heating of tobacco and carbohydrate-rich food as well as widely applied in industries has been known as a well-established neurotoxic pollutant. Although the precise mechanism is unclear, enhanced apoptosis, oxidative stress and inflammation have been demonstrated to contribute to the ACR-induced neurotoxicity. In this study, we assessed the possible anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin, the most active component in a popular spice known as turmeric, on the neurotoxicity caused by ACR in rats.Methods: Curcumin at the dose of 50 and 100 mg/kg was orally given to ACR- intoxicated Sprague-Dawley rats exposed by ACR at 40mg/kg for 4 weeks. All rats were subjected to behavioral analysis. The HE staining and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) staining were used to detect histopathological changes and apoptotic cells, respectively. The mRNA and protein expressions of apoptosis-related molecule telomerase reverse transcriptase (TERT) were detected using real-time PCR and immunohistochemistry, respectively. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as the indicators for evaluating the level of oxidative stress in brain. The levels of pro-inflammatory cytokinestumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the cerebral homogenates were detected using ELISA assay.Results: ACR-induced weigh loss, deficits in motor function as well as pathological alterations in brains were significantly improved in rats administrated with 50 and 100 mg/kg curcumin. TUNEL-positive apoptotic cells in curcumin-treated ACR intoxicated brains were less than those in the ACR model group. Curcumin administration especially at the dose of 100 mg/kg upregulated the TERT mRNA expression and enhanced the number of TERT-positive cells in ACR-intoxicated cortex tissues. Moreover, curcumin treatment reduced the concentrations of TNF-α, IL-1β and MDA, while increased the GSH contents as well as the SOD and GSH-Px activities in the cerebral homogenates, in comparison to ACR control group.Conclusions: These data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. Maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

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Anti-Acetylcholinesterase, Anti-Inflammatory and Anti-Oxidant Activities of Raw-Extract Centella Asiatica (RECA) on Lipopolysaccharide (LPS)-Induced Neuroinflammation Sprague Dawley Rats

International Journal of Engineering & Technology ◽

10.14419/ijet.v7i4.14.27479 ◽

2019 ◽

Vol 7 (4.14) ◽

pp. 96

Author(s):

Z Hafiz ◽

N Shamsuddin ◽

S M Mukhtar ◽

R J James ◽

M I Adenan

Keyword(s):

Oxidative Stress ◽

Centella Asiatica ◽

In Vivo Studies ◽

Ache Inhibitor ◽

Dependent Manner ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Anti Oxidant ◽

Anti Inflammatory ◽

And Oxidative Stress

The present study was designed to investigate the potential of raw-extract of Centella asiatica (RECA) in suppressing acetylcholinesterase (AChE), inflammations and oxidative stress via induction of lipopolysaccharide (LPS) on animal model of Sprague Dawley rats. Centella asiatica is a plant that has been used as a traditional herbal remedy for the management of several diseases, including memory improvement, treatment of mental fatigue and wound healing. Pre-treatment with RECA in vitro significantly reduced the AChE activity in a concentration-dependent manner with IC50 value of 57.47 ± 13.55 µg/ml. Interestingly, this result was parallel with in vivo studies. Moreover, the level of pro-inflammatory cytokines and oxidative stress were significantly reduced by RECA in dose-dependent manner. Overall, our findings clearly dictate the potential of RECA as AChE inhibitor as well anti-inflammatory and anti-oxidant agents.

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Administration of probiotic lactobacillus rhamnosus GG together with celecoxib attenuates oxidative stress and modulates colonic morphology in 1,2-dimethylhydrazine-induced colon cancer in sprague dawley rats

International Journal of Pharma and Bio Sciences ◽

10.22376/ijpbs.2018.9.4.b197-205 ◽

2018 ◽

Vol 9 (4) ◽

Cited By ~ 1

Author(s):

LEILA KAEID SHARAF ◽

MRIDUL SHARMA ◽

GEETA SHUKLA

Keyword(s):

Oxidative Stress ◽

Colon Cancer ◽

Lactobacillus Rhamnosus ◽

Sprague Dawley ◽

Lactobacillus Rhamnosus Gg ◽

Sprague Dawley Rats ◽

Probiotic Lactobacillus

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Levosimendan as a therapeutic strategy to prevent neuroinflammation after aneurysmal subarachnoid hemorrhage?

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2021-017504 ◽

2021 ◽

pp. neurintsurg-2021-017504

Author(s):

Stefan Wanderer ◽

Lukas Andereggen ◽

Jan Mrosek ◽

Sepide Kashefiolasl ◽

Gerrit Alexander Schubert ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Severe Heart Failure ◽

Prostaglandin F2alpha ◽

Sprague Dawley ◽

Delayed Cerebral Vasospasm ◽

Sprague Dawley Rats ◽

Solvent Control ◽

Anti Inflammatory

BackgroundPoor patient outcomes after aneurysmal subarachnoid hemorrhage (SAH) occur due to a multifactorial process, mainly involving cerebral inflammation (CI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia, followed by neurodegeneration. CI is mainly triggered by enhanced synthesis of serotonin (5-HT), prostaglandin F2alpha (PGF2a), and cytokines such as interleukins. Levosimendan (LV), a calcium-channel sensitizer, has already displayed anti-inflammatory effects in patients with severe heart failure. Therefore, we wanted to elucidate its potential anti-inflammatory role on the cerebral vasculature after SAH.MethodsExperimental SAH was induced by using an experimental double-hemorrhage model. Sprague Dawley rats were harvested on day 3 and day 5 after the ictus. The basilar artery was used for isometric investigations of the muscular media tone. Vessel segments were either preincubated with LV or without, with precontraction performed with 5-HT or PGF2a followed by application of acetylcholine (ACh) or LV.ResultsAfter preincubation with LV 10−4 M and 5-HT precontraction, ACh triggered a strong vasorelaxation in sham segments (LV 10−4 M, Emax 65%; LV 10−5 M, Emax 48%; no LV, Emax 53%). Interestingly, SAH D3 (LV 10−4, Emax 76%) and D5 (LV 10−4, Emax 79%) segments showed greater vasorelaxation compared with sham. An LV series after PGF2a precontraction showed significantly enhanced relaxation in the sham (P=0.004) and SAH groups (P=0.0008) compared with solvent control vessels.ConclusionsLV application after SAH seems to beneficially influence DCVS by antagonizing 5-HT- and PGF2a-triggered vasoconstriction. Considering this spasmolytic effect, LV might have a role in the treatment of SAH, additionally in selected patients suffering takotsubo cardiomyopathy.

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