Increased oxidative stress and mitochondrial impairments associated with increased expression of TNF‐α and caspase‐3 in palmitic acid‐induced lipotoxicity in myoblasts

2021 ◽  
Author(s):  
Mohammad Lukman Mansuri ◽  
Garima Sharma ◽  
Priyanka Parihar ◽  
Kirti Tiwari Dube ◽  
Tejasweta Sharma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Palmitic Acid ◽  
Caspase 3 ◽  
Tnf Α

Mitigation of IL-1β, IL-6, TNF-α, and markers of apoptosis by ursolic acid against cisplatin-induced oxidative stress and nephrotoxicity in rats

2021 ◽  
Vol 40 (12_suppl) ◽  
pp. S397-S405
Author(s):  
Pankaj Tripathi ◽  
Saeed Alshahrani
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Uric Acid ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Caspase 9 ◽  
Histological Damage ◽  
Tnf Α ◽  
Mda Content ◽  
Pro Inflammatory Cytokines

Background: Ursolic acid (UA) is a natural pentacyclic triterpenoid that is known for its benefits under several pathological conditions. Cisplatin (CP) is among the most preferred chemotherapeutic agents; however, its nephrotoxicity limits its clinical utility. Purpose: This study was aimed to determine the role of UA in the reduction of CP-induced nephrotoxicity and mitigation of pro-inflammatory cytokines and apoptosis in a rat model. Methodology: Male Wistar rats were randomized into vehicle control, CP (7.5 mg/kg), UA 10 mg/kg, and CP with UA 5 and 10 mg/kg groups. Kidney and blood samples were collected for assessment of renal function, measurement of pro-inflammatory cytokines, apoptosis markers, antioxidant activity, and tissue histology. Results: CP significantly increased the levels of serum Cr, BUN, and uric acid; it also induced histological damage reflecting the pathophysiology observed during nephrotoxicity. CP has also shown its pro-oxidant activity in kidney tissue because CP decreased the levels of GSH, SOD, and CAT; it increased the lipid peroxidation as measured by MDA content. In addition, CP significantly upregulated the activity of pro-inflammatory cytokines and expression of apoptotic markers, that is, there were increased levels of IL-1β, IL-6, TNF-α, caspase-3, and caspase-9. Two weeks of continuous treatment of UA showed significant recovery against CP-induced nephrotoxicity; UA decreased the levels of Cr, BUN, and uric acid and ameliorated histological damage. UA also downregulated the activities of IL-1β, IL-6, and TNF-α as well as expression of caspase-3 and caspase-9. Furthermore, CP-induced oxidative stress that was antagonized by UA—the levels of GSH, SOD, and CAT were significantly increased while MDA content was decreased. Conclusions: UA has a protective effect against CP-induced nephrotoxicity, which may be due to its antioxidant activity and mitigation of ILβ-1, ILβ-6, TNF-α, and markers of apoptosis.

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 Effects of enalapril and paricalcitol treatment on diabetic nephropathy and renal expressions of TNF-α, P53, Caspase-3 and Bcl-2 in STZ-induced diabetic rats

2019 ◽  
Author(s):  
Osama M. Ahmed ◽  
Tarek M. Ali ◽  
Mohamed A. Abdel Gaid ◽  
Ahmed A. Elberry
Keyword(s):  
Oxidative Stress ◽  
Wistar Rats ◽  
Antioxidant Defense ◽  
Caspase 3 ◽  
Enzyme Inhibitor ◽  
Elevated Serum ◽  
Antioxidant Defense System ◽  
Diabetic Rats ◽  
Defense System ◽  
Tnf Α

AbstractThis study aimed to assess the renopreventive effect of the angiotensin converting enzyme inhibitor (ACEI), enalapril, and/or vitamin D receptor (VDR) activator, paricalcitol, on streptozotocin (STZ) diabetes-induced nephropathy and to elucidate the mechanisms of action through investigation of the effects on renal oxidative stress, antioxidant defense system and expressions of TNF-α, P53, caspase-3, and Bcl-2. Diabetes mellitus was induced in fasting male Wistar rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer pH 4.5. Ten days after STZ injection, the diabetic rats were treated with enalapril (25 mg/l of drinking water) and/or paricalcitol (8 µg/kg b.w.per os) dissolved in 5% DMSO daily for 4 weeks. The obtained data revealed that the treatment of diabetic Wistar rats with enalapril and/or paricalcitol led to a significant decrease in the elevated serum urea, uric acid, creatinine and sodium, potassium levels; thereby reflecting improvement of the impaired kidney function. The deteriorated kidney lipid peroxidation, GSH content and GST and catalase activities in diabetic rats were significantly ameliorated as a result of treatment with enalapril and/or paricalcitol. The elevated fasting and post-prandial serum glucose levels and the lowered serum insulin and C-peptide levels were also improved. Moreover, the treatment of diabetic rats successfully prevented the diabetes-induced histopathological deleterious changes of kidney and islets of Langerhans of pancreas. In association, the immunohistochemically detected pro-inflammatory cytokine TNF-α and apoptotic mediators P53 and caspase-3 were remarkably decreased in kidney of diabetic rats as a result of treatment, while the expression of anti-apoptotic protein Bcl-2 was increased. Based on these findings, it can be concluded that enalapril and paricalcitol can prevent STZ diabetes-induced nephropathy though amelioration of the glycemic state and antioxidant defense system together with the suppression of oxidative stress, inflammation and apoptosis.

Protective Effects of Astaxanthin on Nephrotoxicity in Rats with Induced Renovascular Occlusion

2020 ◽  
Vol 23 ◽  
Author(s):  
Erkan Arslan ◽  
Hakan Turk ◽  
Murat Caglayan ◽  
Tugba Taskin Turkmenoglu ◽  
Ataman Gonel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Olive Oil ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Control Group ◽  
Tubular Damage ◽  
Total Thiol ◽  
Tnf Α ◽  
Anti Inflammatory

Background: Various effects of Astaxanthin was shown in the studies including its antioxidant, anti-inflammatory, anti-tumor and immunregulator effects. Objective: The aim of this study was to evaluate the beneficial effects of Astaxanthin on renovascular occlusion induced renal injury and to investigate the possible mechanisms. Methods: The rats were randomly assigned into three groups as follows: Group 1: control group (n=12), Group 2: renal ischemiareperfusion injury group (n=12), Group 3: renal ischemia-reperfusion + asthaxantine treated group (n=12). The control group and the renal ischemia-reperfusion group were given 2cc/kg/g olive oil for 7 days before establishing ischemia to renal tissue. Astaxanthin dissolved in olive oil was given orally to the renal ischemia+astaxanthin group for 7 days before inducing renal ischemia. Caspase-(3, 8, 9), GSH, SOD, Total Thiol, TNF-α, IL-6, 8-OHdG were performed for each group. Results: Renal IRI was verified by analysing the pathological changes of renal tissues and the renal functions after renal reperfusion. Much less renal tubular damage was determined the IRI+ASX group in comparison to the IRI group. Caspase-8, -9 and -3 immunoreactivity was observed to be minimal in the control group. Apoptosis was observed to be significantly reduced in the IRI + ASX group with respect to IRI group and close to the level of the control group (p <0.05). Caspase-3 levels of tissue samples were significantly increased in IRI group compared to other groups, but significantly lower in IRI+ASX group with respect to the IRI group (p<0.05). The TOS and OSI levels, indicating increased oxidative stress, were significantly lower in the IRI+ASX group with respect to the IRI group (p <0.001), but still higher than the control group (p <0.001). In addition to GSH, SOD and Total Thiol levels, TAS levels were also significantly higher in IRI + ASX group in comparison to the IRI group (p <0.05). TNF-α, IL-6, lipid hydroperoxide, AOPP and 8-OHdG levels were lower in the IRI+ASX group than the IRI group (p <0.001). MPO, IL-6, TNF-α levels, representing the parameters indicating neutrophil infiltration and inflammation of the renal tissues, significantly increased in IRI group with respect to the other groups (p <0.005). Conclusion: When all the data obtained in our study were evaluated, ASX was determined to prevent renal damage due to renovascular occlusion to a great extent, through complex mechanisms involving antioxidant, anti-inflammatory and antiapopitotic effects. Biochemical, histological and oxidative stress parameters were improved due to ASX.

scholarly journals Comparative Study of the Effects of GLP1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

Biomedicines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 43 ◽  
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Medhat Taha ◽  
Rami M. Elshazli ◽  
Raouf Fekry Bedir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Sglt2 Inhibitor ◽  
Diabetic Rats ◽  
Tnf Α ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic

The present study investigated the possible cardioprotective effects of GLP1 and SGLT2i against diabetic cardiomyopathy (DCM) in type 2 diabetic rats and the possible underlying mechanisms. Methods: Thirty-two male Sprague Dawley rats were randomly subdivided into 4 equal groups: (a) control group, (b) DM group, type 2 diabetic rats with saline daily for 4 weeks, (c) DM + GLP1, as DM group with GLP1 analogue (liraglutide) at a dose of 75 µg/kg for 4 weeks, and (d) DM + SGLT2i as DM group with SGLT2 inhibitor (dapagliflozin) at a dose of 1 mg/kg for 4 weeks. By the end of treatment (4 weeks), serum blood glucose, homeostasis model assessment insulin resistance (HOMA-IR), insulin, and cardiac enzymes (LDH, CK-MB) were measured. Also, the cardiac histopathology, myocardial oxidative stress markers (malondialdehyde (MDA), glutathione (GSH) and CAT) and norepinephrine (NE), myocardial fibrosis, the expression of caspase-3, TGF-β, TNF-α, and tyrosine hydroxylase (TH) in myocardial tissues were measured. Results: T2DM caused significant increase in serum glucose, HOMA-IR, serum CK-MB, and LDH (p < 0.05). Also, DM caused significant myocardial damage and fibrosis; elevation of myocardial MDA; NE with upregulation of myocardial caspase-3, TNF-α, TGF-β, and TH; and significant decrease in serum insulin and myocardial GSH and CAT (p < 0.05). Administration of either GLP1 analog or SGLT2i caused a significant improvement in all studied parameters (p < 0.05). Conclusion: We concluded that both GLP1 and SGLT2i exhibited cardioprotective effects against DCM in T2DM, with the upper hand for SGLT2i. This might be due to attenuation of fibrosis, oxidative stress, apoptosis (caspase-3), sympathetic nerve activity, and inflammatory cytokines (TNF-α and TGF-β).

scholarly journals Conditioned medium from human gingival mesenchymal stem cells protects motor-neuron-like NSC-34 cells against scratch-injury-induced cell death

2017 ◽  
Vol 30 (4) ◽  
pp. 383-394 ◽  
Author(s):  
Thangavelu Soundara Rajan ◽  
Francesca Diomede ◽  
Placido Bramanti ◽  
Oriana Trubiani ◽  
Emanuela Mazzon
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Cell Death ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Motor Neuron ◽  
Conditioned Medium ◽  
Caspase 3 ◽  
Tnf Α ◽  
Anti Inflammatory

Neuronal cell death is a normal process during central nervous system (CNS) development and is also involved in the death of motor neurons in diverse spinal motor neuron degenerative diseases. Here, we investigated the neuroprotective effect of secretory factors released from human gingival mesenchymal stem cells (hGMSCs) in mechanically injured murine motor-neuron-like NSC-34 cells. The cells were exposed to scratch injury and the markers for apoptosis and oxidative stress were examined. Immunocytochemistry results showed that proapoptotic markers cleaved caspase-3 and Bax were elevated while anti-apoptotic protein Bcl-2 was suppressed in scratch-injured NSC-34 cells. Oxidative stress markers SOD-1, inducible nitric oxide synthase (iNOS), Cox-2, and proinflammatory cytokine tumor necrosis factor alpha (TNF-α) were activated. Conditioned medium (CM) derived from hGMSCs (hGMSC-CM) significantly blocked the cell death by suppressing SOD-1, iNOS, TNF-α, cleaved caspase-3, and Bax. Bcl-2 and anti-inflammatory cytokine anti-interleukin 10 (IL-10) were increased in hGMSC-CM-treated injured cells. Moreover, hGMSC-CM treatment upregulated neurotrophins anti-brain-derived neurotrophic factor (BDNF) and NT3. Western blot data of hGMSC-CM revealed the presence of neurotrophins nerve growth factor (NGF), NT3, anti-inflammatory cytokines IL-10, and transforming growth factor beta (TGF-β), suggesting their positive role to elicit neuroprotection. Our results propose that hGMSC-CM may serve as a simple and potential autologous therapeutic tool to treat motor neuron injury.

scholarly journals HCl-induced acute lung injury: a study of the curative role of mesenchymal stem/stromal cells and cobalt protoporphyrin

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Reham A. EL-Shahat ◽  
Reda S. EL-Demerdash ◽  
El Said El Sherbini ◽  
Entsar A. Saad
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Stromal Cells ◽  
Blood Cells ◽  
Caspase 3 ◽  
White Blood Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Cobalt Protoporphyrin

Abstract Background This study was designed to investigate bone marrow mesenchymal stem/stromal cells (BM-MSCs) and cobalt protoporphyrin (CoPP) curable effects on HCl-induced acute lung injury (ALI) and its underlying mechanisms hoping this might aid to offer a therapeutic opportunity for ALI. Results Forty male Sprague Dawley rats were randomly allocated into four groups; normal (normal rats), ALI (rats injected with 2 ml hydrochloric acid (HCl)/kg via trachea), ALI + BM-MSCs (ALI rats intravenously injected twice with 1 × 106 BM-MSCs/rat/week), and ALI + CoPP (ALI rats intraperitoneally injected twice with CoPP (0.5 mg/100 g/week)). White blood cells (WBCs), red blood cells (RBCs), hemoglobin (Hb), serum tumor necrosis factor-alpha (TNF-α), lung histopathology, apoptosis markers (caspase-3 and Bcl2), and oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT)) were measured. ALI caused increases in WBCs, TNF-α, caspase-3, and MDA, and morphological damage score of lungs with decreases in RBCs, Hb, Bcl2, SOD, and CAT (p < 0.05). BM-MSCs or CoPP treatment reversed these ALI-induced changes (p < 0.05) towards normal. Conclusions BM-MSCs and CoPP could attenuate ALI by modulation of inflammation, oxidative stress, and apoptosis. Curative roles of BM-MSCs were more effective than those of CoPP. This highlights BM-MSCs as a potent therapy for HCl-associated ALI.

scholarly journals Trigonoside II mitigates sepsis-induced myocardial injury via reduction in oxidative stress and regulation of TLR- 4/NF-kB inflammatory pathway

2020 ◽  
Vol 19 (6) ◽  
pp. 1161-1166
Author(s):  
Fengru Wang ◽  
Lili Wu ◽  
Qun Liang
Keyword(s):  
Oxidative Stress ◽  
Myocardial Injury ◽  
Caspase 3 ◽  
Cecal Ligation ◽  
Rat Serum ◽  
Inflammatory Pathway ◽  
Post Surgery ◽  
Tnf Α ◽  
Protein Expressions ◽  
Cecal Ligation Puncture

Purpose: To investigate the protective effect of trigonoside II against sepsis-induced myocardial injury in rats, and the mechanism involved. Methods: Adult male Sprague Dawley rats (n = 30) weighing 200 - 230 g (mean weight = 215 ± 15 g) were used for this study. The rats were randomly assigned to 3 groups (10 rats/group): sham, cecal ligation puncture (CLP), and trigonoside II. Rats in the treatment group received trigonoside II at a dose of 2 mg/kg intraperitoneally (i.p.) at 3, 12 and 24 h post-surgery. Sepsis was induced using CLP method. Lactate  dehydrogenase (LDH) and creatine kinase (CK-MB) activities, and hemodynamic functions were determined in the rats. The levels of interleukin (IL)-1β and IL-6, and tumor necrosis factor α (TNF-α) were assayed in rat serum. Oxidative stress and myocardial cell apoptosis were determined by measuring malondialdehyde (MDA) levels, while activities of glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO), as well as levels of expression of bax, bcl-2 and caspase-3 were also assessed. Results: Treatment of myocardial injury rats with trigonoside II led to significant reductions in the activities of LDH, CK-MB and MPO, and decreases in levels of IL-1β, IL-6 and TNF-α (p < 0.05). It also significantly reversed the effects of sepsis on rat hemodynamic functions (p < 0.05). Trigonoside IItreatment significantly reduced MDA levels in rat myocardial tissues, but significantly increased SOD and GPx activities (p < 0.05). It significantly down-regulated protein expressions of NF-kB and TLR-4 in myocardial tissues (p < 0.05). The number of apoptotic cells and activity of caspase-3 were significant increased in myocardial tissues of rats in CLP group, when compared with sham group, but were reduced significantly in myocardial tissues of trigonoside II-treated rats (p < 0.05). Similarly, trigonoside II treatment down-regulated the protein expressions of caspase-3 and bax, but upregulated bcl-2 protein expression in the rat myocardial tissues (p < 0.05). Conclusion: The results of this study indicate that trigonoside II confers protection on sepsis-induced myocardial injury via reduction in oxidative stress and regulation of TLR-4/NF-kB inflammatory pathway. Keywords: Cecal ligation puncture, Myocardial injury, Oxidative stress, Sepsis, Trigonoside II

scholarly journals Benfotiamine Ameliorates High Carbohydrate Diet-Induced Hepatic Oxidative Stress, Inflammation and Apoptosis in Megalobrama Amblycephala

2020 ◽  
Author(s):  
Chao Xu ◽  
Wen-Bin Liu ◽  
Hua-Juan Shi ◽  
Xiang-Fei Li
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Megalobrama Amblycephala ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Caspase 9 ◽  
Carbohydrate Diet ◽  
High Carbohydrate ◽  
Tnf Α ◽  
Antioxidant Enzymes Activities

Abstract Background: The impairment of immunity induced by high-carbohydrate diet is closely associated with the development of glucose metabolic disorders. In the study of diabetes, benfotiamine can prevent β-cell dysfunction by inhibiting inflammation, thereby improving insulin resistance. However, information regarding the effects of this substance on aquatic animals is extremely scarce.Methods: A 12-week nutritional research was conducted to evaluate the influences of benfotiamine on the growth performance, oxidative stress, inflammation and apoptosis in Megalobrama amblycephala (45.25 ± 0.34 g) fed high-carbohydrate (HC) diets. Six experimental diets were formulated, containing a control diet (30% carbohydrate, C), a HC diet (43% carbohydrate), and the HC diet supplemented with four graded benfotiamine levels (0.7125 (HCB1), 1.425 (HCB2), 2.85 (HCB3), and 5.7 (HCB4) mg/kg).Results: HC diet intake remarkably decreased daily growth coefficient (DGC), growth rate per metabolic body weight (GRMBW), feed intake (FI), liver antioxidant enzymes activities, sirtuin-1 (SIRT1) protein expression as well as liver mRNA levels of SIRT1, nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (CAT), manganese superoxide dismutase (Mn-SOD), interleukin10 (IL10) than those of the control group, but the opposite was true for plasma activities of alanine transaminase (AST) and aspartate aminotransferase (ALT), and contents of interleukin 1β (IL1β) and interleukin 6 (IL6), liver contents of malondialdehyde (MDA), and mRNA levels of kelch-like ECH associating protein 1 (Keap1), nuclear factor kappa B (NF-κB), tumour necrosis factor α (TNF α), IL1β, IL6, Bax, Caspase 3, Caspase 9 and P53. As with benfotiamine supplementation, HCB2 diet remarkably increased DGC, GRMBW, liver antioxidant enzymes activities, SIRT1 protein expression as well as liver mRNA levels of SIRT1, Nrf2, CAT, Mn-SOD, IL10 and Bcl2, while the opposite was true for plasma activities of AST and ALT, and contents of IL1β and IL6, liver MDA contents as well as mRNA levels of Keap1, NF-κB, TNF α, IL1β, IL6, Bax, Caspase 3, Caspase 9 and P53.Conclusion: Benfotiamine at 1.425 mg/kg can improve the growth performance and alleviate the oxidative stress, inflammation and apoptosis of M. amblycephala fed HC diets through the activation of the SIRT1 pathway.

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