scholarly journals Rutaecarpine Ameliorates Ethanol-Induced Gastric Mucosal Injury in Mice by Modulating Genes Related to Inflammation, Oxidative Stress and Apoptosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Sichen Ren ◽  
Ying Wei ◽  
Ruilin Wang ◽  
Shizhang Wei ◽  
Jianxia Wen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Nuclear Translocation ◽  
Mucosal Injury ◽  
Gastric Mucosal Injury ◽  
Mrna Levels ◽  
Immunofluorescence Analysis ◽  
Ulcer Index ◽  
Gastroprotective Effect ◽  
Tnf Α

Background: Rutaecarpine (RUT), a major quinazolino carboline alkaloid compound from the dry unripe fruit Tetradium ruticarpum (A. Juss.) T. G. Hartley, has various pharmacological effects. The aim of this present study was to investigate the potential gastroprotective effect of rutaecarpine on ethanol-induced acute gastric mucosal injury in mice and associated molecular mechanisms, such as activating Nrf2 and Bcl-2 via PI3K/AKT signaling pathway and inhibiting NF-κB.Methods: Gastric ulcer index and histopathology was carried out to determine the efficacy of RUT in gastric ulceration, and the content of SOD, GSH in serum and CAT, MDA, MPO, TNF-α, IL-6, IL-1β in tissue were measured by kits. Besides, in order to illustrate the potential inflammatory, oxidative, and apoptotic perturbations, the mRNA levels of NF-κB p65, PI3K, AKT, Nrf2, Nqo1, HO-1, Bcl-2 and Bax were analyzed. In addition, the protein expression of NF-κB p65 and Nrf2 in cytoplasm and nucleus, AKT, p-AKT, Bcl-2 Bax and Caspase 3 were analyzed for further verification. Finally, immunofluorescence analysis was performed to further verify nuclear translocation of NF-κB p65.Results: Current data strongly demonstrated that RUT alleviated the gross gastric damage, ulcer index and the histopathology damage caused by ethanol. RUT inhibited the expression and nuclear translocation of NF-κB p65 and the expression of its downstream signals, such as TNF-α, IL-6, IL-1β and MPO. Immunofluorescence analysis also verifies the result. In the context of oxidative stress, RUT improved the antioxidant milieu by remarkably upregulating the expression Nqo1 and HO-1 with activating Nrf2, and could remarkably upregulate antioxidant SOD, GSH, CAT and downregulate levels of MDA. Additionally, RUT activate the expression of Bcl-2 and inhibited the expression of downstream signals Bax and Caspase 3 to promote gastric cellular survival. These were confirmed by RUT activation of the PI3K/AKT pathway manifested by enhanced expression of PI3K and promotion of AKT phosphorylation.Conclusion: Taken together, these results strongly demonstrated that RUT exerted a gastroprotective effect against gastric mucosal injury induced by ethanol. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis system.

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.

scholarly journals Transglutaminase 2 Up-Regulation Is Associated with Inflammatory Response in PBMC from Healthy Subjects with Hypovitaminosis D

2018 ◽  
Vol 6 (4) ◽  
pp. 103 ◽  
Author(s):  
Daniela Caccamo ◽  
Nadia Ferlazzo ◽  
Monica Currò ◽  
Sergio Ricca ◽  
Riccardo Ientile
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Transglutaminase 2 ◽  
Hypovitaminosis D ◽  
Mrna Levels ◽  
Vitamin D Status ◽  
Vitamin D Levels ◽  
Tnf Α

Recent evidence indicated that transglutaminase 2 (TG2) is involved in the adaptive immune response. Peripheral blood mononuclear cells (PBMC) have largely been used to characterize molecular mechanisms occurring in the activation of immune response. Given that the maintenance of immune system functions requires an optimal vitamin D status, we aimed to assess the involvement of TG2/NF-κB signaling in cytokine production in PBMC isolated from adult subjects with different vitamin D status. We observed TG2 up-regulation and a significant positive correlation between TG2 expression and tumor necrosis factor (TNF)-α mRNA levels in PBMC of recruited patients. The mRNA levels of TG2 and TNF-α were higher in PBMC of subjects having hypovitaminosis D, namely plasma 25(OH)vitamin D3 levels lower than 50 nmol/L, than in those with normal vitamin D levels. Moreover, NF-κB up-regulation and nuclear translocation were detected, concomitantly with TG2 as well as TNF-α increased expression, in PBMC of vitamin D-deficient subjects. The present findings confirm that an increase in TG2 expression exacerbates the activation of NF-κB and the production of pro-inflammatory cytokines, and suggest a link between vitamin D deficiency, TG2 up-regulation, and inflammation.

scholarly journals Physiological Responses and Gene Expression in Ultrasound-Guided Supraclavicular Brachial Plexus Block: a Comparative Study

2018 ◽  
Vol 46 (6) ◽  
pp. 2412-2420 ◽  
Author(s):  
Hayam G Sayyed ◽  
Naglaa K. Idriss ◽  
Marwa A. Gaber ◽  
Sherif Sayed ◽  
Rasha Ahmed
Keyword(s):  
Oxidative Stress ◽  
Brachial Plexus Block ◽  
Mrna Levels ◽  
Oxidative Stress Markers ◽  
Ultrasound Guided ◽  
Stress Markers ◽  
Pain Scores ◽  
Tnf Α ◽  
Supraclavicular Brachial Plexus Block ◽  
Plexus Block

Background/Aims: Ultrasound-guided supraclavicular brachial plexus block (BPB) has come into wider use as a regional anesthetic during upper limb operations. This study assessed the neurological and hemodynamic changes and gene expression after co-administration of midazolam or neostigmine with bupivacaine during supraclavicular BPB. Methods: The study involved 90 adults divided into three groups: control (bupivacaine), midazolam (bupivacaine plus midazolam), and neostigmine (bupivacaine plus neostigmine). Blood samples were taken and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA levels were measured by real-time PCR, and oxidative stress markers were identified. In addition to the hemodynamic variables, the onset and duration of sensory and motor blockades, duration of analgesia, pain scores, time of first request for an analgesic, and amounts of analgesics ingested were evaluated. Results: Compared with the control and neostigmine groups, the midazolam group experienced longer sensory and motor blockades, prolonged analgesia, lower pain scores at 12 h and 24 h, and lower need for postoperative analgesics. Moreover, the midazolam group exhibited lower oxidative stress markers with a higher fold change in IL-6 and TNF-α mRNA levels. Conclusion: Midazolam co-administered with bupivacaine provided better analgesic quality than did neostigmine with bupivacaine. This might be due to its superior antioxidant and anti-inflammatory effects.

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.

Gastroprotective Effect Of Cyperus rotundus Extract against Gastric Mucosal Injury Induced by Ischemia and Reperfusion in Rats

2010 ◽  
Vol 6 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Muhammet E. Guldur ◽  
A. Ozgonul ◽  
Ibrahim H. Kilic ◽  
O. Sogut ◽  
M. Ozaslan ◽  
...  
Keyword(s):  
Mucosal Injury ◽  
Gastric Mucosal Injury ◽  
Cyperus Rotundus ◽  
Ischemia And Reperfusion ◽  
Gastroprotective Effect

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 Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice

2020 ◽  
Vol 53 (1) ◽  
Author(s):  
Jintao Gao ◽  
Fangru Chen ◽  
Huanan Fang ◽  
Jing Mi ◽  
Qi Qi ◽  
...  
Keyword(s):  
Skin Lesion ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Nuclear Translocation ◽  
Marker Gene ◽  
Inflammatory Factors ◽  
Mrna Levels ◽  
Hacat Keratinocytes ◽  
Tnf Α

Abstract Background Psoriasis is a common chronic inflammatory skin disease. Keratinocytes hyperproliferation and excessive inflammatory response contribute to psoriasis pathogenesis. The agents able to attenuate keratinocytes hyperproliferation and excessive inflammatory response are considered to be potentially useful for psoriasis treatment. Daphnetin exhibits broad bioactivities including anti-proliferation and anti-inflammatory. This study aims to evaluate the anti-psoriatic potential of daphnetin in vitro and in vivo, and explore underlying mechanisms. Methods HaCaT keratinocytes was stimulated with the mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish psoriatic keratinocyte model in vitro. Cell viability was measured using Cell Counting Kit-8 (CCK-8). Quantitative Real-Time PCR (qRT-PCR) was performed to measure the mRNA levels of hyperproliferative marker gene keratin 6 (KRT6), differentiation marker gene keratin 1 (KRT1) and inflammatory factors IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. Western blotting was used to detect the protein levels of p65 and p-p65. Indirect immunofluorescence assay (IFA) was carried out to detect p65 nuclear translocation. Imiquimod (IMQ) was used to construct psoriasis-like mouse model. Psoriasis severity (erythema, scaling) was scored based on Psoriasis Area Severity Index (PASI). Hematoxylin and eosin (H&E) staining was performed to examine histological change in skin lesion. The expression of inflammatory factors including IL-6, TNF-α, IL-23A and IL-17A in skin lesion was measured by qRT-PCR. Results Daphnetin attenuated M5-induced hyperproliferation in HaCaT keratinocytes. M5 stimulation significantly upregulated mRNA levels of IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. However, daphnetin treatment partially attenuated the upregulation of those inflammatory cytokines. Daphnetin was found to be able to inhibit p65 phosphorylation and nuclear translocation in HaCaT keratinocytes. In addition, daphnetin significantly ameliorate the severity of skin lesion (erythema, scaling and epidermal thickness, inflammatory cell infiltration) in IMQ-induced psoriasis-like mouse model. Daphnetin treatment attenuated IMQ-induced upregulation of inflammatory cytokines including IL-6, IL-23A and IL-17A in skin lesion of mice. Conclusions Daphnetin was able to attenuate proliferation and inflammatory response induced by M5 in HaCaT keratinocytes through suppression of NF-κB signaling pathway. Daphnetin could ameliorate the severity of skin lesion and improve inflammation status in IMQ-induced psoriasis-like mouse model. Daphnetin could be an attractive candidate for future development as an anti-psoriatic agent.

scholarly journals Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2032
Author(s):  
Vishnu Raj ◽  
Balaji Venkataraman ◽  
Saeeda Almarzooqi ◽  
Sanjana Chandran ◽  
Shreesh K. Ojha ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
In Vitro Models ◽  
Mrna Levels ◽  
Colonic Inflammation ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Ht 29

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-α-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 µM and 50 µM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1β, IL-6, and TNF-α) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-α-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.

scholarly journals The effect of long-term dehydration and subsequent rehydration on markers of inflammation, oxidative stress and apoptosis in the camel kidney

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Mahmoud A. Ali ◽  
Hassan Abu Damir ◽  
Osman M. Ali ◽  
Naheed Amir ◽  
Saeed Tariq ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Water Conservation ◽  
Mesangial Cells ◽  
Expression Level ◽  
Kidney Cortex ◽  
Mrna Levels ◽  
Sod Activity ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Different Response

Abstract Background Dehydration has deleterious effects in many species, but camels tolerate long periods of water deprivation without serious health compromise. The kidney plays crucial role in water conservation, however, some reports point to elevated kidney function tests in dehydrated camels. In this work, we investigated the effects of dehydration and rehydration on kidney cortex and medulla with respect to pro-inflammatory markers, oxidative stress and apoptosis along with corresponding gene expression. Results The cytokines IL-1β and IL-18 levels were significantly elevated in the kidney cortex of dehydrated camel, possibly expressed by tubular epithelium, podocytes and/or mesangial cells. Elevation of IL-18 persisted after rehydration. Dehydration induced oxidative stress in kidney cortex evident by significant increases in MDA and GSH, but significant decreases in SOD and CAT. In the medulla, CAT decreased significantly, but MDA, GSH and SOD levels were not affected. Rehydration abolished the oxidative stress. In parallel with the increased levels of MDA, we observed increased levels of PTGS1 mRNA, in MDA synthesis pathway. GCLC mRNA expression level, involved in GSH synthesis, was upregulated in kidney cortex by rehydration. However, both SOD1 and SOD3 mRNA levels dropped, in parallel with SOD activity, in the cortex by dehydration. There were significant increases in caspases 3 and 9, p53 and PARP1, indicating apoptosis was triggered by intrinsic pathway. Expression of BCL2l1 mRNA levels, encoding for BCL-xL, was down regulated by dehydration in cortex. CASP3 expression level increased significantly in medulla by dehydration and continued after rehydration whereas TP53 expression increased in cortex by rehydration. Changes in caspase 8 and TNF-α were negligible to instigate extrinsic apoptotic trail. Generally, apoptotic markers were extremely variable after rehydration indicating that animals did not fully recover within three days. Conclusions Dehydration causes oxidative stress in kidney cortex and apoptosis in cortex and medulla. Kidney cortex and medulla were not homogeneous in all parameters investigated indicating different response to dehydration/rehydration. Some changes in tested parameters directly correlate with alteration in steady-state mRNA levels.

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