Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation, and amyloidogenesis: possible role of brain-derived neurotrophic factor

2017 ◽  
Vol 95 (7) ◽  
pp. 850-860 ◽  
Author(s):  
Waleed A.I. Khallaf ◽  
Basim A.S. Messiha ◽  
Amira M.H. Abo-Youssef ◽  
Nesrine S. El-Sayed
Keyword(s):  
Nitric Oxide ◽  
Cognitive Impairment ◽  
Angiotensin Ii ◽  
Nitrosative Stress ◽  
Histopathological Examination ◽  
Control Group ◽  
Angiotensin Ii Receptor Blocker ◽  
Protective Effects ◽  
Brain Levels ◽  
Tnf Α

Angiotensin II has pro-inflammatory and pro-oxidant potentials. We investigated the possible protective effects of the Angiotensin II receptor blocker telmisartan, compared with the superoxide scavenger tempol, on lipopolysaccharide (LPS)-induced cognitive decline and amyloidogenesis. Briefly, mice were allocated into a normal control group, an LPS control group, a tempol treatment group, and 2 telmisartan treatment groups. A behavioral study was conducted followed by a biochemical study via assessment of brain levels of beta amyloid (Aβ) and brain-derived neurotropic factor (BDNF) as amyloidogenesis and neuroplasticity markers, tumor necrosis factor alpha (TNF-α), nitric oxide end products (NOx), neuronal and inducible nitric oxide synthase (nNOS and iNOS) as inflammatory markers, and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH), and nitrotyrosine (NT) as oxido-nitrosative stress markers. Finally, histopathological examination of cerebral cortex, hippocampus, and cerebellum sections was performed using routine and special Congo red stains. Tempol and telmisartan improved cognition, decreased brain Aβ deposition and BDNF depletion, decreased TNF-α, NOx, nNOS, iNOS, MDA, and NT brain levels, and increased brain SOD and GSH contents, parallel to confirmatory histopathological evidences. In conclusion, tempol and telmisartan are promising drugs in managing cognitive impairment and amyloidogenesis, at least via upregulation of BDNF with inhibition of neuroinflammation and oxido-nitrosative stress.

The protective effect of chrysin against carbon tetrachloride-induced kidney and liver tissue damage in rats

2020 ◽  
pp. 1-12 ◽  
Author(s):  
Burcu Gul Baykalir ◽  
Aslihan Sur Arslan ◽  
Seda Iflazoglu Mutlu ◽  
Tuba Parlak Ak ◽  
Ismail Seven ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Group Treatment ◽  
Histopathological Examination ◽  
Kidney Tissue ◽  
Control Group ◽  
Protective Effects ◽  
Sod Activity ◽  
Tnf Α ◽  
Liver And Kidney ◽  
Factor Α

Abstract: The aim of this study was to investigate the possible protective effects of chrysin on oxidative status and histological alterations against carbon tetrachloride (CCl4)-induced liver and kidney tissue in rats. The animals were randomly divided into four groups; the control, chrysin (100 mg/kg), CCl4 (0.5 ml/kg) and chrysin + CCl4 groups. Liver and kidney injuries were assessed by biochemical and histopathological examinations. The levels of malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) activity were measured in tissues. Serum tumor necrosis factor-α (TNF-α), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine levels were also measured in blood samples. MDA, serum TNF-α, AST, ALT, urea, and creatinine levels (p < 0.05) were significantly higher, and SOD activity and GSH level were significantly (p < 0.05) lower in the CCl4 group than in the control group. Treatment with chrysin in the chrysin + CCl4 group decreased MDA, AST, ALT, creatinine, and TNF-α levels (p < 0.05), and increased SOD activity, GSH levels (p < 0.05), and serum TNF-α levels (p < 0.05). In addition, body weight change (BWC) (p < 0.05) and feed intake (FI) were significantly lower (p < 0.001) in the CCl4 group than in the control group. Moreover, treatment with chrysin increased BWC and FI in the chrysin + CCl4 group compared with that in the CCl4 group. These findings also confirmed by histopathological examination. The chrysin treatment ameliorated the CCl4-induced biochemical and pathological alterations. These results demonstrated that chrysin provided amelioration on the rat liver and kidney tissues CCl4-induced injury by increasing the antioxidant activity.

The effects of melatonin on brain nitrosative stress and energy balance in fructose-mediated metabolic syndrome model / Fruktoz-aracılı metabolik sendrom modelinde melatoninin beyinde nitrozatif stres ve enerji dengesi üzerine etkisi

2016 ◽  
Vol 41 (1) ◽  
Author(s):  
Gonca Ozan ◽  
Filiz Sezen Bircan ◽  
Turgut Topal ◽  
Nurten Türközkan
Keyword(s):  
Nitric Oxide ◽  
Metabolic Syndrome ◽  
Nitrosative Stress ◽  
Tap Water ◽  
Serum Triglyceride ◽  
Experimental Period ◽  
Control Group ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Male Adult

AbstractObjective: Metabolic syndrome (MetS), one of the common health problems seen with increasing frequency in today’s modern societies, is also a important risk factor for neurological disorders such as stroke, depression, Alzheimer’s disease. On the other hand, melatonin is a neurohormone, has potent antioxidant and neuroprotective activities. In the present study, we aimed to investigate the possible protective effects of melatonin administration on brain tissue in fructose-mediated MetS model.Methods: Male adult Sprague-Dawley rats were randomly divided into four groups (n=8); control, fructose, melatonin and fructose plus melatonin. MetS was induced by fructose solution 20% in tap water, and melatonin was administered at the dose of 20 mg/kg bw/day by oral gavage. Systolic blood pressures (SBP) were measured by tail-cuff method. After the experimental period of 8 weeks, serum triglyceride, glucose, insulin, and tissue ATP/ADP ratio, nitric oxide (NOx) and 3-nitrotyrosine (3-NT) levels were measured. Also tissue endothelial and inducible nitric oxide synthase (eNOS and iNOS) protein levels were determined.Results: Fructose consumption increased SBP, serum triglyceride, insulin levels and induced insulin resistance significantly compared to control group and MetS model was successfully demonstrated. In comparison with control group, fructose administration did not cause significant changes in tissue ATP/ADP ratio and 3-NT levels. NOx levels did not change significantly among groups, and iNOS-eNOS proteins were not detected in any groups. Interestingly, tissue 3-NT levels were elevated significantly while ATP/ADP ratio was diminished in fructose plus melatonin group compare with both control and fructose groups.Conclusion: These results indicate that high fructose diet for 8 weeks does not influence nitric oxide production, energy metabolism and protein nitration in brain. Nevertheless melatonin acted as a pro-oxidant at that dose when administered with fructose.

Protective effect of an L-type calcium channel blocker, amlodipine, on paracetamol-induced hepatotoxicity in rats

2018 ◽  
Vol 37 (11) ◽  
pp. 1169-1179 ◽  
Author(s):  
H Kaya ◽  
B Polat ◽  
A Albayrak ◽  
T Mercantepe ◽  
B Buyuk
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Transforming Growth Factor Beta ◽  
Channel Blocker ◽  
Transforming Growth Factor ◽  
Histopathological Examination ◽  
Control Group ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Paracetamol (P), one of the most popular and commonly used analgesic and antipyretic agents, causes hepatotoxicity in overdoses. Amlodipine (AML), an L-type calcium channel blocker, has been shown to have anti-inflammatory activity by reversing the effect of calcium in the inflammation pathogenesis. In this study, the hepatoprotective activity of AML on P-induced hepatotoxicity was evaluated. Thirty male albino Wistar rats were divided into five groups: (1) control, (2) 2 g/kg of P, (3) 2 g/kg of P + 5 mg/kg of AML, (4) 2 g/kg of P + 10 mg/kg of AML, and (5) 10 mg/kg of AML. Some liver enzymes, oxidative parameters, cytokine mRNA expressions, histopathology, and immunohistochemical studies were performed in liver and blood samples. The serum levels of alanine aminotransferase and aspartate aminotransferase and the mRNA expression of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta in the liver tissues were significantly increased in the group treated with P. The superoxide dismutase and glutathione parameters decreased and malondialdehyde levels increased in the livers of the rats treated with P. All these parameters were increased with both doses of the AML similar to the control group. A histopathological examination of the liver showed that AML administration ameliorated the P-induced inflammatory liver damage. In immunohistochemical staining, the expression of TNF-α in the cytoplasm of the hepatocytes was increased in the P group but not in other treatment groups when compared to the control. In conclusion, AML treatment showed significant protective effects against P-induced hepatotoxicity by increasing the activity of antioxidants and reducing inflammatory cytokines.

Withdrawn: Hepatoprotective effects of Tribulus terrestris L. (Zygophyllales: Zygophyllaceae) hydro-alcholic extract on non-alcoholic fatty liver-induced rats

2016 ◽  
Vol 3 (5) ◽  
pp. 143
Author(s):  
Fatemeh Almasi ◽  
Mozafar Khazaei ◽  
Shima Chehrei ◽  
Ali Ghanbari
Keyword(s):  
Fatty Liver ◽  
Liver Tissue ◽  
Serum Lipid ◽  
Histopathological Examination ◽  
Serum Levels ◽  
Lipid Profiles ◽  
Control Group ◽  
Tribulus Terrestris ◽  
Protective Effects ◽  
Alcoholic Fatty Liver

Non-alcoholic fatty liver induces many complications to the liver tissue and also serum related parameters. Medicinal plants are the safe therapeutic strategy for the treatment of diseases. In this regards, the present study was conducted to evaluate the effect of Tribulus terrestris L. (Zygophyllales: Zygophyllaceae) extract on non-alcoholic fatty liver in rats. In this experimental study, thirty male Wistar rats were divided into five groups (n = 6). Animals in experimental groups were received high fructose diet (70%) (HDF) daily alone or in combined with daily intraperitoneal injection of 500, 700 and 1,000 mg/kg extract of T. terrestris. Control group of rats was feed with standard chow. The serum levels of biomarkers of liver and serum lipid profiles were assessed, also histopathological examination of liver tissue done. Data were analyzed using One-way ANOVA method followed by Tukey’s post-hoc multiple comparison test and P < 0.05 was considered statistically significant. There were significant improvements for biomarkers of liver tissue (P < 0.05) and serum lipid profiles (P < 0.01) in the HFD-fed rats that were treated with T. terrestris extract compare to HFD-fed group. In addition, accumulation of lipids in hepatocytes was significantly reduced in the HFD-fed + extract administrated groups in comparison to HFD-fed rats (P < 0.01). T. terrestris extract has protective effects against non-alcoholic fatty liver by changing biomarkers of liver tissue, serum lipid profiles and histopathological anomalies of liver tissue, to normal range.

scholarly journals Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haidy A. Saleh ◽  
Eman Ramdan ◽  
Mohey M. Elmazar ◽  
Hassan M. E. Azzazy ◽  
Anwar Abdelnaser
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Response ◽  
Raw 264.7 Cells ◽  
Inos Mrna ◽  
No Production ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Protective Effects ◽  
Tnf Α ◽  
Ifn Γ

AbstractDoxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

scholarly journals Hepatoprotective effect of galangin on carbon tetrachloride-induced hepatotoxicity via the LKB1/AMPK pathway

2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Meng Chen ◽  
Xinyan Song ◽  
Jifang Jiang ◽  
Lei Xing ◽  
Pengfei Wang
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Toxicity ◽  
Corn Oil ◽  
Histopathological Examination ◽  
Hepatoprotective Effect ◽  
Control Group ◽  
Group Model ◽  
Protective Effects ◽  
Model Group ◽  
Expression Levels

To investigate the protective effects of galangin on liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress. Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly ( p < 0.01); the activity of SOD and GSH decreased significantly ( p < 0.01); and the histopathological examination revealed liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced liver damage indicators. Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels ( p < 0.01). This study supports the hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.

Effect of Curculigo orchioides on Reflux Esophagitis by Suppressing Proinflammatory Cytokines

2012 ◽  
Vol 40 (06) ◽  
pp. 1241-1255 ◽  
Author(s):  
Sae-Kang Ku ◽  
Jae-Soo Kim ◽  
Young-Bae Seo ◽  
Yong-Ung Kim ◽  
Seung-Lark Hwang ◽  
...  
Keyword(s):  
Reflux Esophagitis ◽  
Group Treatment ◽  
Control Group ◽  
Esophageal Mucosa ◽  
Dependent Manner ◽  
Protective Effects ◽  
Model Group ◽  
Curculigo Orchioides ◽  
Intact Group ◽  
Tnf Α

This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were all assayed and the expression of TNF-α and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of α-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-α, IL-1β and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-α and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with α-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-α in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage.

scholarly journals Alpha-Asarone Protects Endothelial Cells from Injury by Angiotensin II

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hai-Xia Shi ◽  
Jiajun Yang ◽  
Tao Yang ◽  
Yong-Liang Xue ◽  
Jun Liu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Cell Injury ◽  
Fluorescent Dyes ◽  
Umbilical Vein ◽  
Protective Effects ◽  
Ang Ii ◽  
Versus Model

α-Asarone is the major therapeutical constituent ofAcorus tatarinowiiSchott. In this study, the potential protective effects ofα-asarone against endothelial cell injury induced by angiotensin II were investigatedin vitro. The EA.hy926 cell line derived from human umbilical vein endothelial cells was pretreated withα-asarone (10, 50, 100 µmol/L) for 1 h, followed by coincubation with Ang II (0.1 µmol/L) for 24 h. Intracellular nitric oxide (NO) and reactive oxygen species (ROS) were detected by fluorescent dyes, and phosphorylation of endothelial nitric oxide synthase (eNOS) atSer1177was determined by Western blotting.α-Asarone dose-dependently mitigated the Ang II-induced intracellular NO reduction (P<0.01versus model) and ROS production (P<0.01versus model). Furthermore, eNOS phosphorylation (Ser1177) by acetylcholine was significantly inhibited by Ang II, while pretreatment for 1 h withα-asarone partially prevented this effect (P<0.05versus model). Additionally, cell viability determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay (105~114.5% versus control,P>0.05) was not affected after 24 h of incubation withα-asarone at 1–100 µmol/L. Therefore,α-asarone protects against Ang II-mediated damage of endothelial cells and may be developed to prevent injury to cardiovascular tissues.

scholarly journals In Vivo and In Vitro Evaluation of the Protective Effects of Hesperidin in Lipopolysaccharide-Induced Inflammation and Cytotoxicity of Cell

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 478 ◽  
Author(s):  
Rasha Al-Rikabi ◽  
Hanady Al-Shmgani ◽  
Yaser Hassan Dewir ◽  
Salah El-Hendawy
Keyword(s):  
Breast Cancer ◽  
Chromatin Condensation ◽  
Control Group ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Protective Effects ◽  
Mcf7 Cells ◽  
Tnf Α

(1) Background: Plant flavonoids are efficient in preventing and treating various diseases. This study aimed to evaluate the ability of hesperidin, a flavonoid found in citrus fruits, in inhibiting lipopolysaccharide (LPS) induced inflammation, which induced lethal toxicity in vivo, and to evaluate its importance as an antitumor agent in breast cancer. The in vivo experiments revealed the protective effects of hesperidin against the negative LPS effects on the liver and spleen of male mice. (2) Methods: In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH) and catalase (CAT), whereas in spleen, the concentration of cytokines including IL-33 and TNF-α was measured. The in vitro experiments including MTT assay, clonogenity test, and sulforhodamine 101 stain with DAPI (4′, 6-diamidino-2-phenylindole) were used to assess the morphological apoptosis in breast cancer cells. (3) Results: The results of this study revealed a significant increase in the IL-33 and TNF-α cytokine levels in LPS challenged mice along with a considerable elevation in glutathione (GSH); moreover, the catalase (CAT) level was higher compared to that of the control group. Cytotoxicity of the MCF-7 cell line revealed significant differences among the groups treated with different concentrations when compared to the control groups, in a concentration-dependent manner. Hesperidin significantly inhibited the colony formation of MCF7 cells when compared to that of control. Clear changes were observed in the cell shape, including cell shrinkage and chromatin condensation, which were associated with a later apoptotic stage. (4) Conclusion: The results indicate that hesperidin might be a potential candidate in preventing diseases.

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