Protective effect of Linomide on TNF-α-induced hepatic injury

Acetaminophen (APAP) is one of the most used analgesics and antipyretic agents in the world. Intoxication with APAP is the main cause of acute liver toxicity in both the US and Europe. Spore-forming probiotic bacteria have the ability to resist harsh gastric and intestinal conditions. The aim of this study was to investigate the possible protective effect of Bacillus (B) species (sp) spores (B. licheniformis, B. indicus, B. subtilis, B. clausii, B. coagulans) against hepatotoxicity induced by APAP in rats. A total of 35 rats were randomly divided into seven groups: group I served as control; group II received silymarin; group III received MegaSporeBioticTM (MSB); group IV received APAP and served as the model of hepatotoxicity; group V received APAP and silymarin; group VI received APAP and MSB; group VII received APAP, silymarin and MSB. The livers for histopathological examination and blood samples were collected on the last day of the experiment. We determined aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total antioxidant capacity (TAC) levels and zonula occludens (ZO-1), tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) expression. APAP overdose increased AST and ALT. It slowly decreased TAC compared to the control group, but pretreatment with silymarin and MSB increased TAC levels. Elevated plasma concentrations were identified for ZO-1 in groups treated with APAP overdose compared with those without APAP or receiving APAP in combination with silymarin, MSB or both. The changes were positively correlated with the levels of other proinflammatory cytokines (TNF-α, IL-1β). In addition, histopathological hepatic injury was improved by preadministration of MSB or silymarin versus the disease model group. Bacillus sp spores had a protective effect on acute hepatic injury induced by APAP. Pretreatment with MSB resulted in a significant reduction in serum AST, ALT, TNF-α, IL-1β, ZO-1, TAC and also hepatocyte necrosis, similar to the well-known hepatoprotective agent—silymarin.

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Protective effect of a new heterocyclic compound on acute tracheobronchitis via reducing IL-6 and TNF-α content and PKA-NF-κB pathway activation

Main Group Chemistry ◽

10.3233/mgc-210006 ◽

2021 ◽

Vol 20 (1) ◽

pp. 41-48

Author(s):

Ai-Ping Han ◽

Li Li

Keyword(s):

Protective Effect ◽

Heterocyclic Compound ◽

Biological Study ◽

Elisa Assay ◽

Mice Model ◽

X Ray ◽

X Ray Crystallography ◽

Pathway Activation ◽

Tnf Α ◽

Amino Benzoic Acid

The new heterocyclic compound 4-methyl-3-((4-(pyridin-3-yl) pyrimidin-2-yl) amino) benzoic acid (1) designed utilizing methyl 3-amino-4-methylbenzoate (2) as a starting material was successfully fabricated and eventually characterized utilizing single crystal X-ray crystallography, 1H NMR and IR. In biological study, to evaluate the protective effect of compound on acute tracheobronchitis ICR mice model, the ELISA assay was performed to determine the level of inflammatory mediators IL-6 and TNF-α in serum. Then, the western blot was performed to determine the activation of PKA-NF-κB pathway in tissues.

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Role of endogenous TNF-α in cardiomyocyte apoptosis induced by bacteria lipoprotein and the protective effect of IL-10

European Journal of Inflammation ◽

10.1177/1721727x15597363 ◽

2015 ◽

Vol 13 (2) ◽

pp. 117-125 ◽

Cited By ~ 3

Author(s):

Zhicai Li ◽

Jing Zhou ◽

Dongmei Zhu ◽

Qian Zhang ◽

Min Huang ◽

...

Keyword(s):

Protective Effect ◽

Cardiomyocyte Apoptosis ◽

Tnf Α

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Lipopolysaccharide andd-galactosamine-induced hepatic injury is mediated by TNF-α and not by Fas ligand

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.278.5.r1196 ◽

2000 ◽

Vol 278 (5) ◽

pp. R1196-R1201 ◽

Cited By ~ 77

Author(s):

Michael D. Josephs ◽

F. Rena Bahjat ◽

Kunitaro Fukuzuka ◽

Riadh Ksontini ◽

Carmen C. Solorzano ◽

...

Keyword(s):

Liver Injury ◽

Hepatic Injury ◽

Fas Ligand ◽

Nuclear Dna ◽

Spontaneous Mutation ◽

Hepatic Expression ◽

Soluble Fas ◽

Tnf Α ◽

Necrosis Factor

Tumor necrosis factor (TNF)-α and Fas ligand (FasL) are trimeric proteins that induce apoptosis through similar caspase-dependent pathways. Hepatocytes are particularly sensitive to inflammation-induced programmed cell death, although the contribution of TNF-α and/or FasL to this injury response is still unclear. Here, we report that d-galactosamine and lipopolysaccharide-induced liver injury in C57BL/6 mice is associated with increased hepatic expression of both TNF-α and FasL mRNA. Pretreatment of mice with a TNF-binding protein improved survival, reduced plasma aspartate aminotransferase concentrations, and attenuated the apoptotic liver injury, as determined histologically and by in situ 3′ OH end labeling of fragmented nuclear DNA. In contrast, pretreatment of mice with a murine-soluble Fas fusion protein (Fasfp) had only minimal effect on survival, and apoptotic liver injury was either unaffected or exacerbated depending on the dose of Fasfp employed. Similarly, mice with a spontaneous mutation in FasL (B6Smn.C3H- Faslgldderived from C57BL/6) were equally sensitive tod-galactosamine/lipopolysaccharide-induced shock. We conclude that the shock and apoptotic liver injury afterd-galactosamine/lipopolysaccharide treatment are due primarily to TNF-α release, whereas increased FasL expression appears to contribute little to the mortality and hepatic injury.

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Protective Effect of Ethanol Extract of Roots of Tetracera akara (Burm. f.) Merr., on Carbon Tetrachloride-induced Hepatic Injury in Wistar Rats

10.36468/pharmaceutical-sciences.580 ◽

2019 ◽

Vol 81 (5) ◽

Author(s):

R. R. Nair ◽

S. R. Suja ◽

V. Vilash ◽

A. L. Aneeshkumar ◽

S. Rajasekharan ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Protective Effect ◽

Wistar Rats ◽

Hepatic Injury ◽

Ethanol Extract

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Umbelliferone alleviates hepatic injury in diabetic db/db mice via inhibiting inflammatory response and activating Nrf2-mediated antioxidant

Bioscience Reports ◽

10.1042/bsr20180444 ◽

2018 ◽

Vol 38 (4) ◽

Cited By ~ 9

Author(s):

Jiangning Yin ◽

Hanqing Wang ◽

Guoyuan Lu

Keyword(s):

Blood Glucose ◽

Inflammatory Response ◽

Protective Effect ◽

High Mobility ◽

Hepatic Function ◽

Tolerance Test ◽

Oral Glucose ◽

Stress Indicators ◽

Tnf Α ◽

Oxidative Stress Indicators

The current study was designed to investigate the protective effect and possible mechanisms of umbelliferone (Umb) on liver injury in diabetic C57BL/KsJ-db/db (dbdb) mice. Mice were divided into five groups: wild-type mice group (WY), dbdb mice group, dbdb mice + Metformin (100 mg/kg) group, dbdb mice + Umb (20, 40 mg/kg) group. Blood glucose regulation was assessed by an oral glucose tolerance test (OGTT). At 28 days after drug administration, blood samples were obtained for the analysis of lipids and enzymes related to hepatic function, including alanine aminotransferase (ALT), aspartate aminotransaminase (AST) and total cholesterol (TC) and triglyceride (TG). Expression levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and oxidative stress indicators (SOD and MDA) were measured with ELISA kit. The expressions of high-mobility group box 1 (HMGB1), Toll-like receptor (TLR) 4 (TLR4), Myd88, NF-κB, IκB, Nrf2, and HO-1 proteins were also evaluated by Western blotting analysis. The results showed that Umb significantly restored the blood glucose in OGTT, and inhibited the levels of insulin, TG, TC, as well as activities of ALT and AST. Moreover, Umb inhibited diabetic inflammation through down-regulating the expression of HMGB1, TLR4, NF-κB, and IκB. In addition, Umb alleviated oxidative damage in the liver by activating Nrf2-mediated signal pathway. These findings demonstrated that Umb exhibited protective effect against diabetic live injury, which may be through inhibiting HMGB1-induced inflammatory response and activating Nrf2-mediated antioxidant.

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The Protective Effect of Picroside II on Isoflurane-Induced Neuronal Injury in Rats via Downregulating miR-195

NeuroImmunoModulation ◽

10.1159/000519779 ◽

2021 ◽

pp. 1-9

Author(s):

Hui Li ◽

Weijia Du ◽

Yawei Yuan ◽

Jingjing Xue ◽

Qiang Li ◽

...

Keyword(s):

Inflammatory Response ◽

Protective Effect ◽

Inflammatory Cytokines ◽

Escape Latency ◽

Neuronal Cells ◽

Neuronal Injury ◽

Morris Water Maze Test ◽

Picroside Ii ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Introduction: Numerous pieces of evidence demonstrated that isoflurane induces hippocampal cell injury and cognitive impairments. Picroside II has been investigated for its anti-apoptosis and antioxidant neuroprotective effects. We aimed to explore the protective effects of picroside II and the role of microRNA-195 (miR-195) on isoflurane-induced neuronal injury in rats. Methods: The Morris water maze test was used to evaluate the effects of isoflurane on rats regarding escape latency and time in quadrant parameters. Real-time quantitative PCR was used to detect the expression levels of miR-195 and pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) mRNA, in the hippocampal tissues and neuronal cells. Results: The picroside II significantly improves isoflurane-induced higher escape latency and lower time spent in the quadrant compared with the control rats. Picroside II also promotes cell viability and suppresses cell apoptosis of isoflurane-induced neuronal cells. Besides, picroside II suppresses the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and miR-195 in vivo and in vitro. Furthermore, overexpression of miR-195 abrogates the effects of picroside II on the expression of pro-inflammatory cytokines. The appropriate dose of picroside II is 20 mg/kg. Conclusion: Picroside II could protect the nervous system possibly through inhibiting the inflammatory response in the isoflurane-induced neuronal injury of rats. The protective effect of picroside II may be achieved by downregulating the expression of miR-195 and then inhibiting the inflammatory response.

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Apoptosis perturbations and expression of regulatory inflammatory factors in cisplatin-depleted rat livers under l-arginine protection

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2018-0706 ◽

2019 ◽

Vol 97 (5) ◽

pp. 359-369 ◽

Cited By ~ 1

Author(s):

Rehab M. El-Sayed ◽

Hebatalla I. Ahmed ◽

Abd El-Lateef S. Abd El-Lateef ◽

Azza A. Ali

Keyword(s):

Liver Function ◽

Hepatic Injury ◽

Inflammatory Factors ◽

Protective Effects ◽

Tnf Α ◽

Apoptotic Marker ◽

Apoptosis Markers ◽

Anti Inflammatory ◽

Rat Livers ◽

Inflammatory Effect

Hepatic injury is one of the most common complications associated with cisplatin (CIS) use. Recently, liver protection lines are being discovered to stop the hepatic cell death due to inflammatory and apoptotic perturbations. l-arginine has protective effects in several models of liver injury. This study was designed to investigate the possible protective effect of l-arginine against CIS-induced acute hepatic injury in rats. Rats were divided into 4 groups: control, l-arginine, CIS, l-arginine + CIS. Liver function, oxidative stress, inflammatory cytokines, and apoptosis markers were assessed. l-arginine pretreatment protected the liver against CIS-induced toxicity as indicated by significantly alleviating the changes in liver function along with restoration of the antioxidant status. This finding was confirmed with the markedly improved pathological changes. l-arginine showed anti-inflammatory effect through the reduction of liver expression of iNOS, TNF-α, and NF-κβ, which were ameliorated to significant levels. Furthermore, l-arginine administration downregulated the liver expression of the apoptotic marker, caspase-3. The results recommend l-arginine as a hepatoprotective agent against CIS toxicity. Mostly, this hepatoprotective effect of l-arginine involved anti-inflammatory and anti-apoptotic activities.

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Hepatoprotective effect of Omega-3 PUFAs against acute paracetamol-induced hepatic injury confirmed by FTIR

Human & Experimental Toxicology ◽

10.1177/0960327120954522 ◽

2020 ◽

pp. 096032712095452

Author(s):

Zeinab A El-Gendy ◽

Seham A El-Batran ◽

SAH Youssef ◽

A Ramadan ◽

Walid El Hotaby ◽

...

Keyword(s):

Hepatic Injury ◽

Ldl Cholesterol ◽

Hdl Cholesterol ◽

Hepatoprotective Effect ◽

Omega 3 ◽

Oral Ingestion ◽

Tnf Α ◽

Hepatoprotective Agent ◽

Biochemical Analyses ◽

Protein Alterations

Acute paracetamol over dose-induced hepatotoxicity is considered an important medical hazard especially among women. Omega-3 long-chain polyunsaturated fatty acids (Omega-3 PUFAs) daily doses are nowadays recommended for their antioxidant and anti-inflammatory potentials. Fourier transform infrared (FTIR) spectroscopy is considered a reliable method in analyzing cellular alterations and is now efficiently used to diagnose several diseases and the efficacy of drugs even in the early stages. The aim of our study was to evaluate the hepatoprotective effect of Omega-3 PUFAs against paracetamol-induced hepatotoxicity in rats confirmed through measuring protein alterations in hepatocytes by FTIR. Rats were pretreated with Omega-3 PUFAs (50 and 100 mg/kg) for 21 days prior to oral ingestion of paracetamol. FTIR results revealed that Omega-3 PUFAs (50 mg/kg) limited the toxic effects of paracetamol by restoring the hepatic amide I to amide II ratio. In addition; biochemical analyses demonstrated that serum ALT, AST, Cholesterol, LDL-cholesterol and Il-6 levels as well as hepatic TNF-α, MDA, NOx levels were decreased. Besides; serum HDL-cholesterol level and hepatic GSH level were increased. Histopathological examinations of hepatic sections validated the hepatoprotective potential. The overall effect of this dose was comparable to those of the usual recommended hepatoprotective supplement; silymarin. In conclusion; it would be recommended to use Omega-3 PUFAs in low doses on daily bases as a hepatoprotective agent.

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Protective effect of Cordyceps sinensis extract on lipopolysaccharide-induced acute lung injury in mice

Bioscience Reports ◽

10.1042/bsr20190789 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 6

Author(s):

Shuiqiao Fu ◽

Weina Lu ◽

Wenqiao Yu ◽

Jun Hu

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Protective Effect ◽

Weight Ratio ◽

Cordyceps Sinensis ◽

Myeloperoxidase Activity ◽

Mrna Levels ◽

Dependent Manner ◽

Tnf Α ◽

Cox 2

Abstract Background: To study the protective effect of Cordyceps sinensis extract (Dong Chong Xia Cao in Chinese [DCXC]) on experimental acute lung injury (ALI) mice. Methods and results: ALI model was induced by intratracheal-instilled lipopolysaccharide (LPS, 2.4 mg/kg) in BALB/c male mice. The mice were administrated DCXC (ig, 10, 30, 60 mg/kg) in 4 and 8 h after receiving LPS. Histopathological section, wet/dry lung weight ratio and myeloperoxidase activity were detected. Bronchoalveolar lavage fluid (BALF) was collected for cell count, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and nitric oxide (NO) in BALF was detected by ELISA, the protein and mRNA expression of nuclear factor-κB p65 (NF-κB p65), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissue was detected by Western blot and RT-PCR. The result showed that DCXC could reduce the degree of histopathological injury, wet/dry weight ratio (W/D ratio) and myeloperoxidase activity (P<0.05) with a dose-dependent manner. The increased number of total cells, neutrophils and macrophages in BALF were significantly inhibited by DCXC treatment (P<0.05). The increased levels of TNF-α, IL-1β, IL-6 and NO in BALF after LPS administration was significantly reduced by DCXC (P<0.05). In addition, the increased protein and mRNA levels of iNOS, COX-2 and NF-κB p65 DNA binding ability in LPS group were dose-dependently reduced by DCXC treatment (P<0.05). Conclusion: DCXC could play an anti-inflammatory and antioxidant effect on LPS-induced ALI through inhibiting NF-κB p65 phosphorylation, and the expression of COX-2 and iNOS in lung. The result showed that DCXC has a potential protective effect on the ALI.

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