scholarly journals Thymoquinone Attenuates Immune Mediated Liver Injury Induced by Concanavalin A in Mice

2021 ◽  
Vol 30 (2) ◽  
pp. 50-57
Author(s):  
Halla A. Ahmad ◽  
Sarmed H. Kathem
Keyword(s):  
Liver Injury ◽  
Inflammatory Cytokines ◽  
Liver Damage ◽  
Concanavalin A ◽  
Liver Tissue ◽  
Tissue Homogenate ◽  
Control Group ◽  
Dependent Manner ◽  
Immune Mediated ◽  
Dose Dependent

Autoimmune hepatitis is an inflammatory disease and its incidence has been increasing. The features of hepatitis are the release of inflammatory cytokines, the elevation of AST and ALT, and hepatocyte apoptosis and necrosis. Concanavalin A considered as essential model represents the acute immune-mediated liver damage in rodents. Thymoquinone is well known herbal compound that exert hepatoprotective, anti-inflammatory, and antioxidant activity. In this study, we focus on the immunoregulatory and liver protective effect of thymoquinone in a mouse model of concanavalin A-induced liver injury. Twenty-four male mice were randomly divided into four groups each containing six animals: Negative control group, concanavalin A model group, thymoquinone 15mg/kg group, and thymoquinone 30mg/kg group. Blood was collected to detect the activities of alanine transaminase (ALT) and aspartate transaminase (AST) as well as liver tissue for the detection of tumor necrosis factor  levels, after 8 hours of concanavalin A injection. Injecting mice with concanavalin resulted in a dramatic increase in serum level of both ALT and AST which indicate severe liver tissue damage with a significant increase in inflammatory cytokines TNF alpha - and INF  levels, with a notable increase in NF-kB gene expression in mice liver tissue homogenate. Thymoquinone pretreatment revealed a dose-dependent increase in liver tissue protection. Conclusion: Thymoquinone has hepatoprotective and immune modulatory effects in concanavalin A induced immune mediated liver damage. Thymoquinone exerted its effect through attenuating NF and its downstream effectors TNF  and INF  in a dose dependent manner.

scholarly journals Study on the Hepatoprotective Effect of Oyster Mushroom (Pleurotus Florida) Against Paracetamol Induced Liver Damage in Wistar Albino Rats

1970 ◽  
Vol 5 (2) ◽  
pp. 46-52 ◽  
Author(s):  
Afroza Khanam Sumy ◽  
Nasim Jahan ◽  
Nayma Sultana
Keyword(s):  
Liver Damage ◽  
Liver Tissue ◽  
Treated Group ◽  
Oyster Mushroom ◽  
Tissue Homogenate ◽  
Control Group ◽  
Albino Rats ◽  
Pleurotus Florida ◽  
Wistar Albino Rats ◽  
Group B

Background: Liver damage can be occurred due to prolonged use of higher doses of some drugs, exposure to some chemicals or infectious agents. But liver protective drugs are not available in modern medicine. Some hepatoprotective herbal medicines are often used in the treatment of liver damage. Objective: This experimental study was carried out to observe the hepatoprotective effect of Oyster mushroom (Pleurotus florida) against paracetamol induced liver damage in Wistar albino rats. Method: This experimental study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC), Dhaka from 1st July 2009 to 30th June 2010. A total number of 34 Wistar albino rats, age ranged from 90 to 120 days, weighing between 150 to 210 grams were selected for the study. After acclimatization for 14 days, they were divided into two groups, control group (Group A) and experimental group (Group B- mushroom pretreated and paracetamol treated group). Control group again subdivided into group A1 (baseline control) and group A2 (paracetamol treated control group). All groups of animals received basal diet for 30 consecutive days. Group A1 consisted of 10 rats, received propylene glycol (2 ml/kg bw, orally) only on 30th day. Group A2 consisted of 14 rats, received single dose of paracetamol suspension (750 mg/ kg bw, orally) only on 30th day. Group B consisted of 10 rats, received mushroom extract (200 mg/ kg bw, orally) for 30 consecutive days and paracetamol suspension (750 mg/ kg bw, orally) only on 30th day. All the animals were sacrificed on 31st day. Then blood and liver samples were collected. Initial body weight, final body weight and liver weight were measured. Then measurement of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and assessment of malondialdehyde (MDA) concentration in liver tissue homogenate were done by using standard laboratory kits. The statistical analysis was done by one way ANOVA and Bonferroni test as applicable. Result: The mean serum AST, ALT levels and in the liver tissue MDA concentration were significantly (p<0.001) higher in paracetamol treated group in comparison to those of baseline control group. Again, the mean serum AST (p<0.05), ALT (p<0.05) levels and in the liver tissue homogenate MDA concentration (p<0.001) were significantly lower in mushroom pretreated and paracetamol treated group (experimental group) when compared to those of only paracetamol treated group (control). Conclusion: This study reveals that Oyster mushroom (Pleurotus florida) which is excellently edible and nutritious, may have some hepatoprotective role. Key words: hepatoprotective; oyster mushroom; malondialdehyde; tissue homogenate DOI: 10.3329/jbsp.v5i2.6776J Bangladesh Soc Physiol. 2010 December; 5(2): 46-52

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

scholarly journals Effect of lemon peel flavonoids on anti-fatigue and anti-oxidation capacities of exhaustive exercise mice

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Guili Bao ◽  
Yinglong Zhang ◽  
Xiaoguang Yang
Keyword(s):  
Skeletal Muscle ◽  
Superoxide Dismutase ◽  
Manganese Superoxide Dismutase ◽  
Fatty Acid Content ◽  
Hepatic Tissue ◽  
Control Group ◽  
Dependent Manner ◽  
Lemon Peel ◽  
Tnf Α ◽  
Dose Dependent

AbstractIn this study, lemon peel flavonoids (LPF) were administered to investigate its effect on the anti-fatigue and antioxidant capacity of mice that undergo exercise until exhaustion. LPF (88.36 min in LPFH group mice) significantly increased the exhaustion swimming time compare to the untreated mice (40.36 min), increased the liver glycogen and free fatty acid content in mice and reduce lactic acid and BUN content in a dose-dependent manner. As the concentration of lemon peel flavonoids increased, the serum creatine kinase, aspartate aminotransferase, and alanine aminotransferase levels of mice gradually decreased. LPF increases superoxide dismutase (SOD) and catalase (CAT) levels in mice and reduces malondialdehyde levels in a dose-dependent manner. And LPF raises hepatic tissue SOD, CAT activities and reduces skeletal muscle tissue iNOS, TNF-α levels of mice compared to the control group. LPF also enhanced the expression of copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT mRNA in mouse liver tissue. LPF also enhanced the expression of alanine/serine/cysteine/threonine transporter 1 (ASCT1) mRNA and attenuate the expression of syncytin-1, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α in mouse skeletal muscle. According to high-performance liquid chromatography (HPLC) analysis, it was found that LPF contains flavonoids such as rutin, astragalin, isomangiferin, naringin, and quercetin. Our experimental data show that LPF has good anti-fatigue effects and anti-oxidation ability. In summary, LPF has high prospects to be developed and added to nutritional supplements.

scholarly journals Silica nanoparticles induce NLRP3 inflammasome activation in human primary immune cells

2017 ◽  
Vol 23 (8) ◽  
pp. 697-708 ◽  
Author(s):  
Diana M Gómez ◽  
Silvio Urcuqui-Inchima ◽  
Juan C Hernandez
Keyword(s):  
Physicochemical Properties ◽  
Silica Nanoparticles ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Deep Understanding ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Pro Inflammatory Cytokines

In recent years, the potential use of silica nanoparticles (SiNPs) among different biomedical fields has grown. A deep understanding of the physicochemical properties of nanoparticles (NPs) and their regulation of specific biological responses is crucial for the successful application of NPs. Exposure to NP physicochemical properties (size, shape, porosity, etc.) could result in deleterious effects on cellular functions, including a pro-inflammatory response mediated via activation of the NLRP3 inflammasome. The aim of this study was to evaluate the potential in vitro immunomodulatory effect of 12-nm and 200-nm SiNPs on the expression of pro-inflammatory cytokines and NLRP3 inflammasome components in human primary neutrophils and PBMCs. This study demonstrates that regardless of the size of the nanoparticles, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Induced IL-1β production after exposure to SiNPs suggests the involvement of NLRP3 inflammasome components participation in this process. In conclusion, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, our data suggest that the production and release of IL-1β possibly occurs through the formation of the NLRP3 inflammasome.

Toxicopathological effects of lambda-cyhalothrin in female rabbits (Oryctolagus cuniculus)

2010 ◽  
Vol 30 (7) ◽  
pp. 591-602 ◽  
Author(s):  
Abdul Basir ◽  
Ahrar Khan ◽  
Riaz Mustafa ◽  
Muhammad Zargham Khan ◽  
Farzana Rizvi ◽  
...  
Keyword(s):  
Blood Cell ◽  
Oryctolagus Cuniculus ◽  
Hemoglobin Concentration ◽  
Control Group ◽  
Mean Corpuscular Hemoglobin ◽  
Dependent Manner ◽  
Cell Counts ◽  
Lambda Cyhalothrin ◽  
Group A ◽  
Dose Dependent

The aim of this study was to investigate effects of lambda-cyhalothrin (LCT) on clinical, hematological, biochemical and pathological alterations in rabbits (Oryctolagus cuniculus). New Zealand white female rabbits (n = 24) of 4-5 months age having 997.92 ± 32.83 g weight were divided into four equal groups. Group A (control) received normal saline intraperitoneally (ip). Animals in groups B, C and D were treated with LCT 1.0, 4.0 and 8.0 mg/kg bw ip. Each group received seven consecutive doses at an interval of 48 hours. Blood and serum samples were collected at an interval of 96 hours. Blood analysis revealed a significant (p < 0.05) decrease in red blood cell and white blood cell counts, hemoglobin concentration and lymphocytes, while mean corpuscular hemoglobin concentration, mean corpuscular volume, neutrophils, monocytes and eosinophils were increased. Serum biochemical analysis revealed significant (p < 0.05) decrease in serum total proteins and serum albumin, while an increase was seen in serum alanine aminotransferase and aspartate aminotransferase activities compared with the control group. Serum globulin values varied non-significantly in all treatment groups as compared to control group. A dose-dependent increase in the incidence of micronucleated polychromatic erythrocyte was observed. All gross and histopathological lesions observed in LCT-treated rabbits were dose-dependent. Liver of the treated rabbits exhibited extensive perihepatitis, hyperplasia of bile duct, necrosis, hemorrhages and congestion. In lungs, there were hemorrhages, thickened alveolar walls, congestion, emphysema, collapsed alveoli and accumulation of extensive inflammatory cells. Kidneys were congested and hemorrhagic whereas renal parenchyma and stroma were normal. Microscopically, heart showed congestion of blood vessels and nuclear pyknosis, myodegeneration. It was concluded from the study that LCT produced toxicopathological alterations in rabbits in a dose-dependent manner. On the basis of the results, it can be suggested that overdosing of LCT be avoided while treating animals for ectoparasites.

scholarly journals Hepatoprotective effects of Sapium sebiferum in paracetamol-induced liver injury

2015 ◽  
Vol 10 (2) ◽  
pp. 393 ◽  
Author(s):  
Liaqat Hussain ◽  
Muhammad Sajid Hamid Akash ◽  
Madeha Tahir ◽  
Kanwal Rehman
Keyword(s):  
Liver Injury ◽  
Serum Levels ◽  
Therapeutic Effects ◽  
Sapium Sebiferum ◽  
Dependent Manner ◽  
Protective Effects ◽  
Drug Induced ◽  
Standard Drug ◽  
Hepatoprotective Effects ◽  
Dose Dependent

<span><em>Sapium sebiferum</em> leaves were used to determine its hepatoprotective effects against paracetamol-induced hepatotoxicity in mice. A dose dependent study was conducted using two different doses (200 mg/kg and 400 mg/kg) of the extract of </span><em>S. sebiferum</em><span> against toxic effects of paracetamol (500 mg/kg) in experimental animal model. Silymarin (50 mg/kg) was used as standard drug to compare therapeutic effects of </span><em>S. sebiferum</em><span> with control and paracetamol-treated groups. Paracetamol significantly increased the serum levels of liver enzyme markers like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin. The extract showed protective effects by normalizing the liver enzymes markers in a dose dependent manner. Histopathological results confirmed the hepatoprotective effects of leaves of </span><em>S. sebiferum</em><span>. We conclude that leaves of </span><em>S. sebiferum</em><span> have strong hepatoprotective effects against paracetamol-induced liver injury and can be used in liver injuries caused by drug-induced toxicity.</span>

scholarly journals A Preliminary Study on the Effect of Hydrogen Gas on Alleviating Early CCl4-Induced Chronic Liver Injury in Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1933
Author(s):  
Jianwei Wang ◽  
Quancheng Cheng ◽  
Jinyu Fang ◽  
Huiru Ding ◽  
Huaicun Liu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Tissue ◽  
Uncoupling Protein ◽  
Liver Cells ◽  
Hydrogen Gas ◽  
Chronic Liver ◽  
Control Group ◽  
Protective Mechanism ◽  
Chronic Liver Injury ◽  
Ucp2 Expression

As a small-molecule reductant substance, hydrogen gas has an obvious antioxidant function. It can selectively neutralize hydroxyl radicals (•OH) and peroxynitrite (ONOO•) in cells, reducing oxidative stress damage. The purpose of this study was to investigate the effect of hydrogen gas (3%) on early chronic liver injury (CLI) induced by CCl4 and to preliminarily explore the protective mechanism of hydrogen gas on hepatocytes by observing the expression of uncoupling protein 2 (UCP2) in liver tissue. Here, 32 rats were divided into four groups: the control group, CCl4 group, H2 (hydrogen gas) group, and CCl4 + H2 group. The effect of hydrogen gas on early CLI was observed by serological tests, ELISA, hematoxylin and eosin staining, and oil red O staining. Immunohistochemical staining and Western blotting were used to observe the expression of UCP2 in liver tissues. We found that CCl4 can induce significant steatosis in hepatocytes. When the hydrogen gas was inhaled, hepatocyte steatosis was reduced, and the UCP2 expression level in liver tissue was increased. These results suggest that hydrogen gas might upregulate UCP2 expression levels, reduce the generation of intracellular oxygen free radicals, affect lipid metabolism in liver cells, and play a protective role in liver cells.

scholarly journals Dectin-1-Mediated Production of Pro-Inflammatory Cytokines Induced by Yeast β-Glucans in Bovine Monocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana R. V. Pedro ◽  
Tânia Lima ◽  
Ricardo Fróis-Martins ◽  
Bárbara Leal ◽  
Isabel C. Ramos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Surface ◽  
Inflammatory Cytokines ◽  
Surface Expression ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
Feed Supplements ◽  
Surface Receptor ◽  
Dose Dependent ◽  
Pro Inflammatory Cytokines

Yeast-derived products containing β-glucans have long been used as feed supplements in domesticated animals in an attempt to increase immunity. β-glucans are mainly recognized by the cell surface receptor CLEC7A, also designated Dectin-1. Although the immune mechanisms elicited through Dectin-1 activation have been studied in detail in mice and humans, they are poorly understood in other species. Here, we evaluated the response of bovine monocytes to soluble and particulate purified β-glucans, and also to Zymosan. Our results show that particulate, but not soluble β-glucans, can upregulate the surface expression of costimulatory molecules CD80 and CD86 on bovine monocytes. In addition, stimulated cells increased production of IL-8 and of TNF, IL1B, and IL6 mRNA expression, in a dose-dependent manner, which correlated positively with CLEC7A gene expression. Production of IL-8 and TNF expression decreased significantly after CLEC7A knockdown using two different pairs of siRNAs. Overall, we demonstrated here that bovine monocytes respond to particulate β-glucans, through Dectin-1, by increasing the expression of pro-inflammatory cytokines. Our data support further studies in cattle on the induction of trained immunity using dietary β-glucans.

ATI-2341 Trifluoroacetic Acid (TFA) Promotes Menstrual Blood-Derived Mesenchymal Stem Cell Recruitment and Enhances Uterine Repair Through Gi Pathway in Asherman’s Syndrome

2022 ◽  
Vol 12 (3) ◽  
pp. 506-513
Author(s):  
Ying Lv ◽  
Liyan Ye ◽  
Xiujuan Zheng
Keyword(s):  
Menstrual Blood ◽  
Control Group ◽  
Dependent Manner ◽  
Asherman’S Syndrome ◽  
Expression Levels ◽  
Endometrial Cells ◽  
Injury Model ◽  
Recruitment Effect ◽  
Dose Dependent

This study aimed to explore the role of ATI-2341 in Asherman’s syndrome and its impact on menstrual blood-derived mesenchymal stem cells (MenSCs). Following establishment of endometrial injury model, MenSCs were extracted from rats and cultured. They were treated with ATI-2341 TFA at different concentrations (10 ng/mL, 50 ng/mL, 100 ng/mL) and MenSCs treated without ATI-2341 TFA were taken as controls. Flow cytometry was conducted to detect the cell cycle. MTT was carried out to evaluate proliferation of endometrial cells. The expression levels of MMP-9, TIMP-1, CK, and VIM were determined with staining used to reflect morphology of endometrium. Administration with ATI-2341 TFA resulted in decreased expression of MMP-9 and increased expression of TIMP-1 in a dose-dependent manner. Of note, the increase of ATI-2341 TFA concentration was accompanied with elevated cell proliferation rate, increased number of glands in the endometrium, and decreased fibrosis area. As treated with 100 ng/mL ATI-2341 TFA, the cells exhibited more glands than that under other concentrations with uniformly arranged glands and lowest expression levels of CK and VIM, control group had plenty of blue-stained collagen fibers in the intima and least amount of glands. ATI-2341 TFA 100 ng/mL induced endometrial epithelial recruitment effect on MenSCs and promoted endometrial repair more significantly than Gi-3 pathway agonists. Collectively, ATI-2341 TFA enhances MenSC recruitment and facilitates endometrial epithelial cells proliferation and the repair of uterine damage in Asherman’s syndrome through Gi pathway. These findings provide a\ novel insight into the MenSC-based treatment against Asherman’s syndrome and deserve further investigation.

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