scholarly journals Mitigation of Arsenic-induced Increases in Pro-Inflammatory Cytokines and Haematological Derangements by Ethanol Leaf Extract of Irvingia gabonensis

Author(s):  
Efosa Godwin Ewere ◽  
Ngozi Paulinus Okolie ◽  
Oboso Edem Etim ◽  
Samson Adewale Oyebadejo

Aim: To investigate the effect of ethanol leaf extract of Irvingia gabonensis (ELEIG) on sodium arsenite (SA)-induced hepatic pro-inflammatory cytokines and haematological derangements in Wistar rats. Study Design: Fifty five Wistar rats weighing between 100 g and 161 g were randomly distributed to eleven (11) groups (n=5). Group 1 (control) had feed and water only. Group 2 received SA at a dose of 4.1 mg/kg body weight (kgbw) for 14 days. Groups 3-11 received ELEIG with or without SA. Place and Duration of Study: Biochemistry Department, University of Uyo and Biochemistry Department, University of Benin. The duration of the study was 14 days. Methodology: Treatment was done orally for 14 days. Immunological markers: tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-10 (IL-10), and haematological indices: red blood cell (RBC) count, haemoglobin (HB) concentration, packed cell volume (PCV), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC), mean corpuscular volume (MCV), white blood cell (WBC) count and its differentials and platelet (PLT) count were used to determine the immunomodulatory and haematological effects of the extract. Results: Intoxication with SA caused significant (p ˂ 0.05) increases in hepatic TNF-α, IL-1β, and IL-4 levels and a significant decrease in hepatic IL-10 level, relative to control. The SA treatment also caused significant (p ˂ 0.05) decreases in RBC, HB, PCV MCH, MCHC, MCV, PLT and monocyte counts as well as significant (p ˂ 0.05) increases in WBC, lymphocyte, basophil, eosinophil and neutrophil counts, relative to control. However, post-treatment and concomitant treatment with ELEIG ameliorated the noxious effect of SA. In addition, ELEIG alone at various doses produced results with most of the assayed parameters having values comparable with those control. Conclusion: These results indicate that ELEIG mitigates SA-induced inflammation and haematological perturbations in Wistar rats.

2021 ◽  
Vol 15 (1) ◽  
pp. 027-037
Author(s):  
Efosa Godwin Ewere ◽  
Ngozi Paulinus Okolie ◽  
Jessie Idongesit Ndem ◽  
Samson Adewale Oyebadejo

This study investigated the effect of ethanol stem bark extract of Irvingia gabonensis (ESEIG) on sodium arsenite (SA)-induced pro-inflammatory cytokines and hematological perturbations in Wistar rats. Fifty-five Wistar rats weighing 100 g - 179 g were distributed into eleven groups (n=5). Group 1 had feed and water only. Group 2 received 4.1 mg/kg body weight (kgbw) of SA. Groups 3-11 received SA and/or ESEIG. Treatment was done orally for 14 days. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-4 (IL-4) concentrations, hemoglobin (HB) concentration, red blood cell (RBC) count, packed cell volume (PCV), mean cell hemoglobin concentration (MCHC), mean cell hemoglobin (MCH), mean corpuscular volume (MCV), white blood cell (WBC) count and its differentials and platelet (PLT) count were used to investigate the immunological and hematological effects of ESEIG. Exposure to SA produced significant (p ˂ 0.05) increases in hepatic IL-1β, TNF-α, IL-10 and IL-4 concentrations relative to control. Administration of SA also caused significant (p ˂ 0.05) decreases in HB, RBC, PCV, MCHC, MCH, MCV and PLT and significant (p ˂ 0.05) increases in WBC, lymphocytes, monocytes, eosinophils and neutrophils compared with control. Treatment with ESEIG concomitantly and 2 weeks after SA exposure, mitigated the deleterious effect of SA. However, ESEIG alone at various doses caused significant (p ˂ 0.05) increases in some of the assayed parameters, compared with control. These results imply that ESEIG may be protective against SA-induced inflammation and hematological derangements in Wistar rats. Its exclusive administration on chronic basis may also be slightly toxic.


2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.


Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.


Author(s):  
Hadi Nobari ◽  
Jason M. Cholewa ◽  
Jorge Pérez-Gómez ◽  
Alfonso Castillo-Rodríguez

Abstract Objective Systemic elevations in pro-inflammatory cytokines are a marker of non-functional over reaching, and betaine has been shown to reduce the secretion of pro-inflammatory cytokines in vitro. The aim of this study was to investigate the effects of betaine supplementation on tumor necrosis factor alpha (TNF-α), interleukins-1 beta (IL-1β), − 6 (IL-6) and the complete blood cell (CBC) count in professional youth soccer players during a competitive season. Methods Twenty-nine soccer players (age, 15.5 ± 0.3 years) were randomly divided into two groups based on playing position: betaine group (BG, n = 14, 2 g/day) or placebo group (PG, n = 15). During the 14-week period, training load was matched and well-being indicators were monitored daily. The aforementioned cytokines and CBC were assessed at pre- (P1), mid- (P2), and post- (P3) season. Results Significant (p < 0.05) group x time interactions were found for TNF-α, IL-1β, and IL-6. These variables were lower in the BG at P2 and P3 compared to P1, while IL-1β was greater in the PG at P3 compared to P1 (p = 0.033). The CBC count analysis showed there was significant group by time interactions for white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), and mean corpuscular hemoglobin concentration (MCHC). WBC demonstrated increases at P3 compared to P2 in PG (p = 0.034); RBC was less at P3 compared to P1 in BG (p = 0.020); Hb was greater at P2 compared to P1, whilst it was less at P3 compared to P3 for both groups. MCHC was greater at P3 and P2 compared to P1 in BG, whereas MCHC was significantly lower at P3 compared to P2 in the PG (p = 0.003). Conclusion The results confirmed that 14 weeks of betaine supplementation prevented an increase in pro-inflammatory cytokines and WBC counts. It seems that betaine supplementation may be a useful nutritional strategy to regulate the immune response during a fatiguing soccer season.


Author(s):  
◽  
◽  
◽  

Objective: The study evaluated the hypolipidemic and anti-inflammatory potential of the hydroalcoholic extract of P. Aculeata (HEPa/EtOAC) in Wistar rats fed with Westernized diet. Methods: The experiment was approved by the Ethics Committee (Federal University of Pernambuco-23076.027165 / 2010-21). The hydroalcoholic extract (HEPa/EtOAc) was obtained from the aerial parts of P. Aculeata and portioned by acetate/ethanol in different concentrations. 36 male Wistar rats were initially divided into two groups: Control (C, n = 6), fed a commercial diet (26g / 100g of protein; 63g / 100g of carbohydrates; 11g / 100g of lipids) and Westernized (W; n = 30) – fed an experimental diet (15g / 100g of protein; 51g / 100g of carbohydrates; 34 g/100g of lipids) receving water ad libitum. After 4 months of diet, W group was arbitrarily redistributed into six subgroups according to water supplementation, or different extracts concentrations: (n = 6 animals/group): W- distilled water (1mL/kg; po); WG – genfibrozil (140 mg/kg; p.o.); W35- 35 mg/kg; W70 – 70 mg /kg; p.o. and W140- 140 mg/kg; p.o for 30 days. The lipid profile and pro-inflammatory cytokines were analyzed. Results: The westernized diet caused dyslipidemia and the treatment with HEPa-EtOAc (140mg / kg), promoted a significant reduction in the concentration of pro-inflammatory cytokines, in total cholesterol, in the LDLc and serum triglycerides. Conclusion: The reduction of dyslipidemia and pro-inflammatory cytokines from the of P. Aculeata extract corroborate the ethnopharmacological potential of the plant, already used by the population for hypoglycemic purposes.


2021 ◽  
Vol 8 (21) ◽  
pp. 1731-1732
Author(s):  
Prashant Ramesh Chakkarwar

Coronavirus disease-19 (COVID-19) is the deadliest pandemic that the whole world is facing today. COVID-19 is different from normal flu by its two lethal manifestations which includes deadly pneumonia which may lead to acute respiratory distress syndrome (ARDS) due to hyper-inflammation of alveolar tissues and pulmonary intravascular coagulopathy (PIC).1,2 It is noteworthy here to mention that both these lethal manifestations of COVID-19 are due to abnormally high levels of pro-inflammatory cytokines like interleukin (IL) - 1β, IL - 6, and tumour necrosis factor (TNF) - α, termed as “cytokine storm.”3,4 There is a certain link between pro-inflammatory cytokines like IL - 1β, IL - 6, and TNF - α and its pro-coagulatory influence on coagulation pathway mediated by tissue factor that binds and activate factor VII, leading to formation of tissue factor – VII a complexes which results in the activation of clotting factor X and IX.4 Recently the researchers in China and some European countries have found raised level of pro-inflammatory cytokines particularly IL - 6 in severe cases of COVID-19. They also found raised D-dimer, fibrinogen levels and prothrombin time in moderate to severe COVID-19 cases.5,6 Both of these lethal manifestations of COVID-19 – ARDS and PIC are linked to raised levels of pro-inflammatory cytokines, particularly, IL - 6. It is not very clear that the pro-inflammatory action of cytokines is mediated through leukotrienes as the biochemical assay for leukotrienes are not widely available but possibility of this probable mechanism cannot be ruled out. Hence, development of any molecule with ability to inhibit pro-inflammatory cytokines, particularly IL-6 may be able to tame the lethal nature of COVID-19, and may ultimately reduce the mortality of this deadly pandemic. Montelukast sodium is such molecule which has capacity to inhibit proinflammatory cytokines such as IL - 1β, IL - 6, and TNF - α.7 Montelukast sodium is leukotriene receptor antagonist that inhibits the cysteinyl leukotriene type-1 receptor. Leukotrienes modulate the production of pro-inflammatory cytokines.8 Its antagonist action on leukotriene receptors can inhibit the production of these pro-inflammatory cytokines. Even recent in silico study by Jacobson at Oak Ridge National Lab, was found that excess bradykinin production may be responsible for pulmonary, cardiac, neurological and nephrological lethal manifestations of COVID-19.9 Crimi et al.10 already found that Montelukast is effective to control bradykinin induced bronchoconstriction. Thus, theoretically, montelukast seems to be best molecule to deal with deadly manifestation of COVID-19 even if we go by cytokine storm hypothesis or bradykinin hypothesis.


2012 ◽  
Vol 27 (3) ◽  
pp. 223-230 ◽  
Author(s):  
Renata Cristiane Gennari Bianchi ◽  
Eduardo Rochete Ropelle ◽  
Carlos Kiyoshi Katashima ◽  
José Barreto Campello Carvalheira ◽  
Luiz Roberto Lopes ◽  
...  

PURPOSE: To study if the pre-radiotherapy physical activity has radio-protective elements, by measuring the radio-induced activation of pro-inflammatory cytokines as interleukin-6 (il-6), transforming growth factor -β (tgf -β), tumor necrosis factor -α (tnf-α) and protein beta kinase β (ikkβ), through western blotting analysis. METHODS: A randomized study with 28 Wistar hannover rats, males, with a mean age of 90 days and weighing about 200 grams. The animals were divided into three groups: (GI, GII and GIII). GIII group were submitted to swimming for eight weeks (zero load, three times a week, about 30 minutes). Then, the groups (except the control group) were submitted to irradiation by cobalt therapy, single dose of 3.5 gray in the whole body. All animals were sacrificed by overdose of pentobarbital, according to the time for analysis of cytokines, and then a fragment of the lower lobe of the right lung went to western blotting analysis. RESULTS: The cytokines IKK β, TNF-α and IL-6 induced by radiation in the lung were lower in the exercised animals. However, exercise did not alter the radiation-induced increase in tgf-β. CONCLUSION: The results show a lower response in relation to inflammatory cytokines in the group that practiced the exercise pre-radiotherapy, showing that exercise can protect tissues from tissue damage due to irradiation.


2013 ◽  
Vol 26 (1) ◽  
pp. 37-48 ◽  
Author(s):  
S.M. Nanjundaiah ◽  
J.P. Stains ◽  
K.D. Moudgil

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, bone erosion, and cartilage destruction in the joints. It is increasingly being realized that inflammation might play an important role in inducing bone damage in arthritis. However, there is limited validation of this concept in vivo in well-controlled experimental conditions. We addressed this issue using the adjuvant arthritis (AA) model of RA. In AA, the draining lymph nodes are the main sites of activation of pathogenic leukocytes, which then migrate into the joints leading to the induction of arthritis. We tested the temporal kinetics of mediators of bone damage [e.g., receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and osteopontin (OPN)] and inflammation (pro-inflammatory cytokines and chemokines) in the draining lymph node cells (LNC) at different phases of AA, and then examined their inter-relationships. Our study revealed that, together with cytokines/chemokines, some of the mediators of bone remodeling are also produced in LNC. Various cytokines/chemokines showed distinct kinetics of expression as well as patterns of correlation with mediators of bone remodeling at different phases of the disease. Pro-inflammatory cytokines such as TNF-α are known to play an important role in bone damage. Interestingly, there was a positive correlation between TNF-α and RANKL, between RANKL and each of the 3 chemokines tested (RANTES, MIP-1α, and GRO/KC), and between TNF-α and RANTES. Our results in the AA model lend support to the concept of osteo-immune crosstalk during the course of autoimmune arthritis.


Sign in / Sign up

Export Citation Format

Share Document