Tannic Acid Exhibits Adjuvant Activity by Enhancing Humoral and Cell-Mediated Immunity Against BSA as a Protein Antigen

2021 ◽  
Vol 28 ◽  
Author(s):  
Nidia Cabral-Hipólito ◽  
Brenda Sarahí Molina-Ramírez ◽  
Irais Castillo-Maldonado ◽  
Rocío Meza-Velázquez ◽  
Rubén García-Garza ◽  
...  
Keyword(s):  
Tannic Acid ◽  
Wistar Rats ◽  
Lethal Dose ◽  
Peritoneal Macrophages ◽  
Protein Antigen ◽  
Cell Mediated Immunity ◽  
Vaccine Adjuvants ◽  
Adjuvant Activity ◽  
Toxic Dose

Background: Immunization or vaccination is the process of inducing artificial immunity against an antigen taking advantage of the mechanisms of immunological memory. Current vaccines include substances known as adjuvants, which tend to improve the immunogenicity of the antigen, reduce the antigen quantity employed, and boost the immune response in weak responders. Unfortunately, only a few vaccine adjuvants are approved for human use. Objective: Thus, the objective of this study was to investigate the effect of Tannic acid on humoral and cell-mediated immunity against bovine serum albumin (BSA) as a protein antigen in Wistar rats. Method: In order to establish the Tannic acid concentration to test it as an adjuvant, the lethal dose 50 and maximum non-toxic dose were calculated through cytotoxicity and hemolytic assays with J774 A.1 cell line and rat erythrocytes by resazurin reduction method and UV/vis spectrophotometry. Thirty Wistar rats were divided into 5 groups that included two controls without antigen and three treatment groups of adjuvants plus BSA as a protein antigen. The rats were immunized in a 30-day scheme. Blood samples were collected for humoral immunity analysis by means of immunoglobulin quantification, isotyping and antigen-antibody precipitation inhibition analysis. Rat peritoneal macrophages and splenocytes were isolated for cell-mediated immunity analysis by means of nitric oxide quantification from adjuvant stimulated peritoneal macrophages and lymphocytes proliferation assay. Results: Tannic acid was capable of increasing the immunogenicity of the antigen; besides, it was able to stimulate cell-mediated immunity by means of increased lymphocyte proliferation. Moreover, Tannic acid improved the humoral response by means of increased specific antibodies titers. These activities may be attributed to pattern recognition receptors stimulation. Conclusion: Tannic acid was considered biocompatible when tested in vivo because the concentration tested did not show cytotoxicity or hemolytic effect, and there was no detrimental effect observed on the animals’ health. These results show Tannic acid as a promising candidate for vaccine adjuvant.

scholarly journals Delving into the Antiurolithiatic Potential of Tribulus terrestris Extract Through –In Vivo Efficacy and Preclinical Safety Investigations in Wistar Rats

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jyoti Kaushik ◽  
Simran Tandon ◽  
Rishi Bhardwaj ◽  
Tanzeer Kaur ◽  
Surinder Kumar Singla ◽  
...  
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Kidney Stones ◽  
Wistar Rats ◽  
Lethal Dose ◽  
Tribulus Terrestris ◽  
Oral Toxicity ◽  
Preclinical Safety

Abstract Modern treatment interventions for kidney stones are wrought with side-effects, hence the need for alternative therapies such as plant-based medicines. We have previously documented through in vitro studies that statistically optimized aqueous extract of Tribulus terrestris (Zygophyllaceae family) possesses antiurolithic and antioxidant potential. This provides strong scientific foundation to conduct in vivo efficacy and preclinical safety studies to corroborate and lend further proof to its ability to prevent and cure kidney stones. The preventive and curative urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats, along with preclinical toxicity was evaluated following oral administration of statistically optimized aqueous extract of T. terrestris. Treatment showed augmented renal function, restoration of normal renal architecture and increase in body weight. Microscopic analysis of urine revealed excretion of small sized urinary crystals, demonstrating that treatment potentially modulated the morphology of renal stones. Tissue enzymatic estimation affirmed the antioxidant efficacy of treatment with reduced free radical generation. Significant upregulation of p38MAPK at both the gene and protein level was noted in hyperoxaluric group and interestingly treatment reversed it. Acute oral toxicity study established the Median Lethal Dose (LD50) to be greater than 2000 mg/kg body weight (b.wt.) No observed adverse effect level (NOAEL) by repeated oral toxicity for 28 days at 750 mg/kg b.wt. was noted. This study lends scientific evidence to the safe, preventive and curative potential of statistically optimized aqueous extract of T. terrestris at a dose of 750 mg/kg b.wt. and suggests that the extract shows promise as a therapeutic antiurolithic agent.

scholarly journals The Immunomodulatory Effects of AlbuminIn VitroandIn Vivo

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Derek S. Wheeler ◽  
John S. Giuliano ◽  
Patrick M. Lahni ◽  
Alvin Denenberg ◽  
Hector R. Wong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lethal Dose ◽  
Intraperitoneal Administration ◽  
Peritoneal Macrophages ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Dose Dependent

Albumin appears to have proinflammatory effectsin vitro. We hypothesized that albumin would induce a state of tolerance to subsequent administration of lipopolysaccharide (LPS)in vitroandin vivo. RAW264.7 and primary peritoneal macrophages were treated with increasing doses of bovine serum albumin (BSA) and harvested for NF-κB luciferase reporter assay or TNF-αELISA. In separate experiments, RAW264.7 cells were preconditioned with 1 mg/mL BSA for 18 h prior to LPS (10 μg/mL) treatment and harvested for NF-κB luciferase reporter assay or TNF-αELISA. Finally, C57Bl/6 mice were preconditioned with albumin via intraperitoneal administration 18 h prior to a lethal dose of LPS (60 mg/kg body wt). Blood was collected at 6 h after LPS administration for TNF-αELISA. Albumin produced a dose-dependent and TLR-4-dependent increase in NF-κB activation and TNF-αgene expressionin vitro. Albumin preconditioning abrogated the LPS-mediated increase in NF-κB activation and TNF-αgene expressionin vitroandin vivo. The clinical significance of these findings remains to be elucidated.

scholarly journals PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Dool-Ri Oh ◽  
Hu Won Kang ◽  
Jong-Ro Kim ◽  
Sunoh Kim ◽  
In-Kyu Park ◽  
...  
Keyword(s):  
Active Component ◽  
Mucosal Vaccine ◽  
Vaccine Adjuvant ◽  
Vaccine Adjuvants ◽  
Adjuvant Activity ◽  
Independent Manner ◽  
Etoh Extract ◽  
Croton Tiglium ◽  
Fractionation Column

Toll-like receptor (TLR) ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that potentiate the adjuvant activity of flagellin, we screened a plant library using HEK293T cells transiently cotransfected with phTLR5 and pNF-κB-SEAP plasmids. The 90% EtOH extract fromCroton tigliumshowed significant NF-κB transactivation in a TLR5-independent manner along with the increase of a flagellin activity. We have studied to characterize an active component fromCroton tigliumand to elucidate the action mechanisms. Phorbol 12-myristate 13-acetate (PMA) was isolated as an active component ofCroton tigliumby activity-guided fractionation, column chromatography, HPLC, NMR, and MS. PMA at a range of nM induced PKC-dependent NF-κB activation and IL-8 production in both TLR5− and TLR5+ assay systems. In in vivo mouse vaccination model, PMA induced antigen-specific IgG and IgA antibody responses and increased IL-12 production corresponding to T cell responses in spleen lymphocytes. These results suggest that PMA would serve as an efficacious mucosal vaccine adjuvant.

scholarly journals Toxicity and Antileishmanial Activity of a New Stable Lipid Suspension of Amphotericin B

2003 ◽  
Vol 47 (12) ◽  
pp. 3774-3779 ◽  
Author(s):  
Malika Larabi ◽  
Vanessa Yardley ◽  
Philippe M. Loiseau ◽  
Martine Appel ◽  
Philippe Legrand ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Leishmania Donovani ◽  
Lethal Dose ◽  
Peritoneal Macrophages ◽  
Lipid Complex ◽  
Complex Formulation ◽  
Cd1 Mice ◽  
New Formulation ◽  
Lipid Formulations

ABSTRACT The aim of the present study was to evaluate the toxicity and the activity of a new lipid complex formulation of amphotericin B (AMB) (LC-AMB; dimyristoyl phosphatidylcholine, dimyristoyl phosphatidylglycerol, and AMB) that can be produced by a simple process. Like other lipid formulations, this new complex reduced both the hemolytic activity of AMB (the concentration causing 50% hemolysis of human erythrocytes, >100 μg/ml) and its toxicity toward murine peritoneal macrophages (50% inhibitory concentration, >100 μg/ml at 24 h). The in vivo toxicity of the new formulation (50% lethal dose,> 200 mg/kg of body weight for CD1 mice) was similar to those of other commercial lipid formulations of AMB. The complex was the most effective formulation against the DD8 strain of Leishmania donovani. It was unable to reverse the resistance of an AMB-resistant L. donovani strain. In vivo LC-AMB was less efficient than AmBisome against L. donovani.

scholarly journals Thymoquinone ameliorates Pachycondyla sennaarensis venom-induced acute toxic shock in male rats

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ibrahim M. Alhazza ◽  
Hossam Ebaid ◽  
Bahaa Abdel-Salam ◽  
Jameel H. Al-Tamimi ◽  
Iftekhar Hassan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Plant Extract ◽  
Therapeutic Potential ◽  
Nigella Sativa ◽  
Lethal Dose ◽  
Male Rats ◽  
Allergic Reactions ◽  
Immunological Parameters ◽  
Toxic Dose

Abstract Background For many decades, the sting of Samsun ant (Pachycondyla sennaarensis) has been a serious clinical challenge for the people living in some of the major Middle East and Asian countries. In the present study, the therapeutic potential of Nigella sativa derived plant extract component, thymoquinone (TQ) has been tested against the Samsun ant venom (SAV) at the toxic dose in the rats. Methods The adult male rats were divided into four groups (n = 10): control, SAV treated, SAV + TQ treated and TQ alone treated. It was found that the sub-lethal dose of SAV alters not only many of the kidney and liver function markers but also induces oxidative stress in the animals. Moreover, the SAV also disturbs various immunological parameters including expression of PMNs, CD-80, CD-86, interleukins and other cytokines compromising the affected organism towards mild to severe allergic reactions including life-risking anaphylaxis. Results The plant extract, TQ, effectively restores many of the biochemical and oxidative stress parameters comparable to the normal concomitant with improving the immunological aspects that might attributive in relieving from SAV-induced toxicity and allergic reactions in the affected organism to a greater extent. Conclusion Hence, TQ has an excellent antidote property against SAV-induced toxicities in vivo. Although the study is a vivid indication of the potential therapeutic potential of TQ against the SAV induced in vivo toxicity, yet the actual mechanism of interaction translating the toxicity amelioration warrants further investigations.

scholarly journals Percutaneous Toxicity and Decontamination of Soman, Vx, and Paraoxon in Rats Using Detergents

2013 ◽  
Vol 64 (2) ◽  
pp. 211-217 ◽  
Author(s):  
Jan Misík ◽  
Růžena Pavliková ◽  
Kamil Kuča
Keyword(s):  
Survival Rate ◽  
Military Personnel ◽  
Wistar Rats ◽  
Organophosphorus Compounds ◽  
Lethal Dose ◽  
Distilled Water ◽  
Median Lethal Dose ◽  
Agricultural Pesticides ◽  
Male Wistar Rats

Highly toxic organophosphorus compounds (OPs) were originally developed for warfare or as agricultural pesticides. Today, OPs represent a serious threat to military personnel and civilians. This study investigates the in vivo decontamination of male Wistar rats percutaneously exposed to paraoxon and two potent nerve agents - soman (GD) and VX. Four commercial detergents were tested as decontaminants - NeodekontTM, ArgosTM, DermogelTM, and FloraFreeTM. Decontamination performed 2 min after exposure resulted in a higher survival rate in comparison with non-decontaminated controls. The decontamination effectiveness was expressed as protective ratio (PR, median lethal dose of agent in decontaminated animals divided by the median lethal dose of agent in untreated animals). The highest decontamination effectiveness was consistently achieved with ArgosTM (PR=2.3 to 64.8), followed by DermogelTM (PR=2.4 to 46.1). NeodekontTM and FloraFreeTM provided the lowest decontamination effectiveness, equivalent to distilled water (PR=1.0 to 43.2).

scholarly journals Kinetics of phagocyte response to group B streptococcal infections in newborn rats

1980 ◽  
Vol 28 (2) ◽  
pp. 319-324
Author(s):  
K E Schuit ◽  
R DeBiasio
Keyword(s):  
Lethal Dose ◽  
Group B Streptococcus ◽  
Peritoneal Macrophages ◽  
Adult Rats ◽  
Colony Forming Units ◽  
Type Ia ◽  
Intraperitoneal Infection ◽  
Group B ◽  
Kinetics Of

To test the hypothesis that inadequate in vivo mobilization of leukocytes may contribute to the unique susceptibility of neonates to infection, we studied the kinetics of phagocyte response to neonatal and adult rats to intraperitoneal infection with group B streptococcus, type Ia. The 50% lethal dose was considerably greater for adults than for neonates (1.1 x 10(7) colony-forming units per g versus 2.7 x 10(2) colony-forming units per g). After challenge with group B streptococcus, type Ia, the number of neonatal peritoneal leukocytes increased more slowly than did those of adult rats. For example, at 4 h, the adult neutrophil count was 41 times greater than that of the neonate, but at 24 h, neonatal peritoneal neutrophils had not yet reached the adult 4-h level. Peritoneal macrophages also increased more rapidly in adults than in neonates. After intraperitoneal infection, both adults and neonates developed bacteremia, but adults cleared the bacteria with greater efficiency. Adult blood neutrophils increased 247% by 12 h and then decreased; neonatal neutrophils steadily decreased to a 57% reduction by 24 h. These data suggest that the neonatal neutrophil response to group B streptococcus, type Ia, infection is inadequate and may contribute to the high mortality associated with this infection.

Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-α release

1996 ◽  
Vol 81 (5) ◽  
pp. 2304-2311 ◽  
Author(s):  
Anastasia Kotanidou ◽  
Augustine M. K. Choi ◽  
Richard A. Winchurch ◽  
Leo Otterbein ◽  
Henry E. Fessler
Keyword(s):  
Mrna Expression ◽  
Biological Effects ◽  
Lethal Dose ◽  
Peritoneal Macrophages ◽  
Organ Injury ◽  
In Vivo Studies ◽  
Myeloperoxidase Activity ◽  
Neutrophil Sequestration ◽  
Tnf Α

Kotanidou, Anastasia, Augustine M. K. Choi, Richard A. Winchurch, Leo Otterbein, and Henry E. Fessler. Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-α release. J. Appl. Physiol. 81(5): 2304–2311, 1996.—Urethan is a commonly used animal anesthetic for nonrecovery laboratory surgery. However, urethan has diverse biological effects that may complicate the interpretation of experimental findings. This study examined the effect of urethan on the response to an intravenous bolus of lipopolysaccharide (LPS; 30 mg/kg) in rats. In instrumented rats, urethan (1.2 gm/kg ip) completely prevented the fall in arterial pressure immediately after LPS administration but did not prevent late cardiovascular collapse. In uninstrumented rats, urethan also attenuated indexes of organ injury measured 4 h after LPS administration, including mural bowel hemorrhage, hemoconcentration, hypoglycemia, metabolic acidosis, and lung myeloperoxidase activity, a measure of neutrophil sequestration. The peak increase in tumor necrosis factor-α (TNF-α) 90 min after LPS administration was reduced 88% by urethan (2,060 ± 316 vs. 16,934 ± 847 pg/ml; P < 0.001). In uninstrumented animals, urethan at 1.2 gm/kg reduced the 90% mortality rate of a lethal dose of LPS to 0–10% when given up to 24 h before LPS administration but did not reduce mortality when given 2 h after LPS. Urethan neither directly bound LPS by Limulus assay nor inhibited LPS-stimulated TNF-α mRNA expression in cultured mouse peritoneal macrophages, but TNF-α mRNA expression was suppressed by serum from a urethan-treated rat. Moreover, rauwolscine, which shares α2-adrenoceptor-blocking activity with urethan, also prevented death from a subsequent 90% lethal dose LPS bolus. We conclude that urethan or its metabolites protect against LPS, in part, by reducing TNF-α release and speculate that this may be mediated by α2-adrenoceptors. These actions of urethan make it an undesirable anesthetic agent for in vivo studies of sepsis or LPS.

scholarly journals Enhancement of Macrophage Function by the Antimicrobial Peptide Sublancin Protects Mice from Methicillin-Resistant Staphylococcus aureus

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Shuai Wang ◽  
Qianhong Ye ◽  
Ke Wang ◽  
Xiangfang Zeng ◽  
Shuo Huang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptide ◽  
Peritoneal Macrophages ◽  
Mapk Signaling ◽  
Cell Mediated Immunity ◽  
Protective Activity ◽  
Methicillin Resistant ◽  
Macrophage Function ◽  
Innate Defense

Methicillin-resistant Staphylococcus aureus (MRSA) is the major pathogen responsible for community and hospital bacterial infections. Sublancin, a glucosylated antimicrobial peptide isolated from Bacillus subtilis 168, possesses antibacterial infective effects. In this study, we investigated the role and anti-infection mechanism of sublancin in a mouse model of MRSA-induced sublethal infection. Sublancin could modulate innate immunity by inducing the production of IL-1β, IL-6, TNF-α, and nitric oxide, enhancing phagocytosis and MRSA-killing activity in both RAW264.7 cells and mouse peritoneal macrophages. The enhanced macrophage function by the peptide in vitro correlated with stronger protective activity in vivo in the MRSA-invasive sublethal infection model. Macrophage activation by sublancin was found to be partly dependent on TLR4 and the NF-κB and MAPK signaling pathways. Moreover, oral administration of sublancin increased the frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes. The protective activity of sublancin was associated with in vivo augmenting phagocytic activity of peritoneal macrophages and partly improving T cell-mediated immunity. Macrophages thus represent a potentially pivotal and novel target for future development of innate defense regulator therapeutics against S. aureus infection.

scholarly journals Interleukin 18 Contributes to Host Resistance and Gamma Interferon Production in Mice Infected with VirulentSalmonella typhimurium

1999 ◽  
Vol 67 (2) ◽  
pp. 478-483 ◽  
Author(s):  
Pietro Mastroeni ◽  
S. Clare ◽  
S. Khan ◽  
J. A. Harrison ◽  
C. E. Hormaeche ◽  
...  
Keyword(s):  
Host Resistance ◽  
Lethal Dose ◽  
Peritoneal Macrophages ◽  
Gamma Interferon ◽  
Interleukin 18 ◽  
Mouse Splenocytes ◽  
Key Factor ◽  
Ifn Γ ◽  
Rag 1

ABSTRACT Spleen and peritoneal macrophages obtained from innately resistant A/J mice released low levels of interleukin 18 (IL-18) upon infection with Salmonella typhimurium C5 RP4. Incubating the cells with recombinant gamma interferon (rIFN-γ) enhanced IL-18 production. A/J mice treated in vivo with anti-IL-18 antibodies showed impaired resistance to infection, with increased bacterial loads in the liver and spleen. Administration of rIL-18 could protect A/J mice from challenge with a lethal dose of virulent salmonellae, with a dramatic reduction in bacterial numbers in the tissues. rIL-18 administration did not ameliorate the disease in IFN-γ-R−/− mice. IL-18 proved to be required for IFN-γ production by mouse splenocytes from conventional, scid, andrag-1 −/− mice; in vivo IL-18 neutralization caused a decrease in circulating IFN-γ levels. Thus, IL-18 is a key factor in early host resistance to Salmonella and probably acts via IFN-γ.

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