The comparison of effects of applications of compound 48/80 and mast cell mediator suspension on inflammation in rats: A methodological study for acute inflammatory pain

Torun

Çetinkaya

et al. 2021

Eur J of Neuroscience

Self Cite

Neuroinflammation plays a key role in the pathogenesis of epilepsy, but the underlying mechanisms are not well understood. Mast cells are multifunctional immune cells that are also activated by stress. The effects of activated mast cells on epileptogenesis are not yet known. This study investigated the effects and mechanisms of compound 48/80‐stimulated mast cell activation on pentylenetetrazole‐induced epileptic seizures in rats. Male Wistar rats were separated into seven groups (n = 12). Group‐1(NS+PTZ) received intraperitoneal saline solution, while groups 2(C‐48/80+PTZ‐1), 3(C‐48/80+PTZ‐2), and 4(C‐48/80+PTZ‐3) received compound‐48/80 at doses of 0.5, 1, and 2 mg/kg, respectively, 30 min before 45 mg/kg pentylenetetrazole administration. Similarly, Group‐5(Cr+C‐48/80+PTZ) received 10 mg/kg cromolyn plus 2 mg/kg compound‐48/80 before pentylenetetrazole, and Group‐6(MC Dep+C‐48/80+PTZ) was exposed to a mast cell‐depletion process, and then received 2 mg/kg compound‐48/80. Group‐7(5‐HT+PTZ) received 10 mg/kg serotonin. Seizure stages were evaluated using Racine's scale. Compound‐48/80 at 2 mg/kg induced anticonvulsive effects against pentylenetetrazole‐induced seizures by extending onset‐times of both myoclonic‐jerk and generalized tonic–clonic seizures (p = 0.0001), and by shortening the duration of generalized tonic–clonic seizure (p = 0.008). These effects were reversed by cromolyn (p = 0.0001). These effects were not observed in mast cell‐depleted rats. Similarly to compound 48/80, serotonin also exhibited anticonvulsive effects against seizures (p < 0.05). Compound 48/80 acts as an anticonvulsant by activating mast cells in a dose‐dependent manner. The anticonvulsive effects of mast cell activation may be mediated by serotonin. Mast cell activation may therefore provide protective activity against seizures under appropriate circumstances.

Section: Discussionmentioning

confidence: 99%

Mast cell activation ameliorates pentylenetetrazole‐induced seizures in rats: The potential role for serotonin

Torun

Çetinkaya

et al. 2021

Eur J of Neuroscience

Self Cite

“…When activated, MCs release a wide range of the pre-formed and de novo synthesized mediators mediating those physiological and pathophysiological situations through their degranulation (14,15). MCs store a large number of vasoactive and pro-inflammatory mediators, proteases, cytokines, chemokines, and growth factors such as substance P (SP), serotonin, prostaglandins, bradykinin, histamine, tumor necrosis factor-α (TNF-α) interleukin (IL)-1β, granulocyte-macrophage colony stimulating factor etc in their cytoplasmic granules (16)(17)(18). MCs can be activated by immunologic and non-immunologic stimuli such as IgE, antigens, anaphylatoxins, viruses, bacteria, toxins, detergents, food additives/ preservatives, xenoestrogens, neuropeptides, cold, exercise, radiation and pollutants (19,20).…”

Section: Mast Cellsmentioning

confidence: 99%

Mast cell stabilizers as a supportive therapy can contribute to alleviate fatal inflammatory responses and severity of pulmonary complications in COVID-19 infection

Anadolu Kliniği Tıp Bilimleri Dergisi

Baranoğlu

2020

SARS-CoV-2(COVID-19) leads to severe acute respiratory syndrome by settling the pulmonary system. Mast cells (MCs) are multifunctional immune cells that are extensively distributed throughout the body and mostly present in pulmonary system. MCs play a vital role in acquired and innate immunity, and to maintain immune homeostasis of the body through a wide range of mediators in their cytoplasmic granules. Severe acute respiratory syndrome with proinflammatory cytokine release and pneumonia during COVID-19 infection can result in the death, in particular in debilitated individuals or those suffering from related chronic disorders. In this review, we attempt to discuss potential relationship between COVID-19 symptoms and mast cells as well as potential use of mast cell stabilizers as a supportive therapeutic option in COVID-19 infection. MCs are main source of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α as well as bronchoconstrictor mediators such as histamine, prostaglandin-D2 and leukotriene-C4 that can lead to fatal inflammatory responses and pulmonary complications during COVID-19 infection. SARS-CoV-2 may activate MCs through toll-like receptors or by inducing the crosslinking of the IgE-FcεRI, thus leading to release of those mediators. SARS-CoV-2-induced abnormal production and release of these mediators from MCs can further exacerbate inflammation in respiratory system, consequently pulmonary complications. Therefore administration of MC stabilizers as a supportive therapy may be useful to alleviate inflammatory responses and pulmonary complications in order to reduce deaths from SARS-CoV-2 infection.

“…MCs are extensively distributed through the body and are located in most tissues such as the lungs, meninges, skin and gastrointestinal tracts. MCs contain a wide range of vasoactive, pro-inflammatory and pro-nociceptive mediators such as substance P (SP), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating peptide (PACAP), serotonin, prostaglandins, bradykinin, histamine and many cytokines including tumor necrosis factor-α (TNF-α) in their cytoplasmic granules (2,3). MCs are able to trigger and promote inflammatory responses by releasing mixed mediators via the process of degranulation.…”

mentioning

confidence: 99%

Akciğer Mast Hücre Davranışının Migren Sıçan Modelinde İncelenişi: Migren Baş Ağrısı İçin Çıkarımlar

Anadolu Kliniği Tıp Bilimleri Dergisi

Balcı

2018

In this study, we aimed to investigate the potential role of lung mast cells in migraine by using a nitroglycerin-induced migraine model in rats. Materials and Methods: Thirty-five adult male Wistar rats were divided into five groups. Each treatment being performed intraperitoneally, the NS group received 0.2 ml normal saline, the NTG group 10 mg/kg nitroglycerin, the NTG vehicle group 0.2 ml 0.1% ethanol in normal saline, the L-NAME+NTG group 50 mg/kg L-NAME + nitroglycerin, and the NS+NTG group normal saline + nitroglycerin. Two hours after the nitroglycerin and other treatments, the rats under anesthesia were intracardially perfused with a solution of 150 ml 4% paraformaldehyde. The lungs were harvested and stained with toluidine blue to observe mast cells. The data were analyzed by using one-way ANOVA. Results: Nitroglycerin increased significantly both number (from 94±3.8 to 131±6.7, p=0.0035) and percent of degranulation (from 11.8±1.3% to 35.5±5.7%, p=0.003) of lung mast cells. However, L-NAME prevented the effects of nitroglycerin on the number and degranulation of lung mast cells, attenuating the increase in both number (from 136±5.1 to 93±2.5, p=0.0011) and degranulation percentage of lung mast cells (from 37.3±1.0% to 13.6±3.1%, p=0.001) induced by nitroglycerin. Discussion and Conclusion: Our findings demonstrate that nitroglycerin treatment leads to an increase in the number and degranulation of lung mast cells in a rat model of migraine induced by nitroglycerin. Moreover, L-NAME prevented these effects, suggesting that nitric oxide released from nitroglycerin directly or indirectly leads to the activation of lung mast cells. The results obtained in the current study can pioneer new research on the role of lung mast cells in migraine.