scholarly journals A Phospholipase A2-Related Snake Venom (from Crotalus durissus terrificus) Stimulates Neuroendocrine and Immune Functions: Determination of Different Sites of Action*

Endocrinology ◽  
1998 ◽  
Vol 139 (2) ◽  
pp. 617-625 ◽  
Author(s):  
Andrea Chisari ◽  
Eduardo Spinedi ◽  
Marie-Jeanne Voirol ◽  
Andrés Giovambattista ◽  
Rolf C. Gaillard
Keyword(s):  
Hpa Axis ◽  
Anterior Pituitary ◽  
Immune Functions ◽  
Inflammatory Stress ◽  
Crotalus Durissus Terrificus ◽  
Main Component ◽  
Sites Of Action ◽  
Crotalus Durissus

Abstract Immune neuroendocrine interactions are vital for the individual’s survival in certain physiopathological conditions, such as sepsis and tissular injury. It is known that several animal venoms, such as those from different snakes, are potent neurotoxic compounds and that their main component is a specific phospholipase A type 2 (PLA2). It has been described recently that the venom from Crotalus durissus terrificus [snake venom (SV), in the present study] possesses some cytotoxic effect in different in vitro and in vivo animal models. In the present study, we investigated whether SV and its main component, PLA2 (obtained from the same source), are able to stimulate both immune and neuroendocrine functions in mice, thus characterizing this type of neurotoxic shock. For this purpose, several in vivo and in vitro designs were used to further determine the sites of action of SV-PLA2 on the hypothalamo-pituitary-adrenal (HPA) axis function and on the release of the pathognomonic cytokine, tumor necrosis factor α (TNFα), of different types of inflammatory stress. Our results indicate that SV (25 μg/animal) and PLA2 (5 μg/animal), from the same origin, stimulate the HPA and immune axes when administered (ip) to adult mice; both preparations were able to enhance plasma glucose, ACTH, corticosterone (B), and TNFα plasma levels in a time-related fashion. SV was found to activate CRH- and arginine vasopressin-ergic functions in vivo and, in vitro, SV and PLA2 induced a concentration-related (0.05–10 μg/ml) effect on the release of both neuropeptides. SV also was effective in changing anterior pituitary ACTH and adrenal B contents, also in a time-dependent fashion. Direct effects of SV and PLA2 on anterior pituitary ACTH secretion also were found to function in a concentration-related fashion (0.001–1 μg/ml), and the direct corticotropin-releasing activity of PLA2 was additive to those of CRH and arginine vasopressin; the corticotropin-releasing activity of both SV and PLA2 were partially reversed by the specific PLA2 inhibitor, manoalide. On the other hand, neither preparation was able to directly modify spontaneous and ACTH-stimulated adrenal B output. The stimulatory effect of SV and PLA2 on in vivo TNFα release was confirmed by in vitro experiments on peripheral mononuclear cells; in fact, both PLA2 (0.001–1 μg/ml) and SV (0.1–10 μg/ml), as well as concavalin A (1–100 μg/ml), were able to stimulate TNFα output in the incubation medium. Our results clearly indicate that PLA2-dependent mechanisms are responsible for several symptoms of inflammatory stress induced during neurotoxemia. In fact, we found that this particular PLA2-related SV is able to stimulate both HPA axis and immune functions during the acute phase response of the inflammatory processes.

scholarly journals In vivo and in vitro prospection of the anti-ophidic properties exercised by the extracts of Jacaranda decurrens L.

2021 ◽  
Vol 43 ◽  
pp. e57016
Author(s):  
Marcus Vinícius Cardoso Trento ◽  
Mateus Santos Carapiá ◽  
Pedro Henrique Souza César ◽  
Mariana Aparecida Braga ◽  
Andreimar Martins Soares ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Local Effects ◽  
Crotalus Durissus Terrificus ◽  
Mechanism Of Inhibition ◽  
Local Toxicity ◽  
Sds Page ◽  
Crotalus Durissus ◽  
Venom Proteins

The research and development of alternative treatments for snakebites (e.g., medicinal plants) is necessary due to the high costs of the existing ones. The effects of the aqueous extracts from Jacaranda decurrens leaves, roots, and xylopodium were analyzed upon the venom-induced (Bothrops spp. and Crotalus spp.) systemic and local toxicity. The extracts were able to partially inhibit the phospholipase activity of the venoms from Bothrops jararacussu and Crotalus durissus terrificus. The myotoxic, edema-inducing, coagulant, and hemorrhagic activities were also inhibited. The SDS-PAGE showed that the venom proteins were intact after their incubation with the extracts. This suggests that the possible mechanism of inhibition is not related to the degradation of the protein but rather to their binding to specific sites of the enzymes. The extracts significantly prolonged the survival time of animals in the lethality assay performed with Crotalus durissus terrificus venom and its toxin (crotoxin). The anti-ophidic activity of medicinal plants may aid in the management of snakebites in distant locations by reducing the victim’s local effects and time to heal.

scholarly journals Evaluation of Protection by Caffeic Acid, Chlorogenic Acid, Quercetin and Tannic Acid against the In Vitro Neurotoxicity and In Vivo Lethality of Crotalus durissus terrificus (South American Rattlesnake) Venom

Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 801
Author(s):  
Isadora Oliveira ◽  
Edson Yoshida ◽  
Murilo Dini ◽  
Ana Paschoal ◽  
José Cogo ◽  
...  
Keyword(s):  
Chlorogenic Acid ◽  
Caffeic Acid ◽  
Neuromuscular Blockade ◽  
Tannic Acid ◽  
South American ◽  
Variable Effect ◽  
Crotalus Durissus Terrificus ◽  
Crotalus Durissus

Systemic envenomation by Crotalus durissus terrificus (South American rattlesnake) can cause coagulopathy, rabdomyolysis, acute kidney injury, and peripheral neuromuscular blockade, the latter resulting in flaccid paralysis. Previous studies have shown that plant products such as tannic acid and theaflavin can protect against the neuromuscular blockade caused by C. d. terrificus venom in vitro. In this work, we used mouse-isolated phrenic nerve-diaphragm preparations to examine the ability of caffeic acid, chlorogenic acid, and quercetin to protect against C. d. terrificus venom-induced neuromuscular blockade in vitro. In addition, the ability of tannic acid to protect against the systemic effects of severe envenomation was assessed in rats. Preincubation of venom with caffeic acid (0.5 mg/mL), chlorogenic acid (1 mg/mL), or quercetin (0.5 mg/mL) failed to protect against venom (10 μg/mL)-induced neuromuscular blockade. In rats, venom (6 mg kg−1, i.p.) caused death in ~8 h, which was prevented by preincubation of venom with tannic acid or the administration of antivenom 2 h post-venom, whereas tannic acid given 2 h post-venom prolonged survival (~18.5 h) but did not prevent death. Tannic acid (in preincubation protocols or given 2 h post-venom) had a variable effect on blood creatinine and urea and blood/urine protein levels and prevented venom-induced leukocytosis. Tannic acid attenuated the histological lesions associated with renal damage in a manner similar to antivenom. The protective effect of tannic acid appeared to be mediated by interaction with venom proteins, as assessed by SDS-PAGE. These findings suggest that tannic acid could be a potentially useful ancillary treatment for envenomation by C. d. terrificus.

scholarly journals Hypothalamic-Pituitary-Adrenal Axis Hyporesponsiveness to Restraint Stress in Mice Deficient for Large-Conductance Calcium- and Voltage-Activated Potassium (BK) Channels

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5496-5506 ◽  
Author(s):  
Paula J. Brunton ◽  
Matthias Sausbier ◽  
Georg Wietzorrek ◽  
Ulrike Sausbier ◽  
Hans-Guenther Knaus ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Anterior Pituitary ◽  
Restraint Stress ◽  
Plasma Concentrations ◽  
Bk Channels ◽  
Patch Clamp Recording ◽  
Hypothalamic Pituitary Adrenal ◽  
Neurosecretory Neurons

Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing ACTH from the anterior pituitary gland and glucocorticoids from the adrenal cortex. Stress also activates the sympathetic nervous system, evoking adrenaline release from the adrenal medulla. Large-conductance calcium- and voltage-activated potassium (BK) channels have been implicated in regulation of cellular excitability in these systems. Here, we examine the functional role of BK channels in HPA axis regulation in vivo using female mice genetically deficient (BK−/−) for the pore-forming subunits of BK channels. BK−/− phenotype in the HPA was confirmed by immunohistochemistry, Western blot analysis, and corticotrope patch-clamp recording. Restraint stress-induced plasma concentrations of ACTH and corticosterone were significantly blunted in BK−/− mice compared with wild type (WT) controls. This stress hyporesponsiveness was associated with reduced activation of hypothalamic paraventricular nucleus (PVN) neurons. Basal expression of CRH, but not arginine vasopressin mRNA in the PVN was significantly lower in BK−/− mice compared with WT controls. Total anterior pituitary ACTH peptide content, but not proopiomelanocortin mRNA expression or corticotrope number, was significantly reduced in BK−/− mice compared with WT. However, anterior pituitary corticotropes from BK−/− mice fully supported ACTH output, releasing a significantly greater proportion of stored ACTH in response to secretagogue in vitro compared with WT. These results support an important role for BK channels in both the neural circuitry and endocrine output of the HPA axis and indicate that the stress hyporesponsiveness in BK−/− mice primarily results from reduced activation of hypothalamic PVN neurosecretory neurons.

Studies on the mechanism of acute inhibition of thyroglobulin hydrolysis by iodine

1985 ◽  
Vol 108 (4) ◽  
pp. 511-517 ◽  
Author(s):  
Nandalal Bagchi ◽  
Birdie Shivers ◽  
Thomas R. Brown
Keyword(s):  
Time Course ◽  
Period 2 ◽  
Iodotyrosine Deiodinase ◽  
Rate Of Hydrolysis ◽  
Underlying Mechanisms ◽  
Excess Iodide ◽  
Sites Of Action ◽  
Hydrolysis Of

Abstract. Iodine in excess is known to acutely inhibit thyroidal secretion. In the present study we have characterized the time course of the iodine effect in vitro and investigated the underlying mechanisms. Labelled thyroid glands were cultured in vitro in medium containing mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the proportion of labelled iodotyrosines and iodothyronines recovered at the end of culture and was used as an index of thyroidal secretion. Thyrotrophin (TSH) administered in vivo acutely stimulated the rate of thyroglobulin hydrolysis. Addition of Nal to the culture medium acutely inhibited both basal and TSH-stimulated thyroglobulin hydrolysis. The effect of iodide was demonstrable after 2 h, maximal after 6 h and was not reversible upon removal of iodide. Iodide abolished the dibutyryl cAMP induced stimulation of thyroglobulin hydrolysis. Iodide required organic binding of iodine for its effect but new protein or RNA synthesis was not necessary. The inhibitory effects of iodide and lysosomotrophic agents such as NH4C1 and chloroquin on thyroglobulin hydrolysis were additive suggesting different sites of action. Iodide added in vitro altered the distribution of label in prelabelled thyroglobulin in a way that suggested increased coupling in the thyroglobulin molecule. These data indicate that 1) the iodide effect occurs progressively over a 6 h period, 2) continued presence of iodide is not necessary once the inhibition is established, 3) iodide exerts its action primarily at a post cAMP, prelysosomal site and 4) the effect requires organic binding of iodine, but not new RNA or protein synthesis. Our data are consistent with the hypothesis that excess iodide acutely inhibits thyroglobulin hydrolysis by increasing the resistance of thyroglobulin to proteolytic degradation through increased iodination and coupling.

scholarly journals Dual Role of Interleukin-10 in Murine NZB/W F1 Lupus

2021 ◽  
Vol 22 (3) ◽  
pp. 1347
Author(s):  
Anaïs Amend ◽  
Natalie Wickli ◽  
Anna-Lena Schäfer ◽  
Dalina T. L. Sprenger ◽  
Rudolf A. Manz ◽  
...  
Keyword(s):  
B Cell ◽  
Disease Model ◽  
Interleukin 10 ◽  
Immune Functions ◽  
Murine Lupus ◽  
Anti Inflammatory ◽  
In Vivo Effects

As a key anti-inflammatory cytokine, IL-10 is crucial in preventing inflammatory and autoimmune diseases. However, in human and murine lupus, its role remains controversial. Our aim was to understand regulation and immunologic effects of IL-10 on different immune functions in the setting of lupus. This was explored in lupus-prone NZB/W F1 mice in vitro and vivo to understand IL-10 effects on individual immune cells as well as in the complex in vivo setting. We found pleiotropic IL-10 expression that largely increased with progressing lupus, while IL-10 receptor (IL-10R) levels remained relatively stable. In vitro experiments revealed pro- and anti-inflammatory IL-10 effects. Particularly, IL-10 decreased pro-inflammatory cytokines and slowed B cell proliferation, thereby triggering plasma cell differentiation. The frequent co-expression of ICOS, IL-21 and cMAF suggests that IL-10-producing CD4 T cells are important B cell helpers in this context. In vitro and in vivo effects of IL-10 were not fully concordant. In vivo IL-10R blockade slightly accelerated clinical lupus manifestations and immune dysregulation. Altogether, our side-by-side in vitro and in vivo comparison of the influence of IL-10 on different aspects of immunity shows that IL-10 has dual effects. Our results further reveal that the overall outcome may depend on the interplay of different factors such as target cell, inflammatory and stimulatory microenvironment, disease model and state. A comprehensive understanding of such influences is important to exploit IL-10 as a therapeutic target.

Vasopressin as a neuroendocrine regulator of anterior pituitary hormone secretion

1993 ◽  
Vol 129 (6) ◽  
pp. 489-496 ◽  
Author(s):  
Andreas Kjær
Keyword(s):  
Arginine Vasopressin ◽  
Mode Of Action ◽  
Anterior Pituitary ◽  
Hormone Secretion ◽  
Pituitary Hormones ◽  
Pituitary Hormone ◽  
Anterior Pituitary Hormones ◽  
Anterior Pituitary Hormone

Secretion of the anterior pituitary hormones adrenocorticotropin (ACTH), β-endorphin and prolactin (PRL) is complex and involves a variety of factors. This review focuses on the involvement of arginine-vasopressin (AVP) in neuroendocrine regulation of these anterior pituitary hormones with special reference to receptor involvement, mode of action and origin of AVP. Arginine-vasopressin may act via at least two types of receptors: V1− and V2−receptors, where the pituitary V1−receptor is designated V1b. The mode of action of AVP may be mediating, i.e. anterior pituitary hormone secretion is transmitted via release of AVP, or the mode of action may be permissive, i.e. the presence of AVP at a low and constant level is required for anterior pituitary hormones to be stimulated. Under in vivo conditions, the AVP-induced release of ACTH and β-endorphin is mainly mediated via activation of hypothalamic V1− receptors, which subsequently leads to the release of corticotropin-releasing hormone. Under in vitro conditions, the AVP-stimulated release of ACTH and β-endorphin is mediated via pituitary V1b− receptors. The mode of action of AVP in the ACTH and β-endorphin response to stress and to histamine, which is involved in stress-induced secretion of anterior pituitary hormones, is mediating (utilizing V1− receptors) as well as permissive (utilizing mainly V1− but also V2−receptors). The AVP-induced release of PRL under in vivo conditions is conveyed mainly via activation of V1−receptors but V2−receptors and probably additional receptor(s) may also play a role. In stress- and histamine induced PRL secretion the role of AVP is both mediating (utilizing V1 −receptors) and permissive (utilizing both V1− and V2− receptors). Arginine-vasopressin may be a candidate for the PRL-releasing factor recently identified in the posterior pituitary gland. Arginine-vasopressin of both magno- and parvocellular origin may be involved in the regulation of anterior pituitary hormone secretion and may reach the corticotrophs and the lactotrophs via three main routes: the peripheral circulation, the long pituitary portal vessels or the short pituitary portal vessels.

scholarly journals Intercellular communication in the rat anterior pituitary gland: an in vivo and in vitro study

1975 ◽  
Vol 67 (2) ◽  
pp. 469-476 ◽  
Author(s):  
WH Fletcher ◽  
NC Anderson ◽  
JW Everett
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Hormone Secretion ◽  
In Vitro Study ◽  
Anterior Pituitary Gland ◽  
Stimulus Secretion Coupling ◽  
Unpublished Observation ◽  
Cellular Ca

The concept of "stimulus-secretion coupling" suggested by Douglas and co-workers to explain the events related to monamine discharge by the adrenal medulla (5, 7) may be applied to other endocrine tissues, such as adrenal cortex (36), pancreatic islets (4), and magnocellular hypothalamic neurons (6), which exhibit a similar ion-dependent process of hormone elaboration. In addition, they share another feature, that of joining neighbor cells via membrane junctions (12, 26, and Fletcher, unpublished observation). Given this, and the reports that hormone secretion by the pars distalis also involves a secretagogue-induced decrease in membrane bioelectric potential accompanied by a rise in cellular [Ca++] (27, 34, 41), it was appropriate to test the possibility that cells of the anterior pituitary gland are united by junctions.

scholarly journals An initial exploration of in vivo hair cortisol responses to a brief pain stressor: latency, localization and independence effects

2009 ◽  
pp. 757-761
Author(s):  
CF Sharpley ◽  
KG Kauter ◽  
JR McFarlane
Keyword(s):  
Hpa Axis ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Hair Follicles ◽  
Repeated Measurements ◽  
Single Observation ◽  
Target Organs ◽  
Cortisol Responses

Cortisol is secreted by the central hypothalamo-pituitary-adrenal axis and affects many target organs and tissues, particularly in response to stressor demands and infection. Recent data reporting cortisol synthesis in hair follicles have shown the existence of a parallel “peripheral” HPA-axis. However, although there is evidence from in vitro studies and single-observation comparisons between groups that cortisol from hair follicles reflects endocrine changes associated with stressor demands, there are no reports to date of repeated measurements of in vivo cortisol responsivity in hair to transitory stressors. This issue was investigated with three males who underwent 1 min cold pressor test (CP). Cortisol response in hair to stressor demand appears to be (a) swift but transitory, (b) localized to the site of the demand and (c) independent of central HPA-axis activity.

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