Autonomic Regulation of Anti-Inflammatory Activities from Salivary Glands

Author(s):  
Ronald D. Mathison ◽  
Joseph S. Davison ◽  
Chris D. St. Laurent ◽  
A. Dean Befus
2020 ◽  
Author(s):  
Carine Teles Sangaleti ◽  
Keyla Yukari Katayama ◽  
Kátia De Angelis ◽  
Tércio Lemos de Moraes ◽  
Amanda Aparecida Araújo ◽  
...  

AbstractBackgroundThe metabolic syndrome (MetS) is an obesity-driven disorder with pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered autonomic regulation, are important components of MetS pathophysiology. We recently reported that galantamine, an acetylcholinesterase inhibitor and an FDA-approved drug (for Alzheimer’s disease) alleviates the inflammatory state in MetS subjects. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS.MethodsThe effects of galantamine treatment, 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n=22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment.ResultsGalantamine treatment significantly increased antioxidant enzyme activities, including SOD (+1.65 USOD/mg protein, [95% CI 0.39 to 2.92], P=0.004) and CAT (+0.93 nmol/mg, [95% CI 0.34 to 1.51], P=0.011), decreased lipid peroxidation (thiobarbituric acid reactive substances, -5.45 pmol/mg, [95% CI -10.97 to 0.067], P=0.053) and systemic nitrite levels (-0.05 nit/mg protein, [95% CI -0.21 to 0.10], P=0.038) compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment.ConclusionLow-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with galantamine to ameliorate MetS pathophysiology.


2015 ◽  
Vol 8 (1) ◽  
Author(s):  
Lin Wei ◽  
Chunjing Huang ◽  
Hailong Yang ◽  
Min Li ◽  
Juanjuan Yang ◽  
...  

2021 ◽  
Author(s):  
Hailah M. ALmohaimeed ◽  
Emad A. Albadawi ◽  
Zuhair M. Mohammedsaleh ◽  
Hadel M. Alghabban ◽  
Hanan S. Seleem ◽  
...  

Abstract BackgroundAcute and chronic stresses affect the salivary glands which are the source of plasma BDNF during stressful conditions. Pumpkin is a medicinal plant with an evident antioxidant, anti-inflammatory and potential antidepressant effects. This work was conducted to assess the impact of chronic unpredictable mild stress (CUMS) on the structure of albino rats’ salivary glands and evaluate the role of pumpkin extract (Pump) in ameliorating this effect. MethodsFour groups (n=10 each) of male albino rats included in this study; the control, CUMS, CUMS+fluoxetine and (CUMS+Pump). Corticosterone, pro-inflammatory cytokines (TNF-α & IL-6) and the oxidant/antioxidant profile were all assessed in the serum. BDNF mRNA level was measured in the salivary glands using qRT-PCR. Histopathological changes of the salivary glands were also assessed. ResultsDepression was confirmed behaviorally and biochemically. Exposure to CUMS significantly (p< 0.001) up-regulated the level of serum corticosterone. CUMS induced degenerative changes in the secretory and ductal system, atrophy of acini and increased apoptosis of the acinar and ductal cells. Both fluoxetine and Pump significantly up-regulated (p<0.001) BDNF expression in the salivary glands and ameliorated the CUMS-induced histopathological alterations in the salivary glands. Pumpkin significantly (p<0.001) increased the serum levels of antioxidant enzymes SOD, GPX and CAT and reduced the serum levels of the pro-inflammatory cytokines TNF-α, IL-6.ConclusionPumpkin ameliorates chronic stress-induced depression in rats by exerting a promising anti-inflammatory, antioxidant and anti-depressant-like effects in rats exposed to CUMS. Pump subsequently improved stress-induced structural changes in the salivary glands that might be due to the glands up-regulation of BDNF expression.Trial registrationNot applicable.


2009 ◽  
Vol 296 (3) ◽  
pp. C514-C524 ◽  
Author(s):  
K. E. Morris ◽  
C. D. St. Laurent ◽  
R. S. Hoeve ◽  
P. Forsythe ◽  
M. R. Suresh ◽  
...  

The autonomic nervous system regulates the secretion of bioactive proteins and peptides from salivary glands that can be important in systemic physiological responses. The prohormone submandibular rat-1, which is highly expressed in rat submandibular glands, can be cleaved to produce polypeptides with analgesic and anti-inflammatory activities. Human genes related to submandibular rat-1 have conserved biological functions and are potentially important in pain suppression, erectile function, and inflammation. In this study we describe the differential expression and posttranslational modification of submandibular rat-1 protein in salivary glands, the urogenital tract, lung, blood, and saliva in male Sprague-Dawley and Brown Norway rats. Submandibular rat-1 protein is secreted into saliva after the administration of β-adrenergic or cholinergic agonists. Removal of the sympathetic ganglion that innervates the salivary glands results in increased levels of submandibular rat-1 protein in salivary glands. The secretion of submandibular rat-1 in response to physiological stress may provide a large pool of submandibular rat-1-derived peptide products that can promote analgesia and decrease inflammation locally and systemically. This pathway may be conserved among mammals and may constitute an important anti-inflammatory and analgesic response to stress.


2021 ◽  
Vol 12 ◽  
Author(s):  
Carine Teles Sangaleti ◽  
Keyla Yukari Katayama ◽  
Kátia De Angelis ◽  
Tércio Lemos de Moraes ◽  
Amanda Aparecida Araújo ◽  
...  

Background: The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS.Trial Design and Methods: The effects of galantamine treatment, 8 mg daily for 4 weeks or placebo, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n = 22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment.Results: Galantamine treatment significantly increased antioxidant enzyme activities, including SOD [+1.65 USOD/mg protein, [95% CI 0.39–2.92], P = 0.004] and CAT [+0.93 nmol/mg, [95% CI 0.34–1.51], P = 0.01], decreased lipid peroxidation [thiobarbituric acid reactive substances [log scale 0.72 pmol/mg, [95% CI 0.46–1.07], P = 0.05], and systemic nitrite levels [log scale 0.83 μmol/mg protein, [95% CI 0.57–1.20], P = 0.04] compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment.Conclusion: Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates neural autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with the cholinergic drug galantamine to ameliorate MetS.


1988 ◽  
Vol 33 (7) ◽  
pp. 519-523 ◽  
Author(s):  
K. Izutsu ◽  
W. Ensign ◽  
Bonnie Ramsey ◽  
M. Schubert ◽  
Barbara Allan ◽  
...  

2015 ◽  
Vol 308 (7) ◽  
pp. R569-R575 ◽  
Author(s):  
Chris D. St. Laurent ◽  
Katherine E. St. Laurent ◽  
Ron D. Mathison ◽  
A. Dean Befus

Salivary glands are involved in the production and exocrine and endocrine secretion of biologically active proteins, polypeptides, and hormones involved in growth and differentiation, homeostasis, and digestion. We have previously studied the prohormone submandibular rat 1 (SMR1), product of the Vcsa1 gene, which is highly expressed in the testes and salivary glands of rats, and can be cleaved to produce polypeptides with analgesic, erectile function, and anti-inflammatory activities. Humans lack the Vcsa1 gene, but homologous sequences and functions for analgesia and erectile function exist in the human genes Prol1, SMR3a, and SMR3b located on the human chromosomal region close to where Vcsa1 lies in the rat. Here we show the human protein calcium-binding protein spermatid-specific 1 (CABS1) contains a similar sequence to the anti-inflammatory sequence in rat SMR1, thus CABS1 may be another human gene with homologous function to Vcsa1. Using Western blot and PCR, we discovered that the human protein CABS1, previously thought to only be expressed in the testes, is also expressed in the salivary glands and lung, in a tissue-specific manner. Peptides derived from CABS1 were tested in an in vivo mouse model of lipopolysaccharide (LPS)-induced neutrophilia and an ex vivo rat model of antigen-induced intestinal anaphylaxis and significantly reduced both neutrophil accumulation in bronchoalveolar lavage fluid and antigen-induced ileal contractions, respectively. Thus human CABS1 has a peptide motif homologous to the anti-inflammatory peptide sequence of rat SMR1. Whether this similarity of CABS1 extends to the neuroendocrine regulation of the anti-inflammatory activity seen for SMR1 remains to be determined.


Author(s):  
P.J. Dailey

The structure of insect salivary glands has been extensively investigated during the past decade; however, none have attempted scanning electron microscopy (SEM) in ultrastructural examinations of these secretory organs. This study correlates fine structure by means of SEM cryofractography with that of thin-sectioned epoxy embedded material observed by means of transmission electron microscopy (TEM).Salivary glands of Gromphadorhina portentosa were excised and immediately submerged in cold (4°C) paraformaldehyde-glutaraldehyde fixative1 for 2 hr, washed and post-fixed in 1 per cent 0s04 in phosphosphate buffer (4°C for 2 hr). After ethanolic dehydration half of the samples were embedded in Epon 812 for TEM and half cryofractured and subsequently critical point dried for SEM. Dried specimens were mounted on aluminum stubs and coated with approximately 150 Å of gold in a cold sputtering apparatus.Figure 1 shows a cryofractured plane through a salivary acinus revealing topographical relief of secretory vesicles.


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