Enterochromaffin cells as the source of melatonin: key findings and functional relevance in mammals

2019 ◽  
Vol 2 (4) ◽  
pp. 61-82
Author(s):  
Palash K. Pal ◽  
Swaimanti Sarkar ◽  
Aindrila Chattopadhyay ◽  
Dunxian X Tan ◽  
Debasish Bandyopadhyay

The enteroendocrine cells in gastrointestinal (GI) tract synthesize more than thirty hormones in mammals. Among these cells, the enterochromaffin (EC) cells are probably the most important one due to the fact that they produce melatonin. The rate-limiting enzymes for melatonin synthesis including arylalkylamine-N-acetyltransferase (AANAT, currently the SNAT) and hydroxyindole-O-methyltransferase (HIOMT, currently the ASMT) have been identified in EC cells and this has confirmed the local melatonin production in GI tract by these cells. EC cells play a critical role in regulation of gastrointestinal physiology, particularly, in protection of the GI tract from free radical attack and inflammatory reaction. GI tract is the major site exposed to the oxidative stress and inflammation because of the food residue metabolism and the presence of trillions of microbes including the pathological bacteria. Thus, it requires strong protection. Melatonin synthesized by the EC cells provides the onsite protection in GI tract since this molecule is the potent free radical scavenger and effective ant-inflammatory agent. In this review we summarize the available information regarding the structural and functional variability of the EC cells as well as their pathophysiological roles in the GI tract. The focus is given to the protective effects of melatonin produced by the EC cells on the oxidative stress, inflammation and microbiota balance in GI tract. 

2019 ◽  
Vol 2 (2) ◽  
pp. 158-184 ◽  
Author(s):  
Palash K Pal ◽  
Bharati Bhattacharjee ◽  
Aindrila Chattopadhyay ◽  
Debasish Bandyopadhyay

The excessive production of free radicals and/or reactive oxygen species (ROS) in gastrointestinal (GI) tract leads to oxidative damages in GI tissues with development of varied pathological conditions and clinical symptoms. Many endogenous as well as exogenous factors are involved in such pathogenesis, herein, focus was given to the factors of metal toxicity, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion, consumption of high fat diet and alcohol, and different pathological conditions and diseases. Since ROS is more or less involved in the GI damages caused by these factors, therefore attempts have been made to develop appropriate therapeutic agents that possess antioxidant properties. Being a potent antioxidant and free radical scavenger, melatonin was suggested as a potent therapeutic answer to these GI damages. The discovery of different binding sites and receptors of melatonin in the GI tissues further proves its local actions to protect these tissues from oxidative stress.  In the review, we attempt to try our best to summarize the current developments regarding the GI injuries caused by oxidative stress and the potential beneficial effects of melatonin on these injuries. The important molecular mechanisms associated with these changes were also highlighted in the discussion. We hope that this review will provide valuable information to consider melatonin as a suitable molecule used for GI tract protection.


2013 ◽  
Vol 85 (2) ◽  
pp. 585-594 ◽  
Author(s):  
LEONARDO P. FRANCHI ◽  
NILZA N. GUIMARAES ◽  
LAISE R. DE ANDRADE ◽  
HELOISA H.R. DE ANDRADE ◽  
MAURICIO LEHMANN ◽  
...  

Noni, a Hawaiian name for the fruit of Morinda citrifolia L., is a traditional medicinal plant from Polynesia widely used for the treatment of many diseases including arthritis, diabetes, asthma, hypertension and cancer. Here, a commercial noni juice (TNJ) was evaluated for its protective activities against the lesions induced by mitomycin C (MMC) and doxorrubicin (DXR) using the Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. Three-day-old larvae, trans-heterozygous for two genetic markers (mwh and flr3 ), were co-treated with TNJ plus MMC or DXR. We have observed a reduction in genotoxic effects of MMC and DXR caused by the juice. TNJ provoked a marked decrease in all kinds of MMC- and DXR-induced mutant spots, mainly due to its antirecombinagenic activity. The TNJ protective effects were concentration-dependent, indicating a dose-response correlation, that can be attributed to a powerful antioxidant and/or free radical scavenger ability of TNJ.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Tomomi Masuda ◽  
Masamitsu Shimazawa ◽  
Hideaki Hara

Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO). An excess amount of reactive oxygen species (ROS) can lead to functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells (RGCs). Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models. These data suggest that the therapeutic strategy for targeting oxidative stress may be important for the treatment of these ocular diseases, and edaravone may be useful for treating retinal diseases associated with oxidative stress.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Changyan Li ◽  
Xiangcheng Shi ◽  
Qiudi Shen ◽  
Chen Guo ◽  
Zepeng Hou ◽  
...  

As a new antioxidant, nanoceria is of significant importance in applications of medical and biological fields. In comparison with conventional organic antioxidants, nanoceria has multienzyme mimetic activity by Ce4+/Ce3+ redox cycle. This unique regenerative/autocatalytic property has been widely used in the aspects of free-radical scavenger, radiation protection, oxidative-stress-related disease, drug delivery, biosensor, tissue engineering, cancer biomarker, and anti-inflammatory. This paper reviews the latest breakthrough of nanoceria as an antioxidant in applications of medical and biological fields on the base of the authors’ research works on resistance to oxidation and cytotoxicity. The challenges of nanoceria encountered in applications in medical and biological fields are commented as well.


Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1871
Author(s):  
Rita Martín-Ramírez ◽  
Rebeca González-Fernández ◽  
Jairo Hernández ◽  
Pablo Martín-Vasallo ◽  
Angela Palumbo ◽  
...  

An excess of oxidative stress (OS) may affect several physiological processes fundamental to reproduction. SIRT1, SIRT6 and SIRT7 are involved in protection stress systems caused by OS, and they can be activated by antioxidants such as celastrol or melatonin. In this study, we evaluate SIRT1, SIRT6 and SIRT7 gene expression in cultured human granulosa-lutein (hGL) cells in response to OS inductors (glucose or peroxynitrite) and/or antioxidants. Our results show that celastrol and melatonin improve cell survival in the presence and absence of OS inductors. In addition, melatonin induced SIRT1, SIRT6 and SIRT7 gene expression while celastrol only induced SIRT7 gene expression. This response was not altered by the addition of OS inductors. Our previous data for cultured hGL cells showed a dual role of celastrol as a free radical scavenger and as a protective agent by regulating gene expression. This study shows a direct effect of celastrol on SIRT7 gene expression. Melatonin may protect from OS in a receptor-mediated manner rather than as a scavenger. In conclusion, our results show increased hGL cells survival with melatonin or celastrol treatment under OS conditions, probably through the regulation of nuclear sirtuins’ gene expression.


2018 ◽  
Author(s):  
Min Soo Choo ◽  
SongZhe Piao ◽  
Seung-June Oh

AbstractAIMSTo investigate the effect of a free radical scavenger (tempol) after relief of partial bladder outlet obstruction (pBOO) on bladder function in a rat model.METHODSpBOO was induced in 50 eight-week-old female Sprague-Dawley rats and relieved 3 weeks later. The rats were divided randomly into 5 groups: sham-operated, tempol-treated for 1 week (Treat-1w) or 3 weeks (Treat-3w), and no treatment for 1 week (nonTreat-1w) or 3 weeks (nonTreat-3w). Awaken cystometrograms were obtained 1 or 3 weeks after relief according to the grouping. The bladders were isolated and weighed. H&E, Masson’s trichrome and TUNEL staining were used to analyze histological changes. The oxidative stress assessed using malondialdehyde. The expression of beta-3 adrenoreceptor was examined by Western blotting.RESULTSThe tempol-treated groups exhibited a significant decrease in the number of IDCs per voiding cycle (nonTreat-1w vs. Treat-1w, 1.18±0.82 vs. 0.36±0.40, P=0.010; nonTreat-3w vs. Treat-3w, 1.51±0.69 vs. 0.23±0.25, P=0.002). The thickness and collagen fiber deposition of the detrusor muscle layer was significantly decreased in the treated groups. Apoptosis detected was mainly observed in the urothelial cell layer, although the rate of apoptosis was significantly decreased in the treated groups (48.9±3.36% vs. 32.7±11.10%, P=0.024; 25.8±4.67% vs. 15.7±9.83%, P=0.314). The tempol-treated groups showed significant decreases in the MDA concentrations at both 1 and 3 weeks after relief. The expression of the beta-3 adrenoreceptor was increased in the tempol-treated rats.CONCLUSIONSIschemic reperfusion injury after relief of pBOO caused histological and functional changes in the bladder. Free radical scavenger treatment prevented this oxidative stress.


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