Next Article in Journal
Understanding Calcium-Dependent Conformational Changes in S100A1 Protein: A Combination of Molecular Dynamics and Gene Expression Study in Skeletal Muscle
Previous Article in Journal
Insights into Activation Mechanisms of Store-Operated TRPC1 Channels in Vascular Smooth Muscle
Previous Article in Special Issue
Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma
Open AccessArticle

Study of Melatonin as Preventive Agent of Gastrointestinal Damage Induced by Sodium Diclofenac

1
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
2
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain
3
Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 180; https://doi.org/10.3390/cells9010180
Received: 30 November 2019 / Revised: 4 January 2020 / Accepted: 8 January 2020 / Published: 10 January 2020
(This article belongs to the Special Issue Melatonin in Human Health and Diseases)
Safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) has been widely studied and both therapeutic and side effects at the gastric and cardiovascular level have been generally associated with the inhibitory effect of isoform 1 (COX-1) and 2 (COX-2) cyclooxygenase enzymes. Now there are evidences of the involvement of multiple cellular pathways in the NSAIDs-mediated-gastrointestinal (GI) damage related to enterocyte redox state. In a previous review we summarized the key role of melatonin (MLT), as an antioxidant, in the inhibition of inflammation pathways mediated by oxidative stress in several diseases, which makes us wonder if MLT could minimize GI NSAIDs side effects. So, the aim of this work is to study the effect of MLT as preventive agent of GI injury caused by NSAIDs. With this objective sodium diclofenac (SD) was administered alone and together with MLT in two experimental models, ex vivo studies in pig intestine, using Franz cells, and in vivo studies in mice where stomach and intestine were studied. The histological evaluation of pig intestine samples showed that SD induced the villi alteration, which was prevented by MLT. In vivo experiments showed that SD altered the mice stomach mucosa and induced tissue damage that was prevented by MLT. The evaluation by quantitative reverse transcription PCR (RT-qPCR) of two biochemical markers, COX-2 and iNOS, showed an increase of both molecules in less injured tissues, suggesting that MLT promotes tissue healing by improving redox state and by increasing iNOS/NO that under non-oxidative condition is responsible for the maintenance of GI-epithelium integrity, increasing blood flow and promoting angiogenesis and that in presence of MLT, COX-2 may be responsible for wound healing in enterocyte. Therefore, we found that MLT may be a preventive agent of GI damages induced by NSAIDs. View Full-Text
Keywords: melatonin; NSAIDs; gastric injuries; antioxidant melatonin; NSAIDs; gastric injuries; antioxidant
Show Figures

Graphical abstract

MDPI and ACS Style

Sánchez, A.B.; Clares, B.; Rodríguez-Lagunas, M.J.; Fábrega, M.J.; Calpena, A.C. Study of Melatonin as Preventive Agent of Gastrointestinal Damage Induced by Sodium Diclofenac. Cells 2020, 9, 180.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop