Title:

MECHANISMS OF THE GASTROPROTECTIVE EFFECTS OF CURCUMIN IN ACUTE MUCOSAL LESIONS

Author:

Czekaj, Renata

Subject:

curcumin ; gastroprotection ; prostaglandins ; nitric oxide ; CGRP

Abstract:

Curcumin is a biologically active component of the root of Curcuma longa, used for many centuries as a culinary spice in the Far East. Its use in traditional medicine in the treatment of various diseases, such as diabetes, gastrointestinal diseases, rheumatic diseases, atherosclerosis, infections and cancer, also stretches back many centuries. In modern medicine there is increasing interest in the multidirectional therapeutic effects of curcumin which exhibits antioxidant and anti-inflammatory activity. One key feature of curcumin is its excellent tolerability, low toxicity and a lack of side effects after its administration; however, curcumin's bioavailability is low, and therefore it exhibits its effects mainly within the gastrointestinal tract.Gastroprotection means the ability of certain mechanisms, including in particular the prostaglandins, to prevent the formation of acute injury to the mucosa, whereas this effect occurs regardless of their inhibitory effect on the secretion of gastric acid.The purpose of the study was to examine whether curcumin exhibits gastroprotective effects in experimental acute ethanol- and stress-induced injuries of the gastric mucosa and which factors and mechanisms mediate this effect.In the first stage of the study an evaluation was made of the effect of intragastrically applied curcumin on basal and histamine- or pentagastrin-stimulated gastric secretion. In the course of further study it was demonstrated that curcumin exhibits gastroprotective effects in an experimental model of acute ethanol- and stress-induced injury, and that these effects are accompanied by an increase in gastric blood flow and in secretion of gastrin.Curcumin reduces the expression of mRNA inflammatory factors, and increase of mRNA expression of anti-inflammatory and antioxidant factors in gastric mucosa exposed to the damaging effects of ethanol or stress. In the course of the study it has been demonstrated that both PG synthesized by COX-1 and COX-2 take part in the gastroprotective mechanisms of curcumin. In the course of further study an evaluation was made of the involvement of endogenous NO in the mechanisms of the gastroprotective effects of curcumin. In the final stage of the study an examination was made of the involvement of capsaicin-sensitive visceral-sensory fibres in the mechanisms of the protective effects of curcumin.In conclusion, the intragastric application of curcumin inhibits both basal gastric acid secretion and the secretion stimulated by histamine or pentagastrin. Curcumin exhibits dose-dependent gastroprotective, hyperemic and gastrin secretion-increasing effect in a model of acute experimental ulceration of the gastric mucosa caused by administration of 75% ethanol or under conditions that cause systemic stress. Intragastric administration of ethanol or application of stress results in an increase in mRNA expression of inflammatory factors studied and the reduction of mRNA expression of anti-inflammatory and antioxidant agents studied in the gastric mucosa, while intragastric application of curcumin in a dose-dependent manner, results in the reduction of mRNA expression of inflammatory factors studied and an increase of mRNA expression of antioxidant and anti-inflammatory factors under study. The mechanisms of the gastroprotective effect of curcumin in the ethanol and stress model of acute gastric mucosal injury are mediated by the endogenous prostaglandins and nitric oxide, the activity of capsaicin-sensitive visceral-sensory fibres that release CGRP and vanilloid receptor (TRPV1) of these fibres.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

choroby układu trawiennego

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Lekarski.

Promoter:

Agata Ptak-Belowska

Date:

2016

Date issued:

2016

Type:

Praca doktorska

Format:

application/pdf

Call number:

ZB-126419

ControlNumberVIRTUA:

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Language:

pol

Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

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