Magnesium availability, inflammatory bowel disease and the role of the magnesium channels TRPM6 and TRPM7.

Hamersma, W.R. (2015) Magnesium availability, inflammatory bowel disease and the role of the magnesium channels TRPM6 and TRPM7. thesis, Medicine.

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Abstract

Background: Magnesium is an essential mineral that is fundamental in many pathophysiological processes. A mild hypomagnesaemia is a common condition associated to dietary deficiency of magnesium. Hypomagnesaemia is a well-known enhancer of oxidative stress and inflammation. Inflammatory Bowel Disease (IBD) is a collection of chronic inflammatory conditions leading to a variety of nutritional deficiencies due to reduced absorption and/or increased loss of essential nutrients, which among other conditions can induce hypomagnesaemia. Objective: To investigate the influence of magnesium availability in the diet on the pathogenesis and pathophysiological consequences in a well-established murine model of dextran sodium sulphate (DSS)-induced acute colitis. Methods: Mice were exposed to 2.5% DSS in the drinking water and fed three different magnesium-containing diets (low (30mg/kg), normal (1000mg/kg) and high (4000mg/kg) MgSO4 content). Both acute colitis (5 days exposure to DSS) and recovery after the acute colitis (7 days of recovery without DSS) were studied. The severity of the colitis was scored daily using a four point Disease Activity Index (DAI) based on 1) the faecal consistency, 2) weight loss and 3) faecal blood loss. Colon and kidney samples and serum were collected at the sacrifice. Magnesaemia was analysed using atomic absorption spectrometry and severity of the inflammation of the colon was scored on morphological examination of haematoxylin/eosin stained slides. TRPM6 and TRPM7 mRNA expression was analysed using Real Time PCR. Results: Dietary magnesium deficiency increased the severity of the DSS-induced colitis as scored with the Disease Activity Index, whereas magnesium supplementation seemed to score more or less like controls. Serum magnesium measurements showed that while magnesium in the diets positively correlated with the magnesaemia, the exposure to DSS reduced magnesaemia in all conditions. However, high magnesium content in the diet compensated for DSS-induced hypomagnesaemia Interestingly, morphological analysis of the colon showed that while the low magnesium diet enhanced mucosal damage and impaired mucosal recovery, magnesium supplementation clearly protected the colonic mucosa against DSS-induced damage.

Item Type:	Thesis (Thesis)
Supervisor name:	Vugt, Prof. dr. M.A.T.M. van
Supervisor name:	Wolf, Prof. dr. F.I. and Istituto di Patologia generale and Facoltà di Medicina and Università Cattolica del Sacro Cuore and Roma, Italy
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:43
Last Modified:	25 Jun 2020 10:43
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/450

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