Intestinal anti-inflammatory activity of calcium pyruvate in the TNBS model of rat colitis : comparison with ethyl pyruvate

Algieri, F., Rodriguez-Nogales, Al., Garrido-Mesa, J., Camuesco, D., Vezza, T., Garrido-Mesa, N., Utrilla, P., Rodriguez-Cabezas, M.E., Pischel, I. and Galvez, J. (2016) Intestinal anti-inflammatory activity of calcium pyruvate in the TNBS model of rat colitis : comparison with ethyl pyruvate. Biochemical Pharmacology, 103, pp. 53-63. ISSN (print) 0006-2952

Official URL: https://doi.org/10.1016/j.bcp.2015.12.022

Abstract

Pyruvate is a key intermediate of the carbohydrate metabolism with endogenous scavenger properties. However, it cannot be used in clinics due to its instability. Ethyl pyruvate (EP) has shown better stability as well as an antioxidant and anti-inflammatory activity. Calcium pyruvate monohydrate (CPM) is another stable pyruvate derivative that could also provide the benefits from calcium, fundamental for bone health. Considering everything, we propose CPM as a therapeutic strategy to treat diseases with an immune component in which there is also a significant dysregulation of the skeletal homeostasis. This could be applicable to inflammatory bowel disease, which is characterized by over-production of pro-inflammatory mediators, including cytokines and reactive oxygen and nitrogen metabolites that induces intestinal mucosal damage and chronic inflammation, and extra-intestinal symptoms like osteopenia and osteoporosis. The effects of CPM and EP (20, 40 and 100mg/kg) were evaluated on the trinitrobenzenesulfonic acid (TNBS) model of colitis in rats, after a 7-day oral treatment, with main focus on colonic histology and inflammatory mediators. Both pyruvates showed intestinal anti-inflammatory effects in the TNBS-induced colitis. They were evident both histologically, with a recovery of the mucosal cytoarchitecture and a reduction of the neutrophil infiltration, and through the profile of inflammatory mediators (IL-1, IL-6, IL-17, IL-23, iNOS). However, CPM appeared to be more effective than ethyl pyruvate. In conclusion, CPM exerts intestinal anti-inflammatory effect on the TNBS-induced colitis in rats, although further experiments are needed to explore its beneficial effects on bone health and osteoporosis.

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