title: Intestinal anti-inflammatory activity of calcium pyruvate in the TNBS model of rat colitis: Comparison with ethyl pyruvate.
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.
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, CIBM, University of Granada, Granada, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Algieri
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, CIBM, University of Granada, Granada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez-Nogales
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, CIBM, University of Granada, Granada, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Garrido-Mesa
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, CIBM, University of Granada, Granada, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Camuesco
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, CIBM, University of Granada, Granada, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Vezza
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, CIBM, University of Granada, Granada, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Garrido-Mesa
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, CIBM, University of Granada, Granada, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Utrilla
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, CIBM, University of Granada, Granada, Spain.
authors.forename: M E
authors.initials: ME
authors.lastname: Rodriguez-Cabezas
authors.affiliation: PhytoLab GmbH & Co. KG, Vestenbergsgreuth, Germany; Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy, University of London, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Pischel
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, CIBM, University of Granada, Granada, Spain. Electronic address: jgalvez@ugr.es.
authors.forename: J
authors.initials: J
authors.lastname: Galvez
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration; D010766:Phosphorylation; D011773:Pyruvates / Q000494:pharmacology / Q000627:therapeutic use*; D019289:Pyruvic Acid / Q000494:pharmacology / Q000627:therapeutic use; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D016328:NF-kappa B; D011773:Pyruvates; C046522:ethyl pyruvate; D019289:Pyruvic Acid; D014302:Trinitrobenzenesulfonic Acid
keywords: Calcium pyruvate; Ethyl pyruvate; Intestinal anti-inflammatory activity; TNBS rat colitis