Carnosine Supplementation on Quantity/Quality of Oral Salivae.

Overview

The aim of this study is to elucidate the mutual relationship between salivae characteristics and oral microbiome and to compare them with common oral disease; furthermore, by using specific bioinformatic tools to analyse the data, the potentials of Carnosine in preventing/treating oral diseases and its mechanism of action will be addressed by using quantitative proteomics.

The pH of the oral cavity is a synthetic parameter that underlies a multifactorial process of continuous adjustment that includes the effect of salivae as a buffer and the contribution of the oral cavity microbiome. In some diseases of the oral cavity an alteration of these adjustment mechanisms is supposed to alter the normal flow of salivae and, consequently, the pH and the oral microbiome with the expansion of potentially pathogenic strains such as e.g. streptococcus viridans. Carnosine (Car) is an endogenous dipeptide, composed of β-alanine and L-histidine, that was originally discovered in larger amounts in skeletal muscle of some vertebrates, including humans, showing a greater dependence on non-oxidative forms of energy metabolism. This peculiar association with muscular tissue and its pH-buffering properties has led to associate Car with the intracellular acid-base homeostasis of muscles. More recently, the physiological role of Car has been expanded beyond the intracellular buffering properties, supporting a role in sarcoplasmic Ca2+ regulation and neutralisation of reactive oxygen species (ROS). It is well known that ROS induce the formation of reactive electrophilic carbonyl species by reacting with lipids and sugars which, in turn, react with proteins forming irreversible adducts (AGEs, ALEs and EAGLEs) and cross-links that may affect the cardiovascular wall matrix that becomes less distensible, especially during the ageing process and/or diseases. Thus it is thought that Car and, indeed, other histidine-containing peptide (HCD), may prevent chronic diseases via their anti-inflammatory, anti-oxidative, anti-glycating, anti-ischaemic and chelating properties. Furthermore, the localisation of Car in other tissues such as brain, olfactory bulb, heart, stomach, pancreas, kidney has suggested further potential uses in preventing e.g. neurodegenerative disorder and cognitive function or the development of type II diabetes. The oral microbiome (OM) is a relevant part of the whole human MO since it contains several different niches, with distinct microbial communities, colonising the oral cavity (OC), including not only bacteria but also fungi, viruses, archaea and protozoa. These communities form a complex ecological system that influences OC and systemic health. Indeed the prevalent oral diseases (OD), namely dental caries and periodontal diseases, are believed to be microbiota-related. Furthermore, several evidences support the theory that many systemic diseases are associated with an altered OM, among these the most frequently associated diseases are metabolic, such as diabetes, cardiovascular and oncological ones. For their prevalence worldwide, among OD, periodontal infection, including gingivitis and chronic periodontitis, is possibly the most prevalent human microbial diseases (HMD). In order to protect the OC from HMD, in the present project Car has been chosen as a possible preventive and/or therapeutic principle for its aforementioned multiple biological effects. Thus the safety and efficacy of AqualiefTM (Metis Healthcare s.r.l., Milano, Italy) a 400 mg mucoadhesive oral tablet (13 x 4 mm), that recognise Car as main ingredient, will be tested on healthy volunteer and in subjects affected by common OD. The main objectives of this protocol are to estimate the quantity/quality of oral salivae and OM in healthy volunteer and in patients affected by common OD, before and after 7 days of treatment with AqualiefTM, 1 tablet twice. The characteristics of oral salivae (Sal) that will be studied are: a - unstimulated and stimulated (paraffin-activated) salivary flow rates, pH and buffering power; b - quantitative proteomics (QP), on selected targets, representing the main metabolites/components of OM. By matching Sal characteristics with OM and comparing them with OD, it is expected to elucidate their mutual relationship; furthermore, by using specific bioinformatic tools to analyse the data, the potentials of Car in preventing/treating OD and its mechanism of action will be addressed by using QP. The study will take place at the Odontoiatric University Clinic (OUC), Istituto Stomatologico Italiano (ISI) of Milan, Italy, in a prospective, randomised, double-blind, placebo-controlled fashion.

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