SUMMARY OF THE INVENTION [0009] The inventors of the present invention have identified among the patients with metabolic syndrome, when associated to NASH, a group of patients presenting a lipidomic profile alteration associated with high values of TBARS in serum, and have surprisingly discovered that treatment with a composition including silybin allows normalization of said lipidomic profile, thus having effects in the treatment of non-alcoholic steatohepatitis. [0010] The invention thus relates to a composition for use in the treatment of metabolic oxidative alterations in patients with non-alcoholic steatohepatitis (NASH), wherein said composition comprises silybin, and wherein the treatment is administered to patients having an altered lipidomic profile according to the claims. [0011] In the present invention, when the definition "altered lipidomic profile" is used, it is meant the lipidomic profile of a patient with metabolic syndrome, preferably also with NASH, who is positive to the TBARS assay, who specifically show high values of TBARS in the TBARS assay ((2-ThioBarbituric Acid Reactive Substances (TBARS)). The TBARS assay measures in a serum sample of a patient the TBARS, i.e. the by-products generated by a process of lipid peroxidation, through the use of barbituric acid (Armstrong, D., and Browne, R. The analysis of free radicals, lipid peroxides, antioxidant enzymes and compounds to oxidative stress as applied to the clinical chemistry laboratory. Free Radicals in Diagnostic Medicine 366, 43-58 1994). In the present invention, when it is stated that high levels of TBARS or low levels of TBARS are present, it is meant that the values found in the TBARS assay are higher or lower than those observed in healthy subjects. In the present invention, while referring to average values of TBARS in healthy subjects average values of approximately 0.0160.002 mM/mgprot (mM of TBARS with respect to mg of plasma proteins) are meant. [0012] The inventors of the present invention have therefore identified a specific group of patients with the metabolic syndrome and with also NASH, who have an alteration of serum lipidomics and who are responsive to treatment with a composition comprising silybin. The group of patients identified by the inventors in the group of patients with metabolic syndrome with also NASH, have a lipidomic profile associated with altered lipid peroxidation (high values of TBARS) that distinguishes it from the group of patients with metabolic syndrome with also NASH, who, in basic conditions, do not show high levels of circulating lipid peroxidation markers (TBARS). The two groups of patients are in no way overlapping on the basis of the values of TBARS determined by the TBARS assay, as will be evident from the experimental section below. Upon completion of the treatment with the composition including silybin, the group of patients of the invention showed a normalization of the serum lipidomic profile, with a corresponding lowering of the values of TBARS in the TBARS assay, confirming the treatment of oxidative stress typical of NASH pathology. [0013] The invention will now be described in detail and with reference to the following figures.

Silybin for the treatment of metabolic oxidative alterations in patients with non-alcoholic steatohepatitis (NASH)

LOGUERCIO, Carmelina
Investigation
;
FEDERICO, Alessandro
Investigation
;
STIUSO, Paola
Investigation
2019

Abstract

SUMMARY OF THE INVENTION [0009] The inventors of the present invention have identified among the patients with metabolic syndrome, when associated to NASH, a group of patients presenting a lipidomic profile alteration associated with high values of TBARS in serum, and have surprisingly discovered that treatment with a composition including silybin allows normalization of said lipidomic profile, thus having effects in the treatment of non-alcoholic steatohepatitis. [0010] The invention thus relates to a composition for use in the treatment of metabolic oxidative alterations in patients with non-alcoholic steatohepatitis (NASH), wherein said composition comprises silybin, and wherein the treatment is administered to patients having an altered lipidomic profile according to the claims. [0011] In the present invention, when the definition "altered lipidomic profile" is used, it is meant the lipidomic profile of a patient with metabolic syndrome, preferably also with NASH, who is positive to the TBARS assay, who specifically show high values of TBARS in the TBARS assay ((2-ThioBarbituric Acid Reactive Substances (TBARS)). The TBARS assay measures in a serum sample of a patient the TBARS, i.e. the by-products generated by a process of lipid peroxidation, through the use of barbituric acid (Armstrong, D., and Browne, R. The analysis of free radicals, lipid peroxides, antioxidant enzymes and compounds to oxidative stress as applied to the clinical chemistry laboratory. Free Radicals in Diagnostic Medicine 366, 43-58 1994). In the present invention, when it is stated that high levels of TBARS or low levels of TBARS are present, it is meant that the values found in the TBARS assay are higher or lower than those observed in healthy subjects. In the present invention, while referring to average values of TBARS in healthy subjects average values of approximately 0.0160.002 mM/mgprot (mM of TBARS with respect to mg of plasma proteins) are meant. [0012] The inventors of the present invention have therefore identified a specific group of patients with the metabolic syndrome and with also NASH, who have an alteration of serum lipidomics and who are responsive to treatment with a composition comprising silybin. The group of patients identified by the inventors in the group of patients with metabolic syndrome with also NASH, have a lipidomic profile associated with altered lipid peroxidation (high values of TBARS) that distinguishes it from the group of patients with metabolic syndrome with also NASH, who, in basic conditions, do not show high levels of circulating lipid peroxidation markers (TBARS). The two groups of patients are in no way overlapping on the basis of the values of TBARS determined by the TBARS assay, as will be evident from the experimental section below. Upon completion of the treatment with the composition including silybin, the group of patients of the invention showed a normalization of the serum lipidomic profile, with a corresponding lowering of the values of TBARS in the TBARS assay, confirming the treatment of oxidative stress typical of NASH pathology. [0013] The invention will now be described in detail and with reference to the following figures.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11591/159978
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