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NAMPT Inhibition and Increased NAD-Bioavailability Atenuate Liver Damage in CCI4-Induced Mice Liver Fibrosis


February 1, 2023

Suarez-Cuenca, J.


Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme within the NAD+ salvage biosynthetic pathway and also a cytokine modulator with effects on inflammation and fibrogenesis. FK866 (NAMPT inhibitor) has shown anti-inflammatory properties. However, FK866-induced depletion of NAD+ may also impair liver bioenergetic metabolism during Chronic Liver Disease (CLD). The aim of this study was to evaluate the effects of NAMPT inhibition and NAD+ restoration on experimental CLD...NAMPT inhibition resulted in a mild attenuation of histological and biochemical features of the CCl4-induced liver damage. NAD+ restoration, by the concomitant administration of its precursor NMN, resulted in a significant improvement of the histological characteristics; evidenced by a lower inflammatory infiltrate and fibrosis as well as lower levels of bilirubin. NAMPT inhibition and adequate NAD+ restoration were confirmed by a colorimetric assay of NADH and NAD+ and biochemical features were measured by routinary Liver Function Tests. This study shows that NAMPT inhibition concomitant to NAD restoration significantly attenuate experimental liver damage.

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