Amoxicillin/clavulanate (Co-Amox), a commonly used antibiotic for the treatment of
bacterial infections, has been associated with drug-induced liver damage. Quercetin (QR), a naturally
occurring flavonoid with pleiotropic biological activities, has poor water solubility and low
bioavailability. The objective of this work was to produce a more bioavailable formulation of QR
(liposomes) and to determine the effect of its intraperitoneal pretreatment on the amelioration of
Co-Amox-induced liver damage in male rats. Four groups of rats were defined: control, QR liposomes
(QR-lipo), Co-Amox, and Co-Amox and QR-lipo. Liver injury severity in rats was evaluated for all
groups through measurement of serum liver enzymes, liver antioxidant status, proinflammatory
mediators, and microbiota modulation. The results revealed that QR-lipo reduced the severity of
Co-Amox-induced hepatic damage in rats, as indicated by a reduction in serum liver enzymes and
total liver antioxidant capacity. In addition, QR-lipo upregulated antioxidant transcription factors
SIRT1 and Nrf2 and downregulated liver proinflammatory signatures, including IL-6, IL-1, TNF-,
NF-B, and iNOS, with upregulation in the anti-inflammatory one, IL10. QR-lipo also prevented
Co-Amox-induced gut dysbiosis by favoring the colonization of Lactobacillus, Bifidobacterium, and
Bacteroides over Clostridium and Enterobacteriaceae. These results suggested that QR-lipo ameliorates
Co-Amox-induced liver damage by targeting SIRT1/Nrf2/NF-B and modulating the microbiota.