The Potential Effects of Quercetin-Loaded Nanoliposomes on Amoxicillin/Clavulanate-Induced Hepatic Damage: Targeting the SIRT1/Nrf2/NF-κB Signaling Pathway and Microbiota Modulation

• Main Authors: Mahran Mohamed Abd El-Emam (Author), Mahmoud Mostafa (Author), Amina A. Farag (Author), Heba S. Youssef (Author), Azza S. El-Demerdash (Author), Heba Bayoumi (Author), Mohammed A. Gebba (Author), Sawsan M. El-Halawani (Author), Abdulrahman M. Saleh (Author), Amira M. Badr (Author), Shorouk El Sayed (Author)
• Format: Book
• Published: MDPI AG, 2023-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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-1β, TNF-α, NF-κB, and iNOS, with upregulation in the anti-inflammatory one, IL10. QR-lipo also prevented Co-Amox-induced gut dysbiosis by favoring the colonization of <i>Lactobacillus</i>, <i>Bifidobacterium</i>, and <i>Bacteroides</i> over <i>Clostridium</i> and <i>Enterobacteriaceae</i>. These results suggested that QR-lipo ameliorates Co-Amox-induced liver damage by targeting SIRT1/Nrf2/NF-κB and modulating the microbiota.

Item Description

10.3390/antiox12081487
2076-3921