Doxorubicin Loaded Gold Nanoparticles Mitigate Liver Fibrosis and Inflammatory Cytokines Gene Expression in Rat

Recent Adv Drug Deliv Formul. 2022 Oct 20. doi: 10.2174/2667387817666221020090050. Online ahead of print.

Abstract

Background: Gold nanoparticles have the potential to be used as a carrier in drug delivery system due to their small size, large surface area and short circulation time in blood.

Objective: This study aims that doxorubicin conjugation with gold nanoparticles (AuNPs) may reduce its toxicity as well as improve therapeutic efficacy.

Methods: Five groups of Albino rats were used; 1: healthy control, 2: Injured, 3: injured and treated with Dox, 4: Injured and treated with AuNPs, 5: Injured and treated with AuNPs: Dox. At the end of the experiment, blood and liver tissues were processed for biochemical and histopathological analysis. The expression of collagen, HO-1, IL-6 and TNF-α genes involved in liver fibrosis was observed through real-time PCR.

Results: At the end of the experiment, it was observed that the body weights of DOX treated rats decreased by 0.72%, however, AuNPs and Au: DOX treated rats were 15.3% and 29.13% respectively. The percentage of liver protection determined through alanine aminotransferase and aspartate aminotransferase levels in DOX, AuNPs and AuNPs: DOX treated groups were 39.21%, 79.26%, 98.17% and 47.77%, 84.17%, 97.92% respectively. That represents better recovering liver in Dox-AuNPs treated rats compared to others. Histopathological and gene expression studies further support the findings. The mRNA expression levels of inflammatory and oxidative stress related genes HO-1, IL-6 and TNF-α were upregulated in the injured group but downregulated in the treated group.

Conclusion: As depicted through biochemical, histopathological and gene expression studies, Au: DOX conjugate group seems to be protective against liver fibrosis.

Keywords: Collagen; Heam oxygenase; drug delivery; gene expression; liver fibrosis; toxicity..