Curcumin-containing Silver Nanoparticles Prevent Carbon Tetrachloride- induced Hepatotoxicity in Mice

Abstract

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl₄)-induced hepatic injury.

Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl₄ challenge.

Results: Administration of CCL₄ resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL₄ challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that the CCl₄ challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPscurcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%.

Conclusion: Administration of AgNPs-curcumin resulted in significant anti-oxidant activity in vivo. This agent has the potential to prevent hepatic tissue destruction and DNA damage that results from direct exposure to CCL₄.

Keywords: Carbon tetrachloride; curcumin.; hepatotoxicity; liver function; oxidative stress; silver nanoparticles.