# Curcumin Nanocarriers in the Protection Against Iron- and Alcohol-Induced Oxidative Stress in a Cellular Model of Liver Disease

## TL;DR

This study shows that curcumin nanoformulations can protect liver cells from damage caused by alcohol and excess iron, suggesting a potential new treatment for alcohol-related liver disease.

## Contribution

The study introduces curcumin nanoformulations as a novel approach to combat oxidative stress in alcohol-related liver disease combined with iron overload.

## Key findings

- Alcohol and iron together significantly reduced liver cell survival and increased oxidative stress.
- Curcumin nanoformulations improved cell survival and reduced oxidative stress in treated cells.
- Encapsulated curcumin showed therapeutic potential in models of alcohol-related liver disease with iron dysregulation.

## Abstract

Excessive alcohol consumption can lead to liver damage, partly due to excess iron buildup in the liver. Excess iron in the liver can cause further damage due to oxidative stress, an imbalance of free radicals, and antioxidants in the body, which leads to cell damage. In this study, curcumin, a natural antioxidant found in turmeric, was developed into nanoformulations which enhance the properties of conventional drugs, to understand if curcumin can protect liver cells from damage. Liver cells were exposed to alcohol and iron to mimic the effects seen in alcohol-related liver disease. The results showed that alcohol and iron together significantly reduced cell survival and increased oxidative stress levels. However, when the curcumin nanoformulation was added, cell survival improved, and oxidative stress was reduced. Overall, curcumin nanoformulated drugs demonstrated strong protective effects against alcohol- and iron-induced liver cell damage. This suggests that curcumin formulations could be a promising future treatment option for liver disease associated with alcohol misuse.

During chronic alcohol misuse, hepatic iron overload occurs, leading to exacerbated oxidative stress and liver injury. The aim was to study formulations encapsulated with the antioxidant curcumin to assess their ability protect against oxidative stress in a model of alcohol-related liver disease (ALD) combined with iron. HepG2 (VL-17A) cells were treated with iron (50 µM) alone or with alcohol (200 to 350 mM) over 72 h and markers of oxidative damage, cell death, and mitochondrial function were assessed. Nanoformulations encapsulating curcumin were also studied. VL-17A cells treated with both ethanol and iron showed significant decreases in cell viability (64%, p < 0.0001) when compared to control, and a 56% decrease (p = 0.0279) when compared to iron-only treatment. Iron-alone treatment caused a 115% increase (p < 0.0001) in ROS at 48 h as well as increases of up to 118% when treated with 200 mM ethanol + 50 μM iron (p < 0.0001), compared to control DMEM. The study found that 10 µM curcumin DSPE-PEG increased cell viability by 17% and 41% when compared to control and iron treatment alone, respectively. Formulations reduced ROS by 36% (p = 0.0015) when compared to iron-alone treatment. In summary, encapsulated curcumin provided antioxidant capacity and reduced oxidative stress, demonstrating the therapeutic potential for curcumin formulations in ALD combined with iron dysregulation.