Antioxidant Delivery System Shields Liver Cells From Drug

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In a new study, researchers have developed a system to deliver antioxidants directly to mitochondria – the "powerhouses of the cell" – in the liver and protect against the effects of oxidative stress in mice. The research is published in Scientific Reports.

Mitochondria are well known as the "powerhouses of the cell" – organelles within cells that generate most of the energy needed to power important biochemical processes. Their main role is to produce the molecule adenosine triphosphate (ATP), which acts as the cells’ energy currency.

However, ATP production can also generate potentially harmful byproducts called reactive oxygen species (ROS). These highly reactive molecules can damage DNA or even whole cells and tissues. Healthy mitochondria keep ROS in check, but when this balance is lost in a phenomenon called oxidative stress, ROS-induced damage can result in premature aging and disease.

Importantly, antioxidants – molecules that inhibit oxidation – can keep these ROS and their subsequent damage under control. In the current study, researchers from Hokkaido University tested a system to deliver antioxidants directly into the mitochondria of liver cells to mitigate the effects of ROS-induced damage.

The research team, led by Prof. Yuma Yamada, Prof. Hideyoshi Harashima and Dr. Mitsue Hibino, had previously developed a drug delivery system they named CoQ10-MITO-Porter.

"This system consists of the antioxidant molecule Coenzyme Q10 (CoQ10) – which is also required by mitochondria for ATP production – encapsulated by a lipid nanoparticle that would target mitochondria. In this study, we aimed to test if this system could work in living organisms," explained Hibino.

The researchers tested the efficacy of this system using mouse models of liver damage caused by the painkilling drug acetaminophen. Acetaminophen overdoses increase ROS levels in the mitochondria which consequently damages liver cells.

The findings from these animal models revealed that CoQ10-MITO-Porter was transported to the liver and reduced ROS-induced damage. Additionally, when they reduced the size of CoQ10-MITO-Porter particles and increased the packaging of CoQ10 liver damage was more effectively treated compared to the original preparation.

"Our study has shown that the MITO-Porter system we developed can be used to deliver CoQ10 to the liver, making it an important therapeutic strategy against conditions that cause oxidative stress," said Yamada. "Our future work will focus on elucidating the mechanism responsible for the therapeutic effect of CoQ10."

Reference: Hibino M, Maeki M, Tokeshi M, Ishitsuka Y, Harashima H, Yamada Y. A system that delivers an antioxidant to mitochondria for the treatment of drug-induced liver injury. Sci Rep. 2023;13(1):6961. doi: 10.1038/s41598-023-33893-7

This article is a rework of a press release issued by Hokkaido University. Material has been edited for length and content.