(P19-034-24) Collaborative Impact of Curcumin, Astaxanthin, and Nicotinamide Riboside on Sustaining Mitochondrial Integrity and Alleviating Heat-Induced Oxidative Stress

Objectives: We have previously reported that curcumin, astaxanthin, and nicotinamide riboside individually prevent heat-induced mitochondrial dysfunction and skeletal muscle injury. However, the common challenge of limited bioavailability frequently restricts the practical effectiveness of these supplements. This study aims to examine their combined effects on mitochondrial integrity and oxidative stress in heat-induced conditions.

Methods: Prior to exposure to heat stress (41 °C for 2 hours), mouse C2C12 myoblasts underwent pre-treatment with a combination of low doses of curcumin (1 μM), astaxanthin (1 μM), and nicotinamide riboside (0.5 mM). When administered individually, these substances did not show any noticeable effects.

Results: Exposure to heat stress resulted in increased mitochondrial Ca²⁺ accumulation, excessive fragmentation, membrane potential depolarization, along with elevated levels of reactive oxygen species (ROS), activation of caspase 3/7, and induction of apoptosis. The combined action of curcumin, astaxanthin, and nicotinamide riboside notably influenced the maintenance of mitochondrial Ca²⁺ homeostasis and the preservation of their integrity. Moreover, their collective impact effectively inhibited the overproduction of ROS and apoptosis in mouse C2C12 myoblasts exposed to heat stress conditions.

Conclusions: These results validate the collaborative impact of curcumin, astaxanthin, and nicotinamide riboside in maintaining mitochondrial integrity and relieving oxidative stress induced by heat. The study proposes a promising therapeutic strategy to address cellular responses to heat challenges and improve mitochondrial function.

Funding Sources: This research is funded through a grant from the NIH Office of Dietary Supplements.