Mechanistic Understanding of D-Glucaric Acid to Support Liver Detoxification Essential to Muscle Health Using a Computational Systems Biology Approach
V.A. Shiva Ayyadurai, Prabhakar Deonikar, and Christine Fields
Liver and muscle health are intimately connected. Nutritional strategies that support liver detoxification are beneficial to muscle recovery. Computational–in silico–molecular systems’ biology analysis of supplementation of calcium and potassium glucarate salts and their metabolite D-glucaric acid (GA) reveals their positive effect on mitigation of liver detoxification via four specific molecular pathways: (1) ROS production, (2) deconjugation, (3) apoptosis of hepatocytes, and (4) β-glucuronidase synthesis. GA improves liver detoxification by downregulating hepatocyte apoptosis, reducing glucuronide deconjugates levels, reducing ROS production, and inhibiting β-Glucuronidase enzyme that reduces re-absorption of toxins in hepatocytes. Results from this in silico study provide an integrative molecular mechanistic systems explanation for the mitigation of liver toxicity by GA..
Materials and Method
The methodology used to identify the mechanisms of action of liver detoxification and to quantitatively predict the effects of GA on such mechanisms is described in this section. The CytoSolve® computational systems biology platform was employed in this process. The protocol for setting up and using CytoSolve® is explained in detailed by Ayyadurai and Deonikar, 2022 , and briefly described in Supplementary File S1.
This study provides three results: (1) A curated set of literature related to liver toxicity, (2) the identification of molecular pathways involved in the liver toxicity, and (3) in silico efficacy analysis of effect of GA on four molecular pathways involved in liver toxicity.