Stimulation of de novo glutathione synthesis by nitrofurantoin for enhanced resilience of hepatocytes.

ABSTRACT: Toxicity is not only a function of damage mechanisms, but is also determined by cellular resilience factors. Glutathione has been reported as essential element to counteract negative influences. The present work hence pursued the question how intracellular glutathione can be elevated transiently to render cells more resistant toward harmful conditions. The antibiotic nitrofurantoin (NFT) was identified to stimulate de novo synthesis of glutathione in the human hepatoma cell line, HepG2, and in primary human hepatocytes. In intact cells, activation of NFT yielded a radical anion, which subsequently initiated nuclear-factor-erythroid 2-related-factor-2 (Nrf2)-dependent induction of glutamate cysteine ligase (GCL). Application of siRNA-based intervention approaches confirmed the involvement o

SUBMITTER: Wijaya LS 

PROVIDER: S-EPMC9525367 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature