Molecular hydrogen suppresses free-radical-induced cell death by mitigating fatty acid peroxidation and mitochondrial dysfunction1

• Published in: Canadian journal of physiology and pharmacology 2019, Vol.97 (10), p.999-1005
• Main Authors: Iuchi, Katsuya, Nishimaki, Kiyomi, Kamimura, Naomi, Ohta, Shigeo
• Format: Article
• Language: English
• Subjects: cardiovascular diseases; cell death; cellules THP-1; dysfonctionnement des mitochondries; fatty acid peroxidation; hydrogène moléculaire; maladies cardiovasculaires; mitochondrial dysfunction; molecular hydrogen; mort cellulaire; oxidative stress; peroxydation des acides gras; stress oxydatif; tert-butyl hydroperoxide; tert-butyl hydroperoxyde; THP-1 cells
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2018-0741

Molecular hydrogen (H 2 ) was believed to be an inert and nonfunctional molecule in mammalian cells; however, we overturned the concept by reporting the therapeutic effects of H 2 against oxidative stress. Subsequently, extensive studies revealed multiple functions of H 2 by exhibiting the efficacies of H 2 in various animal models and clinical studies. Here, we investigated the effect of H 2 on free-radical-induced cytotoxicity using tert-butyl hydroperoxide in a human acute monocytic leukemia cell line, THP-1. Cell membrane permeability was determined using lactate dehydrogenase release assay and Hoechst 33342 and propidium iodide staining. Fatty acid peroxidation and mitochondrial viability were measured using 2 kinds of fluorescent dyes, Liperfluo and C11-BODIPY, and using the alamarBlue assay based on the reduction of resazurin to resorufin by mainly mitochondrial succinate dehydrogenase, respectively. Mitochondrial membrane potential was evaluated using tetramethylrhodamine methyl ester. As a result, H 2 protected the cultured cells against the cytotoxic effects induced by tert-butyl hydroperoxide; H 2 suppressed cellular fatty acid peroxidation and cell membrane permeability, mitigated the decline in mitochondrial oxidoreductase activity and mitochondrial membrane potential, and protected cells against cell death evaluated using propidium iodide staining. These results suggested that H 2 suppresses free-radical-induced cell death through protection against fatty acid peroxidation and mitochondrial dysfunction.