Your browser doesn't support javascript.
loading
ATP-generating glycolytic substrates prevent N-nitrosofenfluramine-induced cytotoxicity in isolated rat hepatocytes.
Nakagawa, Yoshio; Tayama, Sumiko; Ogata, Akio; Suzuki, Toshinari; Ishii, Hidemi.
Affiliation
  • Nakagawa Y; Division of Pharmacology, Tokyo Metropolitan Institute of Public Health, 3-24-1, Hyakunin-cho, Shinjuku-ku, Tokyo 169-0073, Japan. Yoshio_1_Nakagawa@member.metro.tokyo.jp
Chem Biol Interact ; 164(1-2): 93-101, 2006 Dec 01.
Article in En | MEDLINE | ID: mdl-17056023
ABSTRACT
The relationship between cytotoxicity induced by N-nitrosofenfluramine and mitochondrial or glycolytic adenosine triphosphate (ATP) synthesis-dependent intracellular bioenergetics was studied in isolated rat hepatocytes. The supplementation of fructose, an ATP-generating glycolytic substrate, to hepatocyte suspensions prevented N-nitrosofenfluramine-induced cell injury accompanied by the formation of cell blebs, abrupt loss of intracellular ATP and reduced glutathione and mitochondrial membrane potential (DeltaPsi), and the accumulation of oxidized glutathione and malondialdehyde, indicating lipid peroxidation, during a 2h incubation period. Fructose (1-20mM) resulted in concentration-dependent protection against the cytotoxicity of N-nitrosofenfluramine at a concentration of 0.6mM, a low toxic dose. Pretreatment with xylitol, another glycolytic substrate, at concentration of 15mM also prevented the cytotoxicity caused by the nitroso compound, but neither glucose nor sucrose exhibited protective effects. In addition, fructose inhibited N-nitrosofenfluramine (0.5 and 0.6mM)-induced DNA damage, as evaluated in the comet assay, indicating that nuclei as well as mitochondria are target sites of the compound. These results indicate that (a) the onset of N-nitrosofenfluramine-induced cytotoxicity in rat hepatocytes is linked to mitochondrial failure, and that (b) the insufficient supply of ATP in turn limits the activities of all energy-requiring reactions and consequently leads to acute cell death.
Subject(s)
Search on Google
Collection: 01-internacional Database: MEDLINE Main subject: Mitochondria, Liver / Adenosine Triphosphate / Hepatocytes / Fenfluramine / Glycolysis / Membrane Potentials Limits: Animals Language: En Journal: Chem Biol Interact Year: 2006 Document type: Article Affiliation country: Japan
Search on Google
Collection: 01-internacional Database: MEDLINE Main subject: Mitochondria, Liver / Adenosine Triphosphate / Hepatocytes / Fenfluramine / Glycolysis / Membrane Potentials Limits: Animals Language: En Journal: Chem Biol Interact Year: 2006 Document type: Article Affiliation country: Japan