In vitro tests of 1,3-dithia-2-thioxo-cyclopent-4-ene to evaluate the mechanisms of its hepatoprotective action.
Some in vitro tests were performed using 1,3-dithia-2-thioxo-cyclopent-4-ene (DT827A) to evaluate its mode of action on hepatoprotection. Experiments with leucine, uridine and thymidine uptakes using L-132 cells showed no increase in leucine uptake, but did show a tendency toward increases in both uridine and thymidine uptakes, which suggested a stimulating effect on RNA and DNA synthesis in vitro. DT827A did not influence GSH levels in the HepG2 cultured cell system, and did not show inhibition of cytochrome P450 2El in microsomes obtained from mouse liver. There may be no possibility for DT827A to protect a liver injury through its influence on liver GSH levels and inhibiting metabolic activation of CCl4 in this in vitro system. However, the inhibitory effect of DT827A on lipid peroxidation was observed in vitro, the same as the observation in vivo. Furthermore, when DT827A was incubated with Alamar Blue in the presence of a mixture of mouse liver S9 and mitochondrial fractions for 20 hr, DT827A showed more reducibility than it did in a case of non-incubation, and it was suggested that DT827A would be metabolized in the S9-mitochondrial fraction in vitro to show an increase of Alamar Blue reducibility. The protective effect of DT827A on a liver injury is due neither to its influence on liver GSH levels nor inhibition of the metabolic activation of CCl4, but a possible mechanism of action for the DT827 series of compounds to indicate an antioxidative effect would be brought about by the role of the compounds as a radical scavenger as well as its reductive effect.
Sadanobu
S
S
Department of Hygienic Chemistry, College of Pharmacy, Nihon University, Chiba, Japan.
Watanabe
M
M
Nakamura
C
C
Tezuka
M
M
D000818:Animals; D002251:Carbon Tetrachloride / Q000378:metabolism; D002478:Cells, Cultured; D004396:Coloring Agents / Q000494:pharmacology; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D016166:Free Radical Scavengers; D005978:Glutathione / Q000032:analysis; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects; D010078:Oxazines; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D013871:Thiones / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014529:Uridine / Q000378:metabolism; D014966:Xanthenes
C111193:1,3-dithia-2-thioxocyclopent-4-ene; D004396:Coloring Agents; D016166:Free Radical Scavengers; D006573:Heterocyclic Compounds, 1-Ring; D010078:Oxazines; D013871:Thiones; D014966:Xanthenes; C005843:resazurin; D012313:RNA; D004247:DNA; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1; D005978:Glutathione; D007930:Leucine; D013936:Thymidine; D014529:Uridine