[Effect of synthesized GYY4137, a slowly releasing hydrogen sulfide donor, on cell viability and distribution of hydrogen sulfide in mice].
OBJECTIVE
To improve a method of a new hydrogen sulfide slow-releasing donor, to observe its cellular toxicity in HepG2 cells and tissue distribution and metabolic pathway after administration of the donor by intraperitoneal injection in ICR mice and to afford experimental evidences for rationally using this donor in hydrogen sulfide research.


METHODS
We synthesized the new chemical compound which slowly released hydrogen sulfide. After administration of the donor, the cell toxicity was evaluated for cell viability using trypan blue staining in HepG2 cells and lactate dehydrogenase (LDH) activity in culture medium. After administration of this donor by intrasperitoneal injection, we measured the tissue hydrogen sulfide content in the liver, heart, kidney and brain using sensitive-sulfur electrode assay.


RESULTS
We successfully prepared the donor which could release hydrogen sulfide. The releasing ability of the donor solution stored at 4 °C or 20 °C did not change as compared with the freshly-prepared one. Treated at various concentrations of the donor (0.062 5, 0.125, 0.25, 0.5, 1 and 2 mmol/L) for 24 hours in HepG2 cells, the cell viability and LDH leak from the cells were not different as compared with the controls. The donor (2 mmol/L) was administrated everyday and the culture medium was changed every 3 days. After 9 days, the cell viability and LDH leak did not change. Administration of the donor (200 μmol/kg) quickly increased the tissue hydrogen sulfide concentrations in the liver and heart and maintained about 20 min; the hydrogen sulfide level in the kidney elevated and maintained a longer time, then recovered after 2 hours, which implicated that the donor might exclude the kidney; the hydrogen sulfide concentration in the brain did not change in the present study, which suggested that the donor could not pass the blood-brain barrier. Long time (4 weeks) treatment with this compound might induce hepatic or cutaneous injury.


CONCLUSIONS
The new chemical compound is a relative stable, slow-releasing donor of hydrogen sulfide with low cellular toxicity, which may be used to study the regulatory role of hydrogen sulfide in the cellular physiological and pathophysiological mechanism of the animal model with acute diseases.
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
Fang
F
Yu
Jing
J
Zhao
Chao-shu
CS
Tang
Bin
B
Geng
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009025:Morpholines / Q000138:chemical synthesis* / Q000378:metabolism*; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis* / Q000378:metabolism*; D014018:Tissue Distribution
C529376:GYY 4137; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D007770:L-Lactate Dehydrogenase; D006862:Hydrogen Sulfide