Abstract 13017: Rescue of Impaired Blood Flow in CSEKO Mice Critical Limb Ischemia With Diallyl Trisulfide (DATS); A Hydrogen Sulfide Donar
Introduction: Cystathionine gamma-Lyase (CSE) is one of the prime enzymes to produce hydrogen sulfide in our body. Hydrogen sulfide (H2S) is reported to have a lot of beneficiary effects in our body such as vasodilatory, anti-inflammatory, anti-oxidant, cytoprotective and pro-angiogenic effects. However, H2S production is impaired due to lack of the CSE enzyme which may attenuate the pro-angiogenic effect of sulfide. Diallyl trisulfide (DATS); a potent H2S donor, has sulfide like effect but the angiogenic effect of DATS in CSE knock out (CSEKO) mice yet to be reported.
Objective: We sought to investigate that restoration of blood flow is impaired and this defective blood flow is restored by DATS in hind limb ischemia of CSEKO mice.
Methods: Permanent unilateral hind limb ischemia was induced in 12 weeks old CSEKO and wild type mice. Mice were assigned to two experimental groups (n=8-10, in each group) after surgery. PBS and DATS (200ug/kg) were administered retro-orbitally twice daily for until Day 21. Hind limb perfusion was measured using a laser Doppler perfusion probe. Angiogenic index and proliferative index were determined by the ratio of CD31 to DAPI and the ratio of Ki67 to DAPI positive staining respectively. Plasma sulfide level was measured by HPLC method.
Results: Blood perfusion was significantly impaired in CSEKO mice compared to wild type mice during the whole study period. Sulfide level was significantly lower in CSEKO mice compared to wild type mice. The angiogenic index and proliferation index were also significantly decreased in CSEKO mice compared to wild type mice. However, the sulfide donor, DATS restored the blood flow significantly to normal level of blood flow (100%) in CSEKO as well as in wild type mice. The angiogenic index and proliferation index were significantly increased in CSEKO mice after treatment with DATS.
Conclusion: DATS has rescued impaired blood flow in CSEKO mice critical limb ischemia through its proliferative and angiogenic effect.
- © 2011 by American Heart Association, Inc.