Mhatre Susmit, Anjali Rai, Sahai Pulkit, Auden John, Singh Somnath, Njie Mbye Ya Fatou, Ohia Sunny E, Opere Catherine A
Department of Pharmacy Sciences, School of Pharmacy and Health Professionals, Creighton University, Omaha, NE 68178, USA.
Cell and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Pharmaceuticals (Basel). 2024 Oct 21;17(10):1408. doi: 10.3390/ph17101408.
Hydrogen sulfide (HS) is an endogenous transmitter with the potential to regulate aqueous humor dynamics and protect retinal neurons from degeneration. The aim of the present study was two-fold: (a) to evaluate the release of HS from two polysulfides, diallyl disulfide (DADS), and diallyl trisulfide (DATS); and (b) to investigate their ocular hypotensive actions in normotensive male and female rabbits in the presence and absence of GSH.
HS was quantified hourly for up to 6 h using a HS-Biosensor (World Precision Instruments, Sarasota, Fl). Intraocular pressure (IOP) was assessed in normotensive New Zealand Albino rabbits using a pneumotonometer (model 30 classic; Reichert Ophthalmic Instruments, Depew, NY, USA).
In the presence of GSH, there was an increase in the in vitro release of HS produced by DADS and DATS. Both DADS and DATS also caused a dose-dependent reduction in IOP in male and female rabbits, in both treated and untreated eyes. For instance, in male animals, the presence of GSH (3% and 5%) significantly ( < 0.05, = 5) enhanced the ocular hypotensive action of DADS (2%) and DATS (2%) from 14.02 ± 2.89% to 18.67 ± 5.6% and from 16.22 ± 3.48 to 23.62 ± 5.79%, respectively.
GSH enhanced both HS release and ocular hypotensive action of the polysulfides in a manner that was dependent on the number of sulfur atoms present in each polysulfide. Furthermore, female animals were less sensitive to the IOP-lowering action of the polysulfides, when compared to their male counterparts.
硫化氢（HS）是一种内源性递质，具有调节房水动力学和保护视网膜神经元免于退变的潜力。本研究的目的有两个：（a）评估两种多硫化物，即二烯丙基二硫化物（DADS）和二烯丙基三硫化物（DATS）释放HS的情况；（b）在有和没有谷胱甘肽（GSH）存在的情况下，研究它们对正常血压的雄性和雌性家兔的降眼压作用。
使用HS生物传感器（世界精密仪器公司，佛罗里达州萨拉索塔）每小时对HS进行定量，持续6小时。使用气动眼压计（30经典型号；美国纽约州迪皮尤的赖歇特眼科仪器公司）评估正常血压的新西兰白化家兔的眼压。
在有GSH存在的情况下，DADS和DATS产生的HS的体外释放量增加。DADS和DATS在雄性和雌性家兔的治疗眼和未治疗眼中均引起剂量依赖性的眼压降低。例如，在雄性动物中，GSH（3%和5%）的存在显著（P<0.05，n = 5）增强了DADS（2%）和DATS（2%）的降眼压作用，分别从14.02±2.89%提高到18.67±5.6%以及从16.22±3.48提高到23.62±5.79%。
GSH以依赖于每种多硫化物中硫原子数目的方式增强了多硫化物的HS释放和降眼压作用。此外，与雄性动物相比，雌性动物对多硫化物的降眼压作用不太敏感。
