Bo Xuan

Effects of N-nitropyrazoles on ocular blood flow of rabbits and retinal function recovery of rat eyes after ischemic insults.

Twelve compounds of N-nitropyrazoles were studied for their effects on ocular blood flow in rabbits and retinal function recovery in rat eyes after ischemic insults. Of the twelve N-nitropyrazoles examined, nine increased choroidal blood flow while five increased retinal blood flow significantly. On the other hand, all twelve compounds increased blood flow in iris and ciliary muscle without exception. As for retinal function recovery after ischemic insult in rat eyes, eight out of the twelve compounds showed more significant facilitation than the control. The structure activity relationship of the N-nitropyrazoles to increase ocular blood flow and to facilitate retinal function recovery after ischemic insults were discussed.

Relationship between nitric oxide production and choroidal blood flow.

PURPOSE To invent a drug which can specifically facilitate choroid blood flow via increase of nitric oxide (NO). METHOD Cell culture was used for in vitro experiments to determine the production of NO by NO donors and colored microsphere technique was used for in vivo experiments to determine the blood flow in various tissues of rabbit eyes. RESULTS ZX-5 and ZX-4 are two geographic isomers with ZX-5 as trans-form and ZX-4 as cis-form. (1-phenyl-3-[3-methoxy-2-propoxy-5-[4-(3,4,5-trimethoxy-phenyl)-1,3-d lane-2-yl]phenyl]thiourea). It was found that ZX-5 released significant amount of NO at 3, 10, 30 microg/ml concentrations and increased choroid blood flow at 1%, 50 microl instillation into eyes. It was not effective on the blood flow of iris or ciliary body. The corresponding ZX-4 was not effective on ocular blood flow nor it released NO. CONCLUSION ZX-5 can specifically increase the choroidal blood flow which could be useful to suppress the choroidal neovascularization in age-related macular degeneration (AMD). It is hoped that ZX-5 type of compounds could be used for the treatment/prevention of AMD in the elderly.

Release of nitric oxide by N-nitropyrazoles in rabbit lacrimal gland cell culture.

PURPOSE In order to prove the effects of N-nitropyrazoles to increase ocular blood flow and to facilitate retinal function after ischemia are due to nitric oxide (NO) release, eleven N-nitropyrazoles which are known NO donors were used to test their ability to produce NO in rabbit lacrimal gland (RLG) cell cultures. METHODS Nitropyrazoles (0.3-3 microg/ml) were added into RLG cell culture and the NO produced was determined with nitrate-nitrite colorimetric assay. RESULTS All nitropyrazoles (11 compounds) tested produced NO in various degrees with the highest degree by 13 fold over control (DN-5) and the lowest level by only 2.8 fold over control (DN-7). CONCLUSION The results indicated that NO is involved in ocular blood flow increase and retinal function recovery after ischemia by N-nitropyrazoles. However, there is no potency relationship between in vitro data and in vivo data, which is understandable because the experimental environments are different.

Antiuveitis and Inhibition of Fibroblast-Like Corneal and Conjunctival Cell Cultures by Interleukin-1 Blockers, CK 125, CK 126 and CK 128

Three new interleukin-1 (IL-1) blockers, CK 125, CK 126 and CK 128, were studied for their effects on IL-1-induced uveitis in rat eyes. They were more potent (at 3–10 mg/kg t.i.d.) than prednisolone (20 mg/kg t.i.d.) in effectively inhibiting posterior uveitis. They were also found to inhibit fibroblast-like corneal cells at 10–300 µg/ml concentrations and conjunctival cells at 1–30 µg/ml levels. The incorporation of leucine into corneal and conjunctival cells was either stimulated or unaffected by CK 126, indicating that the inhibition of cell growth has nothing to do with the protein synthesis. However, the incorporation of uridine into corneal and conjunctival cells was markedly inhibited by CK 126 at 3–30 µg/ml concentrations whereas the incorporation of thymidine into the cells was inhibited at a lesser extent than that of uridine. These results indicate that cell inhibition by CK 126 could be related mainly to the synthesis of mRNA and, to a lesser extent, to DNA synthesis.

Anti-uveitis and inhibition of fibroblast-like corneal and conjunctival cells by interleukin-1 blockers

Effects of interleukin-1 (IL-1) blockers, CK130 and CK131, on IL-1-induced uveitis and proliferation of fibroblast-like corneal and conjunctival cells were investigated in this study. It was found that CK130 and CK131 inhibited IL-1-induced uveitis in rat eyes effectively at 3 mg/kg and 10 mg/kg, respectively. Further, CK130 and CK131 inhibited fibroblast-like corneal and conjunctival cell growth effectively at 10–300 µg/ml and 30–300 µg/ml, respectively. It was also found that DNA synthesis was markedly reduced by CK130 and CK131 at 30–100 µg/ml. RNA synthesis was also inhibited by these CK compounds but protein synthesis was little affected or enhanced.