Comparison of various lazaroid compounds for protection against ischemic liver injury

Abstract

LAZAROIDS, 21-aminosteroids lacking steroid activity have cytoprotective properties against iron-dependent lipid peroxidation. 1 In addition to their antioxidant properties, lazaroids exert their cytoprotective effect by inhibiting arachidonic acid release, membrane stabilization, suppression of Kuppfer cell activation, and down-regulation of cytokine expression and release. 1-3 While previous reports have shown that lazaroids are effective in reducing ischemia and reperfusion injury to many different organ systems, there have been conflicting reports of the potency of the various lazaroid compounds. 4 In this study, we examined the potency and effectiveness of the three major lazaroid compounds in protecting organs against ischemia and reperfusion injury. RESULTS Except for Group A1, the lazaroid infusion was well tolerated. Infusion of lazaroid A1 (high dose) was associated with arrhythmia and hypotension. Two-week animal survival in the control group (30%) was significantly worse than the treated groups (all but one treated

The effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats

“…It is widely accepted that the formation of ROS in the early phase of reperfusion plays a major role in initiating and propagating oxidative stress after reperfusion in different organs, including the liver [28][29][30]. As mentioned previously, COX is the rate-limiting enzyme in prostaglandin production from arachidonic acid, and ROS are also generated as a side product of this reaction [31].…”

The Effect of the Antioxidant Drug “U-74389G” on Lactate Dehydrogenase Levels during Ischemia Reperfusion Injury in Rats

“…These findings suggest that U-74389G can suppress proinflammatory gene up-regulation and ameliorate endotoxin shock. Ishizaki N et al [24] significantly improved dogs survival 3-fold compared with the control ones after lazaroids administration IV at 5mg/kg before IR. Elevation of liver enzymes after reperfusion was markedly attenuated in treated groups.…”

Scavenging effect of lazaroids U78517F, U74389F, U74500A on oxygen free radicals produced by stimulated human polymorphonuclear leucocytes and by chemical method

“…La letteratura ha dimostrato azioni dei lazaroidi che risultano coerenti con i nostri dati. L'attività di inibizione della lipoperossidazione in modelli animali risulta dimostrata (24,25 Lazaroide U78517F. Questo grafico mostra la percentuale di inibizione del lazaroide U78517F sui RLO prodotti dalla stimolazione di PMN umani stimolati valutata in chemiluminescenza.…”