Effect of Lazaroid U-74389G on Pulmonary Ischemia - Reperfusion Injury in Dogs

Abstract

Lipid peroxidation induced by oxygen free radicals is a contributing factor in ischemia-reperfusion injury. Lazaroid U-74389G (LAZ-G) is a group of new synthetic 21-aminosteroids and inhibits irondependent lipid peroxidation. We investigated the effects of LAZ-G on pulmonary ischemia-reperfusion injury in dogs. Twenty dogs were divided into three groups. In the LAZ-G group (n = 6), LAZ-G was administered 15 min before ischemia. In the St group (n = 5), methylprednisolone was injected 15 min before ischemia and 15 min before reperfusion. In the control group (n = 9), the vehicle of Lazaroid was injected 15 min before ischemia. Warm ischemia was induced for 3 h by clamping the pulmonary artery and veins. Arterial oxygen saturation (SaO2), cardiac output (CO), left pulmonary vascular resistance (L-PVR), and blood levels of interleukin-1beta mRNA were measured. The lung specimen was harvested for histologic study and polymorphonuclear neutrophils (PMNs) counting. SaO2 levels at 30 min and 2 h after reperfusion were significantly higher in the LAZ-G group than in the control group. After 30 min of reperfusion, CO was significantly better in the LAZ-G group than in the St and control groups, and the L-PVR level was significantly lower in the LAZ-G group than in the control group. Survival rates were significantly better in the LAZ-G group than in the control group. Histological damages and PMNs infiltration were more severe in the control group than in the LAZ-G group. Interleukin-1beta mRNA levels were lower in the LAZ-G group than in the control group. Lazaroid U-74389G appears to generate a protective effect against ischemia-reperfusion injury of the lung.

Redox Regulation of Lung Inflammation by Thioredoxin

“…Allopurinol (xanthine oxidase inhibitor), SOD, catalase, deferoxamine (iron chelator), dimethylthiourea (28), or NAC (both thiols) prevented reperfusion injury of the lungs (2, 67,73). Lazaroid, which inhibits iron-dependent lipid peroxidation, also inhibits lung I/R injury in a canine model (141). Antioxidants may also be beneficial to diminish graft rejection after lung transplantation (17).…”

Oxidative Stress and Lung Ischemia-Reperfusion Injury

“…Moreover, when released into the circulation, iron can activate platelet aggregation. An experimental model of lung IR injury using 3 hours of warm ischemia in dogs showed that a new type of lazaroid is able to reduce iron-dependent lipid peroxidation [ 75 ].…”

A lazaroid mitigates postresuscitation myocardial dysfunction

“…It has been documented previously that lazaroids minimize ischemic/reperfusion injury to the lungs (45)(46)(47)(48). Tonoue et al (46) demonstrated that the PaO 2 and PaCO 2 from the lazaroid-treated group were significantly better than control in lung preservation.…”